Color Atlas of Human Poisoning and Envenoming by stikeshi

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                                                Library of Congress Cataloging-in-Publication Data

        Diaz, James H.
          Color atlas of human poisoning and envenoming / James Diaz.
              p. ; cm.
          Includes bibliographical references and index.
          ISBN-13: 978-0-8493-2215-0 (hardcover : alk. paper)
          ISBN-10: 0-8493-2215-4 (hardcover : alk. paper)
          1. Poisoning--Atlases. 2. Poisons--Atlases. 3. Toxicology--Atlases. I. Title.
          [DNLM: 1. Poisoning--Atlases. 2. Toxicology--Atlases. 3. Antidotes
          --Atlases. 4. Poisons--Atlases. 5. Toxins, Biological--Atlases.
          6. Venoms--Atlases. QV 17 D542c 2006]

        RA1211.D53 2006
        615.9--dc22                                                                                                                 2005033450

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The field of medical toxicology can be simply divided into animal and human poisonings from animal, plant,
or man-made sources. Even more precisely, toxinology is the study of poisoning and envenoming by biologi-
cal organisms, and toxicology is the study of human poisoning from manmade sources. Living organisms,
such as animals, plants, and fungi, produce biological toxins. Man-made toxins, or toxoids, are produced by
controlled chemical reactions, often on an industrial scale, designed to produce novel pharmaceuticals, cos-
metics, household cleansers, fertilizers, herbicides, pesticides, and other useful and necessary consumer and
commercial products. Unfortunately, some biological toxins have already been developed, deployed, and used
as bioterror weapons (e.g., ricin from the castor bean and Shiga toxin from Shigella bacteria). Other biologi-
cal toxins, most notably Staphyloccal toxins A and B, botulinum toxins, and a variety of fungal mycotoxins,
can be mass-produced by rogue nations for biological warfare and agricultural and antipersonnel terrorism.
Many biological toxins, such as poison hemlock, pyrethrin, and red squill, and man-made toxoids, such as
arsenic and thallium salts and pyrethroids, have long been used as pesticides, fungicides, and even as human
poisons. Several types of poison gases, including both vesicant and neurotoxic agents, were intentionally
released during World War I and in very recent wars (Iran-Iraq War) and terror attacks (Sarin nerve gas
attacks in Japan).
   This book will serve as a visual and written reminder of the ubiquitous sources of toxins and toxoids in
the environment and the outcomes of accidental or intentional toxic exposures in humans. This book will
not serve as a comprehensive, major reference source for all toxicologic emergencies; many such comprehen-
sive and even subspecialized toxicology texts are now available. The key features and benefits of this book
include serving as a handy atlas and review outline of human poisoning with photographs and diagrams of
toxic plants and animals, their mechanisms of poisoning or envenoming, and the human lesions (anatomic,
electrocardiographic, and radiographic) caused by toxic exposures. In addition, this text combines the four
subspecialties of toxicology (Analytical, Medical, Environmental, and Industrial) into one comprehensive
atlas with bulleted text, tables, and figure legends that treat toxic exposures in both children and adults. This
book will be a useful study guide for emergency physicians, military physicians, pediatricians, public health
physicians and veterinarians, and health science and medical students and graduates in training or practice,
or preparing to take image-intense specialty or subspecialty board examinations. Finally, this text will serve
as a ready reference for current health science students who seek immediate visual association of venomous
species and toxicokinetics with the rapid identification of envenoming species, the clinical and diagnostic
outcomes of envenoming or poisoning, and the recommended treatment strategies to limit toxic exposures
and injuries.
   This text is intentionally organized in a clinical encounter fashion, beginning with a discussion of general
poisoning management and useful antidotes and later detailing specific management strategies and antidotes
for separate poisonings and envenomings. The book concludes with chapters on biochemical warfare agent
exposure and research design and analysis. Biological and chemical terrorism and warfare agents are timely
subjects that are still evolving, particularly in the areas of early detection by biosurveillance monitoring sys-
tems and real-time polymerase chain reaction (PCR) analyses and personnel protection by preventive immu-
nization, rapid decontamination, specific reversal agents, and personal protective equipment.

                                                                                                     Preface | 

The author acknowledges the encouragement and support of the medical editors in Boca Raton, Florida,
at CRC Press, LLC, and the Taylor and Francis Group, LLC. Despite the destruction and havoc, including
loss of digital images and text, caused by several Category 3 and greater hurricanes that struck Florida and
Louisiana in 2004 and 2005, the following medical editors were always available for advice and consultation,
even from temporary evacuation residences: (1) Stephen Zollo, Senior Editor, CRC Press, who provided the
vision and clear direction to guide this book project to completion; (2) Helena Redshaw, Manager, Editorial
Project Development, Taylor and Francis Group, who seamlessly coordinated the text revisions and image
transfers; and (3) Jay Margolis, Project Editor, Taylor and Francis Group, who directed the final production
of the text.
   The author also recognizes and appreciates the cooperation and support of the Audubon Nature Institute
and its dedicated staff of biologists and naturalists in New Orleans, Louisiana. Audubon Institute staff pho-
tographed many of the venomous arthropods, amphibians, and reptiles featured in this book with delicate
care and close attention to natural habitats and settings. In particular, the author recognizes the following
professional biologists, who provided valuable consultation to the author and contributed their personal pho-
tographs to the atlas: (1) Dino Ferri, Assistant Curator of Amphibians and Reptiles; and (2) Zack Lemann,
Curator of Arthropods, both of the Audubon Nature Institute in New Orleans, Louisiana.
    In addition, the author gratefully acknowledges the valuable contribution of the following physician spe-
cialists: (1) Dr. Charles P. Sea, Attending Staff Emergency Medicine Physician, Ochsner Clinic Foundation
Hospital, New Orleans, Louisiana; and (2) Dr. Carlos R. Gimenez, Professor of Radiology, Department of
Radiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
The author also gratefully acknowledges the important artistic and technical contributions of Karen Grady,
Computer Graphic Artist in the Department of Learning Resources at the Louisiana State University Health
Sciences Center in New Orleans, Louisiana; and the dedicated computer and clerical support services of the
following health science students: (1) Paige S. Katz, BS, doctoral candidate in Medical Physiology; and (2)
Melanie A. Sheen, BA, premedical student.

                                                                                     Acknowledgments | ii
                                                     About the Author

A native of New Orleans, Louisiana, Dr. James H. Diaz earned several degrees with distinction from Tulane
University, including Bachelor of Science, Doctor of Medicine, Master of Health Administration, Master of
Public Health and Tropical Medicine, Diploma in Clinical Tropical Medicine and Travel Health, and Doctor
of Public Health. Dr. Diaz is board-certified in anesthesiology, critical care medicine, pain management, gen-
eral preventive medicine and public heath, occupational and environmental medicine, and medical toxicol-
ogy. He currently serves as Professor of Public Health and Program Head, Environmental and Occupational
Health Sciences, at the Louisiana State University (LSU) Schools of Medicine and Public Health in New
Orleans, Louisiana, and as Adjunct Professor of Pathobiological Sciences at the LSU School of Veterinary
Medicine in Baton Rouge, Louisiana.
   Dr. Diaz has published more than 100 original articles and chapters in scientific journals and textbooks
and is the editor and primary contributing author of Perinatal Anesthesia and Critical Care, W.B. Saunders,
Company, 1991. Dr. Diaz’s current clinical interests include the practices of general preventive medicine
and public health, occupational medicine, environmental and travel medicine, and medical toxicology. His
current academic interests include: (1) occupational and environmental cancer and injury risk factors; (2)
environmental and tropical diseases of travelers; (3) emerging environmentally associated infectious diseases,
particularly food-borne, waterborne and vector-borne communicable diseases; (4) human envenomings; and
(5) poisonings with natural, alternative, and over-the-counter pharmaceuticals. In 2001, Dr. Diaz was elected
to lifetime membership in Delta Omega, the national public health honor society, for academic scholarship
and contributions to population health promotion, disease and injury prevention, and preventive medical

                                                                                       About the Author | ix

the Pharmacology of Human Poisonings
                                           Chapter Outline..................................................... 3
                                           Definitions ............................................................. 5
                                           Absorption ............................................................ 6
                                           Distribution .......................................................... 9
                                           Metabolism ......................................................... 11
                                           Excretion ............................................................. 14
                                           Poisoning in the Elderly ....................................... 17
                                           Poisoning in Children .......................................... 18
the General Management of the Poisoned Patient
                                           Chapter Outline................................................... 21
                                           Preventing Gastrointestinal Absorption
                                           of the Toxin ......................................................... 23
                                           Enhancing Elimination of the Toxin .................... 28
Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient
                                           Chapter Outline................................................... 33
                                           Physical Assessment of the Poisoned Patient ........ 35
                                           Pharmacokinetics ................................................ 37
                                           Laboratory Assessment of the Poisoned Patient ... 39
                                           Radiographic Evaluation ..................................... 41
                                           Electrocardiographic (ECG) Assessment ............. 46
                                           Nontoxic Exposures ............................................ 49
                                           Chapter Outline................................................... 53
                                           Toxidromes and Antidotes ................................... 55
                                           Gastrointestinal Decontaminants ........................ 57
                                           Metal Chelators ................................................... 60
                                           Antivenins and Antitoxins ................................... 62
                                           Specific Antagonists ............................................. 64
                                           Vitamins .............................................................. 66
                                           Specific Antidotes ................................................ 68
                                           Nonspecific Antidotes.......................................... 70

                                                                                                   Contents | xi
Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical

Part 1
Poisonings with Over-the-Counter and Opioid analgesics
                                                        Acetaminophen (N-acetyl-para-aminiphenol)
                                                        (APAP) vs. Acetyl Salicyic Acid (ASA) ................. 77
                                                        Nonsteriodal Anti-Inflammatory Drugs
                                                        (NSAIDs) ............................................................. 82
                                                        Opioids ................................................................ 84
Part 2
Poisonings with Pharmaceutical additives
                                                        Glycols ................................................................. 91
                                                        Benzyl Alcohol..................................................... 92
                                                        Bromines/Bromides ............................................. 93
                                                        Chlorobutanol ..................................................... 94
                                                        Thimerosal .......................................................... 95
                                                        Benzalkonium Chloride ...................................... 96
                                                        Phenol .................................................................. 97
                                                        Parabens .............................................................. 98
                                                        Pharmaceutical Additive Tragedies ...................... 99
Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary
                                                        Chapter Outline................................................. 103
                                                        Descriptive Epidemiology of Herbal and
                                                        Vitamin Poisonings ........................................... 105
                                                        Pharmacology of Herbal and Vitamin
                                                        Poisonings.......................................................... 106
                                                        Toxicology of Herbal Poisonings ....................... 107
                                                        Toxicology of Vitamin Poisonings ..................... 110
Poisonings with Common Household Products
                                                        Chapter Outline................................................. 115
                                                        Antiseptics ......................................................... 118
                                                        Disinfectants...................................................... 121
                                                        Hospital Sterilants ............................................. 123
                                                        Hydrocarbons .................................................... 124
                                                        Caustics ............................................................. 126
                                                        Toxic Alcohols ................................................... 130
                                                        Toxic Deafness and Blindness ............................ 135
Reproductie and Perinatal toxicology
                                                        Chapter Outline................................................. 139
                                                        Epidemiology of Reproductive Toxicology ........ 141

xii |   Color Atlas of Human Poisoning and enenoming
                                           Toxins Affecting Fertility, Potency, and
                                           Gestation ........................................................... 142
                                           Pharmacokinetics of Pregnancy ......................... 145
                                           Acute Poisoning in Pregnancy............................ 147
                                           Specific Poisonings in Pregnancy ....................... 148
                                           Theophylline Overdose in Pregnancy................. 149
                                           Substance Abuse in Pregnancy........................... 151
                                           Breast-Feeding ................................................... 152
Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit

Part 1
analgesic adjuvants, Psychotropics, and Sedative-Hypnotics
                                           Caffeine ............................................................. 157
                                           Ergotamines ...................................................... 159
                                           Cyclic Antidepressants (CAs) ............................. 161
                                           Monoamine Oxidase Inhibitors ......................... 163
                                           Neuroleptics ...................................................... 165
                                           Lithium.............................................................. 167
                                           Anticonvulsants ................................................. 168
                                           Sedative-Hypnotics ........................................... 170
Part 2
Illicit Substances
                                           Cocaine ............................................................. 179
                                           Amphetamines................................................... 185
                                           Phencyclidine (PCP) .......................................... 187
                                           Lysergic Acid Diethylamide (LSD) .................... 188
                                           Marijuana.......................................................... 189
                                            “Date-Rape” Drugs .......................................... 190
CHAPteR 10
Poisonings with Cardioascular Medications
                                           Chapter Outline................................................. 193
                                           Cardiac Glycosides ............................................ 195
                                           Beta-Blockers ..................................................... 197
                                           Calcium Channel Blockers ................................. 200
                                           Miscellaneous Antihypertensives ....................... 202
CHAPteR 11
Miscellaneous Poisonings with Commonly Prescribed Drugs: Antibiotics, Cancer
Chemotherapeutics, and Hypoglycemics

Part 1
                                           Antibiotics ......................................................... 211
                                           Antituberculous Agent Toxicity ........................ 214
                                           Antimalarial Agent Toxicity .............................. 217

                                                                                                Contents | xiii
Part 2
Cancer Chemotherapeutics
                                                        Human Carcinogens .......................................... 221
                                                        Classification ..................................................... 222
                                                        Epidemiology ..................................................... 223
                                                        Methotrexate (MTX) ........................................ 224
                                                        Vincristine (VCR) ............................................. 226
                                                        Anthracyclines/Antibiotics ................................. 227
                                                        Nitrogen Mustards ............................................ 228
                                                        Platinoids ........................................................... 229
Part 3

CHAPteR 12
Food Poisonings
                                                        Chapter Outline................................................. 239
                                                        Introduction ...................................................... 241
                                                        Clinical Manifestations ..................................... 242
                                                        Etiologic Agents ................................................. 243
                                                        Top Etiologic Agents ......................................... 244
                                                        Bacterial Diseases .............................................. 245
                                                        Viral Diseases .................................................... 253
                                                        Protozoal Diseases ............................................. 255
                                                        Parasitic Diseases ............................................... 259
                                                        Cruise Ship Diarrhea - Bon Voyage ................... 260
                                                        Conclusions ....................................................... 262
CHAPteR 13
Seafood Poisoning
                                                        Chapter Outline................................................. 265
                                                        History .............................................................. 267
                                                        Epidemiology ..................................................... 268
                                                        Definitions ......................................................... 269
                                                        Shellfish Poisoning ............................................. 271
                                                        Pfiesteria-Complex Organisms (PCOs) ............. 273
                                                        Crustacean Poisoning ........................................ 274
                                                        Finfish Poisoning ............................................... 275
                                                        General Management Strategies ....................... 278
                                                        Prevention Strategies .......................................... 279
                                                        Conclusions ....................................................... 280
CHAPteR 14
Mushroom Poisonings
                                                        Chapter Outline................................................. 283
                                                        Descriptive Epidemiology .................................. 285
                                                        Toxicological Classification ............................... 287

xi |   Color Atlas of Human Poisoning and enenoming
CHAPteR 15
Poisonous Plants
                                            Chapter Outline ................................................ 293
                                            Epidemiology of Plant Poisonings ...................... 295
                                            Plant Toxicology ................................................ 296
CHAPteR 16
terrestrial enenomings
                                            Chapter Outline................................................. 307
                                            Terrestrial Animals ............................................ 309
                                            Arthropods (Insects) .......................................... 314
CHAPteR 17
Marine enenomings
                                            Chapter Outline................................................. 321
                                            Taxonomy.......................................................... 323
                                            Epidemiology ..................................................... 324
                                            Toxic Coelenterates (Invertebrates) ................... 325
                                            Toxic Vertebrates ............................................... 328
CHAPteR 18
Arthropod Vectors of Human Infectious Diseases
                                            Chapter Outline................................................. 333
                                            Mosquitoes ....................................................... 335
                                            Flies ................................................................... 337
                                            Myiasis-Causing Flies ........................................ 340
                                            Fleas, Lice, True Bugs, Ticks, and Mites............ 341
                                            Conclusions ....................................................... 347
CHAPteR 19
Pesticide Poisoning: Insecticides, Rodenticides, and Herbicides
                                            Chapter Outline................................................. 351
                                            Insecticides ........................................................ 353
                                            Rodenticides ..................................................... 355
                                            Herbicides.......................................................... 359
CHAPteR 20
Volatile Organic Chemical (VOC) Poisoning
                                            Chapter Outline................................................. 363
                                            Hydrocarbons (HCs) ......................................... 365
                                            Toxic Volatile Alcohols ...................................... 367
CHAPteR 21
Heay Metal Poisoning
                                            Chapter Outline................................................. 375
                                            Arsenic (As) ....................................................... 377
                                            Cadmium (Cd) ................................................... 379
                                            Chromium (Cr) .................................................. 381
                                            Lead (Pb) ........................................................... 383
                                            Mecury (Hg) ...................................................... 390
                                            Thallium (Th) .................................................... 392
                                            Minor Metal Toxicity ........................................ 394

                                                                                                    Contents | x
CHAPteR 22
Industrial Gas exposures
                                                        Chapter Outline................................................. 399
                                                        Simple Asphyxiants ........................................... 401
                                                        Pulmonary Irritants ........................................... 402
                                                        Smoke Inhalation .............................................. 404
                                                        Carbon Monoxide (CO) Poisoning .................... 405
                                                        Cyanide Poisoning ............................................ 407
                                                        Hydrogen Sulfide (H 2S) Poisoning ..................... 409
CHAPteR 23
Radiation toxicology
                                                        Chapter Outline................................................. 413
                                                        Introduction ...................................................... 415
                                                        Historical Events ............................................... 416
                                                        Definitions ......................................................... 418
                                                        Basic Science of Radioactivity............................ 419
                                                        Types of Radiation............................................. 420
                                                        Units of Measure ............................................... 421
                                                        Sources of Radiation Exposure .......................... 422
                                                        Radioactive Isotopes .......................................... 423
                                                        Types of Radiation Exposure ............................. 424
                                                        Preparing for Arrival of Victims ........................ 425
                                                        Diagnosis .......................................................... 426
                                                        External Contamination .................................... 427
                                                        Internal Contamination ..................................... 428
                                                        External Irradiation ........................................... 429
                                                        Whole Body Radiation/Acute Radiation
                                                        Syndrome (ARS) ................................................ 430
                                                        Radiation Exposures during Pregnancy ............. 432
                                                        Resources for Radiation Emergencies ................ 435
CHAPteR 24
Chemical and Biological Weapons and Warfare (CBW)
                                                        Chapter Outline................................................. 439
                                                        Definitions ......................................................... 441
                                                        Chemical Warfare and Biological Warfare
                                                        Similarities......................................................... 442
                                                        Chemical Warfare and Biological Warfare
                                                        Differences......................................................... 443
                                                        History of Chemical Warfare and Biological
                                                        Warfare .............................................................444
                                                        Chemical Weapons ............................................ 446
                                                        Biological Weapons ........................................... 449
                                                        Emergency Responsiveness ................................ 454
                                                        Hierarchies of Prevention .................................. 455
CHAPteR 25
Workplace Substance Abuse Monitoring
                                                        Chapter Outline................................................. 459
                                                        Introduction ...................................................... 461
                                                        Federal Regulations ........................................... 462

xi |   Color Atlas of Human Poisoning and enenoming
                                                                                  Epidemiology ..................................................... 464
                                                                                  Chemical Dependency ....................................... 467
                                                                                  Abused Substances ............................................ 468
                                                                                  Substance Abuse Professionals (SAPs) ............... 473
                                                                                  Medical Review Officers.................................... 474
                                                                                  Employee Assistance .......................................... 476
                                                                                  Rehabilitation .................................................... 477
                                                                                  Alcohol Testing .................................................. 479
                                                                                  Drug Testing ...................................................... 480
                                                                                  Chain of Custody (CoC) ................................... 482
                                                                                  MRO Responses ................................................ 488
CHAPteR 26
epidemiological Design and Statistical Analysis of toxicological Inestigations

Part 1
Epidemiological Design
                                                                                  Definitions ......................................................... 495
                                                                                  Disease Natural History and Prevention Levels . 496
                                                                                  Causation .......................................................... 497
                                                                                  Rates.................................................................. 498
                                                                                  Data Sources...................................................... 501
                                                                                  Descriptive Epidemiology .................................. 504
                                                                                  Analytical Epidemiology.................................... 505
                                                                                  Experimental Epidemiology............................... 508
                                                                                  Screening ........................................................... 509
                                                                                  Surveillance ....................................................... 511
Part 2
Biostatistics for Epidemiology
                                                                                  Probability ......................................................... 515
                                                                                  Descriptive Statistics .......................................... 516
                                                                                  Differential Statistics ......................................... 518

Index .......................................................................................................................................................525

                                                                                                                                         Contents | xii
                             Chapter 1

the Pharmacology of
  Human Poisonings

      the Pharmacology of Human Poisonings | 1
Chapter Outline

                  Routes of absorption
                  Routes vs. rates of absorption
                  Rates vs. bioavailabilities
                  Toxin transport mechanisms

                  Bound vs. unbound drugs
                  Physiochemical determinants of xenobiotic
                  Bioavailability, concentration, and the volume of
                     distribution (Vd)
                  Classical compartment models of distribution

                  Metabolic reactions
                  Drug interactions
                  Pharmaceutical excipients
                  Therapeutic Index (TI)
                  Dose-response relationships

                  Drug elimination kinetics
                  Plasma clearance of xenobiotics
                  Renal elimination of xenobiotics
                  Enhanced in vivo elimination of xenobiotics
                  Enhanced extracorporeal elimination of xenobiotics

              Poisoning in the elderly
                  Behavioral and physical considerations
                  Pharmacokinetic considerations

              Poisoning in children
                     Ingested agents
                     Most commonly ingested agents
                     General management

                           the Pharmacology of Human Poisonings | 3
Xenobiotics: Foreign, natural, or man-made (syn-
     thetic) chemicals, including drugs, pesticides,
     environmental, and industrial agents.
Pharmacokinetics: The application of mathemati-
     cal models to describe and predict the behavior
     of drugs during their absorption, distribution,
     metabolism, and elimination.
Pharmacodynamics: The relationships of drug con-
     centrations to their observed clinical effects.
Toxicokinetics: The application of mathematical
     models to describe and predict the behavior of
     xenobiotics in toxic or excessive doses during
     their absorption, distribution, metabolism, and
Toxicodynamics: The relationships of toxic concen-
     trations of xenobiotics to their observed clinical

                                                          the Pharmacology of Human Poisonings | 5

Routes of Absorption                                          absorption. Example: enteric-coated tablets,
                                                              long-acting preparations, meprobamate (fre-
Enteral administration                                        quently forms concretions), foods (persimmons
Oral: Variable absorption, yet most commonly used             = form phytobezoars).
     route; subjects all xenobiotics to first-pass       Gastric outlet pylorospasm: Most frequently caused
     hepatic metabolism; oral doses often diluted             by common gastric irritants. Example: iron,
     by foods; intestinal absorption delayed by               salicylates.
     enteric coatings, drug concretions and bezoars,
     anticholinergics, sedatives, and drug-induced       Routes s. Rates of Absorption
     pylorospasm.                                        routes of absorption
Sublingual: Xenobiotics enter systemic circulation
     closer to the central nervous system (CNS)          Enteral: Oral, rectal.
     without first pass, avoiding gastric delays and     Parenteral: Intradermal, subcutaneous, intravascular
     inactivation. Example: nitroglycerin (NTG).              (intravenous, intra-arterial), intramuscular.
Rectal: Also avoids gastric delays and inactivation;     Cutaneous: Topical and transdermal.
     useful during nausea and vomiting; provides         Miscellaneous: Inhalation, sublingual, transmucosal,
     shortcut to central circulation and reduces first        intranasal, intrathecal, intraventricular.
     pass by 50%.
                                                         rates of absorption
Parenteral administration                                Fastest-to-slowest: Intravascular > inhalation > sub-
Intravascular: Intravenous route (iv) most commonly           lingual > intranasal > intramuscular > rectal >
     used; avoids both gastrointestinal tract and             oral > subcutaneous > topical > transdermal.
     first-pass hepatic metabolism; useful for drugs     Rate of absorption: Predicts the onset of action of
     poorly absorbed by or unstable in gastrointesti-         xenobiotics.
     nal tract. Example: insulin, lidocaine.             Extent of absorption: Predicts the bioavailability
Intramuscular and subcutaneous: Good for slow, sus-           of the xenobiotic or the extent of its phar-
     tained delivery of depot preparations of drugs.          macologic effect. Example: digoxin has 50%
     Example: antibiotica.                                    bioavailability.
Intrathecal and intraventricular: Used primarily for
     cancer drugs, local anesthetics, opioids, and       Rates s. Bioaailabilities
     antibiotics. Caution: use only sterile, preserva-
     tive-free medications to avoid risks of chemical    Physiochemical Factors
     arachnoiditis. Example: preservative-free mor-      Influencing Absorption
     phine and clonidine for chronic pain.               Physical Factors
Delayed Gastrointestinal absorption                      Molecular weight (MW): Low MW promotes rapid
                                                              absorption by passive diffusion.
Delayed gastric emptying: Often results from fatty
                                                         Blood flow: High blood flow favors high absorption.
     meals, anticholinergics, antiserotoninergics
                                                              Example: intestinal > gastric absorption.
     (ondansetron), barbiturates, ethanol, glutethi-
                                                         Surface area: High surface area favors high absorp-
     mide, methaqualone, and opioids.
                                                              tion. Example: intestinal > gastric absorption.
Drug coatings, bezoars (undigested food or foreign
                                                         Contact time: Absorption is inversely proportional to
     [hair] proteinaceous materials), concretions:
                                                              gastrointestinal transit time. Example: cathar-
     Will all require initial disintegration prior to
                                                              tics speed transit time and limit absorption.

6 | Color Atlas of Human Poisoning and enenoming
                                    Decreasing rate × constant              to short-acting; Carfentanil > fentanyl > sufen-
                                           bioavailability                  tanil > alfentanil.
                                 Blood concentrations of 3 poisons     Polarity: Lack of polarity or charge favors enhanced
                                 when bioavailability is constant &
                                  rate of absorption is decreasing          absorption by passive diffusion.
                                             over time.                pH: Acidic drugs (ASA) demonstrate increased ab-
                                   1                                        sorption in the acidic stomach; basic drugs
                                                                            demonstrate increased absorption in the alka-

                                                                            line intestine (jejunum > ileum).
                                                    Therapeutic        toxin transport Mechanisms
                                                                       Passive Diffusion
                             0                  Time                   Concentration gradient: The gradient between high-
                                                                             to-low concentrations that provides the driving
FIGURe 1.1a      The blood concentrations of three                           force for passive diffusion.
poisons when bioavailability is constant and rate of                   Saturation potential: None; passive diffusion is not
absorption is decreasing over time.                                          susceptible to saturation or zero-order kinetics.
                                                                       Energy source: Concentration gradients alone.
                                    Constant rate × decreasing         Fick’s Law of Diffusion: Governs the rate of passive
                                         bioavailability                     diffusion = dQ/dT = DAK (C1 − C2)/h, where D
                                 Blood concentrations of 3 poisons           = diffusion constant, A = surface area of mem-
                                 when rate of absorption is constant
                                   & bioavailability is decreasing
                                                                             brane, and C1 − C2 = difference in poison con-
                                             over time.                      centrations on either side of membrane.

                                       4                 Toxic         active transport

                                                                       Carrier protein: Required for active transport against
                                                                            concentration gradients.
                                                                       Saturation potential: High; protein carriers are often
                                                                            saturated in overdose, allowing toxins to accu-
                         0                                                  mulate in the central circulatory compartment.
                             0                 Time
                                                                       Energy source: Energy is provided by the hydrolysis
                                                                            of ATP. Active transport is a highly energy-
FIGURe 1.1b Constant rate x decreasing bioavail-
                                                                            dependent process.
ability. The blood concentrations of three poisons
when rate of absorption is constant and bioavailability
is decreasing over time.

     Chelators of heavy metal toxins enhance the
     bioavailability of safer, complexed toxins, but
     have no impact on transit time or absorption,
     unless combined with cathartics. Example: def-
     eroxamine and Fe, penicillamine and Cu, suc-
     cimer and Pb.

Solubility, Polarity, pH
Water solubility: Water-soluble (hydrophilic) xenobi-
     otics cannot cross lipoprotein membranes and
     must filter through aqueous channels.
Lipid solubility: Lipid-soluble (lipophilic) xenobi-
     otics readily cross lipoprotein membranes for
     increased absorption and often enter entero-
     hepatic cycles that decrease renal elimination.
     Example: Opioids: Fentanyls. From long-acting

                                                                                the Pharmacology of Human Poisonings | 7
                     Passive diffusion
                Favors: Non-polar, unionized                                   Active transport
                    weak acids & bases.                                        Favors: Specific

                                                                     Drug          Carrier


FIGURe 1.2a      Passive diffusion favors nonpolar,   FIGURe 1.2b       Active transport favors specific
unionized weak acids and bases.                       xenobiotics.

8 | Color Atlas of Human Poisoning and enenoming
Bound s. Unbound Drugs                                        biotics and preferentially perfuses brain, liver,
                                                               kidneys > muscle > fat > bone.
Bound Drugs                                                •   Drug structure: Uncharged, hydrophobic,
                                                               and lipophilic drugs readily cross lipoprotein
 • Specialized proteins bind xenobiotics in plasma             membranes.
     and tissue compartments, making toxins                •   Protein binding: Plasma and specialized car-
     unavailable for distribution.                             rier proteins sequester xenobiotics in the central
 •   Albumin: Binds acidic (“A”) drugs with low                plasma compartment and often become satu-
     Vd = aspirin, phenoxyacetic acid herbicides,              rated, resulting in high plasma concentrations
     anticonvulsants, anticoagulants (warfarin or              of unbound toxins.
     coumadin).                                            •   Physiologic barriers: Protect downstream target
 •   α-1-acid glycoprotein: Binds basic (“B”) drugs            organs from xenobiotic distribution and toxic-
     with low Vd = β-blockers, amide local anesthet-           ity. Example: blood–brain barrier, placental
     ics, tricyclic antidepressants (TCAs).                    barrier, blood–testis barrier.
 •   Specialized carrier proteins: Exist in the blood-
     transferrin (carries Fe); in the kidney-metallo-
     thionein (carries Cd, Pb, and Hg); and in the       Bioaailability, Concentration, and
     retina-melanin (carries chloroquine and chlor-      the Volume of Distribution (Vd)
     promazine [CPZ]).
                                                         Definitions and relationships

Unbound Drugs                                              • V : The theoretical volume into which a drug
 • Only unbound drugs freely distribute through            •   Vd: Determines how much of a drug remains
     membranes to tissues.                                     inside or outside the central circulatory
 • Bioavailability:     Applies to unbound drugs               (plasma) compartment sampled by serum
 •   Saturation or zero-order kinetics: Toxic over-        •   Vd: Drugs with Vd < 1 L/kg remain inside the
     doses often saturate protein binders and car-             plasma compartment available for removal by
     riers (albumin-binder, transferrin-Fe carrier),           hemodialysis (HD). Example: ASA Vd = 0.2;
     making large concentrations of unbound drugs              ethylene glycol (antifreeze) Vd = 0.6.
     available for tissue distribution and organ tox-      •   Vd: Drugs with Vd > 1 L/kg distribute from
     icity. Example: ASA-CNS toxicity; Fe-hepato-              plasma to tissues and are unavailable for
     toxic and cardiotoxic.                                    removal by HD. Example: digoxin Vd = 5; TCA
 •   Lab serum concentrations: Of limited value in             Vd = 10–15.
     determining serum concentrations of unbound
     drugs because labs measure both bound and
                                                         Determinants of the Vd
     unbound drugs to determine serum values that
     closely approximate plasma concentration.
                                                           • Drug dose administered
                                                           • Drug bioavailability
Physiochemical Determinants                                • Peak plasma concentration
of Xenobiotic Distribution                                 • Formula: V = dose in mg/kg × bioavailability
                                                               (%)/plasma concentration. Alternatively, plasma
                                                               concentration = dose in mg/kg/Vd × weight in
 • Blood flow: Determined by the cardiac output                kg
     and accounts for initial distribution of xeno-

                                                                    the Pharmacology of Human Poisonings | 9
Classical Compartment                                    two-Compartment Model
Models of Distribution
One-Compartment Model                                      • Definition: Most xenobiotics do not instanta-
                                                              neously equilibrate with tissues, but are initially
                                                              distributed to highly perfused organs, and sub-
  • Definition: Some xenobiotics rapidly enter the            sequently distributed to less perfused periph-
     central circulatory compartment for rapid dis-           eral tissues. Example: Digoxin, barbiturates,
     tribution to tissues; plasma concentrations mir-         lidocaine.
     ror tissue concentrations.

               Input       Distribution                          Input
            (absorption)                                      (absorption)
                             Central                                           Central                     Peripheral
                           compartment                                       compartment                  compartment

                           Elimination                                       Elimination

FIGURe 1.3a One-compartment distribution model.          FIGURe 1.3b Two-compartment distribution model.
Some xenobiotics rapidly enter the central circulatory   Most xenobiotics do not instantaneously equilibrate
compartment for rapid distribution to tissues; plasma    with tissues, but are initially distributed to highly per-
concentrations mirror tissue concentrations.             fused organs, and subsequently distributed to less
                                                         perfused peripheral tissues. Ex: barbiturates, digoxin,

10 | Color Atlas of Human Poisoning and enenoming
Metabolic Reactions                                          • CYP3A4 — Many antiarrhythmics, oral con-
                                                                 traceptive pills (OCPs), warfarin. The most
Phase I Hepatic reactions                                        important member of the CYP-450 family that
                                                                 metabolizes many drugs, including macrolide
  • Mechanisms: Preparative or nonsynthetic reac-                antibiotics (erythromycins), antifungal azoles,
      tions that often precede phase II reactions and            the nonsedating antihistamines (astemizole and
      either add oxygen and introduce polar groups               terfenadine – Seldane®), and cisapride (Propul-
      to (by oxidation > reduction and hydrolysis)               sid®). When two or more drugs metabolized by
      or expose polar groups on (by dealkylation)                CYP-450 3A4 are prescribed, the toxicity of
      xenobiotics to increase their polarity and water           the slowest metabolized drug can be enhanced,
      solubility in preparation for further hepatic              producing adverse effects. Both terfenadine and
      metabolism (by phase II) or renal elimination.             cisapride caused QRS widening and, rarely,
  •   Enzymes: All phase I enzymes are members of                fatal torsades de pointes when prescribed with
      the hepatic microsomal (endoplasmic reticulum              other 3A4-metabolized drugs and were with-
      fraction) mixed function oxidase (oxygen-add-              drawn from the market by the U.S. Food and
      ing) enzyme system (Cytochrome [CY] P-450                  Drug Administration (FDA).
      family). All phase I hepatic reactions require
      the reducing agent nicotinamide adenine dinu-
      cleotide phosphate (NADP) to add O2 to and           Drug Interactions
      increase the polarity of xenobiotics.
                                                           Hepatic Enzyme Inducers
Phase II Hepatic reactions
                                                             • Increase substrate drug metabolism and thereby
                                                                 decrease therapeutic drug efficacy.
  • Mechanisms:        Synthetic reactions that often
                                                             • Anticonvulsants: Barbiturates, carbamazepine,
      replace or follow, but rarely precede, phase I
                                                                 phenytoin, primidone.
      reactions, designed to conjugate polar groups,
      reduce electric charges, and assure water solu-
                                                             •   Sedatives: Ethanol, glutethimide.
      bility for the ultimate renal elimination of xeno-
                                                             •   Antibiotics:    Isoniazid     (INH),   rifampin
                                                                 (decreases efficacy of oral contraceptive pills
      biotics. Conjugation occurs with glucuronide >
                                                                 [OCPs]), griseofulvin.
      sulfate, acetate, methyl groups, or amino acids
      (glycine > taurine and glutamic acid).
                                                             •   Miscellaneous: Omeprazole, polycyclic aro-
                                                                 matic hydrocarbons (PAHs), St. John’s wort (can
  •   Enzymes: Phase II hepatic enzymes may belong               decrease efficacy of cycloserine, indinavir, and
      to either the liver’s microsomal (CYP-450) or              oral contraceptives (OCPs); interacts with selec-
      cytosolic fractions.                                       tive serotonin reuptake inhibitors (SSRIs), and
                                                                 has been associated with suicides and deaths in
Common Members of the CYP-450 Hepatic                            depressed patients on SSRIs, possibly associated
Enzyme Family and their representative                           with central serotonin excess).
Enzyme Substrates
                                                           Hepatic Enzyme Inhibitors
  • CYP1A1 — Polycyclic aromatic hydrocarbons
      (PAHs)                                                 • Decrease    substrate drug metabolism, usually
  • CYP1A2 — Acetaminophen                                       increasing toxicity of drug, but decreasing tox-
  • CYP2A6 — Nicotine                                            icity of metabolites. Example: cimetidine for
  • CYP2D6 — Debrisoquine                                        mushroom poisoning to block the metabolism
  • CYP2F1 — Ethanol                                             of the hepatotoxic poison, amanitin.

                                                                    the Pharmacology of Human Poisonings | 11
  • Antifungals: All azoles.                                Pharmaceutical excipients
  • Antibiotics: All macrolides,   chloramphenicol,
                                                            What are Excipients?
      primaquine,    trimethoprim-sulfamethoxazole,
      ciprofloxacin.                                          • Definition: Excipients are the chemical ingredi-
  •   Antiarrhythmics: Amiodarone, β-blockers,                    ents other than active drugs that are included
      quinidine, verapamil.                                       in pharmaceutical preparations for a variety of
  •   H2-blockers and proton-pump inhibitors:                     reasons.
      Cimetidine, ranitidine, omeprazole.                     •   Uses: Binders, coatings, colors, diluents, disin-
  •   Most antipsychotics and tricyclic antidepres-               tegrators, flavorings, preservatives, sweeteners,
      sants (TCAs).                                               solvents.
  •   Miscellaneous: Allopurinol, OCPs, grapefruit
                                                            Commonly Used Excipients
                                                            Colors: Dyes can cause allergic reactions. Example:
Pharmacogenetics                                                 FD&C Reds 40 and 19, carnine, quinolone
Genetic Polymorphisms                                            yellow.
                                                            Flavorings: Licorice (glycyrrhizic acid) inhibits corti-
                                                                 sol metabolism, causing or exacerbating hyper-
  • Definition:      Inherited (autosomal recessive,
                                                                 tension and promoting hypokalemia.
      often X-linked), inter-individual differences in
                                                            Sweeteners: Aspartame is contraindicated in
      the structure and function of specific hepatic
      microsomal or cytosolic enzymes that alter
                                                            Preservatives: Benzyl alcohol in IV flush solutions
      either phase I or phase II hepatic metabolic reac-
                                                                 and multi-dose medication vials can cause aci-
      tions to promote or, more rarely, to reduce the
                                                                 dosis and shock in preemies – “Gasping Baby”
      toxicity of xenobiotics, usually therapeutically
      administered drugs. Example: fast (decreased
                                                            Solvents: Polyethylene glycol in IV drugs irritates
      efficacy) vs. slow (increased toxicity) acetylators
                                                                 veins and has caused metabolic acidosis and
      of the anti-tuberculosis drug isoniazid (INH).
                                                                 acute renal failure after applying topical anti-
Common Genetic Polymorphisms                                     microbial (sulfonamides) creams for extensive
                                                                 burn therapy.

  • Fast vs. slow INH acetylators: 95% of Asians            therapeutic Index (tI)
      and Blacks are fast (rapid) acetylators of INH at
      lower risk of INH neurotoxicity; 50% of Amer-         What Is the therapeutic Index (tI)?
      icans and >70% of Scandinavians are slow acet-          • Definition: The TI is the ratio of the dose of
      ylators at higher risk of INH toxicity.                     a drug that causes toxicity to the dose that
  •   Pseudocholinesterase deficiency: 2% of Ameri-               produces the desired and intended effect. The
      cans and most Alaskan and Canadian Inuits can-              TI can only be determined by administering
      not metabolize ester local anesthetics (including           increasing drug doses to volunteers and observ-
      cocaine) and succinylcholine with higher risks              ing for toxic responses.
      of toxicity, especially cocaine-induced myocar-
      dial infarction (MI) and CVA, and succinylcho-
      line-prolonged paralysis.                             How Is Drug Safety assessed? (by large vs.
  •   Glucose-6-phosphate dehydrogenase (G-6-PD)            small tIs)
      deficiency: Common in Blacks (confers malaria
      protection) and renders red blood cells incapa-
      ble of responding to oxidative structural stresses
                                                              • Large TI = a large therapeutic window: Large
                                                                  doses of the drug are relatively safe to admin-
      imposed by oxidant drugs (nitrites, sulfa),
                                                                  ister, unless drug allergy exists. Close patient
      resulting in hemolysis or methemoglobinemia,
                                                                  monitoring is unnecessary due to drug’s safety
      often refractory to methylene blue reversal.
                                                                  profile. Example: penicillin, OCPs.
                                                              •   Small TI = a small therapeutic window: Drug
                                                                  toxicity is possible even at low drug doses. Drug

12 | Color Atlas of Human Poisoning and enenoming
     serum concentrations and early toxic effects                               other receptors. Example: Butorphanol, nalbu-
     must be closely monitored. Example: warfarin-                              phine, pentazocine.
     monitor the INR or PTT, digoxin-monitor dig                            Competitive antagonist: Xenobiotic that competes
     levels, serum K.                                                           with agonist for its receptor.
                                                                            Noncompetitive antagonist: Xenobiotic that inter-
                                                                                feres with agonist binding.
Dose-Response Relationships
                                                                            Efficacy vs. Potency (ED50)
receptor theory
                                                                            How Effective Is the Drug?
  • Definition:  Many xenobiotics bind to specific
     protein receptors by ionic forces > hydrophobic                          • Definition: Efficacy is a measure of the maximal
     or hydrophilic forces > Van der Waals forces to                              effective response produced by a drug. Efficacy
     create a stable drug-receptor complex, the key                               depends on the number of drug-receptor com-
     to traversing lipoprotein membrane barriers                                  plexes formed and the efficiency with which the
     and entering organ and tissue compartments.                                  activated complex produces a cellular response.

                                                                            How Potent Is the Drug?
receptor States
                                                                              • Definition: Potency is a measure of how much
Agonist: Xenobiotic that activates protein receptor                               of a drug is required to elicit a given response.
     and opens barriers to tissues.                                           • Potency    is expressed as the effective dose 50
Partial agonist: Xenobiotic that only partially acti-                             [ED50] or the dose of a drug that elicits 50% of
     vates protein receptor.                                                      the maximal response.
Antagonist: Xenobiotic that totally prevents the                              •   The lower the dose required for a given response,
     binding of an agonist to its specific protein                                the more potent the drug.
     receptor.                                                                •   Potent drugs have steep dose-response curves
Partial antagonist: Xenobiotic that partially prevents                            (plasma concentration vs. time) demonstrat-
     the binding of an agonist to its specific protein                            ing that small increases in drug dose will elicit
     receptor.                                                                    large changes in response. Example: digoxin,
Mixed agonist/antagonist: Xenobiotic that both acti-                              warfarin.
     vates some receptors and paradoxically inhibits

                                                                                                               Small TI (warfarin)
                                  Large TI (penicillin)                                                        Therapeutic window
                                   Therapeutic window                                                    100
      Percent of patients

                                                                                   Percent of patients

                                        Desired                                                                           Desired             Unwanted
                                      therapeutic                                                                       therapeutic            adverse
                                                                  adverse                                50
                            50           effect                                                                             effect                effect

                             0                                                                            0
                                   Log concentration of drug                                                    Log concentration of drug
                                   in plasma (arbitrary units)                                                  in plasma (arbitrary units)

FIGURe 1.4a Large therapeutic index. A large ther-                          FIGURe 1.4b Small therapeutic Index. A small ther-
apeutic index reflects a large therapeutic window                           apeutic index reflects a small therapeutic window in
in which large doses of a drug are relatively safe to                       which drug toxicity is possible even at low doses. Ex.:
administer, unless drug allergy exists. Ex.: penicillin.                    digoxin, warfarin.

                                                                                                  the Pharmacology of Human Poisonings | 13
Drug elimination Kinetics                                    Renal elimination of Xenobiotics
First-Order Kinetics
                                                                1. Glomerular filtration (GF): Physical filtering
                                                                   that depends on cardiac output and renal perfu-
  • The    rate of a drug’s elimination is directly
                                                                   sion, and is independent of a drug’s pH or lipid
     proportional to its plasma concentration. The
                                                                   solubility; measured as the glomerular filtration
     higher the concentration, the more rapid the
                                                                   rate (GFR), normally 20% of renal plasma flow
     drug elimination. Drug decay curve is curvilin-
                                                                   (600 mL/minute) or 125 mL/minute.
     ear. Example: 90% of all drugs.
                                                                2. Proximal tubular secretion: Xenobiotics that
                                                                   are not eliminated from the blood in the glo-
Zero-Order Kinetics
                                                                   merular filtrate can be removed later by active
The rate of a drug’s elimination is independent of its             transport using specific carrier proteins within
concentration because (1) the drug’s hepatic metabo-               the proximal tubules.
lizing enzyme system quickly becomes saturated to               3. Distal tubular reabsorption: As high concentra-
capacity, and (2) a constant, predictable amount of                tions of uncharged, water-soluble (hydrophilic)
drug is eliminated per unit of time. Drug decay curve              phase I drug metabolites reach the distal convo-
is linear. Example: ethanol.                                       luted tubules (DCTs), concentration gradients
                                                                   are created between the DCTs and the cen-
Combined Elimination or Michaelis-Menten                           tral circulatory compartment, allowing drug
Kinetics                                                           metabolites to be reabsorbed into plasma. Con-
The rate of a drug’s elimination is initially first order,         versely, phase II hepatically metabolized drugs
and then switches to zero order when the drug’s                    remain highly ionized, become trapped in the
hepatic metabolizing enzyme system becomes satu-                   urine, and are unable to back-diffuse into the
rated to capacity. Combined elimination kinetics                   central circulation. Example: alkalinization of
is also known as Michaelis-Menten kinetics. Drug                   the urine with sodium bicarbonate and forced
decay curve is initially curvilinear and then becomes              diuresis with IV fluids will ion-trap acidic ASA
linear.                                                            and phenoxyacetic acid herbicide metabolites
                                                                   in the urine and augment GFR for enhanced
Plasma Clearance of Xenobiotics                                    elimination of toxic metabolites.

Definition: Clearance (Cl) is measured as the volume
of plasma cleared of a xenobiotic per unit of time.          enhanced In Vivo elimination
                                                             of Xenobiotics
  Cl = Rate of elimination/Plasma concentration ×
       Time                                                  Corporeal Enhanced Elimination
     = Rate of elimination × Vd                              Alkaline diuresis: Traps weak acids and their
     = IV dose administered/Area Under the Curve                  metabolites (barbiturates, phenoxyacetic acid
       (AUC) of C × t                                             herbicides, salicylates-ASA) in the DCTs and
  Where C = concentration and t = time.                           enhances their renal excretion.
                                                             Gut dialysis: Multiple doses of oral activated char-
                                                                  coal (AC) use reverse diffusion gradients to back
                                                                  diffuse xenobiotics with low Vd values (<1 L/kg)
                                                                  from the plasma compartment and back into
                                                                  the gut for fecal excretion. Example: multiple
                                                                  doses of AC are often indicated for theophylline

14 | Color Atlas of Human Poisoning and enenoming
Extracorporeal Enhanced Elimination                         Drug Factors Favoring the Use of Enhanced
Hemodialysis (HD): Most effective means of extra-
     corporeal elimination of xenobiotics.
Hemoperfusion (HP): Only effective for drugs that             • Low      Vd < 1 L/kg; Example: ASA, ethylene
     are absorbed to AC. Example: theophylline.                   glycol
Hemofiltration (HF): Effective for the slow and               •   Low molecular weight (MW): <500 Daltons
     prolonged removal of high-molecular-weight               •   Water-soluble compounds
     (4,500–40,000 Daltons) compounds, not ame-               •   Non-protein-bound compounds
     nable to hemodialysis (<500 Daltons).                    •   Low endogenous renal clearance
Peritoneal dialysis: Ineffective for the enhanced elim-       •   One-compartment model kinetics
     ination of xenobiotics and not recommended
     for poisonings.
                                                            Enhanced Elimination techniques
enhanced extracorporeal                                     Hemodialysis: Success requires that the toxin be
elimination of Xenobiotics                                     of low MW and low Vd, water soluble, and not
Extracorporeal Enhanced Elimination                            protein bound. Complications include bleeding,
                                                               thrombosed access sites, and the elimination
Indications for Enhanced Elimination                           of therapeutic drugs, antidotes (folic acid), and
                                                               water-soluble vitamins (vitamin K). Example: bro-
  • Poisoned patients not responding to supportive             mides, ethanol, methanol, ethylene glycol, chloral
      care.                                                    hydrate, lithium, and ASA are easily dialyzed.
  • Poisoned patients with impaired hepatic or renal        Hemoperfusion: Success requires that the toxin be
      elimination systems.                                     adsorbed to AC. Preferred for poisoning with
  • Severely poisoned patients with high drug con-             theophylline and anticonvulsants (carbamaze-
      centrations associated with high morbidity and           pine, phenobarbital, and phenytoin).
      mortality. Example: ethylene glycol.                  Hemofiltration: Not as effective as HD or HF, but
  •   Poisoned patients at high risks due to advanced          can be continued for days with fewer compli-
      age, pregnancy, or concurrent diseases.                  cations. Advantages include ability to eliminate
  •   Poisoned patients with co-existing and non-              high MW (4500–40,000 Daltons) and pro-
      responsive volume or electrolyte distur-                 tein-bound toxins. Preferred for toxins slowly
      bances. Example: fluid overload, acidosis,               eliminated from tissue binding sites. Example:
      hyperkalemia.                                            aminoglycosides, lithium, and procainamide.



FIGURe 1.5a First-order kinetics. The rate of a             FIGURe 1.5b Zero-order kinetics. The rate of the
drug’s elimination is directly proportional to its plasma   drug’s elimination is independent of its concentration,
concentration. Thus, the higher the drug concentra-         and a constant amount of drug is eliminated per unit
tion, the more rapid is the drug’s elimination. Ex.: most   time. Ex.: ethanol.

                                                                    the Pharmacology of Human Poisonings | 15
                                                                             FIGURe 1.6 Michaelis-Menten Kinetics. The rate of
                               Michaellis-Menten kinetics
                                                                             a drug’s elimination is initially by first-order kinetics,
                                                                             and then switches to zero-order kinetics when the


                                                                             drug’s hepatic metabolizing enzyme system becomes
                                 Curvilinear                       Linear
                                                                             saturated to capacity.

                                Time                            Time

                                                                                            Area under the curve (AUC)
                                                                                            of concentration (C) × time (t)

FIGURe 1.7 Plasma clearance. Plasma clearance                                                      AUC
is reflected by the area under the curve of a drug’s
plasma concentration over time, or clearance = the
rate of elimination/plasma concentration x time.                                                     Time

16 | Color Atlas of Human Poisoning and enenoming
   Poisoning in the elderly
Behaioral and Physical                             • Distribution:   Decreased albumin binding and
     Considerations                                     increased α1-acid glycoprotein binding, coupled
                                                        with decreased gut and hepatic perfusion, may
  • Reduced muscle mass and increased body fat:         increase drug toxicity.
    Promotes increased Vd of lipophilic toxins.     •   Metabolism: Decreased phase I hepatic metab-
  • High total body water: Promotes increased Vd        olism; phase II hepatic metabolism remains
    of water-soluble toxins.                            unchanged.
  • Compliance problems.                            •   Excretion: Decreased renal plasma flow (RPF)
  • Age-related CNS problems: Confusion, depres-        = decreased glomerular filtration rate (GFR) =
    sion, disorientation, dementia.                     decreased excretion by filtration.
  • Dosing   problems: Multiple medications, drug

Pharmacokinetic Considerations

  • Absorption: Decreased gastric acid secretion
    and decreased gut motility may increase drug

                                                           the Pharmacology of Human Poisonings | 17
   Poisoning in Children
epidemiology                                              General Management
                                                          Ipecac: Use at home within 1 hour of ingestion if
  • 67%     of annual poisonings occur in children              directed. Avoid with coma, convulsions, cor-
      ≤19 years old. Ingestion is the route of exposure         rosives, hydrocarbons, coagulants, and in chil-
      in 76% of cases.                                          dren under the age of 6 years.
  •   Children <5 years old have the highest rate of      Position: Left lateral decubitus, Trendelnberg (left
      poisoning visits to emergency departments.                side down, head down).
                                                          Lavage: Only with airway protection and life-threat-
                                                                ening (TCA) overdose within 1 hour.
Ingested Agents                                           AC: Administer 1g/kg within first hour; ineffective
                                                                for alcohols, corrosives, hydrocarbons, metals,
  • Most    commonly ingested agents include cos-               and minerals.
      metics and personal care products.                  MDAC: Consider for carbamazepine, phenobarbital,
  •   52% are medications.                                      theophylline.
  •   48% are non-medications.                            Cathartics (indicated with MDAC): Mg citrate > sor-
  •   Most lethal agents: cocaine, anticonvul-                  bitol, whole-bowel irrigation for slow-release
      sants, antidepressants, cleaning products,                drugs, iron and lithium, body packers and
      hydrocarbons.                                             stuffers (cocaine and heroin).

Most Commonly Ingested Agents

Cosmetics and personal care products
Cleaning products
Cough and cold preparations
Foreign bodies
Topical agents

18 | Color Atlas of Human Poisoning and enenoming
                                         Chapter 2

the General Management
  of the Poisoned Patient

        the General Management of the Poisoned Patient | 19
Chapter Outline
              Preenting gastrointestinal
              absorption of the toxin
                  Gastric emptying
                  Emesis vs. lavage
                  Activated charcoal (AC) and multi-dose activated
                     charcoal (MDAC)
                  Whole-bowel irrigation (WBI)
                  Alternative methods of gastrointestinal emptying

              enhancing elimination of the toxin

                  the General Management of the Poisoned Patient | 21
   Preenting Gastrointestinal
   Absorption of the toxin
Gastric emptying
Indications for Gastric Emptying

  • High-risk, potentially lethal ingestions: Aspirin,
      calcium channel blockers (CCBs) (especially
      verapamil), chloroquine, colchicine, cyanide,
      tricyclic antidepressants (TCAs).
  •   Recent ingestions, less than 1 to 2 hours, espe-
      cially for slow-release drugs.
  •   Consequential toxicity: Seizures, hypotension,
  •   Ineffective or nonexistent antidotes: CCBs, iron,
      colchicine, paraquat, selenious acid.
  •   Enteric-coated or slow, sustained-release tab-
      lets: Aspirin, theophylline, verapamil.
  •   Poisonings with agents that reduce gastroin-
      testinal motility: Anticholinergics, opioids,
  •   Poisonings with agents that cause pylorospasm
      and gastric outlet obstruction: Aspirin, mepro-
      bamate, iron.
  •   Poisonings with agents that form gastric con-
      cretions or masses: Aspirin, enteric-coated and
      sustained-release tablets, iron, meprobamate,       FIGURe 2.1 Non-dissolving radiopacities in the gas-
      phenobarbital.                                      trointestinal tract. Abdominal radiograph of a 3-year-old
                                                          boy with a history of ingesting leaded paint chips peel-
                                                          ing off doors and windows. Note radiopaque leaded
Contraindications to Gastric Emptying                     paint chips in colon and rectum. (Courtesy of Carlos R.
                                                          Gimenez, M.D., Professor of Radiology, LSU School of
  • Caustic acid/alkali ingestions                        Medicine, New Orleans, LA.)
  • Hydrocarbon ingestions
  • Sharp and pointed material ingestions                 Ipecac Emesis
  • Drug packet ingestions
  • Bleeding diathesis, coagulopathies                    Indications
  • Esophageal varices and Mallory-Weiss tears of
      the esophagus                                          • Witnessed ingestions, usually at home
  • Significant vomiting                                     • Home use; contraindicated in the emergency
  • Nontoxic ingestions                                        department (ED)
                                                             • Ingestions of objects too large for lavage tubes
                                                             • Ingestions by infants older than 6 months and
                                                               small children

                                                          the General Management of the Poisoned Patient | 23
                                                             • Mallory-Weiss esophageal tears
                                                             • Pneumomediastinum
                                                             • Aspiration pneumonitis
                                                             • Delaying activated charcoal administration
                                                             • Electrolyte abnormalities
                                                             • Substance abuse = bulimia

                                                           emesis s. Laage
                                                           Orogastric Lavage


FIGURe 2.2 Body stuffer: heroin. Axial abdominal             • High-risk     ingestions when a drug or toxin is
oral and intravenous contrast-enhanced computerized              still accessible in the stomach (<1 hour)
tomogram (CT) at the level of the renal veins that dem-      •   Ingestions that delay gastric emptying, cause
onstrated a rectangular container of heroin in a jejunal         gastric outlet obstruction, or form gastric
loop. (Courtesy of Carlos R. Gimenez, M.D., Professor            concretions
of Radiology, LSU School of Medicine, New Orleans,           •   Ingestions of enteric-coated or sustained-release
LA.)                                                             preparations


  • Potential    or compromised airway protective
      reflexes                                               • Compromised or unprotected airway
  •   Imminent seizure or coma: Isoniazid, camphor,          • Caustic acid or alkali ingestions
      meperidine                                             • Sharp material ingestions
  •   Imminent deterioration: tricyclic antidepres-          • Drug packet ingestions
      sants, meperidinepropoxyphene, propranolol,            • Bleeding diathesis or increased risks of gastro-
      tramadol                                                   intestinal hemorrhage
  •   Caustic acid/alkali ingestions                         •   Prior significant emesis
  •   Hydrocarbon ingestions                                 •   Nontoxic ingestions
  •   Sharp material ingestions
  •   Increased risks of bleeding
  •   Significant vomiting
  •   Nontoxic ingestions
                                                             • Adults: 36–40 French orogastric tube
                                                             • Children: 22–28 French orogastric tube
Dose                                                         • Endotracheal tube if airway is compromised
                                                             • Left lateral decubitus position
  • Adults and children older than 5 years old: 30           • Confirm proper orogastric tube placement by
      ml (2 Tbsp.); may repeat one time                          x-ray
  •   Children 1 to 5 years: 15 mL (1 Tbsp.)                 • Lavage in aliquots: Adults 250 mL/kg and chil-
  •   Infants 6 to 12 months: 10 mL (2 tsp.)                     dren 10 mL/kg of normal saline until clear;
                                                                 maximum 1 L for children.
                                                             •   Instill activated charcoal (AC) via orogastric
Complications                                                    tube

  • Intractable vomiting (rare), delayed emesis while

24 | Color Atlas of Human Poisoning and enenoming

                                                              • Patients at risk for aspiration with unprotected
                                                              • Caustic acid and alkali ingestions
                                                              • Ileus or small bowel obstruction
                                                              • Most hydrocarbon (need endoscopy) and heavy
                                                                  metal ingestions: Hydrocarbons and metals do
                                                                  not bind to AC
                                                              •   Most large-volume (dose usually in grams/kilo-
                                                                  gram) ingestions: Iron, lithium, ethanol
                                                              •   Single-substance ingestions of iron, lithium,
FIGURe 2.3 Orogastric tube-induced gastric perfo-
ration with pneumomediastinum. Computerized axial
tomogram (CT) of the chest that demonstrates a huge        Dose/Procedure
pneumomediastinum surrounding the distal esopha-
gus, heart, and descending thoracic aorta following
the insertion of an orogastric tube for gastric lavage
                                                              • Initial: 1 g/kg for both adults and children; add
                                                                  sorbitol for initial AC dose only
and activated charcoal (AC) administration. (Courtesy
of Carlos R. Gimenez, M.D., Professor of Radiology,           • MDAC: 0.5–1.0 g/kg every 1 to 4 hours, with
LSU School of Medicine, New Orleans, LA.)                         no additional cathartics
                                                              • Consider    nasogastric tube and antiemetics to
                                                                  control vomiting
Complications                                                 •   Allow AC to leave stomach before emptying
  • Inadvertent    tracheal intubation or airway
  •   Esophageal/gastric perforation with pneumo-          Complications
      mediastinum, mediastinitis, or hemorrhage
  •   Emesis                                                  • Aspiration
  •   Aspiration pneumonitis                                  • Emesis
                                                              • Obscuring gastrointestinal mucosa and limiting
                                                                  visibility during endoscopy
Actiated Charcoal (AC) and Multi-                            • Constipation
Dose Actiated Charcoal (MDAC)                                • Small bowel obstruction
  • Activated      Charcoal (AC): Any substance
      known to bind to AC, especially highly toxic
  •   Multi-Dose Activated Charcoal (MDAC): All               • To    speed gastrointestinal transit of drugs or
      drugs and toxins known to bind with small vol-              toxins that remain in the gastrointestinal tract
      umes of distribution (less than 1 L/kg), low renal          and may continue to be adsorbed to or desorbed
      clearance, little protein binding, and enterohe-            from AC
      patic recirculation of toxic metabolites                •   Combine only with the initial dose of AC or
  •   Drugs that reduce gastrointestinal motility,                MDAC and do not repeat
      form gastric concretions, and enteric-coated or
      sustained-release preparations

                                                              • Abdominal trauma

                                                           the General Management of the Poisoned Patient | 25
  • Intestinal ileus or small bowel obstruction            • All liquid ingestions
  • Preexisting diarrhea                                   • Hydrocarbon ingestions
  • Hypovolemia and dehydration                            • Caustic acid and alkali ingestions
  • Renal failure (Mg citrate and Mg sulfate could         • Parenterally administered drugs
      cause further neurologic and respiratory depres-
      sion from hypermagnesemia)
  •   Routine use in children                            Dose
  •   Prior cathartic dose
                                                           • Adults: 2 L/hour
Dose of Cathartics
                                                           • Children: 0.5 L/hour

  • Sorbitol   70% is preferred: Adults 1 g/kg and       Complications
      children 0.5 g/kg
  •   10% Mg citrate: 4 mL/kg for children and             • Vomiting, especially with rapid administration
      adults, maximum 300 mL                               • Bloating
  •   Mg sulfate: Adults 1 g/kg and children 0.5           • Decreased efficiency of activated charcoal
      g/kg                                                 • Rectal itching

Complications                                            Alternatie Methods of
                                                         Gastrointestinal emptying
  • Excessive diarrhea                                   Other Miscellaneous Binding agents
  • Emesis
  • Electrolyte abnormalities
  • Hypermagnesemia (Mg citrate and Mg sulfate)            • Cholestyramine and colestipol: For methotrex-
  • Hypokalemia                                                ate and organochlorine pesticides — lindane
  • Hyponatremia or hypernatremia (sorbitol)                   (Kwell®) and chlordecone (Kepone®)
  • Volume depletion and dehydration                       •   Sodium polystyrene sulfonate (Kayexalate®):
  • Hypernatremic dehydration (sorbitol)                       For lithium and potassium

Whole-Bowel Irrigation (WBI)

  • Sustained-release drugs: Theophylline, calcium
      channel blockers, especially verapamil
  • Enteric-coated drugs: Aspirin, verapamil
  • Drugs or toxins not adsorbed by AC:          Iron,
      heavy metals, lithium, potassium
  •   Slowly dissolving substances: Iron tablets, lead
      paint chips, bezoars, and concretions
  •   Crack vials: body stuffers, cocaine and heroin
  •   Drug packets: Body packers, cocaine and
                                                         FIGURe 2.4 Slowly dissolving substances: enteric-
                                                         coated phenothiazine tablets in stomach. Axial oral
Contraindications                                        and contrast-enhanced computerized tomogram (CT)
                                                         at the stomach level that demonstrates two slowly dis-
                                                         solving radiopaque substances (enteric-coated pheno-
  • Paralytic ileus or small bowel obstruction           thiazine tablets). (Courtesy of Carlos R. Gimenez, M.D.,
  • Abdominal trauma                                     Professor of Radiology, LSU School of Medicine, New
  • Rapidly absorbed drugs and toxins: alcohols          Orleans, LA.)

26 | Color Atlas of Human Poisoning and enenoming
  • Potassium ferricyanoferrate (Prussian blue): For
      thallium and cesium
  • Fuller’s earth (diatomaceous earth): For para-
      quat and diquat

Surgical Emptying

  • Rupture of cocaine drug packets
  • Mechanical bowel obstruction by cocaine drug
      packets, vials, or pipes
  •   Bezoars: Aspirin, bromide, meprobamate

                                                       the General Management of the Poisoned Patient | 27
   enhancing elimination
   of the toxin
Methods                                                  Peritoneal Dialysis
                                                           • Mechanism:      To enhance the elimination of
                                                               water-soluble, low-molecular-weight, poorly
  • Poisons with small volumes of distribution: poi-           protein-bound substances with low volumes of
      son remains in the blood compartment
  • Poison     with low endogenous renal clearance
                                                           •   Indications: Too slow to be useful and not
      rates: alcohols, beta-blockers, lithium, phenyt-
      oin, paraquat, salicylates, theophylline
  •   Poisons that are not lipid-soluble or highly
      protein-bound                                      Hemodialysis

Urinary alkalinization                                     • Mechanism:       To enhance the elimination of
                                                               water-soluble, very low-molecular-weight (less
                                                               than 500 Daltons), non-protein-bound com-
  • Mechanism: To trap weak acids in renal tubular             pounds with low volumes of distribution (less
      fluid to prevent tubular absorption and promote
                                                               than 1 L/kg) and low endogenous renal clear-
      urinary excretion.
                                                               ance rates (less than 4 mL/kg/min).
  •   Indications: Consider urinary alkalinization for
                                                           •   Indications: Bromide, lithium, potassium, salic-
      all weak acids, such as salicylates, phenobar-
                                                               ylates, all alcohols (ethylene glycol, methanol,
      bital, chlorpropamide; formic acid (methanol),
                                                               isopropanol), and chloral hydrate and its pri-
      chlorphenoxyacetic acid herbicides; for metho-
                                                               mary metabolite, trichloroethanol.
      trexate; and to protect the kidneys during myo-
      globinuria from rhabdomyolysis.
                                                           •   Complications: Bleeding, access related compli-
                                                               cations, air embolism, nosocomial infections.
  •   Complications: Volume overload, metabolic
  •   Urine acidification is not recommended.            Charcoal Hemoperfusion

Forced Diuresis                                            • Mechanism:      To enhance the elimination of
                                                               compounds adsorbed by AC in an extracor-
                                                               poreal fashion; can be used in series with
  • Mechanism:       To produce diuresis by volume
      expansion with Na-containing solutions, nor-
      mal saline, or lactated Ringer’s solution; often
                                                           •   Indications: Anticonvulsants: carbamazepine,
                                                               phenobarbital, and phenytoin; theophylline;
      combined with diuretics.
                                                               thallium (exception: thallium is the only heavy
  •   Indications: Not recommended except to pro-
                                                               metal adsorbed to AC). In series with hemodi-
      tect the kidneys from myoglobinuria during
                                                               alysis: carbamazepine, theophylline, procain-
      extensive rhabdomyolysis. Exception: forced Cl
                                                               amide, thallium.
      diuresis with NaCl and mannitol for platinoid
      (cisplatin) overdose.
                                                           •   Complications: Same as dialysis + charcoal
                                                               embolization, leukopenia, thrombocytopenia,
  •   Complications: Volume overload and electro-
      lyte disturbances.

28 | Color Atlas of Human Poisoning and enenoming
Continuous Hemofiltration                                   • Indications:     To remove large protein-bound
                                                                molecules, such as Ag/Ab complexes, especially
                                                                digoxin-Fab complexes.
  • Mechanism: To enhance the elimination of very           •   Complications: Transfusion-related anaphy-
      high-molecular-weight (10,000 to 40,000 Da)
                                                                laxis or allergic manifestations.
      compounds using the patient’s own arterial pres-
      sure (continuous arteriovenous hemofiltration
      [CAVH]) or a blood pump (continuous venove-
                                                         Exchange transfusion
      nous hemofiltration [CVVH]) to continuously
      perfuse a large pore size dialysis membrane.
  •   Indications: To clear very large molecules,           • Mechanism:      Same as plasmapheresis, but the
      such as methotrexate, heparin, protamine,                 replacement of removed blood is with packed
      insulin, myoglobin, and antibiotics, especially           red blood cells (PRBCs).
      vancomycin.                                           •   Indications: Usually reserved for neonates.
  •   Complications: Same as hemodialysis and sec-          •   Complications: All transfusion related.
      ondary to anticoagulation; removal of benefi-
      cial therapeutic drugs = antibiotics, antidotes,


  • Mechanism: To enhance elimination of large-
      molecular-weight compounds (greater than
      15,000 Da) that are not dialyzable and have
      limited endogenous metabolism. Fresh frozen
      plasma (FFP) and albumin are used to replace
      removed plasma.

                                                         the General Management of the Poisoned Patient | 29
                                                          Chapter 3

Physical, Diagnostic, and
Laboratory ealuation of
   the Poisoned Patient

 Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 31
Chapter Outline
                           Physical assessment of the
                           poisoned patient
                              Primary survey and treatment
                              Secondary survey and treatment
                              The unknown overdose
                              Overdose in pregnancy
                              Caustic cutaneous and ocular exposures

                              Drug compartment models
                              Drug elimination kinetics

                           Laboratory assessment of
                           the poisoned patient
                              Types of lab tests
                              Testing methods (and degree of sensitivity and speci-
                                 ficity, + to +++)
                              Blood/serum levels
                              Routine serum toxicology

                           Radiographic ealuation
                              Visualizing toxins
                              Toxin-induced skeletal changes
                              Chest x-rays: Lungs
                              Chest x-rays: Pleura, mediastinum, heart
                              Abdominal x-rays
                              Head computerized tomographic (CT) scan

                           electrocardiographic (eCG) assessment
                              Electrolyte and temperature disturbances
                              Digitalis and tricyclic antidepressants (TCAs)
                              Tachyarrhythmias and common causes
                              Drug-induced tachycardias
                              Drug-induced bradyarrhythmias

                           Nontoxic exposures
                              Epidemiology of nontoxic exposures
                              Categorizing nontoxic exposures
                              Common nontoxic household exposures

        Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 33
   Physical Assessment of
   the Poisoned Patient
Primary Surey and treatment                              Secondary Surey and treatment
Primary Survey                                            Secondary Survey

  • Clear the airway.                                       • Exclude heart murmurs = suspect subacute bac-
  • Assess and protect cervical spine.                          terial endocartitis, common in intravenous drug
  • Intubate comatose patients for             ventila-         users (cocaine and heroin).
      tion, lavage, and activated charcoal (AC)             •   Exclude bradydysrhythmias and tachydysrhyth-
      administration.                                           mias = suspect digitalis, β -blockers, calcium
  •   Order arterial blood gas analysis and carboxy-            channel blockers, tricyclic antidepressants.
      hemoglobin (COHb) level.                              •   Exclude silent abdomen = suspect anticholiner-
  •   Initiate electrocardiographic, temperature, oxy-          gics, opioids.
      genation (STCO2), and central and peripheral          •   Examine extremities for needle tracks (intrave-
      perfusion monitoring.                                     nous drug abusers) and evidence of heavy metal
  •   Start IV, fluid load-normal saline or lactated            poisoning = Mees lines — arsenic, thallium;
      Ringer’s solution; draw complete blood count              arsenical keratoses on hands and feet, arsenic-
      (CBC), glucose, electrolytes, BUN, creatinine,            induced black foot’s disease.
      toxicology screen.
  •   Manage three seizure types: (1) benzodiazepine
      (BZ) responsive seizures — suspect ethanol          Secondary treatment
      withdrawal; (2) special antidote-required sei-
      zures — suspect pyridoxine or isoniazid (INH);        • Gastric emptying: No emesis, orogastric lavage
      (3) tonoclonic seizures and/or persistent seizure         and initial AC with cathartic.
      activity on the electroencephalogram (EEG)            • Consider enhanced elimination beginning with
      — suspect carbon monoxide (CO).                           MDAC.
                                                            •   Consider other      modalities   of   enhanced
Nonspecific treatments = Coma Cocktail
and Oxygen
                                                          the Unknown Oerdose
  • Dextrose:    0.5–1.0 g/kg; use D50W (D10W for         Contraindicated treatments
      children) to manage or exclude hypoglycemia.
  •   Thiamine: 100 mg IV to manage or prevent
      Wernicke-Korsakoff syndrome in alcohol abus-          • No analeptics
      ers (unnecessary in children).                        • No flumazenil
  •   Naloxone: 2 mg IV for both children and adults        • No forced diuresis
      with opioid toxidromes.                               • No urinary acidification
  •   Oxygen at high flow rates, 8–10 L/min.                • No Class IA or Class IC antiarrhythmics = all
                                                                are sodium channel blockers that could pro-
                                                                long QRS duration and precipitate ventricular
                                                                tachyarrhythmias, including torsades de pontes
                                                            •   No long-acting opioid antagonists (only

                                   Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 35
  • Choose      appropriate  vasopressor     sup-         • Normal pulse oximetry may be misleading: tis-
      port to avoid myocardial sensitization and              sue hypoxia may be present with carbon mon-
      arrhythmogenesis.                                       oxide (CO), cyanide (CN), and hydrogen sulfide
                                                              (H 2S) poisoning despite normal pulse oxim-
                                                              etry. Co-oximetry is indicated to exclude tissue
alcohol and Drug Overdose                                     hypoxia and cytotoxicity.

  • Give coma cocktail.
  • Monitor central venous pressure (CVP) and/or         Caustic Cutaneous and Ocular exposures
      pulmonary artery pressure (PAP) prior to fluid
      loading and inotropic treatment.                    • Skin:    (1) Personal protective equipment (PPE)
  •   Suspect concomitant trauma. Head CT scan?               for Emergency Medical Services (EMS) person-
      Cervical spine films?                                   nel — to prevent contamination and poisoning
  •   Secure intensive care unit bed.                         of EMS; (2) identify, remove, and bag all cloth-
  •   Alcohol-smelling breath does not indicate intox-        ing and other personal items; (3) bathe patient
      ication; suspect combined etiologies. Patients          with soap and water two times; (4) never try to
      with sole ethanol overdoses will awaken in 3            neutralize acid or alkali burns; (5) do not apply
      to 4 hours.                                             topical creams or greases, as this may lead to
                                                              prolonged contact with toxin with increased
                                                              absorption and greater risk of burn injury.
Oerdose in Pregnancy                                     •   Eye: (1) Use topical anesthetic and lid retrac-
                                                              tor; (2) irrigate with 1 to 2 L sterile balanced
  • Manage hypotension aggressively.                          salt solution (BSS) preferred over normal saline,
  • Maintain left lateral decubitus position.                 lactated Ringer’s solution, water irrigation; (3)
  • Anticipate respiratory acidosis.                          apply pH strip to fornix to monitor and main-
  • Avoid unusual antidotes, except naloxone.                 tain pH 6.5 to 7.6. Alkalis cause liquefaction
  • Maintain high index of suspicion for carbon               necrosis of lipoproteins and result in more
      monoxide poisoning; measure carboxyhemo-                severe conjunctival and mucosal burns than
      globin (COHb) levels by co-oximetry; order              acids, which produce coagulation necrosis that
      hyperbaric oxygenation (HBO) for COHb lev-              blocks further tissue penetration.
      els greater than 15%.

36 | Color Atlas of Human Poisoning and enenoming
Drug Compartment Models                                            Drug elimination Kinetics

  • One-compartment model: Simple instantaneous                         • First-order: The rate of a drug’s elimination is
      equilibration model in which drug or toxin                            directly proportional to its plasma concentra-
      enters central circulatory compartment and is                         tion; a constant percentage of drug is eliminated
      rapidly distributed to tissues, with plasma con-                      per unit time. A plot of concentration vs. time is
      centrations determining proportional changes                          curvilinear. Example: most drugs.
      in tissue concentrations. Example: ethanol.                       •   Zero-order: A constant amount of drug is elim-
  •   Two-compartment model: Most common                                    inated per unit time, reflecting a saturation of
      model in which drug or toxin instantaneously                          the drug’s metabolizing enzyme systems. Plot
      distributes to two compartments — the more                            of concentration vs. time is linear. Example:
      highly perfused central compartment and its                           alcohol.
      viscera (brain, lungs, heart, liver, kidneys) and                 •   Michaelis-Menten: Drug elimination pattern
      the less perfused tissue compartments (mus-                           changes from first-order to zero-order kinetics
      cle, fat, skin). Example: barbiturates, volatile                      as drug concentration increases, reflecting grad-
      anesthetics.                                                          ual saturation of metabolizing pathways. Both
  •   Three- to five-compartment model: Most com-                           plots of concentration vs. time are curvilinear.
      plex model in which drug or toxin (especially
      heavy metals) distributes first to a central circu-
      latory compartment, then to a highly perfused
      visceral compartment, and finally to the least
      perfused third compartment (bone, teeth, nails,
      hair). The soft tissue and bone compartments
      are often subdivided into labile and stable equil-
      ibrating subcompartments in a five-compart-
      ment model. Example: lead, cadmium.

             Absorption      Distribution           Excretion
                           3rd compartment
                            Half-life = years

Inhalation     Lungs
                           1st compartment
Ingestion     GI tract           Blood               Kidneys            Urine            FIGURe 3.1 Ingested lead dis-
                            Half-life = days                                             tributes in a three-compartment
                                to weeks
               Liver                                                                     model. Ingested lead is distributed
                                                                                         in a three-compartment model in
                                                                                         which the heavy metal is initially
                           2nd compartment                                               distributed to a central circulatory
                              Soft tissues
                                                                hair                     compartment; then to a highly per-
                               Half-life =
                                                                nails                    fused visceral organ compartment;
                            weeks to months
                                                                                         and finally to the least perfused third
                                  Bile                                                   compartment composed of bone,
                                                         GI tract           Feces
                                                                                         teeth, nails, and hair.

                                         Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 37
             Absorption             Distribution              Excretion
                                                                                         FIGURe 3.2 Ingested lead distrib-
                              4th                  5th
                                                                                         utes in a five-compartment model.
                         compartment          compartment                                Ingested lead is distributed in a five-
                        Trabecular bone       Cortical bone                              compartment model in which the
                           Half-life =          Half-life =                              heavy metal is initially distributed to
                        months to years        10–20 years
                                                                                         a central circulatory compartment;
                                                                                         then to a highly perfused visceral
                                                                                         organ compartment; and finally to
Inhalation   Lungs              1st compartment                                          the least perfused third compart-
                                                                                         ment composed of bone and soft
 Ingestion   GI tract                 Blood                   Kidneys            Urine   tissues, subdivided into labile and
                                                                                         stable subcompartments.

                               2nd                   2nd
                          compartment          compartment
                              Labile             Stable soft
                            soft tissue          tissue pool
                               pool             + sold organ
                            Half-life =            brain >
                             weeks to          kidneys > liver
                             months              Half-life =
                                                 months to
                                                          GI tract               Feces

38 | Color Atlas of Human Poisoning and enenoming
   Laboratory Assessment of
   the Poisoned Patient
types of Lab tests                                         Chromatographic assays

  • Monitoring: Requires precision. Example: gen-            • Thin-layer chromatography: Drugs are spotted
      tamicin levels.                                            and coated onto plates, then recoated with silica
  •   Screening: Requires sensitivity (Is a toxin pres-          gels for identification by unique properties.
      ent?). Example: employee urine drug tests.             •   High-pressure liquid chromatography: Drugs
  •   Diagnostic: Requires specificity (What is the              are separated as liquids under high pressure
      toxin?). Example: forensic toxicology (tox) test.          within tightly packed columns for identification
                                                                 by unique properties.
                                                             •   Gas chromatography: Drugs are extracted as
testing Methods (and Degree of                                   gases at specific temperatures for identification
Sensitiity and Specificity, + to +++)                           by unique properties.
                                                             •   Gas chromatography/mass spectrometry GC/
                                                                 MS): Highest sensitivity/specificity; effluent
Chemical Spot tests (+)
                                                                 gases from initial gas chromatography are then
                                                                 ionized and separated by mass spectrometry.
  • Mechanism:        Identify the chemical reactivity,          Example: opioid and amphetamine confirma-
      usually by a color change, between a drug and              tion tests.
      its specific reagent.
  •   Indications: Quick detection of single
      substances.                                          Blood/Serum Leels
  •   Example: Urine ferric chloride test for aspirin.
                                                           Order for Diagnosis (Overdose Levels)

Spectrophotometric tests (+)                                 • Acetaminophen (>150 mcg/mL)
                                                             • Carbon monoxide (>15% COHb levels)
  • Mechanism: Convert target drugs into identifi-           • Ethanol (>0.08–0.10%)
      able light-absorbing compounds.                        • Ethylene glycol (>25 mg/dL)
  • Indications:    Co-oximetry (for carbon monox-           • Iron (>500 mcg/dL)
      ide, cyanide, and hydrogen sulfide poisoning)          • Methanol (>25 mg/dL)
      and colorimetry.                                       • Methemoglobin (MetHb) (>20–30% MetHb
  •   Example: Carboxyhemoglobin (COHb) levels.                  levels)
                                                             • Salicylate (>60 mg/dL)
                                                             • Theophylline (>90–100 mcg/mL)
Immunoassays (++)
                                                           Order for treatment
  • Mechanism:      Wide application; use drug-spe-
      cific antibodies to identify toxic antigens, often
      using fluorescent polarization.                        • Therapeutic    monitoring for all diagnostics,
  •   Indications: Employee urine drug testing;                  except ethanol
      affords rapid turn-around.                             •   Digoxin (>4 ng/mL)
                                                             •   Heavy metals: arsenic, lead, mercury
                                                             •   Lithium (>4 mEq/L)

                                   Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 39
  • Organophosphates: Acetylcholinesterase (AchE)      Characteristics of toxins Not routinely
      levels                                           Detected and Mechanisms of Nondetection
  •   Phenobarbital (>100 mcg/ml)
                                                         • Too     polar (highly water soluble): Antibiotics,
                                                             diuretics, ethylene glycol, isoniazid, lithium,
Routine Serum toxicology
toxins routinely Detected                                •   Too nonpolar: Digoxin, steroids.
                                                         •   Too volatile: Anesthetics (nitrous oxide),
  • Alcohols                                             •   Too nonvolatile: Plant alkaloids.
  • Analgesics                                           •   Too low: Very potent drugs taken in small doses
  • Antihistamines                                           with resulting low serum concentrations — fen-
  • Antidepressants                                          tanyl, sufentanil, alfentanil, colchicine, lysergic
  • Barbiturates and sedatives                               acid diethylamide (LSD).
  • Benzodiazepines                                      •   Too toxic: Anions — bromide, cyanide, fluo-
  • Cardiovascular drugs                                     ride, nitrites.
  • Opioids and neuroleptics                             •   Too new: All new drugs whose unique phys-
  • Miscellaneous: theophylline, caffeine, nicotine,         iochemical signatures have yet to be fully
      sulfonylureas, strychnine

40 | Color Atlas of Human Poisoning and enenoming
   Radiographic ealuation
Visualizing toxins
Unknown radiopaque toxins

  • Radiopacity      = high physical density + high
      atomic number.
  •   Radiopaque medications will contain elemental
      constituents of atomic number greater than 15:
      most heavy metals, barium, bismuth, calcium,
      chlorine, iron, lead, potassium.
  •   CHIPS = anticipate radiopacity with: Chloral
      hydrate, heavy metals (As, Cd, Cr, Fe, Hg, Pb,
      Th, Tl), iron, phenothiazines, sustained-release,
      and enteric-coated tablets (ECTs).

Known radiopaque toxins

  • Iron: Ferrous gluconate/sulfate.
  • Heavy metals: As, Bi, Cd, Cr, Fe, Hg, Pb, Tl.
  • Toxins in radiopaque packets and containers:          FIGURe 3.3 Bismuth subsalicylate (Pepto-Bismal®)
      Illicit packers and stuffers.                       abuse. Abdominal radiograph that demonstrates
  •   Mothballs: Para-dichlorobenzene (densely            ascending right colon and transverse colon radi-
      radiopaque) > naphthalene > camphor                 opaque substances in a patient with chronic bismuth
      (radiolucent).                                      subsalicylate abuse. (Courtesy of Carlos R. Gimenez,
  •   Halogenated hydrocarbons: More chlorine             M.D., Professor of Radiology, LSU School of Medi-
      groups contribute to radiopacity — carbon tet-      cine, New Orleans, LA.)
      rachloride (CCl4), chloral hydrate, chloroform,
                                                          Decreased Bone Density

toxin-Induced Skeletal Changes                              • Corticosteroids: Diffuse osteoporosis and focal
                                                                osteonecrosis (avascular necrosis, especially of
Increased Bone Density                                          the femoral heads) (see Figure 3.5).
                                                            •   Adult hypervitaminosis D: Diffuse osteoporosis.
  • Transverse metaphyseal bands on long bones:             •   Focal, lytic osteomyelitis: Intravenous drug users
      Lead (arsenic) lines (see Figure 3.4).                    (IVDUs) with septic emboli to sternum and ster-
  • Fluorosis    (children and adults): Otosclerosis,           noclavicular joints.
      osteophytosis, ligament calcifications.               •   Distal acro-osteolysis: Vinyl chloride monomer
  •   Pediatric hypervitaminosis A: Subperiosteal               exposure.
      new bone and cortical hyperostosis.
  •   Pediatric hypervitaminosis D: Generalized

                                   Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 41
                                                            FIGURe 3.5 Steroid-induced osteonecrosis. Coronal
                                                            magnetic resonance (MRI) of the left hip in a patient
                                                            on chronic corticosteroid therapy that demonstrates
                                                            the characteristic “double line” sign of steroid-induced
                                                            osteonecrosis with inner and outer hyperintense rim
                                                            lines. (Courtesy of Carlos R. Gimenez, M.D., Professor
                                                            of Radiology, LSU School of Medicine, New Orleans,
FIGURe 3.4 Metaphyseal “Lead Lines.” Frontal
long bone radiograph of the legs of a 3.5-year-old girl
with a chronic history of ingesting lead paint chips.
Note the thickened, transverse, radiodense metaphy-
seal “lead (or arsenic) lines” and the widening of the
metaphyses. (Courtesy of Carlos R. Gimenez, M.D.,
Professor of Radiology, LSU School of Medicine,
New Orleans, LA.)

Chest X-Rays: Lungs
airspace Filling

  • Diffuse filling: Acute respiratory distress syn-
      drome — noncardiogenic pulmonary edema =
      aspirin, opioids, cocaine (see Figure 3.6).
  •   Diffuse filling: Cardiogenic pulmonary edema-
      alcoholic and cobalt cardiomyopathy, barbitu-         FIGURe 3.6 Non-Cardiogenic Pulmonary Edema:
      rate overdoses, cocaine cardiomyopathy.               Heroin Overdose. Frontal chest radiograph that
  •   Diffuse filling: Cholinergic bronchorrhea =           demonstrates normal size and configuration of the
      organophosphate and carbamate pesticides,             cardiomediastinal silhouette with diffuse bilateral
      inhalants, low solubility gases (nitrogen diox-       non-cardiogenic pulmonary edema following heroin
      ide, phosgene).                                       overdose. (Courtesy of Carlos R. Gimenez, M.D., Pro-
  •   Focal filling: Aspiration, especially hydrocarbons.   fessor of Radiology, LSU School of Medicine, New
                                                            Orleans, LA.)

42 | Color Atlas of Human Poisoning and enenoming
Interstitial Patterns

  • Reticulonodular          pattern: Hypersensitivity
      pneumonitis (sulfa drugs — nitrofurantoin) and
      allergic alveolitis (farmer’s lung, bagassosis).
  •   Interstitial fibrosis: Cytotoxic chemothera-
      peutics (busulfan, bleomycin, methotrexate,
  •   Phospholipidosis: Amiodarone; injected par-
      ticles in IVDUs from adulterated cocaine and
      heroin powders — talcosis from adulterated
      cocaine and heroin powders.
  •   Pneumoconioses: Asbestos, beryllium, coal,

Chest X-Rays: Pleura, Mediastinum, Heart

  • Pleural    effusions: Drug-induced lupus syn-            FIGURe 3.7 Pneumomediastinum: crack-cocaine
      dromes = hydralazine and procainamide; iso-            inhalation. Frontal chest radiograph that demonstrates
      niazid, methyldopa, chlorpropamide.                    abnormal scattered radiolucencies in the mediastinum
  •   Pneumomediastinum: Caustic-induced esopha-             and base of neck consistent with pneumomediasti-
      geal perforation, ipecac- or alcohol-induced           num and cervical subcutaneous emphysema follow-
      Mallory-Weiss syndrome.                                ing crack-cocaine inhalation. (Courtesy of Carlos R.
  •   Pleural plaques: Asbestosis.                           Gimenez, M.D., Professor of Radiology, LSU School
  •   Hilar lymphadenopathy: Phenytoin, anthrax.             of Medicine, New Orleans, LA.)
  •   Cardiomegaly: Alcoholic and cobalt cardio-
      myopathy, cardiotoxic chemotherapeutics =
  •   Aortic dissection: Cocaine.

Abdominal X-Rays

  • Pneumoperitoneum: Secondary to gastrointes-
      tinal perforation = caustics (acids, alkalis, iron),
      cocaine, ipecac, lavage tube.
  •   Mechanical obstruction: Secondary to gastric
      outlet bezoars, or small bowel obstruction =
      enteric-coated tablets, concretions, body pack-
      ers and stuffers (see Figure 3.9).
  •   Ileus: Secondary to decreased gastrointestinal
      motility = anticholinergics, antihistamines, tri-
      cyclic antidepressants (TCAs), opioids, ischemic       FIGURe 3.8 Cocaine-induced acute aortic dissec-
      bowel (cocaine, oral contraceptives), hypokale-        tion. Sagittal, oblique, T-1 weighted magnetic reso-
      mia, hypomagnesemia.                                   nance image (MRI) of the chest demonstrating an
  •   Intramural gas: Secondary to intestinal vaso-          intimal flap that divides the lumen of the descending
      spasm, thrombosis, infarction = cocaine, ergots,       aorta into a false lumen and a true lumen with blood
      oral contraceptives, clostridium derfringens           flow, consistent with acute thoracic aortic dissection
      toxin-induced pneumotosis intestinalis (pigbel).       Type B in an intravenous crack-cocaine abuser. (Cour-
                                                             tesy of Carlos R. Gimenez, M.D., Professor of Radiol-
                                                             ogy, LSU School of Medicine, New Orleans, LA.)

                                     Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 43
  • Radiodense foreign bodies = bismuth subsalicy-
     late, calcium carbonate, clay (pica), iron and
     other heavy metals, especially lead.

                                                           FIGURe 3.11 Cocaine-induced intestinal ischemia.
                                                           Abdominal radiograph (KUB) demonstrating gas in the
                                                           main portal vein and its intrahepatic primary and sec-
                                                           ondary branches with diffuse dilation and pneumotosis
                                                           intestinalis of the small bowel and colon in a chronic
FIGURe 3.9 Body stuffer: heroin. Axial abdominal           cocaine abuser with acute mesenteric ischemia and
oral and intravenous contrast-enhanced computer-           multiple small bowel infarctions. Chronic ergot alka-
ized tomogram (CT) at the level of the renal veins that    loid ingestion may also be associated with acute mes-
demonstrated a rectangular container of heroin in a        enteric ischemia and small bowel infarction. (Courtesy
jejunal loop. (Courtesy of Carlos R. Gimenez, M.D.,        of Carlos R. Gimenez, M.D., Professor of Radiology,
Professor of Radiology, LSU School of Medicine,            LSU School of Medicine, New Orleans, LA.)
New Orleans, LA.)

                                                           Head Computerized tomographic (Ct)

                                                             • Intracranial    hemorrhage: Suspect intraparen-
                                                                 chymal cerebrovascular accident or subarach-
                                                                 noid hemorrhage = amphetamines, cocaine,
                                                                 ephedrine and pseudoephedrine, phenylpro-
                                                                 panolamine, phencyclidine (PCP); or subdural
                                                                 = head trauma (alcohol, sedative-hypnotics,
                                                             •   Lucencies: Suspect basal ganglia necrosis =
                                                                 carbon monoxide, cyanide, hydrogen sulfide
                                                                 (H 2S), methanol; suspect vasospasm = cocaine,
                                                                 ergots; septic emboli = intravenous drug users
FIGURe 3.10 Opioid bowel: colonic ileus in a metha-
                                                             •   Atrophy: Cerebral and cerebellar atrophy =
                                                                 alcohol and toluene.
done abuser. Abdominal radiograph (KUB) that demon-
strates air distension of the small bowel and transverse
                                                             •   Calcifications: Basal ganglia = carbon monox-
colon consistent with chronic constipation and colonic           ide and lead.
ileus in a methadone abuser. (Courtesy of Carlos R.
Gimenez, M.D., Professor of Radiology, LSU School of
Medicine, New Orleans, LA.)

44 | Color Atlas of Human Poisoning and enenoming
                   FIGURe 3.12 Subarachnoid hemorrhage: intrave-
                   nous cocaine abuse. Cranial computerized axial tomo-
                   gram (CT) at the level of the pons that demonstrates
                   acute blood hyperdensities in the suprachiasmatic
                   cistern extending into the left Sylvian fissure, consis-
                   tent with acute subarachnoid hemorrhage following
                   intravenous cocaine overdose. (Courtesy of Carlos R.
                   Gimenez, M.D., Professor of Radiology, LSU School of
                   Medicine, New Orleans, LA.)

Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 45
    (eCG) Assessment
electrolyte and temperature                                      Hypothermia Disturbances
Electrolyte Disturbances                                           • Progressive conduction block
                                                                   • Progressive sinus bradycardia
  • Hyperkalemia: Tall tented T waves with pro-                    • Prolonged PR and QT intervals
      gressive widening of the QRS complex (see Fig-
                                                                   • Progressive widening of the QRS complex with
                                                                       the J wave of Osborn, located in the terminal
      ure 3.13a).                                                      phase of the QRS complex
  •   Hypokalemia: Progressive decrease in T wave                  •   Causes: Drugs causing CNS depression (etha-
      amplitude with inverted T waves, U waves, and                    nol, opioids, imidazolines, sedative-hypnotics)
      eventual fusion of T and U waves (see Figure
                                                                       or hypoglycemia (insulin, oral hypoglycemics)
  •   Hypercalcemia: Short QT and ST intervals =
      antacids, vitamins A and D, hydrochlorothia-
      zide (HCTZ) containing diuretics (see Figure
  •   Hypocalcemia: Prolonged QT and ST intervals
      = fluoride, hydrofluoric acid, calcitonin, ethyl-
      ene glycol, phosphates (see Figure 3.14b).
                                                                              Short QT interval
       Hyperkalemia:                   Hypokalemia:                              Hyper Ca++
No P wave, wide QRS complex,   Short-to-inverted T wave,
      tall peak T wave                  U wave

                               P                         P

                                                                              Short QT interval
                               P            T            P
                                                                                     (a) (a)

                               P                 U                          Prolonged QT interval
                       V6                                                        Hypo Ca++

            (a)                    P                         P

FIGURe 3.13 (a) Electrocardiographic evidence of                            Prolonged QT interval
                                                                                     (b) (b)
hyperkalemia. Electrocardiogram (ECG) Lead II tracing
in a patient with hyperkalemia that demonstrates no P            FIGURe 3.14 (a) Electrocardiographic evidence of
wave, wide QRS complex, and a tall peaked T wave.                hypercalcemia. Electrocardiogram (ECG) Lead II trac-
(b) Electrocardiographic Evidence of Hypokalemia.                ing in a patient with hypercalcemia that demonstrates
Electrocardiogram (ECG) Lead II tracing in a patient             a short QT interval (b) Electrocardiographic Evidence of
with hypokalemia that demonstrates short-to-inverted             Hypocalcemia Caption. Electrocardiogram (ECG) Lead
T waves and U waves                                              II tracing in a patient with hypocalcemia that demon-
                                                                 strates a prolonged QT interval.

46 | Color Atlas of Human Poisoning and enenoming
                                                             Digitalis and tricyclic
                                                             Antidepressants (tCAs)
                                                             Digitalis (Digoxin) Effects

                                                               • Initial ectopic rhythms and premature ventricu-
                                                                   lar contractions (PVCs) (10–15%)
                                                               • Progressive bradycardia
                                                               • Increased PR interval progressing to atrioven-
                                                                   tricular (AV) blocks (see Figure 3.16a)
                                                               •   Extrasystoles leading to tachyarrhythmias
FIGURe 3.15 Electrocardiographic evidence of hypo-             •   Pathognomonic bi-directional ventricular tachy-
thermia. Top figure: The ECG J wave trace on the ECG               cardia (see Figure 3.16b)
graph paper. Bottom figure: The annotated J wave
with the J wave trace with the J waves pointed out
by arrows.                                                   tCa Effects

                                                               • Sinus tachycardia
                                                               • Prolonged PR, QRS, QT intervals
     Hypothermia (≥24 °C rectally): note the
                                                               • AV and bundle branch blocks
  characteristic J Wave of Osborn in the terminal              • Prominent S waves in lead I and AVL, promi-
            phase of the QRS complex.                              nent R wave in AVR
                                                               • All   supraventricular and ventricular arrhyth-
  J Wave                                                           mias, including torsades de pointes
                                                               •   Asystole

FIGURe 3.16a Electrocardiographic evidence of                tachyarrhythmias and Common Causes
digoxin toxicity. Electrocardiogram (ECG) Lead II trac-
ing in a patient with digoxin toxicity that demonstrates
atrial tachycardia and atrioventricular conduction             • Anticholinergics and antihistamines: Block fast
block.                                                             inward sodium channels, like quinidine, and
                                                                   amide local anesthetics (LAs).
                                                               •   Adrenergic agonists: Increase cyclic adenosine
                                                                   monophosphate (AMP) = all ß2-agonists.
                                                               •   Phosphodiesterase inhibitors: Increase cyclic
                     Digoxin toxicity
                                                                   AMP = methylxanthines (theophylline, caf-
           Bidirectional ventricular tachycardia                   feine, theobromine) and amrinone; all can cause

                                                                    TCA OD: Prominent S wave in I and aVL, R wave in aVR
            V1                                               aVL                                 aVR

            V2                                               FIGURe 3.17 Electrocardiographic evidence of tricy-
                                                             clic antidepressant overdose. Electrocardiogram (ECG)
                                                             tracing in a patient with a history of suicide attempt by
FIGURe 3.16b Electrocardiographic evidence of                tricyclic antidepressant overdose that demonstrates a
digoxin toxicity. Electrocardiogram (ECG) Lead II trac-      prominent S wave in Lead I and AVL,a prominent R
ing in a patient with digoxin toxicity that demonstrates     wave in AVR, and widened QRS complexes indicative
bi-directional ventricular tachycardia, pathognomonic        of cardiac sodium channel blockage that should correct
of digoxin toxicity.                                         with intravenous sodium bicoarbonate administration.

                                       Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 47
      supraventricular tachyarrhythmias (SVT), atrial
      fibrillation (Afib), atrial flutter (AF).
  •   Diet pills: Amphetamine and serotonin effects
      can cause pulmonary hypertension = phen-
      termine, fenfluramine, dextroamphetamine,
  •   Botanicals: Sympathomimetics = khat, betel
      nut, ginseng (Ginseng Abuse Syndrome [GAS]:
      tachycardia, hypertension, insomnia, morning
  •   Thyroid hormone: Sinus tachycardia.
  •   Metals: Arsenic (As) = increased QT inter-
      vals and torsades de pointes; lithium = mimics
      hypokalemia.                                      FIGURe 3.18 Electrocardiographic Evidence of Chlo-
                                                        ral Hydrate Toxicity. Electrocardiogram (ECG) tracing in
                                                        a patient sedated with oral chloral hydrate for a mag-
Drug-Induced tachycardias                               netic resonance imaging procedure that demonstrates
theophylline Overdose: Supraven-                        the ventricular ectopic or premature beats (prema-
                                                        ture ventricular contractions) characteristic of chlo-
      tricular tachycardia
                                                        rinated hydrocarbon toxicity from chloral hydrate or
Astemizole/terfenadine overdose or CYP 34A Inter-       halogenated hydrocarbon anesthetics (halothane and
actions: torsades de pointes, prolonged QT intervals,   others) with myocardial sensitization to endogenous
and VT.                                                 catecholamines

Prolonged Qt Intervals and torsades de
Pointes                                                 Drug-Induced Bradyarrhythmias

  • Milieu: Hypokalemia, hypomagnesemia, hypo-            • Calcium channel blockers: Decreased inotropy
                                                              and AV conduction, smooth muscle vasodila-
      calcemia; preexisting bradycardia, ischemia, or
                                                              tion, progressive AV blocks.
  •   Toxins: Non-sedating antihistamines = astem-
                                                          •   Beta-blockers: Type IA or quinidine-like effects,
                                                              mimic calcium channel blockers (CCBs), with
      izole and terfenadine; pentamidine; arsenic.
                                                              progressive bradycardia, AV blocks, complete
Ventricular tachycardia (Vt)                                  heart block.
                                                          •   Ischemia: ST segment and T wave changes, Q
                                                              myocardial injury waves from hypotension, cor-
  • Chloral hydrate and all halogenated hydrocar-             onary vasospasm, hypoxia = cocaine and ergot
      bons that sensitize the myocardium to exoge-            alkaloids.
      nous and endogenous catecholamines.
  •   Propoxyphene: Junctional tachycardia, widen-
      ing QRS complex → VT.
  •   Phenothiazines: Quinidine-LA effects = pro-
      longed QT interval and widened QRS complex
      → VT.
  •   Chloroquine: Also has quinidine-like effects =
      prolonged QT intervals → VT.
  •   Amantadine: Blocks dopamine re-uptake, pro-
      longed QT interval → VT.
  •   Botanicals: Monkshood = digitalis and vago-
      mimetic effects; yew = digitalis effects, heart
      blocks, and VT possible.

48 | Color Atlas of Human Poisoning and enenoming
    Nontoxic exposures
epidemiology of Nontoxic exposures                        Categorizing Nontoxic exposures
More than 40% of poison exposures reported to Poi-
son Control Centers are nontoxic exposures.                  • The product must be absolutely identified.
  Nontoxic exposures fall into two categories: (1)           • There is only a single product exposure.
exposures to products unlikely to cause toxicity at          • The exposure must be unintentional.
any dose; and (2) exposures to products that are             • Consumer Product Safety Commission (CPSC)
potential toxins, but at doses that are nontoxic (e.g.,          warnings must not appear on labels: Caution,
acetaminophen ingestions of <150 mcg/kg).                        Warning, Danger!
                                                             •   A reliable approximation of the amount (dose/
                                                                 kg) of exposure must be determined.
                                                             •   The route of exposure must be assured by
                                                             •   The exposed patient is symptom-free.
                                                             •   Follow-up consultation must be available.

Common Nontoxic Household exposures

 tABLe 3.1 Nontoxic Home Products
 Personal-Use Items                  Art Supplies                          toys
 Bath products, deodorants           Charcoal, chalk, clay, crayon         Bath toys
 Shampoos, lotions                   Latex paints                          Caps
 Cosmetics                           Pens, pencils                         Etch-a-Sketch®
 Colognes                            Glues                                 Play-Doh®
 Hairsprays                          Pastes                                toy cosmetics
 toothpastes                         Watercolors                           teething rings

tABLe 3.2 Nontoxic Home Products
Medications                          Cleansers                            Miscellaneous
antacids, antibiotics                Fabric softeners                     Matches, candles
Oral contraceptives, steroids        Bleach, 2–5%                         Newspaper
Calamine lotion                      Detergents                           Grease, motor oils
Mineral oil                          Most soaps                           Incense, putty
Zinc and zirconium oxide             Dishwasher liquids                   Spackle, silica gels

                                   Physical, Diagnostic, and Laboratory ealuation of the Poisoned Patient | 49
   Chapter 4


    Antidotes | 51
52 | LeftRunningHead
   Chapter Outline
toxidromes and antidotes                               Pyridoxine (vitamin B6)
                                                       Thiamine (vitamin B1)
  Toxidromes: Parasympathetic
                                                       Niacin     (nicotinic acid)   and     niacinamide
  Toxidromes: Sympathetic
  Toxidromes: Central nervous system (CNS)
  Toxidromes: Opioid
                                                     Specific antidotes
Gastrointestinal decontaminants                        Ethanol
                                                       Fomepizole (4-methylpyrazole)
  Decontamination: Activated charcoal (AC)
                                                       n-Acetylcysteine (NAC)
  Decontamination: Multi-dose AC (MDAC)
                                                       Pralidoxime (2-PAM)
  Decontamination: Cathartics
                                                       Miscellaneous specific antidotes
  Diluents and neutralizers
  Decontamination: Ipecac
                                                     Nonspecific antidotes
  Decontamination: Whole-bowel irrigation (WBI)
Metal chelators                                        Glucagon
                                                       Methylene blue
  Chelators: Calcium disodium edetate (CaNa 2
                                                       Cyanide Antidote Kit ®
                                                       Sodium bicarbonate
  Chelators: Deferoxamine
                                                       Hyperbaric oxygen (HBO) therapy
  Chelators: British anti-Lewisite (BAL)
                                                       HBO: CO poisoning
  Chelators: Succimer (dimethylsuccinic acid —
  Chelators: D-penicillamine

Antienins and antitoxins
  Crotalid antivenins
  Elapid antivenins
  Centruroides antivenins
  Latrodectus antivenins
  Botulinum antitoxin
  Digoxin-specific Fab (Antibody fragment,

Specific antagonists
  Calcium channel blocker antagonist: Calcium
  Benzodiazepine antagonist: Flumazenil
  Opioid antagonists
  Anticholinesterase      (AchE)       antagonist:
  Heparin antagonist: Protamine

  Folic and folinic acids
  Hydroxocobalamin (vitamin B12 precursor)
  Vitamin K (vitamin K1)

                                                                                           Antidotes | 53
   toxidromes and Antidotes
toxidromes: Parasympathetic
anticholinergic toxidrome

  • Features: “Blind as a bat, hot as Hades, red as a
      beet, dry as a bone, mad as a hatter” = dilated
      pupils, cycloplegia, flushed dry skin, fever,
      thirst, exocrine gland hyposecretion, decreased
      bowel sounds, urinary retention, tachycardia,
  •   Causes: Belladonna alkaloids, antihistamines,
      tricyclic antidepressants (TCAs), antipsychot-
      ics, anti-Parkinson drugs, jimson weed (Datura
      stramonium), Amanita muscaria.
  •   Antidote: Physostigmine.

Cholinergic toxidrome

  • Features:
    − SLUDE         = Muscarinic features: Salivation,    Figure 4.1 Mydriasis, left eye. Pupillary dilation
          Lacrimation, Urination, Defecation, Eme-        or mydriasis characteristic of an anticholinergic
          sis, plus miosis, bronchorrhea and broncho-     toxidrome.
          spasm = DUMBBELS = Diarrhea, Urination,
          Miosis, Bronchorrhea, Bronchospasm, Eme-
          sis, Lacrimation, and Salivation.
      − Nicotinic features: Weakness, fascicula-
          tions, sweating, tachycardia, hypertension.
      − CNS features: Agitation/confusion, seizures,
  •   Causes: Organophosphates, carbamates and
      “stigmines” (neostigmine, physostigimine, pyr-
      idostigmine, edrophonium), nerve gases, echo-
      thiophate = anticholinesterase (AchE) inhibitors;
      pilocarpine; Clitocybe/Inocybe mushrooms.
  •   Antidote: Atropine +/− pralidoxime.

                                                          Figure 4.2 Miosis, left eye. Pupillary constriction
                                                          or miosis characteristic of cholinergic and opioid

                                                                                              Antidotes | 55
toxidromes: Sympathetic                                    Extrapyramidal toxidrome
Sympathomimetic toxidrome
                                                             • Features:    “Drug-induced parkinsonism” =
                                                                 tremor, rigidity, opisthotonus, torticollis, dys-
  • Features: “Fight or flight” = hypertension, tachy-           phonia, oculogyric crisis = tardive dyskinesias.
      cardia, sweating, fever, excitation-psychomotor
      agitation, tremor, seizures, dilated pupils.
                                                             •   Causes:     Phenothiazines,     butyrophenones
                                                                 (haloperidol, droperidol), metoclopramide,
  •   Causes: Amphetamines/diet drugs, cocaine,
      theophylline, caffeine, methylphenidate, mono-
      amine oxidase inhibitors; over-the-counter
                                                             •   Antidote: Diphenhydramine.
      cold medications, especially those containing
      phenylpropanolamine (PPA), ephedrine, and            toxidromes: Opioid
  •   Mechanisms: Increased release of catechol-           Opioid toxidrome
      amines (amphetamines), blockade of cat-
      echolamine re-uptake (cocaine), inhibition of          • Features:    Pinpoint pupils, somnolence, CNS
      catecholamine metabolism (monoamine oxi-                   depression, respiratory depression, bradycardia,
      dase inhibitors), indirect adrenergic receptor             hypotension, hypothermia, decreased gastroin-
      stimulation (ephedrine).                                   testinal motility, constipation.
  •   Antidote: Beta-blockers.                               •   Causes: All opioids, natural and synthetic,
                                                                 including propoxyphene, tramadol, codeine,
                                                                 dextromethorphan. Exception: imidazolines,
Hypermetabolic toxidrome                                         central alpha agonists = clonidine, oxymetazo-
                                                                 line, and tetrahydrolozinE.
  • Features:     “Uncoupling of oxidative phos-             •   Antidote: Naloxone.
      phorylation” = fever, tachycardia, hyperpnea,
      tachypnea, restlessness, convulsions, combined
      metabolic acidosis and respiratory alkalosis.        Withdrawal toxidrome
  •   Causes: Salicylates (ASA), chlorphenoxyacetic
      acid herbicides (2,4-D and 3,4,5-T), triethyl tin,     • Features: Yawning, sneezing, runny nose, lac-
      some phenols (e.g., nitrophenol).                          rimation, “goose bumps,” abdominal cramps,
  •   Antidote: Lavage and activated charcoal,                   diarrhea, restlessness, hallucinations, tachycar-
      supportive.                                                dia, and hypertension.
                                                             •   Causes: Opioid, alcohol, barbiturate, benzodi-
                                                                 azepine cessation/withdrawal.
toxidromes: Central Nerous                                  •   Antidote: “Cold turkey,” agonists as substitutes
System (CNS)                                                     (e.g., methadone, clonidine), antagonists for
Benzodiazepine toxidrome                                         maintenance (naltrexone), aversives (disulfiram)
                                                                 pose increased risks.
  • Features: “Coma with stable vital signs” = mild
      sedation-to-complete unresponsiveness, amne-
      sia, respiratory depression, loss of airway pro-
      tective reflexes, hypotension.
  •   Causes: Benzodiazepines.
  •   Antidote: Physostigmine.

56 | Color Atlas of Human Poisoning and enenoming
   Gastrointestinal Decontaminants

Decontamination: Actiated                                        gradient between blood and gut (known as gut
Charcoal (AC)                                                     dialysis).
                                                              •   Mechanism: Gastrointestinal tract dialysis,
                                                                  especially for large ingestions, enteric, or slow/
                                                                  sustained release drug ingestions, to halt entero-
  • Chemistry: Pyrolyzed carbonaceous materials,                  hepatic circulation of poisons.
      steam — and then CO2 — activated to create              •   Contraindications: Same as AC — coma, seizure,
      pores and increases adsorptive surface area                 vomiting, ileus, SBO, simultaneous WBI; inges-
      (1000–2000 M 2).                                            tions of alcohols, HCs, metals, caustics, lithium.
  •   Mechanism: Adsorption by H 2 ion bonding and
      van der Waals forces of agents that are nonion-
      ized, undissociated, not protein-bound, poorly/       applications
      slowly absorbed and distributed or retained in
      the gastrointestinal tract by reduced gut motil-        • Uses: Digoxin, phenobarbital, carbamazepine,
      ity (often secondary to anticholinergics and                phenylbutazone, dapsone, methotrexate, nal-
      opioids).                                                   dolol, theophylline, ASA, TCAs, cyclosporine,
  •   Contraindications: Coma, seizure, vomiting,                 propoxyphene.
      ileus, small bowel obstruction (SBO), simultane-        •   Dose: 0.25–0.5 g/kg q 2–6 hours, starting
      ous whole-bowel irrigation (WBI) with polyeth-              within 1 hour of ingestion.
      ylene glycol (PEG) administration; ingestions of        •   Side effects: Same as AC — vomiting, aspira-
      alcohols, hydrocarbons (HCs), metals, caustics,             tion, diarrhea, later constipation, possibly SBO;
      lithium.                                                    add a cathartic only to first dose of AC.

applications                                                Decontamination: Cathartics
  • Use:     Most organic and inorganic materi-
      als, ASA, acetaminophen, barbiturates, glu-
      tethamide, phenytoin, theophylline, TCAs.               • Chemistry:     Saline and glucose-based cathar-
  •   Dose: Early (within 1–4 hours) administration               tics composed of nonabsorbable cations (Mg,
      of a flavored 8:1 water slurry, 10:1 AC drug,               Na) that establish an osmotic gradient to draw
      1–2 g/kg body weight (bw).                                  water into gut.
  •   Side effects: Vomiting, aspiration, diarrhea, later     •   Mechanism: Magnesium citrate and sorbitol are
      constipation, possibly small bowel obstruction              osmotic cathartics.
      (SBO); AC is usually combined with a cathar-            •   Contraindications: Adynamic ileus — SBO,
      tic, particularly 70% sorbitol preferred over Mg            abdominal trauma, diarrhea, renal failure (Mg
      citrate.                                                    citrate), more than initial dose of MDAC. Oil-
                                                                  based cathartics (mineral oil) are hydrocarbons
                                                                  (HCs), increase aspiration risk, and increase
Decontamination: Multi-Dose AC (MDAC)                             HC and mothball absorption.

  • Chemistry: Provides constant intestinal clear-
      ance by maintaining a continuous diffusion

                                                                                                    Antidotes | 57
applications                                              Decontamination: Ipecac
  • Use: To reduce constipation with possible SBO
      from AC, to speed delivery of AC to small
      intestine (SI), and to speed fecal elimination of
                                                            • Chemistry: A Cephaelis spp. plant extract con-
                                                                taining two powerful emetic plant alkaloids: (1)
      poorly absorbed, sustained-release, or enterohe-
                                                                cephaline more than (2) emetine.
      patically recirculated toxins.
  •   Dose: Sorbitol 0.5–1.0 g/kg; Mg citrate 4
                                                            •   Mechanism: (1) Local activation of peripheral
                                                                sensory receptors in the first part of the duode-
                                                                num; (2) central stimulation of the chemorecep-
  •   Side effects: Nausea, vomiting, diarrhea,
                                                                tor trigger zone (CTZ) by cephaline.
      abdominal cramping, dehydration-hypovo-
      lemia, hyponatremia, hypokalemia, hypona-
                                                            •   Contraindications: All HC and caustic inges-
                                                                tions, altered mental status, poor airway protec-
      tremic-hypokalemic metabolic alkalosis (Mg
                                                                tive reflexes (aspiration risk); bleeding diathesis;
      citrate), hypernatremic dehydration (sorbitol).
                                                                sharp object and battery ingestions.

Diluents and Neutralizers
Properties of Diluents
                                                            • Use:     Best for at-home use immediately after
  • Chemistry:     Water or milk to dilute ingested             (less than 30 minutes) ingestions without addi-
      alkalis or weak acids.                                    tional oral fluids.
  •   Mechanism: Reduce caustic contact time with           •   Dose: 15 mL (1 Tbsp.) for children, 30 mL
      gastrointestinal mucosa, modify and reduce the            (2 Tbsp.) for adults, may repeat once in 30
      heat dissipated by the initial hydration and sub-         minutes.
      sequent neutralization of the caustic at tissue       •   Side effects: Delays administration of AC or
      (mucosal) expense.                                        specific antidote therapy in the emergency
  •   Contraindications: All noncaustics and strong             department (ED), vagal bradycardia, prolonged
      acids (Exception: HCl — careful removal via               vomiting with Mallory-Weiss esophageal
      nasogastric (NG) may be indicated). Neutraliza-           tears, rarely cerebrovascular accident (CVA) in
      tion of caustics is not recommended, except for           adults.
      nebulized sodium bicarbonate (NaHCO3) fol-
      lowing chlorine and chloramine gas inhalation.
                                                          Decontamination: Whole-
                                                          Bowel Irrigation (WBI)
applications of Diluents

  • Use: Dilution of alkalis and weak acids (e.g.,          • Chemistry: A nonabsorbable mixture of poly-
      milk for ingested fluoride or hydrofluoric acid
      [Ca gluconate preferred]).                                ethylene glycol (PEG) and electrolyte lavage
  •   Dose: Water or milk, 250 mL orally (po), or 15
                                                                solution (ELS) to fluid flush the gut.
                                                                Mechanism: To flush out the entire gastrointes-
      mL/kg of body weight (bw).
  •   Side effects: Could increase heat production by           tinal tract without causing fluid and electrolyte
                                                                shifts to reduce the mucosal contact time avail-
      water contact — increases hydration and neu-
      tralization reactions; acute gastric distension           able for poison absorption.
      with potential for vomiting and aspiration of         •   Contraindications: Any preexisting gastroin-
      caustics.                                                 testinal pathology-ileus, SBO, gastrointestinal

58 | Color Atlas of Human Poisoning and enenoming

  • Use: All sustained-release drug ingestions (the-
      ophylline, verapamil, fenfluramine); all poisons
      unabsorbed by AC (iron, lead, zinc, lithium);
      and for all body packers.
  •   Dose: 0.5 L/h for children, 2 L/h for adults
      orally (po) or NG for 4–6 hours.
  •   Side effects: Gastric distension and vomiting
      (add an antiemetic), anal itching.

                                                         Antidotes | 59
   Metal Chelators
Chelators: Calcium Disodium                                applications
edetate (CaNa2 eDtA)
Properties                                                   • Use: To chelate iron in iron overdose, massive
                                                                 transfusions, hemosiderosis, and thalassemia;
                                                                 to chelate aluminum (Al) in chronic renal fail-
  • Chemistry:     Water-soluble, calcium-containing             ure (CRF).
      ring-structured acid.
      Mechanism: Exchanges its ring-bound Ca for
                                                             •   Dose: 1 g IM, then 0.5 g q 4–12 hours; IV 15
                                                                 mg/kg/min slowly.
      most heavy metals, usually lead, to form a sta-
      ble, nonionized, water-soluble chelate that can
                                                             •   Side effects: Decreases blood pressure; pulmo-
                                                                 nary toxicity (ARDS); oculotoxicity (decreased
      be renally excreted.                                       vision, decreased color vision, night blind-
  •   Contraindications: Dehydration, renal dysfunc-             ness); and ototoxicity (deafness). Acts as a sid-
      tion, coronary artery disease (CAD) chelation,             erophage for some bacteria that cannot absorb
      sole therapy (without BAL initially) in lead               iron — Yersinia enterocolitica and Vibrio spe-
      encephalopathy — give BAL first, then EDTA 4               cies. Increased V. vulnificus sepsis risks. Rose-
      hours later to decrease brain lead delivery.               orange colored urine.

                                                           Chelators: British Anti-Lewisite (BAL)
  • Use: To chelate lead in lead poisoning; in con-
      junction with BAL initially to rapidly chelate
      lead in lead encephalopathy.                           • Chemistry: Nonspecific metal chelator formu-
  •   Dose: IM in procaine or IV (preferred) diluted             lated in peanut oil and developed during World
      in normal saline over 8 to 24 hours.                       War II as an antidote for Lewisite (arsine) and
  •   Side effects: Chelation and subsequent depletion           mustard vesicant gases.
      of essential metals (Cu, Fe, Mn, Zn); elevated         •   Mechanism: A sulfur-donating chelator that
      liver function tests (LFTs); calcinosis at injec-          forms stable bonds with soft metals, especially
      tion sites; thrombophlebitis; nephrotoxicity               As and Hg. Can also bind borderline soft met-
      from lead release in kidneys during excretion.             als, particularly lead.
                                                             •   Contraindications: Peanut allergy, liver dysfunc-
                                                                 tion, glucose-6-phophate dehydrogenase (G-6-
Chelators: Deferoxamine                                          PD) deficiency (hemolytic anemia), organic or
                                                                 methyl Hg poisoning.

  • Chemistry: A water-soluble, specific iron chela-       applications
      tor created by removing ferric iron (Fe3+) from

      Mechanism: Chelates free iron and iron in tran-
                                                             • Use:    To chelate As, elemental and inorganic
                                                                 Hg; to treat arsenical dermatitis; to use in con-
      sit between transferrin and ferritin; but will not         junction with EDTA as initial chelation in lead
      chelate iron complexed to hemoglobin (Hb),                 encephalopathy.
      ferritin, or hemosiderin.
      Contraindications: None.
                                                             •   Dose: Deep IM 2.5 mg/kg q 4–6 hours × 4
                                                                 doses; topical application for mustard gas.
                                                             •   Side effects: Local injection site pain, fever,
                                                                 hypertension, tachycardia, nausea, vomiting,

60 | Color Atlas of Human Poisoning and enenoming
      headache. Can also chelate essential metals                   • Side effects: Transient increases in liver enzymes
      (especially Cu and Zn) and will chelate iron                      (AST) and multiple abdominal complaints —
      during concomitant iron therapy.                                  crampy abdominal pain, flatus, and diarrhea.

Chelators: Succimer                                               Chelators: D-Penicillamine
(Dimethylsuccinic Acid — DMSA)
                                                                    • Chemistry:      A highly toxic, penicillin-derived,
  • Chemistry:      A more water-soluble analog of                      nonspecific metal chelator (Cu > As, Hg, Pb)
      BAL that is less toxic and more specific for lead,                that is orally titrated over weeks.
      a borderline soft metal, than BAL.                            •   Mechanism: Same as succimer, but less effective
  •   Mechanism: Same as BAL, but less toxic, effec-                    and has more side effects; works best for Cu.
      tive orally, will not chelate essential metals (Cu,           •   Contraindications: Penicillin allergy, preexist-
      Fe, Mn, Zn), and can be used with concomitant                     ing skin diseases, or renal dysfunction.
      iron therapy. Succimer does not cause hemolysis
      in G-6-PD deficiency.
  •   Contraindications: None.                                    applications

                                                                    • Uses: Cu chelation in Wilson’s disease (hepato-
                                                                        lenticular degeneration).
                                                                    • Dose: 10 mg/kg/day orally, increased by 10 mg/
  • Use: Lead poisoning (BPb greater than 45 mcg/                       kg/week to 30 mg/kg/day over 10 weeks.
      dL), unapproved for organic and inorganic Hg                  • Side effects: Severe nausea and vomiting, leuko-
      poisoning and As poisoning.                                       penia, thrombocytopenia, eosinophilia, aplastic
  •   Dose: 30 mg/kg/day orally for five (5) doses.                     anemia, myopathy, dermatitis — Stevens-John-
                                                                        son syndrome, nephrotic syndrome.

                                                     Lead concentration
                              Children                                           Adults
                                                     in blood (µg Pb/dl)

                                                            100            Encephalopathy
                                    Nephropathy                            Anemia
                                                                           Decreased longevity
                                                             50            Hemoglobin synthesis
                                                                           Peripheral neuropathies
                          Hemoglobin synthesis               40
                                                                           infertility (men) & nephropathy
                          Vitamin D metabolism               30            Systolic BP (men)
                                                                           Hearing acuity
                       Nerve conduction velocity             20                      (men)
                       Erythrocyte protoporphyrin                          Erythrocyteprotoporphyr
                        Vitamin D metabolism (?)                                  (women)
                           Developmental toxicity
                                                             10            Hypertension (?)
                           Transplacental transfer
                              Increased function                           Decreased function

               Figure 4.3 Clinical Findings and Blood Lead Levels. A correlation of the clinical
               findings and rising blood lead levels in children and adults. (Source: U.S. Govern-
               ment Document, Agency for Toxic Substances and Disease Registry.)

                                                                                                             Antidotes | 61
   Antienins and Antitoxins
Crotalid Antienins                                        applications
                                                             • Use: All proven eastern and western coral snake
  • Chemistry: A polyvalent pit viper IgG antivenin          • Dose: 3–5 vials, up to 10 vials.
      prepared in horses hyperimmunized to venoms
      of the eastern and western diamondback rattle-
                                                             • Side effects: Since less antivenin is used for small
                                                                 coral snake envenomations, there are fewer
      snakes (Crotalus spp.) and the tropical fer-de-
                                                                 hypersensitivity reactions; nevertheless, serum
      lance (Bothrops spp.).
                                                                 sickness remains a high possibility.
  •   Mechanism: Direct Ag/Ab antagonism.
  •   Contraindications: Horse serum allergy, prior
      antivenin allergy; relative contraindication is a    Centruroides Antienins
      positive skin test. Soon to be replaced by less
      antigenic polyvalent Crotalid Fab (CroFab®).         Properties

                                                             • Chemistry: A specific bivalent (C. sculpturatus
                                                                 and C. gertschi) hyperimmune IgG prepared in
                                                                 goats at Arizona State University.
  • Use:     Most rattlesnake envenomations, all             •   Mechanism: Direct Ag/Ab antagonism.
      Mojave rattlesnake bites, 12% of copper-               •   Contraindications: Most adults; reserve for
      head and water moccasin (Agkistrodon spp.)                 severe envenomations in children.
  •   Dose: At least five (5) vials diluted 1:10 in nor-
      mal saline IV.                                       applications
  •   Side effects: Hypersensitivity reactions (20–
      40%) = urticaria, anaphylactoid reactions, ana-        • Use: Severe (grade III–IV) U.S. scorpion enven-
      phylaxis. Serum sickness (50%) = rash, pruritus,           omations in children less than age 6.
      urticaria, arthralgias, lymphadenopathy, rarely        • Dose: 1–2 vials over 30 minutes each.
      immune-complex glomerulonephritis.                     • Side effects: Serum sickness within 2 weeks in
                                                                 85% of recipients.
elapid Antienins
Properties                                                 Latrodectus Antienins
  • Chemistry: A polyvalent elapid IgG antivenin
      prepared in horses hyperimmunized to venoms            • Chemistry:    Latrodectus mactans-specific IgG
      of eastern and western (Texas) coral snakes,               prepared in horses.
      but not to the less venomous Sonoran (Arizona)         •   Mechanim: Direct Ag/Ab antagonism.
      coral snake.                                           •   Contraindications: Prior allergy.
  •   Mechanism: Direct Ag/Ab antagonism.
  •   Contraindications: Horse serum allergy, prior
      antivenin reaction.                                  applications

                                                             • Use: Bites of L. mactans, L. hesperus, L. bish-
                                                                 opi, and L. geometricus that are associated with

62 | Color Atlas of Human Poisoning and enenoming
      severe abdominal pain, myospasm, respiratory        Digoxin-Specific Fab (Antibody
      insufficiency, and not responsive to intensive      Fragment, Antigen-Binding)
  •   Dose: 1 vial in 50 mL normal saline.                Properties
  •   Side effects: Severe bronchospasm (increased
      CFR), serum sickness in more than 85% of              • Chemistry: Purified Fab fragments of intact IgG
      recipients.                                               anti-digoxin Abs. No Fc fragments, which do
                                                                not bind Ag and have increased hypersensitivity
                                                                reaction potential.
Botulinum Antitoxin                                         •   Mechanism: Direct Ag/Ab antagonism of intra-
                                                                vascular free digoxin with enough cross-reactiv-
                                                                ity to also bind digitoxin and the natural cardiac
                                                                glycosides from garden plants (foxglove and ole-
  • Chemistry: Trivalent (toxin types A, B, and E)              ander) and amphibians (toad bufotoxins).
      equine IgG antitoxin.                                 •   Contraindications: Hypercalcemia, concomi-
  • Mechanism: Direct Ag/Ab antagonism.                         tant Ca administration — as in CCB overdose.
  • Contraindications: None; botulism is         fatal.
      Cannot be used to treat infant botulism.

                                                            • Use:    Digitalis (digoxin) toxicity = worsening
                                                                atrioventricular (AV) block, ventricular tachy-
  • Use:    Foodborne botulism before all toxin is              cardia (VT), ventricular fibrillation (VF), rising
      bound and fixed to neuromuscular junction                 K greater than 5 mEq/L; natural glycoside poi-
      (NMJ) receptors. Infant botulism requires pen-            sonings — foxglove, oleander, red squill, toad
      tavalent (A, B, C, D, E) human hyperimmune                bufotoxins.
      globulin.                                             •   Dose: Empiric 10–20 vials; 38 mg Fab per vial
  •   Dose: One (1) or more vials diluted 1:10 IV               will bind 0.5 mg digoxin.
      every 2–4 hours.                                      •   Side effects: Acute hypokalemia, worsening of
  •   Side effects: Hypersensitivity reactions and ana-         congestive heart failure (CHF), rash, potential
      phylaxis common.                                          for hypersensitivity and serum sickness.

                                                                                                  Antidotes | 63
   Specific Antagonists
Calcium Channel Blocker                                   applications
Antagonist: Calcium
Properties                                                  • Use: To reverse pure BZ overdose or therapeutic
                                                                BZ use for “conscious sedation.”
  • Chemistry: Ionized cation essential in all muscle       • Dose: 1–3 mg IV slowly titrated at 0.1 mg/min.
      and nerve functions, especially for excitation-
                                                            • Side effects: Seizure and arrhythmia induction
                                                                in the predisposed with preexisting seizure dis-
      contraction coupling in heart and peripheral              orders, or in overdoses with convulsants; rese-
      circulation.                                              dation; rebound BZ respiratory depression.
  •   Mechanism: Direct antagonist to the cardiac
      effects of calcium channel blockers (CCBs), K,
      and Mg and to the neurological effects of Mg;       Opioid Antagonists
      restores Ca in ethylene glycol and hydrofluoric
      acid (HF) poisoning; complexes with fluoride to     Properties
      limit HF burns.
  •   Contraindications: Digitalis toxicity.                • Chemistry: Pure competitive opioid antagonists
                                                                = naloxone, naltrexone, and nalmefene.
                                                            •   Mechanism: Competitive antagonists most
                                                                potent at the mu receptor, subserving analgesia,
                                                                respiratory and CNS depression.
  • Use: CCB overdose, hyperkalemia, hypermag-              •   Contraindications: Long-acting naltrexone
      nesemia, ethylene glycol poisoning, HF burns.             should not be administered to the potentially
      Questionable use in beta-blocker overdose and             opioid-dependent without an initial short-act-
      to relieve myospasms after black widow spider             ing naloxone opioid withdrawal test.
  •   Dose: 1 g CaCl2 = 3 g calcium gluconate.
  •   Side effects: Increased calcium = nausea, vomit-    applications
      ing, constipation, hypertension, worsening digi-
      talis toxicity, injection site tissue irritation.     • Use: Naloxone to reverse mu receptor effects;
                                                                questionable use in septic shock. Naltrexone
                                                                better than nalmefene for treatment of chronic
Benzodiazepine Antagonist: Flumazenil                           opioid and alcohol addiction.
Properties                                                  •   Dose: 0.4 mg naloxone IV titrated to effect in
                                                                0.1-mg increments; long-acting naltrexone 50
                                                                mg orally four (4) times a day.
  • Chemistry: A competitive benzodiazepine (BZ)            •   Side effects: Withdrawal in the opioid-depen-
      antagonist with little agonist effect.                    dent, opioid resedation; rarely noncardiogenic
  •   Mechanism: Occupies the BZ receptor with                  pulmonary edema, hypertension (HTN), and
      high affinity and without causing functional              dysrhythmias.
      change and displaces the BZ agonist.
  •   Contraindications: In coma cocktails, BZ addic-
      tion, seizure disorders; can provoke seizures or
      arrhythmias in overdoses with tricyclic antide-
      pressants (TCAs), carbamazepine, theophyl-
      line, chloroquine, chlorinated HCs, and chloral

64 | Color Atlas of Human Poisoning and enenoming
Anticholinesterase (Ache)                                   Heparin Antagonist: Protamine
Antagonist: Physostigmine
                                                              • Chemistry: An electropositively charged protein
  • Chemistry:      A carbamate (organophosphate                  derivative of salmon sperm.
      insecticide) anticholinesterase (AchE) agent.           • Mechanism: Complexes with electronegatively
  •   Mechanism: Antagonizes cholinesterase (ChE)                 charged heparin with a greater affinity for hep-
      at both peripheral nervous system (PNS) and                 arin than for antithrombin-III, and dissociates
      CNS sites reversing anticholinergic effects at cen-         the heparin-AT-III complex in favor of a prot-
      tral sites more than at muscarinic and nicotinic            amine-heparin complex.
      receptor sites by increasing Ach concentrations.        •   Contraindications: Prior protamine or fish
  •   Contraindications: TCA overdose, AV block,                  (salmon) allergy, prior vasectomy with sperm
      bronchospastic disease, peripheral vascular dis-            autoantibodies, protamine containing insulin
      ease (PVD), gastrointestinal or bladder outlet              preparations (NPH and PZI), sole administra-
      obstruction.                                                tion without heparin.

applications                                                applications

  • Use:     Peripheral muscarinic (dry mucosa and            • Use: To reverse heparin activity, usually after
      skin, fever, flushing, mydriasis, tachycardia, uri-         cardiopulmonary bypass.
      nary retention = “red as a beet, dry as a bone,         • Dose: 1–1.5 times the heparin dose (100 U hep-
      hot as Hades”) and central (agitation, delirium,            arin = 1 mg) based on an activated clotting time
      hallucinations, seizures = “mad as a hatter”)               (ACT) normal of 150 seconds.
      anticholinergic toxidrome; more effective rever-        •   Side effects: Hypotension from vasodilation,
      sal of CNS effects than muscarinic and nico-                anaphylaxis, bleeding from platelet aggregation
      tinic effects.                                              with quantitative thrombocytopenia.
  •   Dose: 1–2 mg IV slowly.
  •   Side effects: Bradycardia, hypersalivation, bron-
      chospasm; rapid administration = nausea, vom-
      iting, headache, and diaphoresis = cholinergic
      toxidrome = SLUDE = Salivation, Lacrimation,
      Urination, Defecation, Emesis; or DUMB-
      BELS = Diarrhea, Urination, Miosis, Bron-
      chorrhea, Bronchospasm, Emesis, Lacrimation,

                                                                                                  Antidotes | 65
Folic and Folinic Acids                                          fied by the thiosulfate-rhodanase-thiocyanate
                                                                 pathway, especially during CN poisoning.
Properties                                                   •   Contraindications: None.

  • Chemistry: An essential water-soluble vitamin,
      whose active form, folinic acid, is required for     applications
      DNA (purine and thymidine) synthesis.
  •   Mechanism: Folic acid increases formic acid            • Use: Administer along with thiosulfate for cya-
      metabolism and decreases formate levels in                 nide poisoning (not FDA-approved for CN poi-
      methanol (and formaldehyde) poisoning; dihy-               soning in the United States).
      drofolate reductase (DHFR) converts folic acid         •   Dose: 4 g IV, repeat one (1) time, maximum 8 g,
      to its active form, folinic acid. The cancer che-          co-administer 8 g sodium thiosulfate.
      motherapeutic agent, methotrexate (MTX),               •   Side effects: Skin reddening, skin allergy.
      inhibits DHFR and blocks folic acid activation
      to folinic acid.
  •   Contraindications: Use only folinic acid, not        Vitamin K (itamin K1)
      folic acid, for MTX overdose.

applications                                                 • Chemistry: The koagulation factor, an essential
                                                                 fat-soluble vitamin, which exists as two types:
  • Use:    Folic and folinic (leucovorin) acids can             (1) the plant vitamin Ks predominantly, phyl-
      be used to decrease formate levels in methanol             loquinone but also phytonadione (K1); and (2)
      (and formaldehyde) poisoning and reduce risks              the bacterial vitamin K = menaquinone (K 2),
      of oculotoxicity; folinic acid, not folic acid, is         synthesized by gastrointestinal bacteria, except
      the specific antidote for MTX overdose.                    in newborns without an established intestinal
  •   Dose: Folic acid, 70 mg, 1–2 mg/kg every 6                 flora.
      hours; leucovorin, 2 times MTX dose in mg as           •   Mechanism: Activate clotting factors II, VII,
      soon as possible and every 6 hours three times             IX, X.
      a day.                                                 •   Contraindications:    Allergy    to    colloidal
  •   Side effects: None; folic acid is useless for MTX          formulation.
      (a DHFR inhibitor) overdose; must use folinic
      acid, the activated form of folic acid.

Hydroxocobalamin (itamin B12 precursor)                     • Use:     Warfarin (coumadin)-induced vitamin
Properties                                                       K1,2 deficiency and bleeding, newborn vitamin
                                                                 K 2 deficiency, malabsorption syndromes, and
  • Chemistry: A cobalt-containing active vitamin            •   Dose: 25–50 mg IV or subcutaneously 50–100
      B12 (cyanocobalamin) precursor.                            mg PO three times a day for 1–2 days.
  •   Mechanism: Displaces cyanide (CN) from                 •   Side effects: Anaphylactoid reaction from
      cytochrome oxidase to form cyanocobalamin,                 rapid IV administration, hematoma from IM
      which is an essential vitamin that is either               administration.
      excreted in the urine unchanged and/or detoxi-

66 | Color Atlas of Human Poisoning and enenoming
Pyridoxine (itamin B6)                                   applications
                                                            • Use: (1) Alcoholics and ethanol overdoses; (2)
                                                                coma cocktail for all altered mental status cases
  • Chemistry: The stable precursor to active vita-             to prevent wet beriberi (high output CHF) and
      min B6, a cofactor in the metabolism of neu-
                                                                dry beriberi (Wernicke’s encephalopathy and
      rotransmitters, GABA and 5-HT.
                                                                Korsakoff’s psychosis, increased CFR); (3) co-
  •   Mechanism: Isoniazid (INH) and monomethyl-
                                                                administer with hypertonic dextrose; (4) eth-
      hydrazine (MMH) poisoning — anticonvulsant
                                                                ylene glycol (EG) poisoning to promote as a
      effects mediated by enhanced GABA activity.
                                                                co-factor a less toxic metabolic pathway.
      Ethylene glycol (EG) poisoning — redirects the
      metabolism of EG away from the production of
                                                            •   Dose: 100 mg IV or im four (4) times daily.
      its toxic metabolite, oxalic acid.
                                                            •   Side effects: Few; deficiency = wet (CHF) and
                                                                dry (psychosis) bereberi.
  •   Contraindications: None; relative contraindica-
      tion — preexisting peripheral neuropathy.
                                                          Niacin (nicotinic acid) and
                                                          Niacinamide (nicotinamide)
  • Use:     (1) INH overdose and MMH poisoning
      (MMH = gyromitrin from Gyromitra escu-                • Chemistry:       Water-soluble, B-complex vitamin
      lenta mushrooms, MMH-containing jet fuels);               and essential precursor for NAD (and NADP)
      (2) ethylene glycol poisoning.                            metabolism that also binds lipoproteins.
  •   Dose: INH — mg/mg to maximum 5g; MMH                  •   Mechanism: Protects hepatic pentose phosphate
      — 25 mg/kg, maximum 70 g/g; EG-100 mg/d                   pathway; provides precursors to pancreatic B-
      to maximum 5g.                                            islet cells for NAD (and NADP) production.
  •   Side effects: Acute neurotoxicity = ataxia, inco-     •   Contraindications: Preexisting allergy, ASA
      ordination, seizures, all indicate increased case         sensitivity, skin disorders.
      fatality rates (CFR); chronic = delayed sensory
      peripheral neuropathy — axonopathy, poten-
      tially permanent.                                   applications

thiamine (itamin B1)
                                                            • Use:     (1) Niacin in massive doses (10–100 ×
                                                                RDA) to reduce triglyceride and cholesterol lev-
Properties                                                      els; (2) niacinamide (nicotinamide) as a specific
                                                                antidote for Vacor (PNU) rodenticide poisoning
                                                                to prevent toxic acute Type I insulin-dependent
  • Chemistry: Water-soluble essential B     1
                                                                diabetes mellitus (IDDM).
      that maintains the glycolytic pathway, produces
      ATP for cellular energy, and ensures nerve
                                                            •   Dose: Niacinamide (nicotinamide) — 500 mg
                                                                IV stat, then 200 mg IV every 4 hours for 48
  •   Mechanism: Catalyzes pyruvate metabolism to
                                                            •   Side effects: Potentially severe prostaglandin
      acetyl CoA, links glycolysis to Kreb’s cycle, and
                                                                (PG)-mediated vasodilation, flushing, headache,
      promotes ATP generation from cellular energy.
                                                                nausea, vomiting, diarrhea, niacin hepatitis.
  •   Contraindications: None.

                                                                                                 Antidotes | 67
   Specific Antidotes
ethanol                                                         tions; and potentially for severe ethanol-disulfi-
                                                                ram reactions.
Properties                                                  •   Dose: IV load with 15 mg/kg, then 15 mg/kg
                                                                every 12 hours.
  • Chemistry: The highest affinity substrate for the       •   Side effects: Nausea, headache, dizziness,
      hepatic enzyme alcohol dehydrogenase (ADH),               rash, eosinophilia, elevated liver function tests
      which also metabolizes EG to oxalic acid and              (LFTs).
      methanol to formic acid, highly toxic metabo-
      lites of both poison alcohols.
  •   Mechanism: Competitive antagonism of ADH            n-Acetylcysteine (NAC)
      to inhibit toxic alcohol metabolism to oxalic
      and formic acids.
  •   Contraindications: None.
                                                            • Chemistry: A thiol (HS)-containing antioxidant
                                                                and amino acid (cysteine) precursor deacety-
applications                                                    lated in vivo to cysteine that is required for glu-
                                                                tathione synthesis.
  • Use:   To arrest the further metabolism of EG
                                                            •   Mechanism: Replenishes hepatic glutathione
                                                                (an antioxidant free O− radical scavenger) in
      and methanol to their toxic metabolites.
                                                                acetaminophen overdose and limits the alter-
  •   Dose: IV (10%) or orally (20–30%), load 0.8
                                                                nate path P450 metabolism of acetaminophen
      g/kg IV or 8 mL/kg orally over 20–60 minutes,
                                                                to its toxic metabolite, n-acetyl-p-benzoquino-
      to maintain a serum level of 100–150 mg/dL.
                                                                neimine (NAPQI).
  •   Side effects: IV-venous irritation and phlebitis,
                                                            •   Contraindications: Do not co-administer with
      CNS depression, diuresis promotes dehydration
                                                                AC (20% adsorbed), separate administrations
      with hyponatremia, initial hyperglycemia pro-
                                                                by 1–2 hours.
      motes subsequent hypoglycemia.

Fomepizole (4-methylpyrazole)

                                                            • Use:    (1) All acetaminophen overdoses, espe-
                                                                cially in patients with preexisting glutathi-
                                                                one depletion (alcoholics — malnourished,
  • Chemistry:    A specific inhibitor of ADH that              HIV-AIDS, P450 inducing drugs); (2) free
      acts synergistically with ethanol in EG and               radical scavenging in poisonings with carbon
      methanol poisoning to occupy ADH.                         tetrachloride, chloroform, dichloropropane,
  •   Mechanism:      4-MP     blocks    ADH    by              and cyclophosphamide.
      complexation.                                         •   Dose: “Rule of 7s” = administer 140 mg/kg
  •   Contraindications: None.                                  orally within 8 hours, then 70 mg/kg every 4
                                                                hours over 3 days for 17 doses in 72 hours.
                                                            •   Side effects: Oral administration (PO) — antici-
applications                                                    pate vomiting (co-administer an antiemetic), IV
                                                                administration (not approved) — coagulopathy,
  • Use:   Alternative to, or in combination with,              anaphylaxis.
      ethanol for ethylene glycol, diethylene glycol
      (“Haitian Home Tylenol”), and methanol inges-

68 | Color Atlas of Human Poisoning and enenoming
                                                           Pralidoxime (2-PAM)

                                                             • Chemistry:     An oxime nonspecific cholines-
                                                                 terase (both acetyl and pseudocholinesterase)
                                                             •   Mechanism: Greater AchE reactivation at cen-
                                                                 tral and nicotinic (neuromuscular junction) over
                                                                 muscarinic sites, co-administer with atropine
                                                                 for better antimuscarinic coverage.
                                                             •   Contraindications: Sole use without atropine,
                                                                 relative contraindication — carbamate poison-
                                                                 ing — treat with atropine alone as the AchE
                                                                 inhibition will not age and will reverse.

Figure 4.4 X-ray # 40. Cerebral Effects of Carbon
Monoxide Poisoning. Cranial computerized axial tomo-       Applications
gram (CT) at the level of the basal ganglia in a patient
with atypical Parkinson’s disease who suffered carbon        • Use:   Organophosphate pesticide and organo-
monoxide poisoning in a house fire that demonstrates             phosphate nerve gas poisoning; AchE will spon-
bilateral hypodensities in the basal ganglia. (Courtesy
                                                                 taneously reactivate in carbamate poisoning.
of Carlos R. Gimenez, M.D., Professor of Radiology,
LSU School of Medicine, New Orleans, LA.)
                                                             •   Dose: Administer 1–2 g diluted over 30 minutes
                                                                 within 24–48 hours; repeat every 12 hours for
                                                                 48 hours.
                                                             •   Side effects: Rare — dizziness, blurred vision,
                                                                 and elevated diastolic blood pressure with rapid
                                                                 IV administration.

Miscellaneous Specific Antidotes

  tABLe 4.1 Miscellaneous Specific Antidotes
  Drugs or toxins                       Specific Antidotes
  Cesium                                Prussian blue — potassium ferricyanoferrate (chelator)
  Colchicine                            Colchicine Fabs
  Hydrofluoric acid                     Calcium gluconate
  Paraquat                              Fuller’s earth (binder)
  Potassium                             Sodium polystyrene sulfonate (binder)
  Lindane                               Cholestyramine (binder)
  Lithium                               Sodium polystyrene sulfonate (binder)
  Methotrexate                          Folinic acid (leucovorin)
  Nickel                                Dithiocarb (diethyldithiocarbamate)
  Platinum                              Dithiocarb (diethyldithiocarbamate)
  thallium                              Prussian blue (chelator)
  Uranium                               Gallic acid
  Warfarin                              Vitamin K

                                                                                                 Antidotes | 69
   Nonspecific Antidotes
Dextrose                                                    applications
                                                              • Use:    To reverse overdoses of beta-blockers
                                                                  and calcium channel blockers; to promote gas-
  • Chemistry:     Precursor of glucose, the primary
                                                                  trointestinal elimination of ingested button
      energy source for the brain.
  •   Mechanism: Energy substrate.
                                                              •   Dose: Initial bolus, 50 mcg/kg IV.
  •   Contraindications: Relative contraindications =
                                                              •   Side effects: Not arrhythmogenic, dose-depen-
      cerebral ischemia, preemies at risk for intracra-
                                                                  dent nausea and vomiting, hyperglycemia,
      nial hemorrhage, cardiac insufficiency — con-
                                                                  hypokalemia, allergic reactions from beef or
      gestive heart failure (CHF).
                                                                  pork glucagon preparations.

                                                            Methylene Blue

  • Use: Empiric administration to all patients with        Properties
      coma or altered mental status.
  •   Dose: D50W, 0.5–1.0 g/kg bolus IV.                      • Chemistry: A blue dye initially used as a urinary
  •   Side effects: Phlebitis at IV injection sites; sei-         antiseptic and weak antimalarial agent that is
      zures and intracranial hematoma in preemies;                both an Hb oxidizer (high doses) and reducer
      potential osmotic fluid overload in cardiac                 (therapeutic low doses).
      insufficiency.                                          •   Mechanism: Paradoxically both oxidizes oxyHb
                                                                  to metHb at high doses and reduces metHb back
                                                                  to oxyHb at low doses (therapeutic use) via the
Glucagon                                                          NADPH-metHb reductase pathway (requires
                                                                  normal G-6-PD).
                                                              •   Contraindications: Absolute (not variant) G-6-
                                                                  PD deficiency — no NADPH — ineffective for
  • Chemistry:      Hormone secreted by pancreatic                reducing sulfmethemoglobin (H 2S-metHb) in
      alpha cells in response to hypoglycemia.                    H 2S poisoning.
  •   Mechanism: Mobilizes glucose fuel stores; sup-
      presses insulin release; provides direct inotro-
      pic and chronotropic cardiac stimulation like         applications
      β -agonists but outside the β receptor; relaxes
      smooth muscle in lower esophageal sphincter,
      gastrointestinal tract, and biliary tree — all
                                                              • Use: To reverse methemoglobin (metHb) pro-
                                                                  duction by aniline dyes, sulfonamides, sulfones,
      actions mediated via increased cAMP.
                                                                  nitrates and nitrites, KMnO4; to reduce cyan-
  •   Contraindications: Insulin and oral hypogly-
                                                                  met-hemoglobin (cyanmetHb) in CN poisoning
      cemic-induced hypoglycemia; not to be used in
                                                                  treated with nitrites.
      lieu of D50W in the initial therapy of comatose
                                                              •   Dose: 1–2 mg/kg IV over 5 minutes.
                                                              •   Side effects: metHb at high doses >5 mg/kg and
                                                                  in G-6-PD deficiency, blue skin-mucosa-urine,
                                                                  vomiting, ECG changes.

70 | Color Atlas of Human Poisoning and enenoming
Medications causing Methemoglobinemia                             tion; to provide preferred substate with (3) for
                                                                  rhodanase in the presence of CN to form less
                                                                  toxic thiocyanate for renal excretion.
  • Nitrites and nitrates: Amyl and sodium nitrite,           •   Contraindications: No absolute contraindica-
      nitrogylcerin (NTG), nitroprusside, silver
                                                                  tions. Relative contraindication = renal failure.
  •   Local anesthetics: Prilocaine, lidocaine,
  •   Antibiotics: Antimalarials (chloroquine, prima-
      quine), dapsone, sulfonamides.
  •   Miscellaneous: Pyridium, phenacetin, large              • Use: Complete kit — CN poisoning; IV sodium
      doses (>5 mg/kg) of methylene blue.                         nitrite alone — hydrogen sulfide (H 2S) poison-
                                                                  ing; thiosulfate alone — sodium nitroprusside
                                                                  overdose with CN poisoning.
toxic Chemical Exposures                                      •   Dose: (1) Amyl nitrite — for inhalation only; (2)
                                                                  sodium nitrite — 10 mL of the 3% solution IV
                                                                  diluted in 100 mL; (3) sodium thiosulfate — 50
  • Nitrites and nitrates: Butyl and isobutyl nitrite,            mL of the 25% solution IV.
      foods with nitrite or nitrate preservatives (pro-
      cessed meats), nitrophenol, silver nitrate, trini-
                                                              •   Side effects: Methemoglobinemia — consider
                                                                  methylene blue, 1 mg/kg IV.
      trotoluene (TNT), well-water nitrates (infants),
      nitrogen oxide gases.
  •   Aniline dyes.
                                                            Sodium Bicarbonate
  •   Mothballs: Naphthalene only.
  •   Miscellaneous: Potassium permanganate.

Cyanide Antidote Kit®                                         • Chemistry: Nonspecific antidote.
Properties                                                    • Contraindications: Pulmonary edema, conges-
                                                                  tive heart failure (CHF), renal failure, preemies
                                                                  at risk of intracranial hemorrhage.
  • Chemistry: an FDA-approved cyanide antidote
      kit composed of (1) amyl nitrite pearls for inhala-
      tion, (2) 3% sodium nitrite inravenous solution,      applications
      and (3) 25% sodium thiosulphate intravenous
  •   Mechanism: To induce methemoglobinemia                  • Dose: 1–2 mEq/kg IV bolus.
      with (1) and (2) in order to preferentially bind        • Side effects: Metabolic alkalosis,    increased
      CN forming cyanomethemoglobin and limiting                  HCO3, hypernatremia, fluid overload, hyokale-
      poisoning of cytochrome oxidases; to augment                mia, hyocalcemia.
      hepatic blood flow with (1) and (2) by promot-
      ing vasodilation through nitric oxide forma-

                                                                                                   Antidotes | 71
Mechanisms and antidote Uses

  tABLe 4.2 Mechanisms and Antidote Uses: Sodium Bicarbonate
  Mechanisms                                              Antidote Uses
  Overrides cardiac Na channel block by alkalinizing      tCas, cocaine, all quinidine-like antiarrhythmics that
   blood                                                   block Na channels and increase QrS complex
  Ionizes weak acids, trapping them in blood before       Phenobarbital, aSa, formate
   receptor activation
  Ionizes weak acids, trapping them in urine and          Phenobarbital, aSa, chlorpropamide, and
   increasing tubular excretion                            chlorphenoxyacetic acid pesticides (2,4-D; 2, 4, 5-t)
  Buffers metabolic acidosis                              Ethylene glycol, methanol
  Increases solubility of insoluble drugs methotrexate    Methotrexate
  Forced alkaline diuresis prevents myoglogin             rhabdomyolysis
   dissociation and reduces risks of acute tubular
   necrosis (atN) from rhabdomyolysis
  Neutralizes inhaled acid gases, especially chlorine and Chlorine and chloramine gas inhalation-nebulized
   chloramine gas                                          NaHCO3

Hyperbaric Oxygen (HBO) therapy                                   carbon monoxide, and cyanide (CN) poison-
                                                                  ing, methylene chloride poisoning (hepati-
Properties                                                        cally biotransformed to CO), H 2S poisoning,
                                                                  CCL4 hepatotoxicity (by inhibiting the hepatic
  • Chemistry: HBO is the inhalation of oxygen at                 microsomal oxidase system that produces toxic
      pressures >1 atm.                                           metabolites).
  • Mechanism:       (1) Elevates hydrostatic pres-           •   Dose: Not applicable, depth and length of
      sure and decreases gas volumes (air embolism,               “dive.”
      “bends”); (2) hastens dissociation of CO and            •   Side effects: Otic barotrauma, especially rup-
      H 2S from Hb; (3) hastens dissociation of CO                tured tympanic membrane, claustrophobia,
      from cytochrome oxidase; (4) inhibits leukocyte             sinus pain, filled tooth pain.
      sequestration in brain and reduces risks of cere-
      bral reperfusion injury.
  •   Contraindications: Absolute — tension pneu-          HBO: CO Poisoning
      mothorax, bleomycin therapy; relative contra-        Head CT of a patient with permanent mental status
      indications — sinus congestion, otosclerosis.        changes (and later parkinsonism) following CO poi-
                                                           soning. Note characteristic symmetrical lucencies of
                                                           the globus pallidus bilaterally. Neurotoxicity could
                                                           have been prevented by early HBO.

  • Use:    Air embolism (H 2O2), decompression
      sickness, carbon monoxide (CO) poisoning,

72 | Color Atlas of Human Poisoning and enenoming
                                                                        Chapter 5

    Poisonings with Oer-the-
Counter and Opioid Analgesics
 and Pharmaceutical Addities

  Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 73
                                                                                  Part 1

Poisonings with Oer-the-Counter
   and Opioid Analgesics: Outline
                                      Acetaminophen (N-acetyl-para-
                                      aminophenol) (APAP) s. Acetyl salicylic
                                      acid (ASA) aspirin

                                         Clinical manifestations

                                      Nonsteroidal anti-inflammatory
                                      drugs (NSAIDs)

                                         Epidemiology of NSAID overdose
                                         Classification of NSAIDs
                                         Mechanisms of NSAID toxicity
                                         Diagnosis and management of NSAID poisoning
                                         Specific NSAID adverse effects
                                         Drug–drug interactions
                                         Specific NSAID toxicities


                                         Opioid: Ag/Antag
                                         Opioid toxidrome
                                         Opioid differential diagnosis
                                         Clinical effects of opioids
                                         Special consideration opioids
                                         Management of opioid overdose

                                       paracetamol in the United Kingdom.

     Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 75
  Acetaminophen (N-acetyl-
  para-aminiphenol) (APAP) s.
  Acetyl Salicyic Acid (ASA)
epidemiology                                                • Methyl salicylate (oil of wintergreen): 530 mg
                                                                 ASA/mL; 8 mL = 13,325 mg ASA tablets. As
aPaP                                                             little as 4 mL of methyl salicylate can be lethal
                                                                 in children.
 • APAP is contained in over 100 over-the counter
      (OTC) preparations, and fulminant liver failure
      from APAP overdose is the second most com-           toxicology
      mon cause of liver transplantation in the United
      States (No. 1 cause = hepatitis C).
 •    More than 100,000 analgesic overdoses per
      year, over 200 deaths, 46% due to APAP.               • 90% of APAP is hepatically metabolized to harm-
 •    APAP overdose hospitalizations are greater than            less glucuronide (60%) and sulfate (30%) metabo-
      all other overdose hospitalizations.                       lites excreted in the urine.
 •    APAP has replaced ASA as the analgesic-anti-          • 5–15% of APAP is oxidized by the cytochrome
      pyretic of choice, especially for children second-         P450 mixed-function oxidases (MFOs) to
      ary to safety profile, N-acetylcysteine (NAC)              potentially hepatotoxic n-acetyl-p-benzoquino-
      antidote, ASA toxicity, and Reye’s Syndrome.               neimine (NAPQI).
 •    APAP toxicity risk factors: low hepatic gluta-        •    NAPQI is normally immediately detoxified by
      thione stores in alcoholics and malnourished;              hepatic glutathione conjugation to nontoxic
      P450 enzyme induction from INH, rifampin,                  metabolites.
      anticonvulsants, and chronic alcohol abuse.

                                                            • ASA is rapidly absorbed in the stomach over the
 • There are approximately 18,000 aspirin poison-                small intestine, unless absorption is delayed by
      ings per year in the United States.                        pylorospasm, hypomotility, gastric outlet obstruc-
 • ASA causes 26% of all analgesic deaths each year;             tion, bezoars, or concretion formation.
   more than 35 deaths per year.                            • Centrally stimulates the brainstem respiratory
 • ASA and viral illness = Reye’s (nausea, vomiting,             center, causing hyperventilation and respiratory
      low glucose, high liver function tests (LFTs), and         alkalosis.
      hepatic encephalopathy).                              •    Blocks the Krebs cycle uncoupling oxidative
 •    Over-the-counter (OTC) drugs contain APAP or               phosphorylation and reduces ATP production.
      ASA; therefore, toxicity screens should include       •    Promotes anaerobic metabolism with ketosis,
      both analgesics: more than 100 OTC drugs con-              lactic acidosis, and hypoglycemia.
      tain APAP and more than 200 OTC drugs contain
 •    Pepto-Bismal® (bismuth subsalicylate) contains       aPaP Overdose
      8.8 mg ASA/mL.
 •    Increased levels of ASA in ointments, liniments,
      keratolytics (Compound W®), vaporizer oils =          • In     overdose, NAPQI production outstrips
      methyl salicylate, 1–2 tsp. lethal in children.            hepatic ability to detoxify NAPQI by glutathi-

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 77
      one conjugation. NAPQI covalently binds to                      Clinical Manifestations
      and arylates hepatocytes, causing massive cen-
      trilobular hepatic necrosis, reversible by n-ace-
                                                                      acute aPaP Poisoning
      tylcysteine (NAC), a glutathione precursor and                      • Phase 1 (up to 24 hours): Asymptomatic or non-
      substitute. NAPQI causes proximal renal tubu-                           specific symptoms, anorexia, malaise, nausea,
      lar necrosis and ARF in 25% of the overdoses.                           vomiting, pallor, diaphoresis.
  •   Therapeutic plasma concentration: 10–30 mg/                         •   Phase 2 (24–72 hours): Onset of hepatic injury,
      L; 4 hours — NAC action level ≥ 150 mg/L; sig-                          right upper quadrant (RUQ) pain, high aspar-
      nificant plasma toxicity level ≥ 250 mg/L.                              tate aminotransferase (AST), then increased
                                                                              prothrombin time (PT) and alanine amino-
                                                                              transferase (ALT).
aSa Overdose                                                              •   Phase 3 (72–96 hours): Hepatic necrosis, coag-
                                                                              ulopathy, jaundice, encephalopathy, coma, all
  • Adult overdoses present with mixed respiratory                            LFTs high, renal failure (25%), ARDS and pan-
      and metabolic acidosis; children present only                           creatitis possible.
      with metabolic acidosis (>40 mg/dL).                                •   Phase 4 (4 days–2 weeks): Recovery, complete
  •   Unique toxic effects include:                                           hepatic regeneration in survivors.
      − Reye’s Syndrome
      − Non-cardiogenic pulmonary edema from                          acute aSa Poisoning
         hypoxia and pulmonary hypertension
         (HTN)                                                            • Early acute: Nausea, vomiting, fever, diaphore-
      − Hypoprothrombinemia and platelet                                      sis, tinnitus, tachypnea.
         dysfunction                                                      • Late acute: (1) CNS = tinnitus, then deafness,
      − Nausea, vomiting, slow GI motility, hemor-                            vertigo, high fever, hyperventilation, agitation
         rhagic gastritis                                                     hyperactivity, seizures, delirium, hallucinations,
      − Rhabdomyolysis from hypermetabolism, sei-                             coma; (2) acid-base = respiratory alkalosis and
         zure activity, and increased heat production                         metabolic acidosis; (3) gastrointestinal distress;
      − Tinnitus preceding deafness (>20–45                                   (4) coagulopathy; (5) metabolic = hypoglycemia,
         mg/dl)                                                               ketonemia, ketonuria; (5) pulmonary = tachy-
                                                                              pnea, hyperpnea, non-cardiogenic pulmonary
                                                                              edema (NCPE), cardiopulmonary collapse.
                                                    O                                                    O
                                         H    N     C                                        H       N       C
                                                          CH3     UDP-glucuronosyl-                               CH3

                                              OH                    90%                                     −
                                                                                                 O   C6H8O6
                                        Acetaminophen                     Phenolsulfo-   Acetaminophen glucuronide
                                                                           transferase               O
                                                                                             H       N       C
                   NADPH2 + O2                                                                                    CH3
                   Cytochrome P450
                   NADP + 2H2O
                                                                                         Acetaminophen sulfate
                                               O                  NAC1
                                             N C    CH3     Glutathione (GSH)                    N       C

                                         O                                                   OH      SG
                             N-acetylbenzopuinoeimine             NAC2
                                                                                  Acetaminophen glutathione
                                             NAC4                                         conjugate

                          Binding to cellular proteins, leading
                              to hepatic and renal injury                        Cysteine, mercaptate conjugates

FIGURe 5.1 Acetaminophen (N-acetyl-para-aminophenol-APAP): Biotransformation Pathways of Toxicity. The
biotransformation pathways and mechanisms of toxicity of acetaminophen or n-acetyl-para-aminophenol (APAP).

78 | Color Atlas of Human Poisoning and enenoming
                                                                                               H       N       C
                                                   C                                                                CH3
                                        H    N         CH3        UDP-glucuronosyl-
                                                                     90%                               O
                                                                           Phenolsulfo-   Acetaminophen glucuronide
                                                                     NAC3                      H       N       C
                 ADPH2 + O2                                                                                         CH3
                 Cytochrome P450              5−15%
                 DP + 2H2O
                                                                                                       SO3 −
                                                                                          Acetaminophen sulfate
                                             O                                                         O

                                         N C     CH3             Glutathione (GSH)                 N       C       CH3

                                       O                                                       OH     SG
                           N-acetylbenzoquinoneimine                  NAC2
                                                                                   Acetaminophen glutathione
                                            NAC4                                           conjugate
                         Binding to cellular proteins, leading
                             to hepatic and renal injury                           Cysteine, mercaptate conjugates

FIGURe 5.2 Acute Acetaminophen (APAP) vs. Aspirin (ASA) Poisoning. The differential mechanisms of poi-
soning with the common over-the-counter analgesics, acetaminophen and aspirin or acetylsalicylic acid (ASA).

Chronic aPaP Poisoning                                                     • Identify symptoms and signs of hepatic injury:
                                                                               (APAP) plasma concentration 4 hours after over-
                                                                               dose (less than 1 hour useless, 2–4 hours OK);
  • Chronic: Because APAP is a phenacetin metab-                               hepatic AST if (APAP) above lower nomogram
     olite, renal papillary necrosis and nephrotic
                                                                               line at 150 mg/mL or RUQ pain; if hepatic AST
     syndrome are possible = chronic analgesic
                                                                               is 1000+ IU/L, check PT, BUN, and creatinine.
     nephropathy. In addition, patients at risk of
     increased NAPQI production as a result of
                                                                           •   High risk if: (APAP) above lower nomogram line;
                                                                               (APAP) greater than 150 mg/mL and overdose
     CYP40 enzyme induction (from INH, rifampin,
                                                                               time unknown-order AST; repeat hepatic AST in
     most anti-convulsants, ethanol) or reduced glu-
                                                                               4 hours, for extended release-APAP ingestions.
     tathione stores (alcoholism, HIV/AIDS, mal-
     nutrition, starvation) are at increased risk of
     hepatotoxicity from APAP.                                        aSa

Chronic aSa Poisoning
                                                                           • Obtain serum ASA: Therapeutic 15–30 mg/dL,
  • Chronic:    (1) Mainly a CNS constellation of                              toxic when more than 30–40, action level 50 mg/
     tinnitus, deafness, dyspnea, hyperventilation,                            dL, sever toxicity 75 mg/mL, potentially lethal
     tachycardia, hyperthermia, CNS hyperactivity,                             100 mg/mL.
     agitation, confusion, slurred speech, hallucina-                      • Confirm      ASA by bedside FeCl3 test: A few
     tions, seizures, coma; (2) chronic GI distress; (3)                       drops (gtts) and 1 mL urine turns purple for a
     NCPE possible.                                                            positive test (also positive for acetoacetic acid,
                                                                               diflunisalone, phenothiazines, phenylpyruvic
Diagnosis                                                                      acid, phenylbutazone, and phenoxyacetic acid,
aPaP                                                                       •   Pathognomonic respiratory alkalosis and meta-
                                                                               bolic acidosis (sole blood gas manifestation in
  • Overdose    with more than 7.5 g (>20 tablets)                             children).
     in adults, and with more than 150 mg/kg in                            •   Confirm positive urine ketones secondary to
     children.                                                                 anaerobic fatty acid metabolism.

                  Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 79
  tABLe 5.1 Acute vs. Chronic ASA Poisoning
                           Acute                                                         Chronic
  age                      Young                                                         Old
  Etiology                 Overdose                                                      Latrogenic
  Diagnosis                Classic                                                       Unrecognized
  associated diseases      None                                                          Chronic pain
  Suicidal ideation        Yes                                                           No
  Clinical                 rapid progression over 30 mg/dL                               CNS abnormalities, bleeding tendency,
                                                                                          noncardiogenic pulmonary edema
  Mortality                          rare                                                25%
  Serum levels                       High                                                Intermediate


                               250                                for toxicity
                     µmol L

                               100              unlikely
                                                                                   Recommend treatment
                                                                                         if level is
                                20                                                   above broken line

                     Level 1ist
                                     4      8     12       16        20          24           28         32   36
                                                             Hours post-ingestion

FIGURe 5.3 The acetaminophen (APAP) toxicity nomogram. The acetaminophen toxicity nomogram as deter-
mined by amount ingested and time needed for detoxification by nontoxic biotransformation routes. See text for
instructions on how to interpret the nomogram.

treatment                                                                 • NAC: Supplies glutathione to detoxify NAPQI,
                                                                                 effective up to 8 hours post overdose, possible
                                                                                 up to 24 hours post ingestion can even reverse
                                                                                 NAPQI binding to hepatocytes.
                                                                          •      NAC oral dosing: Rule of 7s — orally load 140
  • Gastric  emptying rarely indicated secondary to                              mg/kg, administer 70 mg/kg every 4 hours × 17
     rapid absorption.                                                           doses × 72 hours. Monitor APAP plasma levels
  • AC if overdose occurred less than 4 hours ago,                               every 4 hours.
     separate AC and NAC by 1–2 hours to prevent
     adsorption of NAC (20%). No AC if ≥8 hours
     post ingestion.

80 | Color Atlas of Human Poisoning and enenoming
ASA                                                   n-acetylcysteine (NaC)

 • Orogastric lavage and AC.
 • Replace fluid, K, Na losses from hypermetabo-        • Orally: Nausea and vomiting common, add an
     lism and dehydration; monitor CVP or PAP
                                                          antiemetic; diarrhea.
     (NCPE risk).
 •   Alkalinize blood and urine, IV NaHCO3 (not
                                                        • Intravenous: Anaphylactoid reactions and ana-
                                                          phylaxis possible; not FDA-approved in the
     acetazolamide = metabolic acidosis) for [ASA]
                                                          United States.
     over 35 mg/dL, 1–2 mEq/kg bolus and infuse 3
     amps/L at 150–200 mL/hour.
 •   Maintain arterial pH 7.45–7.50 and urine pH      Indications for IV NAC
     7.5–8.0 (≥7.5).
 •   Support ventilation to maintain respiratory        • Uncontrollable  vomiting, (1–20%) gastrointes-
     alkalosis; high risk when respiration acidosis       tinal bleeding or obstruction, seizure activity,
     and metabolic acidosis present.                      encephalopathy.
                                                        • Fulminant hepatic necrosis and liver failure.
                                                        • Persistently elevated [APAP] over 8 hours post
                                                        • APAP overdoses during pregnancy.
                                                        • Dose: IV load with 140 mg/kg over 1 hour, fol-
                                                          lowed by 1 dose of 70 mg/kg every 4 hours.

                 Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 81
   Nonsteriodal Anti-
   Inflammatory Drugs (NSAIDs)
epidemiology of NSAID Oerdose                                        Classification of NSAIDs

  • NSAIDs      are now the most commonly pre-                            • Pyrazolones: Phenylbutazone only.
      scribed medications, with more than 73 million                      • Fenamates: The anthranilic acids,        meclofe-
      prescriptions each year and costing $2.2 billion                        namate and mefenamic acid.
      annually.                                                           •   Acetic acids: Diclofenac, etodolac, indometha-
  •   NSAID overdoses cause more morbidity than                               cin, ketorolac, nabumetone, sulindac, tolmetin.
      mortality; CFRs are 6 to 7 times higher for APAP                    •   Propionic acids: Ibuprofen, flurbiprofen, keto-
      and ASA overdoses than NSAID overdoses.                                 profen, naproxen.
  •   Lethal overdoes: ASA > APAP > NSAIDs. CFRs                          •   Oxicams: Piroxicam only (Feldene®).
      over 10 years: ASA — 0.38%; APAP — 0.12%;
      NSAIDs — 0.03%
  •   NSAIDs cause 25% of all reported adverse drug                   Mechanisms of NSAID toxicity
      reactions, most commonly gastrointestinal side
      effects.                                                            • Most NSAIDs are nonspecific COX-1 and COX-
  •   Acute renal failure associated with NSAID use                           2 inhibitors that block the synthesis of prosta-
      accounts for about 15% of drug-induced renal                            glandins (PGs), which cause inflammation,
      failure, mostly in the elderly.                                         fever, and pain, especially in osteoarthritis.
                                                                          •   NSAIDs block synthesis of the cytoprotective
                                                                              prostaglandins (PGs), PGE2 and PGI2, which

                                             Cell membranes


                                            Phospholipase A2

                                              Arachidonic acid             Lipooxygenase
                         Cyclooxygenase I and II
                          irreversibly bound by
                          salicylates, reversibly                                           Leukotrienes
                         bound by other NSAIDs
                                             Cyclic endoperoxides

                                                                                            receptor (LR)
                            Prostacyclines Prostaglandins              Thromboxanes
                             anti-platelet erythema, edema,         platelet aggregation,
                             aggregation, pain, fever, uterine        vasoconstriction
                             vasodilation   contraction, GI
                                                                                                (LR antagonist)

FIGURe 5.4 The Mechanisms of toxicity of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Comparative
toxic biotransformation pathways of common over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs).

82 | Color Atlas of Human Poisoning and enenoming
      maintain upper gastrointestinal mucosal bar-          • Assess  for systemic damage: Gastrointestinal,
      rier, potentially causing gastric and duodenal            hematologic, hepatic, renal.
      ulcers with 3% risk of hemorrhage or gastroin-
      testinal perforation.
  •   NSAIDs block synthesis of prostacyclines and        Specific NSAID Aderse effects
      thromboxanes necessary for normal clotting
                                                          Significant Hematologic Side Effects
      mechanisms. NSAIDs increase bleeding risks
      by causing platelet dysfunction.
  •   NSAIDs are mildly hepatotoxic and cause               • Increased bleeding time from decreased platelet
      transient elevations in hepatic transaminases             aggregation: All NSAIDs.
      in 25% of patients. Exception: diclofenac             • Agranulocytosis: Phenylbutazone, naproxen.
      (Voltaren®) can cause hepatocellular necrosis,        • Aplastic anemia: Indomethacin, phenylbuta-
      probably via an immunologic or hypersensitiv-             zone, etodolac.
      ity mechanism.                                        •   Hemolytic anemia: Mefenamic acid.
  •   NSAIDs are more nephrotoxic than hepatotoxic          •   Neutropenia: Indomethacin.
      and can cause chronic renal failure, or analgesic     •   Thrombocytopenia: Indomethacin, ibuprofen,
      nephropathy, by blocking PG support of renal              naproxen.
      perfusion and glomerular filtration rate (GFR)
      with interstitial nephritis, nephrotic syndrome,
      and papillary necrosis in heavy NSAID abusers,      Drug–Drug Interactions
      especially elderly women with osteoarthritis.
                                                            • All anticoagulants and ASA: High gastrointes-
                                                                tinal bleeding.
Diagnosis and Management                                    • Antihypertensives:      Reduced    efficacy    of
of NSAID Poisoning                                              antihypertensives.
                                                            •   Sulfonylureas: Greater hypoglycemic effects.
Diagnosis                                                   •   Lithium: High toxicity.
                                                            •   Digoxin: High toxicity.
  • Acute     overdose: CNS depression, respiratory         •   Aminoglycosides: High toxicity.
      depression, hypotension, hypothermia, gastro-
      intestinal distress, gastrointestinal bleeding,
      elevated LFTs, acute renal failure, rarely hallu-   Specific NSAID toxicities
      cinations and seizures.
  •   Chronic overdose: Chronic renal failure (CRF)         • Phenylbutazone: Most toxic NSAID, seizures,
      in the elderly and alcoholics; bleeding and cog-          coma, hemodynamic instability, NCPE, ARF,
      nitive dysfunction and dementia in elderly.               agranulocytosis, aplastic anemia, hypersensitiv-
  •   Constellation of side effects: Gastrointestinal,          ity hepatitis.
      renal, hypersensitivity reactions, (acetic acids          − Treatment: Immediate orogastric lavage and
      and phenylbutazone > piroxicam > propionic                    AC, MDAC, hemodialysis useless.
      acid) pulmonary, CNS, hematologic, drug-drug          •   Fenamates (anthranilic acids): Nausea, vom-
      interactions.                                             iting, diarrhea (15%); muscle twitching and
Management                                                      − Treatment: Airway and seizure management
                                                                    (BZs), lavage and AC, MDAC.
                                                            •   Acetic acids: Nausea, abdominal cramps, drows-
  • Immediate orogastric lavage and AC, consider                iness, headache, seizures; diclofenac = hypersen-
      MDAC, support.                                            sitivity hepatitis, hepatocellular necrosis.
  • Add misoprostel, a PGE2 analog. For gastro-                 − Treatment: Lavage and AC.
      intestinal mucosal cytoprotection in chronic          •   Propionic acids: Gastrointestinal upset, sei-
      NSAID users.                                              zure, apnea, coma, ARF, hepatotoxicity,
  •   Switch to specific COX-2 inhibitors (become               thrombocytopenia.
      nonspecific in overdose).                                 − Treatment: Lavage and AC.
  •   Hemodialysis useless because of high protein          •   Oxicams: Dizziness, blurred vision, coma.
      binding.                                                  − Treatment: Lavage and AC.

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 83
  tABLe 5.2 Opioids Receptors
  Opioid Receptor                      endogenous Ligand                    Clinical effects
  Mu (µ)                               Endorphins                           Central analog, euphoria,
                                       Naloxone — reversible                 respiratory depression, miosis,
                                                                             dependency, pruritus,
                                                                             cardiovascular depression
  Kappa (κ)                            Dynorphins                           Spinal analog, dyphoria,
                                       Naloxone — reversible                 psychomimesis
  Delta (δ)                            Enkephelins                          Spinal analog, dopamine release
                                       Naloxone — reversible                 modulation
  Sigma (σ)                            Not a true opioid receptor           Psychomimesis, seizures
                                       Not naloxone — reversible             (pentazocine)

Opioids: Ag/Antag                                           • All   alpha2 agonists = clonidine (central only)
                                                                and nasal imidazolines sprays (central and
                                                                periph agonists, mucosal decongestants).
  • Partial agonist: Buprenorphine.                         •   Benzodiazepines: Sedation and normal VS, no
  • Agonists: Codeine, dextromethorphan,                        miosis.
      diphenoxylate (Lomotil®), fentanyl, heroin,
      hydrocodone, hydromorphone, loperamide,
                                                            •   Phencyclidine (PCP): Despite the miosis, nys-
                                                                tagmus is pathognomonic.
      meperidine, methadone, morphine, oxycodone,
      paregoric, propoxyphene, tramadol.
                                                            •   Phenothiazines: Miosis present, severe low
                                                                blood pressure, dysrhythmias quinidine-like
  •   Antagonists: Nalmefene, naloxone, naltrexone.
                                                                local anesthetic (LA) effect.
  •   Agonist/antagonists: Butorphanol, nalbuphine,

Opioid toxidrome

  • Central CNS and respiratory depression.
  • Miosis: Mnemonic for miosis = COPS = cloni-
      dine (imidazolines), cholinergics, opioids,
      organophosphates,      phenothiazines,     phen-
      cyclidine, sedative-hypnotics, subarachnoid
  •   Gastrointestinal hypomotility and constipation,
      sphincter spasm, increased intrabiliary pressure,
      reduced heart rate (HR), not sinus bradycardia.
  •   Mild hypotension from histamine-mediated

Opioid Differential Diagnosis                             FIGURe 5.5        Opioid toxidrome: miosis, left eye.
                                                          Pupillary constriction or miosis characteristic of an opi-
  • All agonist opioids.                                  oid toxidrome.

84 | Color Atlas of Human Poisoning and enenoming
FIGURe 5.6 Opioid ileus: heroin addict. Frontal           FIGURe 5.7 Noncardiogenic pulmonary edema:
abdominal radiograph (KUB) of a heroin addict con-        aspirin overdose. Frontal chest radiograph of a patient
sistent with adynamic bowel or opioid ileus that dem-     following a suicide attempt by aspirin overdose that
onstrates diffuse bowel gas distension of the small       demonstrates noncardiogenic pulmonary edema
bowel, ascending colon, and transverse colon. (Cour-      characterized by normal size and configuration of the
tesy of Carlos R. Gimenez, M.D., Professor of Radiol-     cardiomediastinal silhouette and diffuse bilateral pul-
ogy, LSU School of Medicine, New Orleans, LA.)            monary edema. (Courtesy of Carlos R. Gimenez, M.D.,
                                                          Professor of Radiology, LSU School of Medicine, New
                                                          Orleans, LA.)
Clinical effects of Opioids
                                                                phencyclidine and all phenothiazines also cause
  • Respiratory depression: Low central ventilatory             miosis.
      response to both hypoxia and hypercarbia, cor-        •   CNS: Overdose commonly causes seizures from
      relates better with decreased tidal volume more           hypoxia; seizures pathognomonic with meperi-
      than decreased respiratory rate.                          dine, propoxyphene, and fentanul overdoses;
  •   Non-cardiogenic pulmonary edema: Results                  seizures may occur at therapeutic doses of tra-
      from a combination of (1) hypoxia stress-                 madol (Ultram®).
      induced pulmonary capillary fluid leaks, (2)          •   Muscular rigidity: Acute muscular rigidity with
      attempted inspiration against a closed glottis,           restricted ventilation with rapid IV fentanyl.
      and (3) naloxone-induced massive sympathetic          •   Nausea and vomiting: Apomorphine was a
      discharge.                                                classic emetic, a dopamine agonist within the
  •   Cardiovascular effects: Venous and arteriolar             medullary chemoreceptor trigger zone (CTZ).
      vasodilation, mild hypotension, and reduced               Dopamine antagonists at the CTZ are useful
      heart rate from histamine release. Note: Pro-             antiemetics = ondansetron.
      poxyphene induces wide-complex dysrhythmias
      in a quinidine-like (or local anesthetic-like)
      effect, responsive to NaHCO3.                       Special Consideration Opioids
  •   Miosis: Mechanism of opioid miosis = mu (µ)
      receptor agonism at the Edinger-Westphal            agonists/antagonists
      nucleus of cranial nerve III; often inconsistent;
      meperidine and propoxyphene = normal pupils;          • Mechanism: Synthetic drugs that are agonist at
      but pentazocine (Talwin®), sigma (σ) and kappa            one opioid receptor, either mu (µ) or kappa (κ),
      (κ) agonists cause dilated pupils. Exceptions:

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 85
      rarely sigma (σ, pentazocine), and antagonist at    Diphenoxylate (Lomotil®)
      another, usually mu (µ); may precipitate acute
      withdrawal in the opioid-dependent.
  •   Examples: Butorphanol (Stadol®), nalbuphine
                                                            • Insoluble meperidine analog that delays gastric
                                                                emptying, coats gut, and immobilizes gastroin-
      (Nubain®), pentazocine (Talwin®, kappa (κ)
                                                                testinal tract; used as an antidiarrheal.
      agonist and mu (µ) antagonist).
                                                            •   Formulated with atropine for its antimuscarinic
                                                                effects; overdose may manifest both anticholin-
                                                                ergic and opioid toxidromes.
Long-acting Opioids
                                                            •   Long half-life that results from atropine and
                                                                meperidine analog-induced gastrointestinal
  • Mechanism: Synthetic agonists with durations                immobilization dictates admission for oro-
      of action of >24 hours; used to provide long-             gastric lavage, AC, and continuous naloxone
      term analgesia for cancer patients, maintenance           infusion.
      for addicts, and support during withdrawal;
      overdose problematic due to short naloxone
      reversal time (1 hour), resedation, and respira-    Loperamide (Immodium®)
      tory depress. Continuous naloxone infusions
      will be required.
  •   Examples (duration of mu agonism): Metha-
                                                            • An     OTC insoluble meperidine analog, like
                                                                diphenoxylate, that immobilizes gastrointesti-
      done and MS-Contin® (24 hours), levo-α-acetyl
                                                                nal tract; also used as an antidiarrheal.
      methadol (LAAM, 3 days).
                                                            •   Safer than diphenoxylate because loperamide
                                                                does not contain atropine or delay gastric emp-
                                                                tying, does not have a prolonged half-life, and is
Meperidine (Demerol®)
                                                                not associated with prolonged retention of pills
                                                                in stomach from anticholinergic effects. Over-
  • Normeperidine metabolite is neurotoxic, caus-               dose management may also require continuous
      ing tremors, myoclonus, and seizures, especially          naloxone infusion: (1) wake-up dose = 0.4 mg
      in renal insufficiency.                                   IV boluses every 2 minutes until arousal; (2)
  •   Causes increased presynaptic serotonin release,           infusion dose = 1/3 of wake-up dose in 1 L of
      which can precipitate the serotonin syndrome              saline (NS) or D5W infused at 100 mL/hour.
      (hyperthermia, muscle rigidity, and CNS depres-
      sion), especially when combined with MAOIs
      or SSRIs. Treatment for serotonin syndrome          Methyl-Phenyl-tetrahydropyridine (MPtP)
      includes cooling, benzodiazepines, non-depo-
      larizing muscle relaxants.
                                                            • A neurotoxic byproduct of the illicit lab synthe-
                                                                sis of a meperidine analog, MPPP.
Propoxyphene (Darvon®)
                                                            •   Intravenous drug users (IVDUs) become “fro-
                                                                zen addicts” and develop classical parkinsonism
                                                                from selective destruction of dopamine-secret-
  • Both the parent drug and its norpropoxyphene                ing substantia nigra cells; resistant to L-dopa
      metabolite have quinidine-like (Class IA) effects         treatment.
      and cause QRS widening and dysrhythmias,              •   MPTP is now used to induce experimental par-
      which are responsive to sodium bicarbonate.               kinsonism in laboratory animals.
  •   Overdose may produce acute neurotoxicity
      from norpropoxyphene metabolite with sei-
      zures responsive to benzodiazepines more so         Pentazocine (talwin®)
      than barbiturates.
  •   Often formulated with APAP, suspect co-toxici-
                                                            • Synthetic agonist/antagonist that is agonist at
      ties in overdose, and monitor serum [APAP].
                                                                the kappa (κ) and sigma (σ) receptors (causing
                                                                dysphoria and psychomimesis), but antagonist
                                                                at the mu (µ) receptor (producing little respira-
                                                                tory depression).

86 | Color Atlas of Human Poisoning and enenoming
  • Formerly    mixed with the blue antihistamine,        Imidazolines (afrin®, etc.)
      tripelennamine = “T’s and Blues,” but now
      mixed with methylphenidate (Ritalin®) at all-
      night “Rave” parties.
                                                            • Combined      central and peripheral alpha 2 ago-
                                                                nists used as nasal and conjunctival decon-
                                                                gestants (oxymetazoline, tetrahydrozoline,
                                                                xylometazoline) that produce an opioid toxi-
tramadol (Ultram®)
                                                                drome (bradycardia, hypotension, central CNS
                                                                and respiratory depression) indistinguishable
  • A novel synthetic analog of codeine that is a               from mu agonists due to agonist activity overlap
      combined mu opioid agonist and a serotonin/               at the mu receptor.
      norepinepherine (NE) reuptake inhibitor; only         •   Partially naloxone-reversible, but prolonged
      partially antagonized by naloxone.                        duration of action (4–8 hours) causes reseda-
  •   Can cause seizures in therapeutic doses and               tion and overdose requires treatment with con-
      characteristically in overdoses. Seizures respond         tinuous naloxone infusion.
      to benzodiazepine suppression, but may be pre-
      cipitated by naloxone.
  •   Can precipitate serotonin syndrome, like selec-     Heroin Body Packers
      tive serotonin reuptake inhibitors (SSRIs),
      by blocking serotonin reuptake, especially in
      patients on MAOIs.
                                                            • “Mules”     who ingest large numbers of multi-
                                                                ply wrapped packages of heroin for smuggling,
                                                                home catharsis, and later street distribution.
Dextromethorphan (robitussin®)
                                                            •   Abdominal x-rays confirm status and direct
                                                                whole-bowel irrigation (WBI) with polyethyl-
                                                                ene glycol electrolyte (PEG) in asymptomatic
  • An OTC synthetic opioid agonist and analog of               patients.
      codeine with no analgesic activity that is used       •   Symptomatic heroin packers can be managed
      as a cough suppressant, like codeine.                     medically with AC, naloxone infusion, and WBI
  •   In overdose, causes miosis and CNS depres-                (symptomatic cocaine packers need surgery to
      sion, with choreoathetosis and dystonia from              prevent gastrointestinal ischemic necrosis and
      increased presynaptic serotonin release. Also             high case fatality rates (CFRs).
      acts as a sigma agonist and can cause a PCP-
      like psychosis.
  •   Formulated as a hydrobromide salt = bromism,        Narcotic adulterants (usually white powders)
      CNS depression, ataxia, confusion, coma.
                                                          Quinine: Disguises bitter taste of heroin, causing
  •   Can also precipitate serotonin syndrome, like
                                                               dysrhythmias, headache, vertigo, tinnitus,
      meperidine, by increasing presynaptic release of
                                                               blurred vision, temporary or even permanent
                                                          Scopolamine: CNS and peripheral anticholinergic
Clonidine (Catapress®)                                         toxidrome.
                                                          Fentanyl analogs: “China white” = fentanyl (100X
                                                               the potency of MS), sufentanil (10X fentanyl
  • Centrally acting alpha  2
                              agonist that produces an         or 1000X MS), and methyl-fentanyl (6000X
      opioid toxidrome (lethargy, miosis, bradycar-            MS); superpotent fentanyl-adulterated heroin,
      dia, and respiratory depression) indistinguish-          respiratory arrest, coma, and death. Treatment:
      able from mu agonists due to agonist activity            CPR, naloxone infusions.
      overlap at the mu receptor.                         Miscellaneous adulterants: Amphetamines, cocaine,
  •   CNS and respiratory depression reversed by               lead-thallium, strychnine, talc.
      naloxone; always admit for continuous nalox-
      one infusion.
  •   Used as a sympathetic blocker for hypertension
      and reflex sympathetic dystrophy, and to pro-
      vide sympatholysis during opioid withdrawal.

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 87
                                                                  Yes    Are the symptoms consistent
                                   Is the patient symptomatic?
                                                                                 with cocaine?
                                                                                   No                 Yes
                                                                         Are the symptoms
                                                                          consistent with         Sedate
                                                                             an opioid?          intubate
                                   Order abdominal radiograph                                    Operate
                                                                         Bolus with naloxone
                                                                         and start iv unfusion

                                    Does the radiograph show      Yes
                                       bowel obstruction

                                      Begin multiple dose activated
                                   charcoal and whole bowel irrigation

                                       Is the radiograph clear and have the
                              No   expected number of packets been retrieved?
                                   Obtain contrast radiography
                                       prior to discharge

Figure 5.8 Management: cocaine vs. heroin body packers. A flow chart outlining the clinical practice manage-
ment strategies for body packers of cocaine or heroin.

Management of an Opioid Oerdose
acute Overdose Management

  • Low initial IV naloxone boluses (0.1–0.4 mg),
      rather than a single therapeutic bolus (2 mg)
      to avoid precipitating acute withdrawal in
  •   The aim is to reverse respiratory depression and
      restore respiratory rate greater than 8.
  •   Intubate and ventilate if respiratory depres-
      sion persists, administer 10 mg naloxone IV
      — no infusion, just prolonged mechanical

Naloxone Infusion
                                                                 FIGURe 5.9 Noncardiogenic pulmonary edema:
                                                                 heroin overdose. Frontal chest radiograph that demon-
  • If    diagnostic naloxone bolus is successful,
                                                                 strates normal size and configuration of the cardiomedi-
      administer 2/3 of the initial dose IV per hour.
                                                                 astinal silhouette with diffuse bilateral non-cardiogenic
  •   If withdrawal develops, stop the infusion to let           pulmonary edema following heroin overdose. (Cour-
      symptoms abate and restart at 1/2 rate.                    tesy of Carlos R. Gimenez, M.D., Professor of Radiol-
  •   If respiratory depression recurs during infusion,          ogy, LSU School of Medicine, New Orleans, LA.)
      re-administer 1/2 the initial bolus, and increase
      infusion rate by 1/2.

88 | Color Atlas of Human Poisoning and enenoming
                                                                                Part 2

Poisonings with Pharmaceutical
             Addities: Outline
                                       Propylene glycol
                                       Polyethylene glycol
                                       Diethylene glycol

                                    Benzyl alcohol




                                    Benzalkonium chloride



                                    Pharmaceutical additie tragedies
                                       Diethylene glycol-contaminated acetaminophen
                                       The E-Ferol tragedy
                                       Eosinophilia-myalgia syndrome

   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 89
Propylene Glycol                                           toxicities
Pharmacokinetics and Uses
                                                             • Renal > metabolic toxicities; relatively nontoxic:
  • Pharmacokinetics:      Clear, odorless, viscous,
                                                               − Renal: Potential acute tubular necrosis
                                                                     (ATN) in massive overdose.
      volatile alcohol, sweet to taste, and rapidly
      absorbed; low volume of distribution (V D),
                                                                 −   Metabolic: High MW = serum hyperosmo-
                                                                     larity, and production of lactic and pyruvic
      metabolized by alcohol dehydrogenase (ADH)
                                                                     acids = high-anion gap metabolic acidosis,
      to lactic and pyruvic acids.
                                                                     as with propylene glycol.
  •   Uses: Food and drug preservative, especially
      parenteral drugs (benzodiazapine [BZs],
      antidysrhythmics).                                   Diethylene Glycol
                                                           Pharmacokinetics and Uses
                                                             • Pharmacokinetics:     An industrial alcohol sol-
  • Cardiovascular > metabolic > central nervous                 vent with a low affinity for ADH with negli-
      system (CNS) > dermal:                                     gible metabolism.
      − Cardiovascular: Vagomimetic and directly             •   Uses: Industrial solvent, illicitly substituted for
          cardiotoxic on rapid IV infusion; bradycar-            propylene glycol as a solvent to solubilize APAP
          dia and hypotension, apnea, wide QRS com-              (Tylenol®) manufactured in developing coun-
          plex, low T to inverted T waves, elevated ST           tries (Example: Haiti, Haitian diethylene gly-
          segment.                                               col-contaminated acetaminophen tragedy).
      − Metabolic: Serum hyperosmolarity, meta-
          bolic acidosis (topical silver sulfadiazine in
          burns).                                          toxicities
      − CNS: Severe intoxication causes initial CNS
          depression, then excitation and seizures.          • Initial gastrointestinal and renal > hepatic:
      − Dermal: Thrombophlebitis.                              − Gastrointestinal: Initial nausea and vomiting
                                                                     with severe abdominal cramps and pain.
Polyethylene Glycol
                                                                 −   Renal: Initial polyuria followed within 24
                                                                     hours by oliguria, then anuria and acute
Pharmacokinetics and Uses                                            renal failure (ARF). High case fatality rates
  • Pharmacokinetics: A family of high-molecular-                − Hepatic: Hepatoxicity = hepatomegaly and
      weight (MW) alcohols also oxidized by ADH to
      acid metabolites; high MWs limit gastrointesti-
                                                             •   Treatment: Supportive only with hemodialysis
                                                                 (HD); ethanol and 4-methylpyrazole (4-MP)
      nal absorption — relatively insoluble.
                                                                 ineffective as antidotes.
  •   Uses: Bowel preps and whole-bowel irrigation
      (WBI) solutions (GoLytely ®) to cleanse gut;
      common cosmetic and ointment additives.

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 91
   Benzyl Alcohol
Pharmacokinetics and Uses                               toxicities

  • Pharmacokinetics:      Colorless aromatic alcohol     • Central > Peripheral nervous system toxicities.
      hepatically oxidized rapidly to benzoic acid,       • Gasping-Baby Syndrome: High benzoic acid
      then conjugated with glycine to form hippuric           levels can cause metabolic acidosis, hypotonia,
      acid; excreted in urine-except in preemies, who         gasping respirations, seizures, bradycardia, and
      cannot conjugate benzoic acid due to hepatic            hypotension with subsequent cardiovascular
      immaturity.                                             collapse; high CFRs.
  •   Uses: Common bacteriostatic additive in paren-      •   Demyelinization: Transient MS-like paraplegia
      teral medications and IV flush solutions (Gasp-         in lower extremities following intrathecal and
      ing-Baby Syndrome).                                     epidural administration of local anestherics
                                                              (LAs) and other drugs (methotrexate) contain-
                                                              ing benzyl alcohol.

92 | Color Atlas of Human Poisoning and enenoming
Pharmacokinetics and Uses                             toxicities

  • Uses:  Emulsifiers and flavor carriers for soft     • Dermal > CNS > gastrointestinal:
    drinks (colas, Ruby Red Squirt) and drugs             − Dermal: Bromoderma.
    (ipratropium bromide [Atrovent®], dextro-             − CNS: Somnolence, sedation.
    methorphan bromide [Robitussin®], pan-                − Gastrointestinal: Nausea,           vomiting,
    curonium bromide [Pavulon®]); pesticides                   diarrhea.
    (methyl bromide); permanent hair wave               •   Antidote: None.
    solutions.                                          •   Treatment: Withdrawal; colchicine to cause
                                                            microtubular arrest and to reduce neutro-
                                                            phil chemotaxis and release of inflammatory

                Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 93
Pharmacokinetics and Uses                                toxicities

  • Pharmacokinetics: An antibacterial-antifungal          • CNS > cardiovascular > ocular:
      halogenated hydrocarbon similar chemically to          − CNS: Sedative-hypnotic,           intoxicating
      trichloroethanol, the active metabolite of chlo-            effects, somnolence, then slurred speech,
      ral hydrate (“Mickey Finn”).                                dysarthria, seizures.
  •   Uses: Antimicrobial preservative in cosmetics           −   Cardiovascular: Halogenated hydrocarbon
      and drugs, especially injectables, otic and oph-            that sensitizes the myocardium to catechol-
      thalmic topicals (contact lens cleansers).                  amines with PVCs, serious tachyarrhyth-
                                                                  mias (Vtach, Vfib).
                                                              −   Ocular: Cytotoxic to corneal epithelium,
                                                                  but less damaging than benzalkonium chlo-
                                                                  ride (BAC).

94 | Color Atlas of Human Poisoning and enenoming
Pharmacokinetics and Uses

  • Pharmacokinetics:     An organic mercury com-
      pound, formerly Merthiolate®; contains 49%
      Hg by weight.
  •   Uses: Contact lens disinfectant; vaccine, anti-
      venin, and topical ointment preservative.


  • Initial gastrointestinal and CNS > renal:
    − Gastrointestinal: Initial severe vomiting,
          with later hemorrhagic gastroenteritis.          Figure 5.10 Body stuffer: heroin. Axial abdominal
      −   CNS: Altered mental status (“Mad as a            oral and intravenous contrast-enhanced computerized
          Hatter”), fever, slurred speech, ataxia, later   tomogram (CT) at the level of the renal veins that dem-
          autonomic and ascending sensorimotor             onstrated a rectangular container of heroin in a jejunal
          peripheral polyneuropathies.                     loop. (Courtesy of Carlos R. Gimenez, M.D., Professor
                                                           of Radiology, LSU School of Medicine, New Orleans,

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 95
   Benzalkonium Chloride
Pharmacokinetics and Uses                               toxicities

  • Pharmacokinetics:      A quaternary ammonium          • Ocular > ENT mucosal:
      cationic surfactant with immediate antimicro-         − Ocular: Progressive cytolytic      degeneration
      bial activity and delayed cytotoxic activity.              of corneal epithelium with eye pain and
  •   Uses: The most widely used contact lens dis-               photophobia; chronic keratitis.
      infectant and ophthalmic preservative with             −   ENT: Decreased viscosity of the normal
      immediate onset and long duration of action                protective mucus blanket, nasal drying,
      and tissue penetration; used in most ophthalmic            epistaxis.

96 | Color Atlas of Human Poisoning and enenoming
Pharmacokinetics and Uses                                   toxicities

  • Pharmacokinetics: Also known as carbolic acid,            • CNS > cardiovascular:
      the original surgical antiseptic solution and             − CNS: Drowsiness,        respiratory depression,
      chemical peel agent; rapidly absorbed. Total                   peripheral nerve dissolution (painful periph-
      dose should be limited to less than 50 mg/10                   eral nerve regeneration possible, avoid use
      hours.                                                         as a neurolytic for nonmalignant disease).
  •   Uses: Preservative in injectable meds, chemical            −   Cardiovascular: Dysrhythmias, especially
      peels, injectable neurolytic for cancer pain, dilu-            PVCs.
      ent for lyophilized glucagon powder and other
      powdered medications.

                   Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 97
Pharmacokinetics and Uses                               toxicities

  • Pharmacokinetics: Collectively known as para-         • Allergy > reproductive > hepatic toxicities:
      hydroxybenzoic acids, methylparaben, and              − Allergy: High incidence of allergic reactions
      propylparaben; often used in synergistic combi-            to food, drugs, and cosmetics containing
      nation as antimicrobials and preservatives.                less than 0.1% (1 mg/mL) parabens.
  •   Uses: The second most common preservatives             −   Reproductive: Significant spermicidal activ-
      in cosmetics, next to water.                               ity, which supports use in vaginal contracep-
                                                                 tive creams.
                                                             −   Hepatic: Displaces bilirubin from albumin
                                                                 binding sites in newborns with hyperbiliru-
                                                                 binemia and potentially, kernicterus.

98 | Color Atlas of Human Poisoning and enenoming
Pharmaceutical Additie tragedies
Diethylene Glycol-Contaminated                          the e-Ferol tragedy
                                                         • Pharmacokinetics:      A vitamin E antioxidant
 • Pharmacokinetics: The inexpensive, yet highly             preparation was combined with polysorbate
     nephrotoxic industrial solvent, diethylene gly-         emulsifiers to prevent O2 toxicity in preemies;
     col, was inadvertently substituted for the phar-        pharmacologically similar to the multivitamin
     maceutical grade, non-toxic solvent, propylene          polysorbate-containing drops and injectable
     glycol, in order to solubilize acetaminophen            preparations (Poly-Vi-Sol®, Tri-Vi-Sol®). E-
     preparations locally manufactured by drug               Ferol was recalled in the 1980s.
     companies in Bangladesh, Haiti, Nigeria, and        •   Syndrome: Intralobular cholestasis, hepato-
     South Africa.                                           megaly, renal failure, and thrombocytopenia in
 •   Syndrome: The results of the glycol solvent             preemies; 38 deaths.
     substitution errors were catastrophic and wide-
     spread, resulting in several deaths from acute
     renal failure, mostly in children, in areas with   eosinophilia-Myalgia Syndrome
     insufficient access to either temporary hemodi-
     alysis or renal transplantation.                    • Pharmacokinetics: Contaminated l-tryptophan
                                                             OTC amino acid supplement recommended for
                                                             insomnia, PMS, and anxiety. Recalled 1989.
                                                         •   Syndrome: Unexplained peripheral eosino-
                                                             philia with severe muscular pain, mouth ulcers,
                                                             arthralgias, rashes, peripheral edema, cough,
                                                             dyspnea, and elevated liver function tests (LFTs)
                                                             with thousands of cases worldwide, mostly in
                                                             women; 36 deaths.

                  Poisonings with Oer-the-Counter and Opioid Analgesics and Pharmaceutical Addities | 99
                                                                            Chapter 6

             Poisonings with Vitamins,
                      Minerals, Herbal
               Agents, Alternatie, and
               Complementary Agents

Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary Agents | 101
Chapter Outline

                                         Descriptie epidemiology of herbal
                                         and itamin poisonings

                                         Pharmacology of herbal and
                                         itamin poisonings

                                            Pharmacology — plant oils

                                         toxicology of herbal poisonings

                                            Herbal abortifacients
                                            Cardiovascular toxins
                                            Central nervous system (CNS) toxins
                                            Gastrointestinal toxins
                                            Miscellaneous herbal hepatoxins

                                         toxicology of itamin poisonings

                                            Vitamin therapy
                                            Potential toxic vitamins
                                            Hypervitaminosis A
                                            Hypervitaminosis E
                                            Hypervitaminosis C
                                            Pyridoxine (Vitamin B6) neuropathy
                                            Hypervitaminosis D
                                            Niacin toxicity
                                            Eosinophilia-Myalgia Syndrome

  Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary Agents | 103
 Descriptie epidemiology of
 Herbal and Vitamin Poisonings
• An herb is a leafy plant without a woody stem,        • The most popular herb sales in the United States
    but herbal preparations include all natural,            include Echinacea (10%), garlic (10%), golden-
    alternative, and traditional remedies. Twenty-          seal* (7%), ginseng (6%), Ginkgo (4.5%), and
    five percent of current, proprietary pharmaceu-         saw palmetto (4.4%). [* Goldenseal is often
    ticals come from plant-herb sources.                    used illicitly in unsuccessful attempts to dis-
•   As a result of the Dietary Supplement and               guise urinary marijuana (THC) metabolites.]
    Health Education Act of 1994, the FDA has no        •   There are no toxicologic databases on herbal
    authority over regulating herbal and vitamin            and vitamin toxicity in the United States.
    products, unless they prove to be toxic.            •   In Hong Kong, herbal medicine toxicity
•   80% of the world’s population use herbal prod-          accounts for less than 1% of all acute hospital
    ucts and vitamins daily; most are benign, and           admissions, and Western medicine toxicity and
    offer no health benefit (e.g., vitamin C and            drug–drug interactions account for 4.4% of all
    Echinacea) or potentially lethal drug interac-          acute hospital admissions.
    tions (e.g., St. John’s wort and SSRIs; garlic,     •   Fatalities have resulted from megadoses of the
    ginkgo, and ginseng, and anticoagulants [ASA,           fat-soluble and lipophilic (stored in liver and
    heparin, warfarin]).                                    brain) vitamins A, D, and E; and “therapeutic”
•   The most common herb and vitamin delivery               (homeopathic) doses of niacin and tryptophan.
    forms include capsules (50+%), tablets (15+%),
    teas and drinks (10+%).
•   The most common herb supplement types are
    single herbs (50+%) and combinations (30+%).

           Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary Agents | 105
   Pharmacology of Herbal
   and Vitamin Poisonings
Pharmacology – Plant Oils

  tABLe 6.1 Pharmacology: Plant Oils
  Classes                              toxicities                          examples
  Volatile oils: evaporate at room     Mucous membrane and CNS             Catnip, garlic, chamomile
   temperature                          irritants
  resins: mixtures of oily plant       Strong gastrointestinal irritants   Dandelion, elder, black cohosh
   resins                                                                   root
  Fixed oils: long-chain fatty acids   Safe emollients and cooking oils    Olive oil, peanut oil, canola oil,
                                                                            safflower oil
  alkaloids = belladonnas,             anticholinergic, hepatic            Jimson weed, comfrey, goldenseal
   pyrrolizidines                       veno-occlusion
  Gylcosides:                          Irritating cathartics               aloe, senna (Sennakot®)
  Saponins                             Mucous membrane irritants,          Licorice, ginseng
                                        steroids, anticoagulants
  Cyanophores                          release cyanide                     Prunus pits (apple, apricot, peach,

106 | Color Atlas of Human Poisoning and enenoming
   toxicology of Herbal Poisonings
Herbal Abortifacients                                    Cardioascular toxins
                                                         aconitine Group
  • Aloe
  • Aristolochia (birthwort)*                              • Representative: Monkshood (wolfsbane).
  • Bitter melon                                           • Toxins: Parasympathomimetic aconitine          alka-
  • Black and blue cohosh root                                 loids that cause prolonged opening of sodium
  • Canthardin (Spanish fly)**                                 channels.
  • Compound Q                                             •   Antidote: None.
  • Ergots*                                                •   Diagnosis: Salivation, nausea, vomiting, diar-
  • Feverfew                                                   rhea, bradycardia, muscle weakness, ventricular
  • Juniper                                                    tachycardia, ventricular fibrillation, respiratory
  • Motherwort                                                 failure.
  • Mugwort                                                •   Treatment: Atropine, pacemaker, gastrointesti-
  • Nutmeg                                                     nal decontamination (consider orogastric tube
  • Pennyroyal oil (pulegone)*                                 lavage as determined by level of consciousness
  • Quinine (á oxytocic)*                                      and airway protective reflexes and administer
  • Rue                                                        AC).
  • Sage
  • Tansey
                                                         Cardiac Glycosides
[*Highly effective abortifacients; ** insect (blister
beetle) toxin.]
                                                           • Representatives: Foxglove, oleander, red squill,
abortifacients: Compound Q?                                    lily-of-the-valley.
                                                           •   Toxins: Digitalis and digitoxigenin (foxglove,
                                                               red squill), oleandrin.
What Is Compound Q?
                                                           •   Antidote: DigiBind®.
  • Compound Q is an herbal preparation of the Chi-        •   Diagnosis: “Dig-toxicity” = nausea, vom-
                                                               iting,     diarrhea,    abdominal     cramps,
      nese Trichosanthin plant, which can inactivate
      viral ribosomes and inhibit HIV replication.
  •   Pharmacology: Poor oral availability and intense
                                                           •   Treatment: Monitor digoxin levels and ECG,
                                                               gastrointestinal decontamination (lavage and
      diarrhea on oral administration; severe biphasic
      neurotoxicity on parenteral administration.
  •   Toxicity: CNS > dermatologic (hypersensitivity
      and anaphylaxis) > metabolic (hypoglycemia)
                                                         Central Nerous System (CNS) toxins
      − CNS: (1) Encephalomyelitis in 24–72 hours
          with fever, delirium, dementia, myalgias,      absinthe
          paresis; (2) coma within 1 week.
  •   Treatment: Immediate ipecac on observed              • Representative: Absinthe (wormwood).
      ingestion, lavage and activated charcoal (AC),       • Latin: Artemisa absinthium.
      supportive.                                          • Toxins: Thujones (artemisins). (1) Similar neu-
                                                               rotoxic actions to camphor. (2) Antimalarial
                                                               effects — used effectively as antimalarials in
                                                               China and Southeast Asia, even in mefloquine/

             Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary Agents | 107
      doxycycline-resistant Plasmodium falciparum          Nutmeg and Mace
  •   Diagnosis: Absinthism — hallucinations, intel-
                                                             • Representatives: East and West Indian nutmeg
      lectual deterioration, delirium, psychosis, sei-
      zures (most celebrated case = Vincent Van
                                                             • Latin: Myristica fragrans.
  •   Treatment: Gastrointestinal decontamination
                                                             • Toxin: Myristicin — hepatically biotransformed
                                                                 to methamphetamine metabolites.
      (lavage and AC), supportive therapy.
                                                             • Antidote: None.
                                                             • Diagnosis: Nausea,            vomiting,  dele-
                                                                 rium, euphoria, deep sleep with hypo-
                                                                 thermia    (like   Ecstasy     [MDMA],   or
  • Representatives: Jimson weed (thornapple), hen-          •   Treatment: Gastrointestinal decontamination
      bane, mandrake, nightshade.                                (lavage and AC), supportive therapy.
  •   Toxins: Atropine-hyoscyamine, scopolamine-
  •   Antidote: Physostigmine.                             Gastrointestinal toxins
  •   Diagnosis: “Atropine” poisoning = mydriasis,
      ileus, urinary retention, dry mouth, fever, flush-
      ing, tachycardia, agitation, nervousness (“red as
      a beet, dry as a bone, hot as Hades, mad as a          • Representative: Goldenseal is an herb frequently
      hatter”).                                                  used as an astringent and to reputedly mask the
  •   Treatment: Gastrointestinal decontamination.               presence of illicit drugs, especially marijuana,
                                                                 on urine screens. Goldenseal is, however, inef-
                                                                 fective as an undetected adulterant and is easily
Ephedra                                                          detected by GC/MS (= + drug test).
                                                             •   Latin: Hydrastis canadensis.
  • Representative: Ephedra (ma-huang).                      •   Toxin: Hydrastine.
  • Toxins: Ephedrine, pseudoephedrine.                      •   Antidote: None.
  • Antidote: None.                                          •   Diagnosis: Nausea, vomiting, diarrhea, convul-
  • Diagnosis: Sympathomimetic effects          cause            sions, paralysis, respiratory failure.
      headache, nervousness, anxiety, flushing, vom-         •   Treatment: Gastrointestinal decontamination
      iting, hypertension, tachycardia, mania and                (lavage and AC), supportive therapy.
      psychosis, seizures; myocardial infarction (MI)
      and cerebrovascular accident (CVA) possible.
  •   Treatment: Gastrointestinal decontamination
      (lavage and AC), supportive therapy.
                                                             • Representatives:      Pokeweed, English ivy, yew,
                                                                 horse chestnut.
Nicotine agents                                              • Latin: Phytolacca americana.
                                                             • Toxin: Phytolaccines (pokeweed), enterotoxins
  • Representatives: Betel nut, tobacco, blue cohosh,            = terpene resins.
      broom, chestnut, Lobelia.                              • Antidote: None.
  • Toxins:      Arecholine (betel nut), nicotine            • Diagnosis: Nausea, vomiting, diarrhea, cramps,
      (tobacco), lobeline (Lobelia).                             hemorrhagic gastritis, weakness; later diplo-
  •   Antidote: None.                                            pia, seizures, dysrhythmias, respiratory failure,
  •   Diagnosis: Bronchospasm, chronic obstructive               lymphocytosis.
      pulmonary disease (COPD), coronary artery              •   Treatment: Gastrointestinal decontamination
      disease (CAD), oral and lung cancers.                      (lavage and AC), supportive therapy.
  •   Treatment: Gastrointestinal decontamination
      (lavage and AC), supportive therapy.

108 | Color Atlas of Human Poisoning and enenoming

tABLe 6.2 Hepatotoxins
Class                          toxins                       Diagnosis                       Antidote/treatment
Pennyroyal                     Pulegone — CYP450            Minty breath, seizures,         Gastrointestinal
                                toxin, glutathione           external and vaginal            decontamination, N-
                                depleter                     bleeding                        acetylcysteine (NaC)
Pyrrolizidines = comfrey       Pyrrolizidine alkaloids      Hepatic veno-occlusion,         Gastrointestinal
 and coltsfoot                                               cirrhosis, liver cancer         decontamination,
                                                                                             supportive therapy,
                                                                                             monitor liver function

Miscellaneous Herbal Hepatotoxins

tABLe 6.3 Miscellaneous Herbal Toxins
Class                    toxins                             Diagnosis                       Antidote/treatment
aristolochia                   aristolochic acid            renal fibrosis and renal        Supportive therapy,
 (birthwort-abortifacient)                                   failure, vaginal bleeding       gastrointestinal
Garlic                         Sulfoxides — alliin and      Nausea, vomiting,               Supportive therapy,
                                allicin and ajoene           diarrhea, dermatitis,           gastrointestinal
                                (aSa-like)                   external bleeding, aSa          decontamination
Ginseng                        Panax acid = Ginseng         Hypertension,                   Supportive therapy,
                                abuse Syndrome (GaS)         tachycardia, agitation,         gastrointestinal
                                                             insomnia, morning               decontamination
Chamomile                      Histamine                    Cross reactions with            antihistamines,
                                                             Compsitae annuals               bronchodialators
                                                             (ragweed, daisy,

tABLe 6.4 Toxic Herb–Drug Interactions
Herbs                               Drugs                                      toxicities
Ephedra      a
                                        Blood pressure drugs                   Hypertension, MI, CVa
Feverfew                                aSa, anticoagulants                    Bleeding
Ginkgo   a
                                        aSa, anticoagulants                    Bleeding
Ginsenga                                aSa, anticoagulants                    Bleeding
Kava                                    Benzodiazepines (Xanax®)               Delirium
Licorice a
                                        Digoxin                                Hypertension, CHF
St. John’s worta                        MaOIs, SSrIs                           Depression, suicide, serotonin
Yohimbea                                antihypertensives                      Hypertension, MI, CVa
Note: aSa = acetyl–salicylic acid (aSa); CVa = cerebrovascular accident; CHF = congestive heart failure;
     MaOIs = monoamine oxidase inhibitors; MI = myocardial infarction; SSrIs = selective serotonin reuptake
  Fatal cases reported.

                 Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary Agents | 109
    toxicology of Vitamin Poisonings
Vitamin therapy                                          Clinical Findings

  • Vitamins     are used therapeutically to manage        • Diagnosis:     Desquamation and thinning of
      or prevent several diseases. Example: vitamin            skin and nails, cheilitis, stomatitis, alopecia,
      A for acne, vitamin C for colds, vitamin E for           bone changes, cirrhosis, benign intracranial
      prostate cancer, vitamin D for osteoporosis,             hypertension (BIH) or pseudotumor cerebri =
      niacin for hypercholesterolemia.                         headache, blurred vision, diplopia, optic nerve
  •   Vitamins are not usually reported as                     atrophy, blindness.
      medications.                                         •   Treatment: Withdrawal, support; spinal taps
  •   With the exception of folic acid for women               and diuretics and prednisone for BIH.
      of childbearing age, there are no indications
      for empiric vitamin therapy in developed
      countries.                                         Hyperitaminosis e
Potential toxic Vitamins
                                                           • Common name: Vitamin E.
  Vitamin A*
                                                           • Chemical name: Alpha-tocopherol.
  Vitamin E*
                                                           • Source: Meats, grains, and nuts,
  Vitamin C
                                                           • Recommended Daily Intake: Females,           25–50
                                                               years old, 15 mg/day; males, 20 mg/day.
  Vitamin B6
  Vitamin D* — the most commonly used rat poi-
                                                           •   Toxic dose: 400 mg/day.
     son in the United States.
                                                           •   Antidote: None.
  Niacin — Nicotinic acid *
  Tryptophan (amino acid and serotonin precursor) *      Clinical Findings

[* Fatalities reported with the fat soluble (A, D, and
E) and from niacin-induced anaphylaxis.]
                                                           • Diagnosis:    Nausea, vomiting, diarrhea, flatu-
                                                               lence; vitamin K antagonism can potentiate bleed-
                                                               ing induced by heparin, warfarins, and ASA, by
Hyperitaminosis A                                             further decreasing platelet adhesiveness.
toxicology                                                 •   Treatment: Withdrawal, support therapy.

  • Common         name: Vitamin A (deficiency =
                                                         Hyperitaminosis C
  •   Chemical name: Retinol.                            toxicology
  •   Source: Liver and vegetable carotenoids.
  •   Recommended Daily Intake (RDI): Females, 25–         • Common name: Vitamin C (deficiency = scurvy
      50 years old, 2700 IU; males slightly higher.            = anemia, gingivitis, petechiae, poor wound
  •   Toxic dose: 25,000 IU/kg bolus, 25,000 IU per            healing, bleeding).
      day every 30 days; such doses have been used to      •   Chemical name: Ascorbic acid.
      treat cystic acne.                                   •   Source: Citrus fruits, red fruits, and vegetables.
      Antidote: None.                                      •   Recommended Daily Intake: 60 mg/day.
                                                           •   Toxic dose: 2 g/day.
                                                           •   Antidote: None.

110 | Color Atlas of Human Poisoning and enenoming
Clinical Findings                                          • Recommended Daily Intake: Females, 200 IU/
                                                               day (5 mcg); males, 400 IU/day (10 mcg).
  • Diagnosis: Diarrhea, cystine and calcium oxa-          • Toxic dose: >RDA, increased vitamin D forti-
                                                               fied milk, especially in patients overdosing on
      late urinary crystals and stones, nephrolithia-
                                                               vitamin C.
      sis, urosepsis; increased uric acid excretion
      may mimic acute gout; increased Fe absorption
                                                           •   Antidote: None.
      with hemosiderosis, increases sepsis risks from
      Vibrio and Yersinia. Nephrolithiasis risks are
                                                         Clinical Findings
      increased by vitamin D supplementation, as in
      vitamin D-fortified milk. Vitamin C toxicity
      can induce oxidative stress with hemolysis in        • Diagnosis:    Fatigue, anorexia, nausea, vomit-
      individuals with glucose-6-phosphate dehydro-            ing, diarrhea, hypertension, polydipsia, poly-
      genase (G-6-PD) deficiency.                              uria, hypercalcemia, cardiac and vascular
  •   Treatment: Withdrawal, fluid loading, kidney             and ectopic calcifications, hypercalcuria and
      stone lithotripsy.                                       nephrocalcinosis.
                                                           •   Treatment: Withdrawal, support, fluids, diuret-
Pyridoxine (Vitamin B6) Neuropathy                             ics, prednisone, calcitonin, biphosphonates.

                                                         Niacin toxicity
  • Common name: Vitamin B .                             toxicology
  • Chemical name: Pyridoxine.

  • Source: Meats, cereals, vegetables.                    • Common name: Niacin, vitamin B         (deficiency:
  • Recommended Daily Intake (adults): 2 mg/day.                                                  3
                                                               pellagra = 3Ds = diarrhea, dermatitis, dementia,
  • Toxic dose: 150–500 mg bolus, 150–500                      stomatitis and glossitis).
  • Antidote: None.                                        •   Chemical name: Nicotinic acid — used for high
                                                               cholesterol reduction.
                                                           •   Source: Meat, fish, poultry, cereals, nuts,
Clinical Findings                                              vegetables.
                                                           •   Recommended Daily Intake (adults): 6–13
  • Diagnosis:     Distal, “glove and stocking” sen-       •   Toxic dose: 60+ mg orally bolus, 60–1000
      sory, vibratory, and positional peripheral axo-          mg/day.
      nopathy secondary to axonal degeneration;            •   Antidote: Preemptive ASA for inhibition of
      crippling, painful, sensory peripheral neuropa-          prostaglandin release.
      thy may be permanent. Other findings include
      ataxia, dramatic loss of all peripheral sensa-
      tions (light touch, temperature, vibration, pro-   Clinical Findings
      prioception, pain), and reduced deep tendon
      reflexes (DTRs).
  •   Treatment: Withdrawal, supportive.
                                                           • Diagnosis:     Prostaglandin-mediated cutaneous
                                                               flushing and vasodilation, potentiates migraine,
                                                               pruritus, headache, nausea, vomiting, diarrhea,
Hyperitaminosis D                                             abdominal cramping, niacin hepatitis with cen-
                                                               trilobular cholestasis.
toxicology                                                 •   Treatment: Withdrawal, support, prostaglandin
                                                               inhibitors (ASA, NSAIDs).
  • Common name: Vitamin D (deficiency = rickets
      = softening and deformation of long bones).
  • Chemical name: Cholecalciferol.
  • Source: Produced in skin from ultraviolet (UV)
      light exposed serum cholesterol.

             Poisonings with Vitamins, Minerals, Herbal Agents, Alternatie, and Complementary Agents | 111
eosinophilia-Myalgia Syndrome                              • Treatment: Market withdrawal of recombinant
                                                               l-tryptophan, formerly used for premenstrual
toxicology                                                     syndrome and insomnia.
                                                           •   Mechanism of toxicity: Unknown; tryptophan
  • Common       name: Tryptophan, an amino acid               supplements probably contaminated by caus-
      (protein) and serotonin 5-hydroxytryptamine              ative antigenic agents during manufacturing
      (5-HT) precursor.                                        process.
  •   Chemical name: l-Tryptophan.
  •   Source: All animal proteins.
  •   Recommended Daily Intake (adults): 30–60           Conclusion
  •   Toxic dose: 150+ mg/day for more than 2             “There cannot be two kinds of medicine — con-
      weeks.                                             ventional and alternative. There is only medicine that
  •   Antidote: None.                                    has been adequately tested and medicine that has
                                                         not…. Alternative treatments should be subjected to
                                                         scientific testing no less rigorous than required for
Clinical Findings                                        conventional treatments.”

                                                                              —M. Angell and J.P. Kassirer
  • Diagnosis     of Eosinophilia-Myalgia Syndrome:
      Eosinophilia with no indication of parasitic                            New Engl. J. Med., 339, 1998
      infection or neoplasm (leukemia, eosinophilic
      granuloma) and generalized myalgias, pulmo-
      nary infiltrates, polyarteritis, sclerodermiform
      skin lesions. Resembles toxic rapeseed oil syn-
      drome (Spain, 1981).

112 | Color Atlas of Human Poisoning and enenoming
                                      Chapter 7

Poisonings with Common
     Household Products

        Poisonings with Common Household Products | 113
   Chapter Outline
Antiseptics                               toxic deafness and blindness
  Iodines                                   Reversible vs. irreversible neurotoxic deafness
  Alcohols                                  Ototoxicity from aminoglycoside antibiotics
  Chlorines                                 Neurotoxic blindness

  Chlorine bleaches

Hospital sterilants
  Ethylene oxide

  Hydrocarbon classification
  Hydrocarbon uses
  Hydrocarbon epidemiology
  Hydrocarbon toxicology
  Treatment of HC ingestion
  Volatile HC substance abuse
  Wood distillates

  Symptoms and diagnosis
  Same management
  Special caustics
  Nail and hair care
  Button batteries

toxic alcohols
  Anion gap metabolic acidosis
  Osmol gap metabolic acidosis
  Ethanol (EtOH)
  EtOH: Antabuse (disulfiram) reactions
  Ethylene glycol (EG)
  Methanol (MeOH)

                                           Poisonings with Common Household Products | 115
tABLe 7.1 Household Antimicrobials
Antiseptics                          Disinfectants                          Sterilants
antimicrobials applied to humans.    antimicrobials applied only to         antimicrobials applied to
Example: alcohols, iodophors,         inanimate objects                      inanimate objects to kill all
 chlorhexidine                       Example: bleach, formaldehyde,          microorganisms, including
alcohols                              phenols                                spores
Iodines                              Chlorine bleaches                      Example: ethylene oxide,
Chlorines                            Phenols                                 glutaraldehyde
Oxidants                             Boric acid                             Ethylene oxide
 Hydrogen peroxide (H2O2)            Formaldehyde                           Gluaraldehyde
 Potassium permanganate
Benzalkonium chloride

tABLe 7.2 Antiseptics: Iodines
Iodine                               Iodophor                               Iodide
Elemental I2                         I2 + high-molecular-weight             reduced I−, multiple uses:
Free I2                               nontoxic iodine-carrier (e.g., I2 +    1. SSKI for hyperthyroidism
2% tincture of iodine                 povidone = Betadine®)                  2. NaI added to table salt
Most toxic form of iodine, rarely    relatively safe, mostly skin            3. X-ray contrast agents
 used today                           irritants, commonly used for          Least toxic forms of iodine
                                      surgical procedures

                                                            Poisonings with Common Household Products | 117
Iodines                                                    Isopropanol (70%)

  • Toxicity: Gastrointestinal > dermal > CNS:               • Chemical name: Isopropyl alcohol — more toxic
    − Gastrointestinal: Caustic hemorrhagic gas-                 than ethanol.
          troenteritis, necrotic mucosal ulcerations,        • Toxicity: CNS > pulmonary > gastrointestinal >
          late esophageal stricture.                             dermal (defatting skin irritant):
      − Dermal: Caustic burns, contact dermatitis                − CNS: Intoxication, acetone breath, ataxia
          (iodophor), ioderma acne (iodide).                         then CNS depression > ethanol.
      − CNS: Metabolic acidosis, delirium, vasomo-               − Pulmonary: Tracheobronchitis, respiratory
          tor collapse.                                              depression, ketonemia and ketonuria with-
  •   Treatment: No emesis; careful aspiration;                      out metabolic acidosis.
      lavage with starch, milk, or sodium thiosulfate            − Metabolic: Exception = only toxic alcohol
      to reduce most toxic elemental iodine (I 2) to the             not causing metabolic acidosis.
      least toxic iodide (I−); activated charcoal (AC)           − Gastrointestinal: Nausea, vomiting, crampy
      and early endoscopy.                                           abdominal pain, hemorrhagic gastritis.
                                                             •   Treatment: Orogastric lavage; exception = only
                                                                 alcohol adsorbed by AC; hemodialysis is very
Iodides                                                          effective for all toxic alcohols.

  • Toxicity: Iodism = dermal > airway > gastro-           Chlorines
      − Dermal: Ioderma acne.                              Chlorhexidine
      − Airway: Painful swelling of salivary glands
          with sialorrhea = acute parotitis = “iodine
          mumps,” upper airway obstruction.
                                                             • Brand     name: 4% Hibiclens® — least toxic
      − Gastrointestinal: Metallic taste, nausea,            •   Toxicity: Gastrointestinal > dermal >
          vomiting, gingivitis, sialorrhea, no gastroin-
          testinal mucosal burns.
  •   Treatment: Corticosteroids for parotitis.
                                                                 − Gastrointestinal: Mucosal edema, caustic
                                                                 − Dermal: Contact dermatitis.
Alcohols                                                         − Hematologic: Hemolysis following intrave-
                                                                    nous (IV) administration.
Ethanol (70%)                                                •   Treatment: Endoscopy to assess gastrointestinal
  • Chemical     name: Ethyl alcohol — least toxic
  • Toxicity: CNS > pulmonary > dermal:
    − CNS: Intoxication leads to CNS and respi-
         ratory depression.                                  • Uses:    Na and K chlorates — used as mouth-
      −  Pulmonary: Respiratory depression, aspira-              washes (Chloroseptic®) and toothpastes — more
         tion pneumonitis.                                       toxic than chlorine.
      − Dermal: Defatting skin irritant.                     •   Toxicity: Hematologic > renal > gastro-
  •   Treatment: Supportive.                                     intestinal:
                                                                 − Hematologic: Methemoglobinemia, hemo-
                                                                     lytic anemia.

118 | Color Atlas of Human Poisoning and enenoming
      −  Renal: Proximal tubular damage, anuria,                  −  Hematologic: Methemoglobinemia, hemoly-
         acute tubular necrosis (ATN).                               sis, hemolytic anemia, acute tubular necrosis
      − Gastrointestinal: Earliest symptoms = nau-                   (ATN), hepatotoxicity, ARDS, cardiovascu-
         sea, vomiting, diarrhea, crampy abdominal                   lar collapse.
         pain.                                                    − CNS: Manganism can cause parkinsonism.
  •   Treatment: Lavage, AC, methylene blue,                  •   Treatment: No emesis, endoscopy, methylene
      hemodialysis.                                               blue for methemoglobinemia.

Oxidants                                                    Miscellaneous
Hydrogen Peroxide (3–30%)                                   Benzalkonium Chloride

  • Actions: Gas emboli-forming toxic caustic.                • Brand Name: Zephiran      ®
                                                                                            = a quaternary ammo-
  • Toxicity: Cardiovascular > CNS > gastro-                      nium compound = all are caustics.
      intestinal:                                             •   Toxicity: Gastrointestinal > CNS > cardio-
      − Cardiovascular = air emboli > gastrointes-                vascular:
           tinal.                                                 − Gastrointestinal: Caustic burns of mouth,
      − Cardiovascular: H2O2 and tissue catalase                     tongue, and esophagus.
           activity release O2 bubbles that may embo-             − CNS: Depression.
           lize to portal circulation, right ventricular,         − Cardiovascular/miscellaneous: Metabolic
           pulmonary circulation, and brain (CNS).                   acidosis, elevated liver function tests (LFTs),
      − Gastrointestinal: Vomiting, crampy abdomi-                   low blood pressure (BP).
           nal pain, caustic gastrointestinal burns, ero-     •   Treatment: Supportive and endoscopy.
           sions and ulcers, gastrointestinal bleeding.
  •   Treatment: Chest/abdominal x-rays for gas
      emboli and CVP line aspiration of gas bubbles         Mercurials
      from right atrium; hyperbaric oxygen, no eme-
      sis, early endoscopy to evaluate caustic mucosal        • Uses: Obsolete topicals.
      burns.                                                  • Inorganic: Mercury bichloride and merbromin
Potassium Permanganate
                                                              • Organic:      Thimerosol (49% Hg, merthiolate)
                                                                  still used as a preservative in most hyperim-
                                                                  mune globulins, antivenoms, and many attenu-
  • Actions: Manganese-containing, violet-colored                 ated and polysaccharide vaccines.
      toxic caustic and oxidizer.                             •   Mercury (Hg) poisoning: CNS > gastro-
  • Toxicity: Gastrointestinal > hematologic > hep-               intestinal.
      atorenal > CNS:                                         •   Treatment: Dimethylsuccinic acid (DMSA), oral
      − Gastrointestinal: Nausea, vomiting, muco-                 chelation.
         sal burns of mouth and esophagus > stom-
         ach, gastrointestinal bleeding, perforation
         and stricture.

                                                             Poisonings with Common Household Products | 119
                                                        FIGURe 7.2 Mercurochrome (Merbromin) antiseptic,
                                                        official Boy Scout first aid kit, 1950s. The organic mer-
                                                        cury compounds, mercurochrome (merbromin) and
                                                        thimerosol (merthiolate), were also commonly sold
                                                        over-the-counter worldwide as topical antiseptics well
                                                        into the twentieth century. Thimerosol is still added
                                                        to vaccines and pooled hyperimmune plasma immu-
                                                        noglobulins and antivenoms as a bacteriostatic and
                                                        fungicidal preservative. Repeated topical applications
                                                        or accidental ingestions of the organic mercurials may
                                                        result in mercuric neurotoxicity with slurred speech,
FIGURe 7.1 Over-the-counter mercury bichloride          tremor, and chorea. (From the antique pharmaceutical
Tablets, c. 1890s. Highly caustic, inorganic mercury    collection of James H. Diaz, M.D., Dr.P.H.)
compounds were commonly sold worldwide as over-
the-counter topical antiseptics (mercuric chloride
or mercuric bichloride) and infant teething powders
(calomel) well into the twentieth century. Accidental
ingestions may result in severe oropharyngeal and
esophageal burns, hemorrhagic gastroenteritis, hypo-
volemic shock, acute tubular necrosis, and esophageal
stenosis in survivors. (From the antique pharmaceuti-
cal collection of James H. Diaz, M.D., Dr.P.H.)

120 | Color Atlas of Human Poisoning and enenoming
Chlorine Bleaches                                             −  Dermal: Skin burns with later peeling and
                                                                 light brown staining.
Chlorine                                                  •   Miscellaneous: Brownish-black urine.
                                                          •   Treatment: Skin wash with polyethylene glycol
  • Uses: More toxic bleaches.                                (PEG), careful lavage, endoscopy.
  • Toxicity: Pulmonary > gastrointestinal:
    − Pulmonary: Pulmonary irritants causing
         severe bronchospasm, pulmonary edema,          Substituted Phenol (Phenol + Halogen)
      − Gastrointestinal: Caustic mucosal burns of        • Uses: Obsolete hospital skin cleanser.
         esophagus may cause later gastrointestinal       • Brand example: Hexachlorophene (pHisoHex ).  ®

         strictures.                                      • Toxicity (less toxic): CNS > gastrointestinal >
  •   Treatment: Supportive and endoscopy, later              dermal.
      esophageal dilations.                                   − CNS: Preemies = vacuolar encephalopathy =
                                                                 drowsiness and later cerebral edema.
Sodium Hypochlorite
                                                              − Gastrointestinal: Nausea, vomiting, diar-
                                                                 rhea, sore mouth and throat, crampy
                                                                 abdominal pain with fever.
  • Chemical and brand names: NaOCl, Clorox        ®
                                                          •   Treatment: Supportive.
      — less toxic bleaches.
  •   Toxicity: Gastrointestinal > pulmonary:
      − Gastrointestinal: Gastrointestinal irritant,    Miscellaneous
         mucosal burns, rarely strictures.
                                                        Boric acid
      − Pulmonary: Two highly toxic gases can be
         produced in households by mixing house-
         hold bleach (NaOCl) and acid (HCl) toilet        • Uses: Soaps/detergents, contact lens solutions,
         bowl cleansers, including (1) chlorine gas           roach tablets.
         and (2) chloramine gas.                          • Toxicity (very toxic): Gastrointestinal > dermal
  •   Treatment: Supportive and endoscopy.                    > CNS > renal:
                                                              − Gastrointestinal: Greenish-blue vomitus and
Phenols                                                       − Dermal: “Boiled lobster” erythroderma
                                                                 with desquamation in 1–2 days, and later
Free, Nonsubstituted Phenol                                      patchy alopecia (adults).
                                                              − CNS (children): Lethargy, delirium, sei-
  • Uses of phenol (carbolic acid): Nail bed cauter-             zures, coma.
      izer, chemical peeler, neurolytic.                      − Renal: Low blood pressure, shock-induced
  • Brand     example: Camphophenique® (camphor                  acute tubular necrosis (ATN).
      and phenol).                                        •   Treatment: No AC, lavage, hemodialysis.
  •   Toxicity (very toxic): CNS > gastrointestinal >
      − CNS: Stimulation with seizures.                 Formaldehyde
      − Gastrointestinal: Sweet-smelling breath,
          nausea, vomiting, crampy abdominal pain,        • Uses:   Tissue fixative, used as a pesticide and
          bloody diarrhea; rarely mucosal acid burns          fungicide in insulation.
          and esophageal strictures.

                                                         Poisonings with Common Household Products | 121
  • Toxicity: Gastrointestinal > CNS > pulmonary            −  Pulmonary: Upper airway irritation with
     > dermal/miscellaneous.                                   bronchospasm, acute pneumonitis possible;
     − Gastrointestinal: Nausea, vomiting, diar-               association with nasopharyngeal carcinoma
        rhea, caustic hemorrhagic gastroenteritis,             unproven.
        stomach > small intestine, mucosal necro-           − Dermal/miscellaneous:         Rash     and
        sis, gastric perforation, stricture formation          hepatotoxicity.
        metabolism to formic acid with metabolic        •   Treatment: Lavage, NaHCO3, folic acid as
        acidosis.                                           a cofactor to promote formate metabolism,
     − CNS: Initial depression with subsequent              endoscopy to assess mucosal injury.

122 | Color Atlas of Human Poisoning and enenoming
   Hospital Sterilants
ethylene Oxide                                            Glutaraldehyde

 • Uses: Hot, dry gas sterilization.                        • Uses:     Cold liquid sterilization of endoscopic
 • Toxicity (more toxic than formaldehyde): Potent              and other non-autoclavable, heat-sensitive hos-
     mucosal irritant; mutagen and carcinogen.                  pital instruments.
     − Acute: Upper airway, conjunctival, gastroin-         •   Brand name: Cidex®.
        testinal, and dermal irritation with nausea.        •   Toxicity (least toxic hospital sterilant): Predom-
     − CNS: Malaise, light headedness, syncope,                 inantly a skin and mucosal irritant.
        seizures, coma, sensory and motor neuropa-              − Acute: Increased upper airway reactivity,
        thies, rarely parkinsonism.                                 coryza, epistaxis, occupational asthma,
     − Chronic: High spontaneous abortion rates,                    ocular inflammation, conjunctivitis.
        increased rates of leukemias and gastric                − Dermal: Contact dermatitis.
        cancers.                                            •   Treatment: Removal and supportive therapy.
 •   Treatment: Removal and supportive therapy.

  tABLe 7.3 Mothballs
  Camphor                              Naphthalene                           Para-dichlorobenzene
  High toxicity                        Moderate toxicity                     Low toxicity
  Not radiopaque                       Faintly radiopaque                    Densely radiopaque
  Wet and oily                         White and dry                         White and oily
  Float in tap and saltwater           Sink in tap, float in saltwater       Sink in both tap and saltwater
  treatment: sedation, aC, non-oil     treatment: aC, non-oil cathartic,     treatment: not indicated, the
   cathartic = increased absorption     methemoglobinemia possible,           safest mothball, most commonly
                                        may require methylene blue            used mothball today in U.S.
  acute toxicity: CNS >                acute toxicity: hematologic >         acute toxicity: gastrointestinal >
   gastrointestinal; excitement,        gastrointestinal > CNS; #1            hematologic; mucosal irritant,
   tremor, restlessness, seizures,      hemolysis, methemoglobinemia          rarely causes hemolysis and
   apnea, coma, camphor-smelling        possible, hemolysis in G-6-P          jaundice
   breath, initial nausea, vomiting,    deficiency, cyanosis, anemia,
   cramps                               fever, nausea, vomiting, diarrhea,
  Chronic: mimics reye’s               Chronic: aplastic anemia,             Chronic: rarely causes hepatic
   syndrome–hepatic                     jaundice, hepatic necrosis            necrosis

                                                           Poisonings with Common Household Products | 123
Hydrocarbon Classification                             • There are 20 deaths per year from HC poison-
                                                         ing; 90% of these deaths occur in children under
Mostly Petroleum Distillates                             age 5 years; 33% of these deaths involve gaso-
                                                         line/motor oils; 11% involve Freon® and other
  • Acetone and toluene — aromatic                       spray can propellants (usually in adolescent HC
  • Gasoline, benzene, kerosene — aromatic               inhalation abusers), and 57% involve kerosene.
  • Butane and propane — aliphathic
  • Carbon tetrachloride (CCl ) — halogenated
  • Methylene chloride — halogenated
                                                      Hydrocarbon toxicology
  • Trichloroethane — halogenated
  • Trichloroethylene (TCE) — halogenated              • Toxicities: Pulmonary (50%) > gastrointestinal
  • Tetra(per)chloroethylene (PCE, PERC)                 (5%) > CNS (3%) > cardiovascular > dermal >
      — halogenated                                      hematologic.
  •   n-Hexane and n-heptane — aliphatic                 − Pulmonary: Pulmonary toxicity predomi-
  •   Methyl-isobutyl ketone (MIBK) — aliphatic             nates and results from HC aspiration and
                                                            not with HC absorption, with a resulting
                                                            loss of the surfactant’s capability to main-
Few Wood (Pine) Distillates
                                                            tain alveolar surface tension and subsequent
                                                            ARDS. HC pulmonary toxicity is deter-
  • Pine oil                                                mined by HC physical properties (i.e., low
  • Turpentine                                              surface tension, low viscosity, high volatil-
                                                            ity). These physical characteristics of hydro-
                                                            carbons will greatly increase aspiration risk
Hydrocarbon Uses                                            with resulting pulmonary toxicity.
                                                            − Symptoms: Gagging, coughing, chok-
  • Adhesives and cements                                        ing leading to aspiration with bron-
  • Fuels and propellants                                        chospasm, rales, rhonchi, tachypnea,
  • Paints and coatings                                          hypoxia; later hemorrhagic pulmonary
  • Lacquers and varnishes                                       edema, methemoglobinemia (nitrates,
  • Lubricants and oils                                          nitrites) with cyanosis; chronic URIs
  • Polishes and waxes                                           (upper respiratory infections), bronchi-
  • Paint removers and strippers                                 ectasis, pulmonary fibrosis.
  • Paint thinners                                          − X-ray: Pneumonitis, infiltrates, consoli-
  • Solvents and degreasers                                      dating pneumonias, pleural effusions,
  • Spot removers and dry cleaners                               barotrauma, upright gastric “double-
  • Typewriter correction fluids (Liquid Paper   )
                                                 ®               bubble” sign = (1) air-HC + (2) HC-gas-
                                                                 tric fluid interfaces.
                                                         − Gastrointestinal (5%): Nausea, vomit-
Hydrocarbon epidemiology                                    ing, hematemesis, gastrointestinal mucosal
                                                         − CNS (3%): Seizures, then coma from hypoxia
  • There are 65,000 hydrocarbon (HC) exposures             and inhalation of volatile HC — “anesthet-
      per year; 95% are unintentional; 60% involve          ics” with progression from Stage II (excite-
      children; 90% of deaths are in children under         ment) to Stage IV anesthesia (coma).
      age 5 years; 50% demonstrate minimal toxic         − Cardiovascular: Myocardial sensitization
      effects; and 20% require treatment.                   caused by halogenated hydrocarbons precip-

124 | Color Atlas of Human Poisoning and enenoming
         itates tachydysrhythmias, PVCs, ventricular            CNS and respiratory depression > cardiovas-
         tachycardia, ventricular fibrillation.                 cular = tachyarrhythmias often resulting in
     −   Dermal: Defatting dry dermatitis, oil boils,           “sudden sniffing deaths” > hematologic = met-
         degreaser’s flush (especially with trichlo-            hemoglobinemia > hepatotoxicity (CCL4 can
         roethylene) = facial flushing on consump-              cause centrolobular hepatic necrosis) and CO
         tion of ethanol following trichloroethylene            poisoning (methylene chloride).
         exposure.                                          •   Acute toxicity: Toluene — renal tubular
     −   Hematologic: Methemoglobinemia, hemo-                  acidosis.
         lysis, anemia, disseminated intravascular          •   Chronic toxicity: “Glue-sniffers” encephalopa-
         coagulation (DIC).                                     thy and chronic “painter’s syndrome” — both
     −   Renal: Toluene can cause type I renal tubu-            are characterized by memory and cognitive
         lar acidosis (RTA) with defective tubular              losses, dementia, insomnia, anxiety and depres-
         acidification manifesting as metabolic aci-            sion, personality disorder, ataxia and chorea,
         dosis, hyperchloremia, normal anion gap,               peripheral neuropathy (especially n-hexane and
         and very alkaline (high pH) urine.                     methyl-isobutylketone [MIBK]).

treatment of HC Ingestion                                 Wood Distillates
                                                          Pine Oil
 • Careful     gastrointestinal decontamination: No
     emesis! No activated charcoal! Possibly gastric
     lavage with small nasogastric (NG) for large vol-
                                                            • Brand name: PineSol .  ®

     umes, intentional ingestions, and highly toxic
                                                            • Pine terpenes.
     HCs, including (CHAMP) = camphor, haloge-
                                                            • Toxicity: Pulmonary > CNS:
     nated HCs, aromatic HCs, HCs associated with
                                                              − Pulmonary: Aspiration pneumonitis.
     metals, HCs associated with pesticides.
                                                              − CNS: Excitation with hyperactivity (possi-
                                                                    bly seizures), followed by depression (pos-
 •   No cathartics, especially no olive or mineral oil
                                                                    sibly coma).
     cathartics (oily cathartics will increase absorp-
     tion of lipophilic HCs), no prophylactic antibi-
                                                            •   Treatment: Same as for the petroleum
     otics or corticosteroids.
 •   Mechanical ventilation for ARDS: Barotrauma
     risk = start with low positive end expiratoy pres-   turpentine
     sure (PEEP) → next consider, high frequency jet
     ventilation (HFJV) → for refractory hypoxia,
     consider extracorporeal membrane oxygenation           • Pine terpenes
     (ECMO).                                                • Toxicity: Pulmonary      > tenal > hematologic >
 •   Cardiovascular: Consider avoiding inotropic                CNS:
     support during PEEP, due to myocardial sen-                − Pulmonary: Aspiration pneumonitis.
     sitization to sympathetic catecholamines and               − Renal: Pathognomonic hemorrhagic cystitis,
     potential arrhythmogenesis.                                   possibly acute tubular necrosis (ATN).
                                                                − Hematologic: Pathognomonic of turpentine
                                                                   = TP thrombocytopenic purpura.
Volatile HC Substance Abuse                                     − CNS: Excitation followed by depression.
                                                            •   Treatment: Same as for petroleum distillates.
 • Techniques: “Sniffing,” “huffing,” “bagging.”            •   Unique toxicities: (1) Hemorrhagic cystitis, (2)
                                                                thrombocytopenic purpura.
 • Agents: Toluene (glues, paints), fuels (butane,
     gasoline), trichloroethane and trichloroethyl-
     ene (TCE, typewriter correction fluids, Liquid
     Paper®), perchloroethylene (PCE or PERC), all
     dry cleaning fluids (acetone, CCl4, TCE, PCE).
 •   Acute toxicity: CNS-excitation = euphoria, hal-
     lucinations, ataxia, seizures, headache, then

                                                           Poisonings with Common Household Products | 125
Acids                                                   Alkalis

  • Caustic: Quickly neutralizes to tissue pH.            • Caustic: Quickly neutralizes to tissue pH.
  • Acute: Thermal energy leads to caustic       acid     • Acute: Thermal energy leads to caustic alkali
      burns.                                                  burns.
  • Chemistry: Acid proton donor.                         • Chemistry: Alkali proton acceptor.
  • Toxic pH: <3.0.                                       • Toxic pH: >11.0.
  • Chronic: Coagulation necrosis       (denaturation     • Chronic: Liquefaction necrosis (solubilization of
      of proteins and dessication of fats) causes             proteins and saponification of fats) with result-
      superficial, split-thickness burns on skin and          ing deep, full-thickness burns of skin and oral
      gastric mucosa; squamous epithelium of the              and esophageal mucosa; later esophageal stric-
      oropharnyx and esophagus offers greater pro-            tures possible. The stomach is involved with
      tection from acid burns than columnar epithe-           nucosal burns only 20% of the time following
      lium of stomach.                                        the intentional oral ingestion of alkalis.
  •   Examples: Battery acid contains H 2SO4 and toi-     •   Examples: Drain openers (NaOH) and oven
      let bowl cleaners contain HCl.                          cleaners (NH4OH).

   tABLe 7.4 Sources and Uses of Acids
   Acid Source                                           Acid Uses
   Boric acid                                            roach tablets
   Formaldehyde metabolite (formic acid)                 tissue fixative, pesticide/fungicide effects in foam
   Hydrochloric (muriatic) acid                          toilet, brick, and tile cleaners
   Hydrofluoric acid                                     antirust products
   Oxalic acid                                           Bleaches and whiteners
   Selenious acid                                        Gun bluing agents
   Sulfuric acid                                         automotive batteries

   tABLe 7.5 Sources and Uses of Alkalis
   Alkali Sources                                        Alkali Uses
   ammonium hydroxide (ammonia)                          Glass, oven, and other hard surface cleaners
   Potassium permanganate                                antiseptics, mouthwashes
   Sodium hydroxide                                      Detergents
   Sodium borates, carbonates, phosphates, and           Detergents, dishwasher/scouring powders, water
    silicates                                             softeners
   Sodium hypochlorite (Clorox®)                         Bleaches, whiteners, tile surface cleansers, and

126 | Color Atlas of Human Poisoning and enenoming
Pathophysiology                                          Symptoms and Diagnosis
acid Ingestions                                          acids

  • Immediate tissue burn                                  • Symptoms:       Oropharyngeal burns, crampy
  • Epithelial coagulation necrosis                            abdominal pain, stridor, pleural effusions sug-
  • Epithelial penetration limited     by coagulation          gest gastrointestinal perforation.
      effects                                              •   X-ray: Assess for gastrointestinal perforation =
  •   Systemic metabolic acidosis                              pleural effusion, free air, pneumomediastinum,
  •   Rarely, orogastric burns and, frequently, esoph-         pneumoperitoneum; contrast extravasation sug-
      ageal “skip areas”                                       gests perforation with fistula formation.
  •   Less gastrointestinal ulceration than alkali         •   Lab: Metabolic acidosis.
  •   Few late esophageal strictures
  •   Collateral acid-induced damage to spleen, pan-     alkalis
      creas, and biliary tree
                                                           • Symptoms: More oropharyngeal burns, greater
                                                               gastrointestinal perforation and esopha-
alkali Ingestions                                              geal stricture risks; otherwise similar to acid
  • Immediate tissue burns                                 •   X-ray: Perforation more likely; assess for free
  • Epithelial liquefaction necrosis                           air, pleural effusions, pneumomediastinum, and
  • Deep, full-thickness epithelial penetration                pneumoperitoneum; x-ray contrast extravasa-
  • Tissue necrosis promotes lactic acidosis                   tion suggests gastrointestinal fistula.
  • Oropharyngeal, esophageal, and gastric muco-           •   Lab: Lactic acidosis follows massive tissue liq-
      sal burns                                                uefaction necrosis.
  •   More gastrointestinal ulceration than acid
  •   Late esophageal strictures are common
  •   No extraintestinal damage

                                      FIGURe 7.3 Esophageal stenoisis following lye ingestion. Frontal esoph-
                                      agogram of an adolescent eight months following intentional lye inges-
                                      tion in a suicide attempt that demonstrates a gradual funnel-like tapering
                                      of the distal esophagus and concentric esophageal stenosis. (Courtesy of
                                      Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medi-
                                      cine, New Orleans, LA.)

                                                          Poisonings with Common Household Products | 127
Same Management                                             • Hydrofluoric     acid: Free F− ions rapidly and
                                                                deeply bind to Ca and Mg cations, causing
acids                                                           painful, subcutaneous tissue burn injuries with
                                                                few external dermal manifestations — elevated
  • Immediate upper airway inspection for extent                serum K, reduced serum Ca and Mg; subse-
      of mucosal burns.                                         quent arrhythmias; assess electrolytes imme-
  • Vomiting      (ipecac) contraindicated — could              diately. Treatment: Ca gluconate > CaCl; Ca
      result in greater epithelial damage.                      gluconate may be administered as topical gel,
  •   Activated charcoal (AC) contraindicated due to            intradermally, intra-arterially, no Ca gluconate
      limited absorption and endoscopy interference.            in eyes, Mg citrate orally.
  •   Immediate dilution therapy with milk > water
      — both of limited usefulness.
  •   X-ray assess for gastrointestinal perforation and   Special alkalis
      pleural effusions.
  •   Perform endoscopy within 12 hours — perfo-            • CliniTest   ®
                                                                            glucosuria tablets: Large CuSO4 and
      ration risk increases 2–3 days to 2 weeks post            NaOH tabs can lodge in esophagus, causing
      ingestion.                                                severe localized strictures.
  •   No prophylactic antibiotics or corticosteroids.       •   Ammonia: 3–10% home-use concentrations can
  •   Surgical repair, stricture dilation.                      cause esophageal burns; 28+% can cause severe
                                                                burns and later esophageal strictures.
                                                            •   Bleach: Limited burns and no late esophageal
                                                            •   Sodium azide: Airbag inflator explosive and lab
  • Immediate upper airway inspection for extent                reagent; mimics CN poisoning, causing cyto-
      of mucosal burns.                                         toxic hypoxia.
  • Vomiting      (ipecac) contraindicated — could
      result in greater epithelial damage.
  •   AC contraindicated due to limited absorption        Sodium azide
      and endoscopy interference.
  •   Immediate dilution therapy with milk > water          • Uses: Airbag releasing agent, common clinical
      — both of limited usefulness.                             lab reagent for autoanalyzed samples.
  •   X-ray assess for gastrointestinal perforation and     •   Toxicity: Uncouples oxidative phosphorylation
      pleural effusions.                                        within mitochondria, like CN, by inhibiting
  •   Perform endoscopy within 12 hours — perfo-                cytochrome oxidase, causing cytotoxic hypoxia
      ration risk increases 2–3 days to 2 weeks post            and metabolic acidosis, and, possibly, produc-
      ingestion.                                                ing CN.
  •   No prophylactic antibiotics or corticosteroids.       •   Clinical Poisoning: CNS, cardiovascular, and
  •   Surgical repair, stricture dilation.                      eye > initial gastrointestinal (nausea, vomiting,
                                                                − Cardiovascular: Vasodilation = hypoten-
Special Caustics                                                    sion.
Special acids                                                   − CNS: Biphasic-initial headache and seizures,
                                                                    then hyporeflexia and coma.
  • Phenol: Dermal and mucosal burns; early endos-              − Eye: Deeply penetrating liquefaction
      copy indicated.                                       •   EMS personnel risks: On ingestion, combines
                                                                with gastric HCl to liberate hydrazoic acid
                                                                and pose toxic risks to all attending medical

128 | Color Atlas of Human Poisoning and enenoming
  • Treatment: Supportive, ICU monitoring, copi-         Button Batteries
      ous eye irrigation to pH 7.4 (normal saline
      (NS) > Ringer’s lactate (RL) > tap water). Warn
      EMS personnel of their risks and recommend
                                                            • Uses: Hearing aids, watches, calculators, laser
                                                                pointers, computer games.
      adequate ventilation and personal protective
                                                            • Contents: Combine heavy metal salts (Ni-Cd,
                                                                Li, Cu, Hg, Zn) and a caustic alkali (NaOH,
                                                                KOH). Lithium-containing batteries are the
                                                                most toxic.
Nail and Hair Care
                                                            •   Pathology: Caustic leakage can cause mucosal
artificial Nails                                                burns, pressure necrosis can cause gastroin-
                                                                testinal perforation, electrical gradients across
  • N,N-dimethy-p-toluidine: Methemoglobinemia.                 moist mucosa may cause shocks with muscle
  • Aryl and ethyl acrylate monomers: Hypotension           •
                                                                Diagnosis: Immediate AP/lateral chest and
      and respiratory depression.
                                                                abdominal x-rays.
                                                            •   Epidemiology: 86% of battery ingestions com-
False Nail remover                                              plete gastrointestinal transit in 4 days.

  • Nitroethane: Methemoglobinemia.
False Nail Glue remover                                                             Ingestion of a battery

                                                                              Initial patient evaluation
  • Acetonitrile and proprionitrile: Delayed (3–24                            1. X-ray localization
                                                                              2. Confirmation of ingestion
      hours) CN poisoning due to hepatic P450 bio-
      tranformation to an aldehyde and cyanide.            Battery in airway                                 Battery in esophagus

  •   Acetone: Dermal defatting.                           Emergency bronchoscopy                            Consider: Nitrates,
                                                                                                             nifedipine, or glucagon

                                                                                                                Battery movement
Hair relaxers and Straighteners                                                                                         No

  • Thioglycolates:    Alkalis causing severe dermal
                                                                                    Battery in stomach

      and mucosal irritation and burns.                   Symptomatic
  •   Neutralizers and setting agents.                    1. X-ray assessment of battery          1. Cathartics (consider PEG-ELS)
  •   Bromates: Severe vomiting, abdominal pain,
                                                             location and character
                                                          2. Endoscopic or surgical
                                                                                                  2. Bulk agents: Strain stool
                                                                                                  3. Repeat X-ray in 5–7 days
      and bloody diarrhea in 1–2 hours; then hypo-
                                                                                    Battery in intestines
      tension with resulting oliguria may cause acute
      tubular necrosis (ATN), permanent deafness,
                                                            Patient symptomatic                  Patient asymptomatic
      resembling aminoglycoside, toxicity may also        1. X-ray assessment of battery         1. Cathartics (consider PEG-ELS)
                                                                                                 2. Bulk agents
      occur.                                                 location and character
                                                                                                 3. Strain stool
  •   Treatment: Na thiosulfate to reduce bromates
                                                          2. Surgical removal
                                                                                                  4. Repeat X-ray in 5–7 days

      to less toxic bromides; hemodialysis.                                        Battery stops moving
                                                                                surgical removal in 5–7 days

Depilatories                                             FIGURe 7.4 The management of battery ingestion.
                                                         A clinical flow chart that describes the management
  • Barium     sulfide: Severe hypokalemia, nausea,      of button battery ingestion. Although most ingested
                                                         button batteries will traverse the gastrointestinal tract
      vomiting, diarrhea, hypertension, numbness,
                                                         in 4 days, batteries that are aspirated into the lungs
      weakness, respiratory paralysis.
                                                         should be removed immediately at bronchoscopy, and
  •   Treatment: MgSO4 to promote formation of
                                                         batteries that become lodged in the gastrointestinal
      nontoxic, insoluble barium sulfate (BaSO4), fre-   tract should be removed surgically by 5-7 days.
      quently used as an oral or rectal radiographic
      contrast agent.

                                                          Poisonings with Common Household Products | 129
   toxic Alcohols
Anion Gap Metabolic Acidosis                                   without food increase absorption; hepatically
                                                               oxidized by three pathways:
  • Definition:    [Measured cations − measured
                                                               − Pathway 1: Alcohol dehydrogenase (ADH)
                                                                  [EtOH → (ADH) → Acetaldehyde (acetalde-
      anions] = [Na+] − [Cl− + HCO3 −] = 140 − [110
                                                                  hyde dehydrogenase) → Acetyl CoA → (thia-
      + 24] = 6.
                                                                  mine cofactor) → Kreb’s tricarboxylic acid
      − Normal range: 3–11.                                       (TCA) cycle → CO2 + H 2O].
      − High: MMUDPPIILEESS = Methanol, Met-                   − Pathway 2: CYP-450 (inducible
         formin, Uremia, Diabetic ketoacidosis, Par-
         aldehyde, Phenformin, INH, Iron, Lactic
         acidosis, Ethanol, Ethylene glycol, Salicy-
                                                               − Pathway 3 : hepatic peroxidase-catalase.
         lates, and Solvents. MMETAL ACCIID
                                                           •   Toxicity: CNS > gastrointestinal > metabolic.
         GAPP = Methanol, Metformin, Ethylene
                                                               − CNS: Inebriation, disinhibition, incoordi-
                                                                  nation, blurred vision, diplopia, confusion,
         glycol, Toluene, Alcohol ketoacidosis, Lactic
                                                                  CNS and respiratory depression.
         acidosis, Aspirin, Carbon monoxide, Cya-
         nide, Isoniazid, Iron, Diabetic ketoacidosis,
                                                               − Gastrointestinal: Nausea, vomiting, cramp-
                                                                  ing abdominal pain, gastric bleeding.
         Generalized seizures, Aminoglycosides, Par-
         aldehyde, Phenoformin.
                                                               − Metabolic: High anion gap metabolic aci-
                                                                  dosis, high osmolal gap metabolic acidosis,
      − Low: Bromides (falsely elevated anionic                   hypoglycemia, hypokalemia, hypomagnese-
         chloride levels).
                                                                  mia, hypophosphatemia, hyperamylasemia.

Osmol Gap Metabolic Acidosis                             acute EtOH Intoxication: Blood
                                                                Ethanol Levels

  • Definition: [Measured osmolality] − [calculated        • 0.05% (50 mg/dL)
      osmolality] = [mOsm/kg] − [2Na+ + Glu/18 +
      BUN]                                                 • 0.08% (80 mg/dL)*
      − Normal range: –14 to +10                           • 0.10% (100 mg/dL)
      − Abnormal: >10, an unknown low-molecu-              • 0.20% (200 mg/dL)
         lar-weight osmotically active agent (usually      • 0.30% (300 mg/dL)
         a toxic alcohol) is present in serum.             • 0.40% (400 mg/dL)
      − High: Ethanol, all toxic alcohols, lactic aci-     • 0.70% (700 mg/dL)
         dosis, renal failure, hyperlipidemias, hyper-
                                                         [* Legally intoxicated in most U.S. states.]
         triglyceridemias, and hyperproteinemias
         (multiple myeloma).
                                                                              MEOS (CYP 2EI)

ethanol (etOH)                                                                Catalase
                                                               H H                         H H                  H O−
EtOH Pharmacology and toxicity                                                ADH                      ALDH
                                                          H C      C     OH              H C   C   O          H C   C   O

  • Chemistry:      Colorless, odorless hydrocarbon;           H H                         H                    H

      highly water soluble and highly lipid soluble;                     NAD+      NAD +  H+       NAD+   NADH + H+
      dependence and addiction possible.                       Ethanol                Acetaldehyde           Acetate
  •   Pharmacology: Low molecular weight, low            FIGURe 7.5 Ethanol metabolism. The hepatic bio-
      volume of distribution (Vd) = 0.6 L/kg, rapidly    transformation reactions, which are responsible for the
      diffusible; rapid gastric emptying and drinking    metabolism of ethanol.

130 | Color Atlas of Human Poisoning and enenoming
Clinical Manifestations                                     • Precipitated      by antifungals: Griseofulvin,
  • Disinhibition and incoordination                        •   Mimicked by Mickey Finn: Chloral hydrate
                                                                (and its trichloroethanol metabolite).
  • Decreased reaction time, auto driving impaired          •   Miscellaneous: Coprinus spp. mushrooms
  • Nausea, vomiting, confusion, staggering gait                (Coprinus atramentarius), industrial chemicals:
  • Slurred speech, reduced vision, and reduced                 carbamate pesticides and oximes.
  • Hypothermia,        hydroglycemia, amnesia, sei-
      zures, hyporeactive deep tendon reflexes (DTRs),
      respiratory depression, loss of airway protective
      reflexes, aspiration pneumonia, coma, death         Isopropanol Pharmacology and toxicity

Diagnosis: EtOH Overdose
                                                            • Chemistry: 70% isopropyl alcohol or rubbing
                                                                alcohol; a clear, colorless volatile liquid with
  • Blood      ethanol levels: Determine stage of               an acetone smell; used in toiletries, disinfec-
      intoxication.                                             tants, window cleaners, and solvents. Excep-
  •   Blood glucose: Rule out hypoglycemia.                     tion: the only alcohol adsorbed by AC (activated
  •   CBC and lytes: Decreased Na, K, Mg, Ca, and               charcoal).
      P.                                                    •   Pharmacology: Rapid all-route absorption, espe-
  •   ABGs: High-anion gap metabolic acidosis,                  cially dermal and inhalation; low volume of dis-
      increased osmolal gap.                                    tribution = 0.6 L/kg; 50% rapidly metabolized
  •   Serum amylase: Rule out pancreatitis.                     by alcohol dehydrogenase (ADH) to acetone,
  •   Serum ammonia: Rule out hepatic encepha-                  remaining 50% unmetabolized and excreted by
      lopathy from alcoholic cirrhosis with acute liver         kidneys > exhalation via lungs.
      failure.                                              •   Toxicity: CNS > gastrointestinal > pulmonary
                                                                > metabolic:
                                                                − CNS: Three times more CNS depression
Management: EtOH Overdose                                           than EtOH, lethargy, weakness, headache,
                                                                    ataxia, dysarthria, confusion, apnea, respi-
  • Ipecac contraindicated.                                         ratory depression, hypotension.
  • Orogastric lavage and        AC: Especially for             − Pulmonary and gastrointestinal: Acetone
      co-ingestions.                                                breath, hemorrhagic gastritis and hemor-
  •   Coma cocktail: D50W 0.5–1.0 g/kg + thiamine                   rhagic tracheobronchitis.
      100 mg IV.                                                − Metabolic: Exception: only toxic alcohol not
  •   Multivitamins and folate 1–5 mg IV.                           causing metabolic acidosis or hypoglycemia;
  •   Slow rewarming.                                               euglycemia is maintained; ketonemia and
  •   Correct eletrolytes: Low K-Mg-P.                              ketonuria occur from acetone poisoning.
  •   Enhanced elimination: Hemodialysis very effec-
      tive given ethanol’s low molecular weight and       Diagnosis: Isopropanol Overdose
      volume of distribution, but rarely indicated.
                                                            • Determine serum acetone level.
                                                            • Anticipate falsely elevated creatinine.
etOH: Antabuse (Disulfiram) Reactions                       • Arterial blood gasses: pH will be normal, no
                                                                metabolic acidosis.
  • Antabuse     (disulfiram) reaction: Flushing, dia-      • Glucose: No hypoglycemia.
      phoresis, nausea, vomiting, disorientation,           • Anticipate ketonemia and ketonuria from ace-
      vertigo, headache, palpitations, chest pain mim-          tone metabolites.
      icking acute myocardial infarction (MI).              • Breath: Acetone odor.
  •   Precipitated by antibiotics: Chloramphenicol, n-
      MTT side chain cephalosporins, sulfonamides.

                                                           Poisonings with Common Household Products | 131
                               OH OH
                          H    C    C      H
                               H    H      Ethylene glycol
                               OH O
                          H    C    C      H
                               H           Glycoaldehyde
                               OH O
                           H   C    C      OH
                                H           Glycolic acid
          Lactic dehydrogenase
         or glycolic acid oxidase
                                O   O
         Thiamine cofactor                                            Pyridoxine cofactor
                            H C     C      OH
           Mg++ cofactor                                                                         FIGURe 7.6 Ethylene glycol metab-
                                            Glyoxylic acid
                                                                                   Glycine +     olism. The hepatic biotransformation
  Alpha-hydroxy-               O    O
                                                               Oxalomalic acid benzoic acid
                                                                                                 reactions, which are responsible for
beta-ketoadipic acid                                                                             the metabolism of ethylene glycol, a
                        HO     C    C      OH                gamma-hydroxy-alpha
                             Oxalic acid
                                                               ketoglutaric acid Hippuric acid   common component of antifreeze.
                                                                 formic acid

Management: Isopropanol Overdose                                                  −   Toxic phases 1–3:
                                                                                      − Phase 1, CNS: Ataxia, nausea, vomit-
                                                                                         ing, intoxication, inebriation, nystag-
   • Immediate skin decontamination.                                                     mus, myoclonus, seizures, progressing to
   • Orogastric lavage, then AC: Exception:          only
                                                                                         lethargy and coma within 4 to 8 hours.
       toxic alcohol to be well adsorbed by AC.
   •   Enhanced elimination: Hemodialysis very effec-
                                                                                      − Phase 2, Cardiovascular and metabolic:
                                                                                         Profound high anion gap metabolic
       tive in serious overdoses, especially in children.
                                                                                         acidosis progressing to hypertension,
       Ethanol is not indicated because there is no need
                                                                                         tachycardia, tachyapnea, and cardiovas-
       to block isopropanol’s metabolism to acetone,
                                                                                         cular collapse.
       which is relatively nontoxic and exhaled by the
       lungs and excreted in the urine.
                                                                                      − Phase 3, Renal: Urinary excretion of
                                                                                         toxic metabolites, especially oxalate,
                                                                                         which combines with calcium to form
ethylene Glycol (eG)                                                                     calcium oxalate crystals (calcium oxa-
                                                                                         late and hippuric acid); with calcium
EG Pharmacology and toxicity                                                             oxalate crystalluria causing nephroli-
                                                                                         thiasis, proteinuria, and hematuria, and
   • Chemistry:     A toxic alcohol similar to metha-                                    may progress to acute tubular necrosis.
       nol in toxicity and lethality, with a characteris-
       tic delayed onset of toxicity; used in antifreeze
                                                                           EG Overdose: Diagnosis and Management
       (95%), refrigerating fluids, fire extinguishers,
       solar energy fluids.
   •   Pharmacology: Rapidly absorbed orally, peaks                           • Diagnosis:      Calcium oxalate crystalluria,
       within 1–4 hours; rapidly metabolized by ADH                               urine fluorescein staining under ultraviolet
       to glycoaldehyde and by the glycoaldehyde                                  Wood’s lamp lighting, serum EG levels by gas
       dehydrogenase to its toxic metabolites, glycolic,                          chromatography.
       glyoxalic, and oxalic acids. Pyridoxine and thi-                       •   Initial management: AC ineffective due to rapid
       amine can serve as cofactors to promote non-                               absorption and delayed symptom onset of 4–8
       toxic alternative routes of metabolism.                                    hours; ipecac contraindicated due to existing
   •   Toxicity: (1) CNS > (2) Metabolic > (3) Renal                              vomiting; sodium bicarbonate (NaHCO3) to
       > Initial gastrointestinal toxicity: nausea and                            correct acidosis and increases excretion of weak
       vomiting:                                                                  acids; antidotes = ethanol (and/or 4-methylpyr-

132 | Color Atlas of Human Poisoning and enenoming
      azole [4-MP], an alcohol dehydrogenase inhibi-       MeOH Overdose: Diagnosis and
      tor) as preferred ADH substrates, 0.8 g/kg IV or     Management
      8 mL/kg orally, to maintain serum EtOH level
      of 100–150 mg/dL (EG:EtOH ratio = 1:4).
  •   Enhanced elimination: (1) Urinary alkaliniza-
                                                               • Diagnosis:     Lactic acidosis, unique eye find-
                                                                   ings, increased serum methanol levels by gas
      tion to promote urinary excretion of weak acid
      metabolites; (2) thiamine (100 mg IV) and pyri-
      doxine (50 mg IV) every 6 hours, to promote
                                                               •   Initial management: AC ineffective due to rapid
                                                                   absorption and delayed symptom onset; ipecac
      alternative nontoxic routes of metabolism; (3)
                                                                   contraindicated due to vomiting; NaHCO3 to
      hemodialysis for EG levels >25 mg/dL.
                                                                   correct acidosis; antidotes = ethanol (and/or
  •   Correct hypocalcemia: Treat hypocalcemia
                                                                   fomipazole [4-MP]) as preferred ADH sub-
      from massive calcium losses in calcium oxalate
                                                                   strates, 0.8 g/kg IV or 8 mL/kg orally, to main-
                                                                   tain serum EtOH level 100–150 mg/dL (MeOH:
                                                                   EtOH ratio = 1:4).
EG Ingestion                                                   •   Enhanced elimination: (1) Urinary alkaliniza-
                                                                   tion to promote renal excretion of undissoci-
                                                                   ated formic acid; (2) folic acid, 150 mg IV every
  • Urinary calcium oxalate crystals (ethylene gly-                4 hours, to serve as a cofactor promoting the
      col ingestion requires ethanol and/or 4-methyl-              metabolism of formic acid to CO2 + H 2O; (3)
      pyrazole (fomipazole, 4-MP) therapy, often with              hemodialysis for methanol levels >25 mg/dL.
      hemodialysis (HD) for serum EG levels >25 mg/
      dL to prevent acute tubular necrosis (ATN).

Methanol (MeOH)                                                 H        Alcohol    O Acetaldehyde O
                                                                     dehydrogenase dehydrogenase
MeOH Pharmacology and toxicity                                           (ADH)          (ALDH)
                                                           H    C    OH          H C          H C OH              CO2 + H2O
                                                                          Rate         Rapid         Folate cofactor
  • Chemistry:      Methyl alcohol or wood alco-                H
                                                                      limiting step
      hol; used in windshield washing fluids, deic-
                                                           Methanol           Formaldehyde    Formic acid
      ing solutions, carburetor cleaners, model
      airplane glues, canned heat (Sterno®) fuels,
      paint removers/thinners.                             FIGURe 7.7 Methanol metabolism. The hepatic bio-
  •   Pharmacology: Rapid all-route absorption,            transformation reactions, which are responsible for the
      peaks 1/2–1 hour; 85% rapidly metabolized by         metabolism of methanol or wood alcohol.
      hepatic alcohol dehydrogenase (ADH) to form-
      aldehyde and formic acid metabolites that are
      responsible for retinal toxicity.
  •   Toxicity: Eye/CNS > Metabolic > Initial gas-
      trointestinal toxicity: nausea, vomiting, and
      − Eye: Dimmed and blurred vision, scotomata,
          dilated and sluggishly reactive pupils, hyper-
          emic optic discs, retinal edema, blindness.
      − CNS: Inebriation, headache, vertigo, menin-
          gismus, cerebral edema, seizures, coma.
      − Metabolic: 24-hour delayed onset of high-
          anion gap metabolic acidosis, followed by

                                                           Poisonings with Common Household Products | 133
tABLe 7.6 The Pathophysiology and Management of Toxic Alcohol Poisonings
Alcohol       Uses           toxic   Action   Metabolism          Manifestations                  Management
                             Dose    Leel
Isopropanol   rubbing        2–4     Na       Metabolized by Ketosis without acidosis,            Supportive, no
 (rubbing      alcohol, nail mL/kg              aDH to             inebriation, ataxia,            ethanol
 alcohol)      polish                           acetone —          dysarthria, confusion,
               remover                          exhale or          stupor, coma, acetone
                                                urine secreted     breath, hemorrhagic
Ethylene      antifreeze,    1–1.5   >20–20 Metabolized by Increased anion and                    alkalininze
 glycol        coolants,      mL/kg   mg/dL     aDH to             decreased osmolal gaps,         urine,
 (antifreeze)  brake fluids                     glycolic and       hypocalcemia with and           thiamine, and
                                                oxalic acids.      increased Qt and tetany;        pyriodoxine,
                                                Oxalate            CNS (1–12 hour): ataxia,        to promote
                                                combines           nystagmus seizures,             nontoxic
                                                with calcium       nausea-vomiting;                metabolism,
                                                to cause           Cardiovascular/Metabolic        ethanol IV or
                                                calcium            (12–27 hours):                  4-methyl-
                                                oxalate            hypertension, tachycardia,      pyrazole,
                                                crystalluria.      increased Qt, tachypnea,        orally,
                                                                   cardiovascular collapse         hemodialysis
                                                                  renal (24–72 hours/
                                                                   cardiovascular) tenderness,
                                                                   oliguria, urine fluorescein,
                                                                   acute renal failures
Methanol      Windshield     <1      >50      Metabolized by Increased anion and                  alkalinize
 (wood         washer,        mL/kg   mg/dL     aDH to             osmolal gaps, intoxication.     urine, folic
 alcohol)      radiator                         formaldehyde       Nausea-vomiting,                acid, to
               fluid,                           and formic         hemorrhagic gastritis,          promote
               Sterno®                          acid               photophobia, blurred –          nontoxic
               fuel                                                reduced vision,                 metabolism,
                                                                   “snowfield” blindness,          ethanol IV,
                                                                   retinal edema, hyperemic        hemodialysis
                                                                   optic disks

134 | Color Atlas of Human Poisoning and enenoming
   toxic Deafness and Blindness

Reersible s. Irreersible                    Ototoxicity from Aminoglycoside
Neurotoxic Deafness                            Antibiotics
reversible Neurotoxic Deafness                 Can Be Characterized By:
       May Be Caused By:
                                                 • Permanent      cochlear and vestibular hair cell
  • Antibiotics (quinine > erythromycins)            degeneration (deafness and vertigo)
  • Carbon monoxide                                  − Gentamicin
  • Diuretics                                        − Tobramycin
  • Salicylates and NSAIDs                       •   Cochlear toxicity alone (deafness only)
                                                     − Amikacin
                                                     − Kanamycin
Irreversible Neurotoxic Deafness May Be              − Neomycin
Caused By:                                       •   Permanent vestibular hair cell degeneration
                                                     (vertigo only)
  • Aminoglycosides                                  − Streptomycin
  • Bromates
  • Hydrocarbons (toluene > xylene, styrene)   Neurotoxic Blindness
  • Heavy metals (Hg > As)
                                               Neurotoxic Blindness May Be Caused By:

                                                 • Most common causes: methanol, quinine.
                                                 • Less common causes: antihypertensives (cor-
                                                     tical blindness), carbon monoxide, cocaine
                                                     (retinal vasospasm), ergots (retinal vasospasm),
                                                     hydrogen sulfide.

                                                Poisonings with Common Household Products | 135
                               Chapter 8

  Reproductie and
Perinatal toxicology

      Reproductie and Perinatal toxicology | 137
Chapter Outline
              epidemiology of reproductie toxicology

              toxins affecting fertility, potency, and
                  Toxic priapism and abortifacients

              Pharmacokinetics of pregnancy
                  Factors promoting increases in free drug concentration
                  Factors promoting decreases in free drug concentration
                  Placental transfer

              Acute poisoning in pregnancy
                  General management
                  Neonatal toxicokinetics

              Specific poisonings in pregnancy
                  Acetaminophen (APAP) overdose in pregnancy
                  Iron overdose in pregnancy
                  Maternal carbon monoxide (CO) poisoning

              theophylline oerdose in pregnancy
                  Theophylline metabolism
                  Management: theophylline overdose
                  Specific management: theophylline overdose
                  Theophylline enhanced elimination

              Substance abuse in pregnancy
                  Alcohol abuse and Fetal Alcohol Syndrome (FAS)
                  Cocaine abuse and Fetal Cocaine Syndrome (FCS)
                  Opioid abuse in pregnancy
                  Neonatal Withdrawal Syndrome (NWS)

                  Absolutely contraindicated drugs in breast-feeding
                  Relatively contraindicated drugs

                           Reproductie and Perinatal toxicology | 139
 epidemiology of
 Reproductie toxicology
• There    are more than 90,000 chemicals used             antimicrobials, antiemetics, theophylline, caf-
    commercially in the United States, but only            feine, ethanol, and nicotine.
    2200 have been evaluated for mutagenic and         •   From 15 to 25% of pregnant women report licit
    teratogenic effects in animal models.                  drug use (ethanol > nicotine), or illicit drug use
•   There are more than 20 million women of repro-         (marijuana > cocaine > heroin), or have positive
    ductive age in the U.S. workforce, but only 4 to       urine drug screens during pregnancy.
    6% of birth defects are related to known drug      •   Analgesics, vitamins, iron, antibiotics, theoph-
    or toxin exposures during pregnancy.                   ylline, and psychotropic medications account
•   From 30 to 70% of pregnant women use three             for 50 to 80% of all reported toxic ingestions
    to ten different drugs during pregnancy, espe-         by pregnant women.
    cially vitamins, iron, analgesics, antipyretics,

                                                               Reproductie and Perinatal toxicology | 141
   toxins Affecting Fertility,
   Potency, and Gestation
  tABLe 8.1 Male Infertility
  Drugs or toxins                                     Mechanisms of Infertility
  anabolic steroids                                   Low luteinizing hormone (LH, impair Leydig cells)
                                                       levels, low sperm number, and abnormal sperm
  androgens                                           Low testosterone, low sperm counts
  antineoplastics                                     Direct gonadal toxicity, spermatogenesis ceases
  Carbon disulfide                                    Low luteinizing hormone levels, low follicle
                                                       stimulating hormone levels (FSH, impair Sertoli
                                                       cells), low sperm counts
  Cimetidine                                          Low sperm counts
  1,2-Dibromo-3-chlorpropane                          Low sperm counts
  Epichlorohydrin                                     Low sperm counts
  Ethanol                                             Low testosterone, low sperm counts
  Ethylene dibromide                                  Low sperm counts
  Lead                                                Low sperm counts
  Opioids                                             Low luteinizing levels, low testosterone levels, low
                                                       sperm counts
  Sulfasalazine                                       Low sperm counts
  Marijuana and tobacco                               Low testosterone levels, low sperm counts

  tABLe 8.2 Male Sexual Dysfunction
  Drugs or toxins                                     Mechanisms of Dysfunction
  anabolic steroids                                   Low libido, impotence
  anticholinergics                                    Erectile failure
  antihypertensives (α2-agonists)                     Impotence, erectile failure (neurologic)
  antihypertensives (thiazides)                       Erectile failure (vascular)
  Cimetidine                                          Low libido, impotence
  Dimethylaminoproprionitrile                         Neurogenic bladder, erectile failure
  Ethanol                                             Impotence, erectile failure
  Lead                                                Low libido, erectile failure
  Lithium                                             Erectile failure
  MaOIs                                               Low libido, impotence
  Opioids                                             Low libido
  Phenothiazines                                      Low libido
  tCas                                                Low libido, impotence

142 | Color Atlas of Human Poisoning and enenoming
tABLe 8.3 Female Infertility
Drugs or toxins                                        Mechanisms of Infertility
anabolic steroids                                      Low luteinizing hormone and follicle stimulating
                                                        hormone levels
antineoplastic agents                                  Direct gonadal toxicity, oogenesis ceases
Carbon disulfide                                       Low luteinizing hormone and follicle stimulating
                                                        homone levels
Lead                                                   Increased spontaneous abortions and stillbirths
Oral contraceptives                                    Prolonged hypothalamic-pituitary axis shutdown,
thyroid hormone                                        Increased anovulatory cycles

tABLe 8.4 Female Sexual Dysfunction
Drugs or toxins                                        Mechanisms of Dysfunction
anabolic steroids                                      Low libido
Cimetidine                                             Low libido
Lithium                                                Low libido
Opioids                                                Low libido
Oral contraceptives                                    Low libido
Phenothiazines                                         Low libido
tricyclic antidepressants                              Low libido
SSrIs                                                  Low libido

tABLe 8.5 Aphrodisiacs
Drugs or toxins                                        Mechanisms of toxicity
(“street names”)
Bufotoxins: bufotalin, bufotenine; dried toad skin     Cardiac glycoside (digitalis) toxicity. treatment =
 venom = “love stone, “rock hard”                       digoxin Fabs (DigiBind®)
Cantharidin: crushed blister beetle = “Spanish fly”    Hemorrhagic blistering of mouth, gastrointestinal
                                                        and genitourinary tracts; hemorrhagic bladder
                                                        bullae; priapism; vaginal bleeding
Lead additives: for red color                          Lead colic, anemia, basophilic stippling, infertility,
                                                        impotency, spontaneous abortion, still birth
Nitrites: amyl (crushable-“pop” sound), butyl,         Headache, nausea, syncope, hypotension, reflex
 isobutyl = “poppers”                                   tachycardia, methemoglobinemia
Yohimbine: african yohimbe tree bark extract, an α2-   Unopposed α1-mediated hypertension, tachycardia,
 antagonist and cholinergic agonist = “yo yo”           myocardial infarction, mydriasis, diaphoresis,
                                                        flushing; cholinergic-SLUDE and flushing; treatment
                                                        = aC decontamination, then benzodiazepines (BZs)

                                                                Reproductie and Perinatal toxicology | 143
                   Tracheo-esophageal                                                                 T-E fistula
        Radial limb
       Vertebral                                  umbilical                         10%                                      7%
        defect                                     artery
                                                                                          7%                              3%

              Anal                                                                                     defects
             atresia                    Renal
                                                                                               36%                  27%
                       Genital defect
                                                                     Imperforate                          3%                   Radial
FIGURe 8.1 The VACTREL association 1. The VAC-                             Anus                           5%                   Dysplasia
TREL association is a constellation of birth defects
that may occur in the rare pregnancies conceived dur-                FIGURe 8.2 The VACTREL association 2. A diagram
ing maternal birth control with oral contraceptive pills.            that indicated the ranges of joint association of con-
The mnemonic VACTREL stands for vertebral anoma-                     genital birth defects in the VACTREL association.
lies (spina bifida), imperforate anus, congenital cardiac
defects, tracheo-esophageal fistula, and limb deformi-
ties (radial agenesis or dysplasia).
                                                                        • Pulegone (pennyroyal oil):    Hepatotoxicity from
toxic Priapism and Abortifacients                                           glutathione depletion (like APAP).
Priapism-Inducing agents                                                    − Treatment: N-acetylcysteine (NAC).
                                                                        •   Black cohosh root: Herbal preparation caus-
                                                                            ing gastrointestinal and genitourinary mucosal
  • α-blockers and vasodilators — mechanism: Erec-                          toxicity.
      tion = cholinergic stimulation (increases blood
      in) + α2-antagonism (decreases blood out):
      − Guanethidine (α2-antagonism)                                     Continuous
      − Hydralazine (α2-antagonism)                                     arteriovenous
      − Labetalol (α2-antagonism)                                      hemoperfusion
      − Phenothiazines (α2-antagonism)                                 Hemoperfusion
      − Prazosin (α2-antagonism)
      − Trazadone (α2-antagonism)                                        Hemodialysis
      − Yohimbine (α2-antagonism)
  •   Miscellaneous:                                                   Plasmapheresis

      − Androgens                                                           Peritoneal
      − Anticoagulants                                                       dialysis
      − Cantharidin
      − Nitric oxide agonists
                                                                     activated charcoal
abortifacients                                                            Endogenous
                                                                          clearance of
  • Quinine: Oxytocic anti-malarial.                                                      0          50         100    150        200      250
  • Misoprostel: Synthetic PGE , oxytocic        2α
                                                              used                                                mL/min
      for therapeutic abortions.
  •   Mifepristone (RU 486): “Morning-after” pill                    FIGURe 8.3 Theophylline overdose in pregnancy.
      (Plan B®), an antiprogesterone that must be                    Hemoperfusion offers the most rapid method for extra-
      combined with PGE for therapeutic abortions.                   corporeal clearance of theophylline when ingested in
                                                                     toxic amounts during pregnancy.

144 | Color Atlas of Human Poisoning and enenoming
   Pharmacokinetics of Pregnancy
Factors Promoting Increases in                         Placental transfer
     Free Drug Concentration                           FDa Use-in-Pregnancy ratings
Increased Drug absorption
                                                         • A — Human randomized control trials (RCTs)
  • Reduced gastric emptying times                           show no risk
  • Reduced gastrointestinal tract motility                  − Example: prenatal vitamins (except vitamins
  • Increased gastrointestinal content–mucosal                  A, E, and D in high doses)
      contact times                                      •   B — Animal studies show no risk
  •   Increased skin and mucosal perfusion                   − Example: Acetaminophen (APAP)
  •   Increased respiratory rate (RR) and tidal vol-     •   C — Risk in humans uncertain
      ume (TV)                                               − Example: Albuterol
                                                         •   D — Clear evidence of risk in humans
                                                             − Example Tetracyclines
Increased Drug Distribution                              •   E — Use in pregnancy is contraindicated
                                                             − Example: Isoretinoin
  • High cardiac output                                  •   X — Known teratogen
  • Reduced protein (albumin) binding                        − Example: Iodine, quinine
  • Reduced hepatic biotransformation
  • Increased free fatty acids (FFAs), which release   Mechanisms of Placental transfer
      stored lipophilic drugs (benzodiazepines) and
      displace bound drugs
                                                         • Factors    promoting increased passive diffusion
                                                             across the placental barrier:
Factors Promoting Decreases                                  − Low molecular weight
in Free Drug Concentration                                   − High lipid solubility
                                                             − Low ionization
Increased Drug Excretion                                     − Reduced protein binding
                                                         •   Ion trapping of weak acids in the lower pH
  • Increased extracellular fluid volume (ECFV)              of fetus (7.25–7.30): Valproate (valproic acid),
  • Increased renal blood flow (RBF)                         phenytoin, isoretinoin (isoretinoic acid),
  • Increased glomerular filtration rate (GFR)               thalidomide.
  • Increased urine output                               •   Near-term maternal changes: Increased levels
                                                             of free fatty acids (FFAs) release maternal fat-
                                                             stored drugs. Example: benzodiazepines (BZs).
Placental Barrier Effect                                 •   Near-term fetal changes: Increased serum albu-
                                                             min = increased fetal drug binding near term.
  • Placental biotransformation of drugs
  • Placental ion trapping of acidic drugs             FDa Category E and X Drugs

                                                                         FDA Category E =
                                                             Contraindicated Drugs → Fetal Outcomes:

                                                         • Aminoglycosides:     Deafness

                                                                Reproductie and Perinatal toxicology | 145
  • Anticonvulsants:     Craniofacial defects (CFDs)     • Ethanol: Fetal alcohol syndrome, CFDs
      and neural tube defects (NTDs)                     • Lithium: Ebstein’s anomaly
  •   Antineoplastics: Chromosomal damage and            • Misoprostel: Short limbs, Moebius syndrome
      mutations                                          • Methotrexate: CFDs
  •   Antithyroids, iodine: Neonatal hypothyroidism      • Methyl mercury: Minimata disease
      (cretinism) and goiter                             • Phenytoin and retinoids: CFDs
  •   NSAIDs: Premature closure of the patent duc-       • Tetracyclines: Dark teeth staining
      tus arteriosus (PDA)                               • Thalidomide: Phocomelia
  •   Progestogens      and    androgens:     Female     • Valproate: CFDs and NTDs
  •   Sulfonamides:        Neonatal jaundice and
      kernicterus                                      teratogenic Syndromes
  •   Sulfonylureas: Neonatal hypoglycemia
                                                         • Fetal Hydantoin Syndrome
                                                         • Fetal Valproate Syndrome
  FDA Category X =
Known teratogens → Fetal Outcomes:
                                                         • Moebius Syndrome (vascular        disruption of
                                                             limbs secondary to misoprostel and cocaine)
                                                         •   Minimata Disease (congenital methyl mercury
  • Carbamazepine: CFDs and NTDs                         •   Fetal Isoretinoin Syndrome (Accutane®
  • Cocaine: Intrauterine growth retardation, isch-          embryopathy)
      emic limb reduction, and autoamputation
  • Coumarins: Fetal warfarin syndrome                   •   Fetal Warfarin Syndrome
  • Diethyl-stilbesterol (DES): Vaginal adenosis and

146 | Color Atlas of Human Poisoning and enenoming
  Acute Poisoning in Pregnancy
epidemiology                                              Neonatal toxicokinetics

 • 2–12%      of women who attempt suicide are              • Increased    dermal absorption: Hexachloro-
     pregnant.                                                  phene-vacuolar encephalopathy, aniline dyes
 •   1–5% of pregnancy deaths are results of over-              may cause methemoglobenemia (MetHb),
     dose suicides with over-the-counter and pre-               iodine-containing antiseptics may cause
     scription medications.                                     hypothyroidism.
 •   Analgesics, vitamins, iron, psychotropics, and         •   Increased protein binding: Sulfonamides and
     theophylline account for 50–79% of drug over-              ceftriaxone displace bilirubin from albumin
     doses in pregnancy.                                        and cause kernicterus in neonates.
 •   Warning: Chronic exposures to ethanol and              •   Reduced hepatic P-450 metabolism: High
     most anticonvulsants will cause CFDs (carba-               concentrations of phenytoin, phenobarbital,
     mazepine, phenytoin, valproate) and/or NTDs                theophylline cause reduced glucuronidation
     (valproate).                                               of chloramphenicol with resulting gray baby
                                                                syndrome; benzyl alcohol = gasping baby
General Management                                          •   General management: No ipecac or lavage due
                                                                to existing electrolyte and temperature losses;
 • Ipecac is contraindicated due to excessive vom-              consider exchange transfusion > hemodialysis >
     iting-induced risk of preterm labor.                       hemoperfusion for drug overdoses.
 • Coma      cocktails should contain dextrose and
 •   Activated charcoal (AC) is very useful because
     of gastric axis shift with gastric content stasis.
 •   Whole-bowel irrigation (WBI) with polyeth-
     ylene glycol-electrolyte solution (PEG-ELS)
     is indicated for iron (Fe) overdose to flush out
     slow-release tablets; Fe is not AC-adsorbed.
 •   Most antidotes are FDA category C or better;
     only ethanol is category D.
 •   Never withhold specific antidotes in pregnancy,
     especially NAC for acetaminophen (APAP)
     overdose, a commonly ingested suicidal agent.

                                                                   Reproductie and Perinatal toxicology | 147
   Specific Poisonings in Pregnancy
Acetaminophen (APAP)                                      Maternal Carbon Monoxide
Oerdose in Pregnancy                                     (CO) Poisoning

  • Epidemiology:    The most commonly used and            • Epidemiology:      CO is the leading cause of all
      overdosed analgesic in pregnancy.                        poison fatalities; fetal > maternal toxicity and
  •   Mechanisms: Rapid glutathione depletion first            fatality.
      in mother and then in fetus, with generation of      •   Mechanisms: (1) Fetus has 10–15% higher
      hepatotoxic n-acetyl-para-benzoquinoneimine              baseline carboxyhemoglobin (COHb) levels
      (NAPQI) metabolite; mother > fetus.                      than mother; (2) in CO poisoning, fetus devel-
  •   Management: N-acetylcysteine (NAC).                      ops 58% higher CO levels than mother; (3) both
  •   Warning: Consider induction in late third tri-           maternal and fetal PO2s reduced by COHb, fetal
      mester due to high case fatality rates (CFRs).           (normal fetal PO2 = 20–30 mmHg) > mother; (4)
      Spontaneous abortion or preterm labor often              left shift of O2Hb dissociation curve provides
      occur within weeks of successful treatment               reduced tissue O2; (5) cellular hypoxia results
      with NAC.                                                from inhibition of mitochondrial cytochrome
                                                           •   Management: Hyperbaric oxygen therapy.
Iron Oerdose in Pregnancy

  • Epidemiology:        Another common overdose
      in pregnancy; maternal > fetal toxicity, with
      maternal fatalities resulting from placental bar-
      rier blocking large Fe transfers to fetus.
  •   Mechanisms: Most Fe remains in the mater-
      nal circulation and can be chelated with defer-
      oxamine, which is only minimally transferred
      across the placenta.
  •   Management: Initial deferoxamine chelation;
      whole-bowel irrigation (WBI) with polyethyl-
      ene glycol-electrolyte solutions (PEG-ELS) for
      massive and slow-release Fe tablet overdoses as
      Fe is not adsorbed to AC.

148 | Color Atlas of Human Poisoning and enenoming
   theophylline Oerdose
   in Pregnancy
Pharmacology                                                  − Primidone
                                                              − Rifampin
  • Serum levels: Therapeutic levels 5–15 mcg/mL;             − Cigarette and marijuana smoking
      toxic >20 mcg/mL; hemoperfusion indicated
                                                          •   Metabolism reduced by (toxicity possible):
      levels >90 mcg/mL anytime; and >40 mg/mL
                                                              − Cimetidine
      with seizures, arrhythmias, refractory vomit-
                                                              − Quinolone antibiotics
      ing, or hypotension.
                                                              − Macrolide antibiotics
  •   Mechanisms: Antagonizes adenosine to dimin-
                                                              − Mexilitene
      ish histamine release and inhibits phosphodi-
                                                              − Verapamil
      esterase to increase cAMP activity and release
                                                              − Reduced hepatic perfusion:
      catecholamines promoting bronchodilation and
                                                                − Advancing age
      reversing bronchospasm = smooth muscle relax-
                                                                − Intercurrent infections
      ation, peripheral vasodilation, sympathetic car-
                                                                − Congestive heart failure
      diovascular and CNS stimulation.
                                                                − Hepatic failure
  •   Metabolic: Low volume or distribution (0.5
                                                         Management: theophylline Oerdose
      L/kg); 50% protein bound; 90% P-450 bio-
      transformed to inactive metabolites; 10% renal      • Initial assessment:
      excretion.                                            − ABCs and ECG monitoring.
                                                            − Labs: Theophylline level,         CBC, electro-
                                                                 lytes, Ca, glucose, BUN, creatinine, clotting
toxicity                                                         studies.
                                                              − Avoid β -mimetics (high heart rate,
  • Forme      fruste: Severe nausea and vomiting,               hypotension).
                                                              − Avoid ipecac and most antiemetics, espe-
      tachyarrhythmias, seizures, hypotension, hypo-
      kalemia, metabolic acidosis.                               cially phenothiazines (increased arrhyth-
  •   Cardiovascular: Tachyarrhythmias from β1
                                                                 mias and required seizure threshold).
                                                              Gastrointestinal decontamination:
      stimulation, hypotension from β2 stimulation.
  •   Gastrointestinal: Severe nausea and vomiting,           − Gastric emptying: No ipecac, granisetron
      hypokalemia, hypovolemia.                                  > ondansetron (5-HT blockers) > metoclo-
  •   CNS: Anxiety, tremor, agitation, hyperventila-             pramide for severe vomiting; hemoperfusion
                                                                 for refractory vomiting.
      tion, seizures — all resulting from loss of ade-
      nosine’s anticonvulsant activity.                       − Orogastric lavage: Best to administer AC
  •   Metabolic: Hypokalemia, hypocalcemia, hypo-                and sorbitol; lavage will be limited by slow-
                                                                 release tablets, bezoars, and concretions.
      phosphatemia, metabolic acidosis.
                                                              − AC: 1–2 g/kg, + sorbitol (1 g/kg).
                                                              − MDAC: 0.5 g/kg every 2 hours, no cathartics.
theophylline Metabolism                                       − WBI (whole-bowel irrigation): For sus-
                                                                 tained-release preparations.
                                                              − Consider hemoperfusion: For levels >40
  • Metabolism    increased by (lack of efficacy                 mcg/mL, complicated by seizures, vomiting,
      possible):                                                 hypotension, ventricular arrhythmias; defi-
      − Carbamazepine                                            nite hemoperfusion for levels >90 mcg/mL
      − Phenobarbital                                            anytime.
      − Phenytoin

                                                                  Reproductie and Perinatal toxicology | 149
Specific Management:                                     theophylline enhanced elimination
theophylline Oerdose
                                                          • Acute theophylline toxicity:
  • CNS Toxicity:                                           − Acute charcoal hemoperfusion indications:
    − Agitation and      restlessness, then seizures:       − Theophylline level >90 mcg/mL at any
        D50W + thiamine 100 mg for hypoglycemia;                 time.
        IV benzodiazepines (BZs) > barbiturates for           − Theophylline level >40 mcg/mL when com-
        seizures.                                                bined with:
      − Refractory seizures: Secure airway; BZs                  − Seizures
        and barbituates; consider MRs; control ven-              − Hypotension, refractory to fluid loading
        tilation; avoid phenytoin with quindine-like             − Ventricular dysrhythmias
        tachyarrhythmias.                                        − Protracted vomiting, refractory to
      − Status epilepticus: Aggressive charcoal                      antiemetics
        hemoperfusion to reduce theophylline levels       •   Chronic theophylline toxicity:
        <40 mcg/mL.                                           − Risks increase with advancing age, intercur-
  •   CV toxicity:                                               rent illnesses/infections, and reduced hepatic
      − Hypotension: Fluid load with normal saline               perfusion.
        or Ringer’s lactate (RL); as vasopressors, use        − No role for either emesis or orogastric lavage,
        pure α -agonists, norepinephrine or phen-                unless to instill AC via orogastric tube.
        ylephrine, titrated to effect; avoid mixed            − AC and MDAC for cardiovascular-stable
        agonists with potential for β2-mediated                  patients.
        vasodilation and hypotension.                         − Charcoal HP for unstable patients and for
      − Tachydysrhythmias: Restore electrolyte bal-              AC failures.
        ance, especially K and Ca; as antiarrhythmics,        − Monitor theophylline levels every 4–6 hours
        use adenosine and calcium channel blockers               until <20 mcg/kg.
        (CCBs) (verapamil, diltiazem) rather than β -
        blockers (bronchospasm, hypotension); con-
        sider lidocaine but it may reduce the seizure
        threshold; charcoal hemoperfusion for PVCs,
        which could precipitate VT.

150 | Color Atlas of Human Poisoning and enenoming
  Substance Abuse in Pregnancy
Alcohol Abuse and Fetal Alcohol                           Opioid Abuse in Pregnancy
Syndrome (FAS)
                                                           • Epidemiology:       0.2% of pregnant women use
 • Epidemiology:        20% of pregnant women con-             heroin > methadone; 75,000 neonates/year
     sume alcohol; 1–2% consume >4 drinks/day;                 are exposed to opioid abuse in utero and 60–
     FAS = >2–3 ounces of ethanol/day (4–6 drinks/             90% manifest neonatal withdrawal syndrome
     day) or with frequent binge drinking.                     (NWS).
 •   Mechanism of FAS: Craniofacial dysmorpho-             •   Maternal complications:      Hepatitis, sepsis,
     genesis = early teratogenesis; mental retardation         septic emboli, subacute bacterial endocarditis,
     and cortical defects occur later in gestation.            STDs, AIDS.
 •   FAS: Intrauterine growth retardation (IUGR),          •   OB comp: Spontaneous abortion (SAB), prema-
     microcephaly, epicanthal folds, short palpebral           ture delivery, stillbirth.
     fissures, cleft palate, short philtrum — maxillary    •   Neonatal complications: Small for gestational
     hypoplasia, micrognathia, mental retardation.             age.
                                                           •   Neonatal withdrawal syndrome (NWS): Occurs
                                                               within 24 hours for heroin, but delayed for days
Cocaine Abuse and Fetal Cocaine                                with methadone abuse; increased incidence
Syndrome (FCS)                                                 of sudden infant death syndrome (SIDS) for 2
 • Epidemiology:     1% of U.S. women use cocaine
     during pregnancy.
                                                          Neonatal Withdrawal Syndrome (NWS)
 •   Mechanism of FCS: Vasospastic and vascular
     disruptive effects on uteroplacental and fetal
     end circulations.                                     • Mechanism:        Chronic opioid use leads to tol-
 •   FCS: Intrauterine growth retardation (IUGR),              erance, dependence, and high number of CNS
     microcephaly, neurobehavioral abnormalities,              α2-receptors.
     vascular disruptive phenomena = limb autoam-          •   Definition: WITTHHDDRAAWAL = Wakeful-
     putation (Moebius syndrome), seizures, cere-              ness, Irritability, Tremulousness-low Tempera-
     bral infarctions, visceral and genitounirnary             ture-Tachypnea, Hyperactivity-Hyperreflexia,
     defects.                                                  Diarrhea-Diaphoresis, Rhinorrhea-Respiratory
 •   OB complications: Abruptio placenta, prema-               distress, Apnea-Autonomic dysfunction, Weight
     ture delivery.                                            loss, Alkalosis (respiratory), and Lacrimation.
                                                           •   Treatment: Tincture of opium (paregoric) for
                                                               withdrawal seizures.

                                                                  Reproductie and Perinatal toxicology | 151
toxicokinetics                                           Absolutely Contraindicated Drugs
                                                         in Breast-Feeding Mothers
  • Only free drugs are available for transfer from
      maternal plasma to breast milk.                      • Bromocriptine: Decreased lactation
  • Membrane diffusion factors determine transfer:         • Antineoplastics and radiopharmaceuti-
      Low molecular weight, increased lipid solubil-           cals: Carcinogenesis, myelosuppression,
      ity, decreased ionization, and limited protein           immunosuppression
      binding all promote diffusion across membrane        •   Ergotamines: Increased neonatal vomiting and
      barriers.                                                seizures
  •   Lipid solubility = number-one determinant of         •   Lithium
      milk transfer.                                       •   Metronidazole
  •   High-molecular-weight drugs, like heparin and        •   Substances of abuse
      insulin, do not transfer.                            •   Chloroamphenicol: Gray-baby syndrome
  •   Breast milk, with a lower pH = 7.0, will concen-
      trate weak bases, like sulfacetamide.
                                                         Relatiely Contraindicated Drugs

                                                           • Phenobarbital
                                                           • Sulfonamides:   Hemolysis in G-6-PD deficient

152 | Color Atlas of Human Poisoning and enenoming
                                                                                 Chapter 9

                Poisonings with Analgesic
                Adjuants, Psychotropics,
                 Sedatie-Hypnotics, and
                         Illicit Substances

Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 153
                                                                                                Part 1:

                          Analgesic Adjuants,
                   Psychotropics, and Sedatie-
                            Hypnotics: Outline
Caffeine                                                 Pharmacology
  Therapeutic uses
  General Overdose Management                            History
ergotamines                                              Toxicity
                                                         Enhanced elimination
  Therapeutic uses
  General overdose management                            Classification
                                                         Sodium channel blockers
Cyclic antidepressants (CAs)                             GABA inhibition enhancers
                                                         Combined sodium channel blockers and GABA
  First generation vs. second generation
SSRIs s. Neuroleptics                                   Classification
  Diagnosis and management
Monoamine oxidase inhibitors
                                                         Overdose management
                                                         Bromates vs. bromides
  MAOIs and drugs
  MAOIs and foods
                                                         Benzodiazepines (BZ)
                                                         “Date-rape” drugs

        Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 155
Ethchlorvynol (Placidyl®)
Carbamates and bromides
Withdrawn sedative-hypnotics
New anxiolytics
Short-term anesthestics
Pharmacology                                             Physiology
   Sources: Plant-derived methylxanthines (caffeine,        Cardiovascular: Tachydysrhythmias, PVCs, cere-
theophylline, theobromine); extracts of Coffea ara-      bral vasoconstriction, hypertension, and increased
bica (coffee), Thea sinensis (tea), Cola acuminata       cardiac output.
(cola).                                                     Gastrointestinal: Increased gastric acid and pepsin
   Metabolic: Hepatic demethylation by CYP-450 to        secretion, increased small intestine secretions.
simpler methylxanthines.                                    Metabolic: Respiratory alkalosis, increased
   Caffeinism: Syndrome of miosis, headache, tachy-      cAMP, reduced serum K and Ca leads to osteoporo-
cardia, palpitations, and delirium.                      sis, increased muscle contractility, tremors, increased
                                                         urinary catecholamines.

  tABLe 9.1 Dependency Syndromes and Caffeine Doses
  Dependency Syndromes                                   Caffeine Doses: mg/d (cups/d)
  Nontoxic: increased alertness, decreased drowsiness    Nontoxic: 50–200 mg/d (1–2 cups)
   and fatigue
  Caffeinism: miosis, headache, tremors, palpitations,   Caffeinism: 200–500 mg/d (2–4 cups)
   nervous irritability
  anxiety syndrome: hyperactivity, restless legs         anxiety: >500 mg/d (4–6 cups)
  Hypochondriasis syndrome: body discomfort,             Hypochondriasis: 500–750 mg/d (>6 cups)
   myalgias, chronic pain, fibromyalgia
  Insomnia/headache syndrome                             Insomnia: 500–750 mg/d (>6 cups)
  Depressive syndrome                                    Depressive: >750 mg/d (>6 cups)
  Withdrawal syndrome: headache, nausea, yawning,        Withdrawal: >235 mg/d (>2.5 cups)
   rhinorrhea, drowsiness, lethargy, irritability

                                                                      Figure 9.1 Miosis, Right Eye. Pupillary
                                                                      constriction or miosis characteristic of
                                                                      caffeine, cholinergic, ergotamine, opiod
                                                                      and phencyclidine (PCP) toxidromes.

         Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 157
therapeutic Uses                                          General Oerdose Management

  • Analgesic   adjuvant: Combined with APAP,               • Airway protection.
      ASA, and ibuprofen.                                   • Gastrointestinal decontamination: Early syrup
  •   Migraine headaches: Combined with ergots.                 of ipecac, activated charcoal (AC) and cathartic,
  •   Diet, weight loss: Combined with amphet-                  consider multi-dose activated charcoal (MDAC)
      amines and formerly PPA.                                  without additional cathartic.
  •   Newborn apnea-bradycardia syndrome.                   •   Hemoperfusion: As for all methylxanthines,
                                                                including theophylline.

                                                          Specific Drug therapy
  • Cardiovascular:     SV and ventricular tachydys-
      rhythmias, hypertension.                              • Anticonvulsants:     Benzodiazepines     (BZs)   >
  •   Gastrointestinal: Increased gastric acidity leads         barbiturates.
      to peptic ulcer, nausea and vomiting.                 • Antidysrhythmics: Beta-blockers, calcium chan-
  •   Central nervous system (CNS): Agitation, rest-            nel blockers (CCBs).
      lessness, tremors, seizures.                          • Antiulcerogenics:    H 2-blockers, proton (H)-
  •   Metabolic: Reduced serum K and Ca (chronic                pump inhibitors.
      osteoporosis = 2 cups/day, 100 mg/day).               •   Antiemetics: Ondansetron (5-HT-blocker) >
  •   Muscle: Increased contractility, high creatine            metoclopramide (dopamine and 5-HT-blocker
      phosphokinse (CPK), rhabdomyolysis.                       = chorea and dystonia possible side effects).
                                                            •   Sedatives: BZs > barbiturates.

158 | Color Atlas of Human Poisoning and enenoming
Pharmacology                                                  • Uterine    contraction:    Ergonovine,     methyl-
 • Source:    Plant alkaloids derived from the fun-
     gus, Claviceps purpurea, which contaminates
     rye and other grains.
 •   Metabolic: Poor gastrointestinal absorption,
     significant first-pass hepatic metabolism, vol-          • Central effects: Agitation, headaches, hallucina-
     ume of distribution (Vd) = 2 L/kg, half-life =               tions, cerebral ischemia, fixed miosis, seizures,
     1.4–6.2 hours.                                               facial twitching, nausea and vomiting.
 •   Acute ergotism: Agitation, restlessness, nausea,         •   Peripheral effects: Hypertension and barorecep-
     vomiting, headache, delirium, fixed miosis, sei-             tor-mediated bradycardia.
     zures, cerebral ischemia.                                •   Ischemic effects: Angina then myocardial
 •   Chronic ergotism: St. Anthony’s fire = periph-               infarction, burning and gangrenous extremities
     eral vasospasm-gangrene, burning extremities,                (St. Anthony’s fire), hemorrhagic vesiculations
     purpura, angina, abortion.                                   and bullae, mesenteric and renal infarction.

Physiology                                                  General Oerdose Management

 • CNS: Serotonin reuptake inhibitor.                         • Airway protection during seizures.
 • PNS: Alpha-agonist causing vasospasm        in all
                                                              • Gastrointestinal decontamination:     Syrup of
                                                                  ipecac and orogastric lavage often contraindi-
     vascular beds: cerebral > cardiovascular > mes-              cated due to severe vomiting, AC and sorbitol
     enteric and renal > peripheral vasospasm.                    cathartic.
 •   Cardiovascular: Hypertension with reflex                 •   Consider MDAC.
 •   Gastrointestinal: Centrally induced severe nau-
     sea and vomiting.                                      Specific Drug therapy

                                                              • Cardiac,     cerebral, mesenteric-renal ischemia:
therapeutic Uses                                                  IV nitroglycerin (NTG), sodium nitroprusside,
                                                              •   Mild peripheral vasospasm and ischemia: Orally
 • Migraine:     Ergotamine, ergotamine and caf-                  prazosin, captopril, nifedipine (sublingual).
     feine (Cafergot®), methysergide (retroperitoneal         •   CNS seizures and hallucinations: BZs.
     fibrosis).                                               •   Hypercoagulability: Heparin, dextran, throm-
 •   Lactation inhibition: Bromocriptine.                         bolytics, clot extraction (chronic).

                                                            Figure 9.2 Electrocardiographic Evidence of Tricyclic
                                                            Antidepressant Overdose. Electrocardiogram (ECG)
     TCA DO: Prominent S wave in I and aVL, R wave in aVR   tracing in a patient with a history of suicide attempt
                                  aVR                       by tricyclic antidepressant (TCA) overdose that dem-
                                                            onstrates widened QRS complexes indicative of car-
                                                            diac sodium channel blockade that should correct with
                                                            intravenous sodium bicarbonate administration. In
                                                            addition, the ECG demonstrates a prominent S wave
                                                            in Lead I and aVL and a prominent R wave in aVR, char-
                                                            acteristic of TCA overdose.

         Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 159
  tABLe 9.2 Antidepressants vs. Antipsychotics
  Antidepressants                                     Antipsychotics (neuroleptics)
  tricyclic and other cyclic antidepressants          Phenothiazines
  Selective serotonin reuptake inhibitors (SSrIs)     thioxanthenes
  atypical antidepressants                            Butyrophenones
  Monoamine oxidase inhibitors (MaOIs)                New neuroleptics

160 | Color Atlas of Human Poisoning and enenoming
   Cyclic Antidepressants (CAs)
epidemiology                                               SSrIs
Cas — First Generation
                                                             • CNS: Selectively inhibit serotonin reuptake, do
                                                                 not inhibit dopamine or norepinephrine reup-
  • 1987: 500,000 TCA overdoses/year.                            take, much safer profiles than TCAs.
  • 1995: 12% of all intensive care unit       (ICU)
                                                             •   No quinidine-like effects.
      admissions were due to TCA overdose.
  •   Typical overdose: Female, age 20–29, single,
                                                             •   No anticholinergic effects.
      employed, no history of drug abuse or prior sui-
                                                             •   No alpha blockade.
      cide attempt.
                                                             •   Metabolism: Large Vd, half-life = 1–6 days, not
  •   High case fatality rate (CFR): 70%.

                                                           First Generation s. Second Generation
SSrIs — Second Generation
                                                           First generation (tCas)
  • SSRIs have now surpassed TCAs as much safer
      frontline antidepressants with much lower              • General: Block both NE and serotonin reuptake,
      CFRs.                                                      cause quinidine-like prolonged QRS complex,
  •   SSRIs have (1) no quinidine-like effects, which            anticholinergic, α -blockers, and epileptogenic
      slow cardiac conduction and widen the QRS              •   Examples:
      complex; (2) no alpha-blocking effects (ortho-             − Amitriptyline (Elavil®)
      static hypotension); and (3) no anticholinergic            − Clomipramine (Anafranil®)
      activity.                                                  − Desipramine (Norpramin®)
  •   SSRIs are epileptogenic only in large overdose.            − Doxepin (Sinequan®)
                                                                 − Imipramine (Tofranil®)
                                                                 − Nortriptyline (Pamelor®)
tCas                                                       Second generation (SSrIs, etc.)

  • Cardiovascular:      TCAs inhibit voltage-gated
                                                             • General: Not Na-channel blockers, not anticho-
      myocardial Na channels (quinidine-like effects)
                                                                 linergics, not α -blockers, rarely epileptogenic
      slowing conduction and prolonging QRS
                                                             • Example SSRIs: Fluoxetine (Prozac )    ®

  •   CNS: Block histamine, dopamine, and mus-
                                                             • Paroxetine (Paxil ), Sertraline (Zoloft )
                                                                                   ®                      ®

      carinic cholinergic receptors; inhibit reuptake
                                                             • Example SSRI and alpha-blocker: Trazodone
      of both norepinephrine (NE) and serotonin at
      adrenergic nerve terminals.
                                                             •   Example SSRI and NE/dopamine reuptake
                                                                 inhibitor: Venlafaxine (Effexor®)
  •   Peripheral: α-Adrenergic blockers (orthostasis).
                                                             •   Example NE/dopamine reuptake inhibitor:
  •   Metabolism: Very large Vd = 10–50 L/kg, exten-
                                                                 Buproprion (Wellbutrin®, Zyban®)
      sive first-pass hepatic metabolism, long half-life
      = 1–4 days, not dialyzable.

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 161
toxicity                                                        hypertonicity and lead-pipe hyperrigidity, trem-
                                                                ors, akinesia and choreoathetosis.
tCas                                                        •   Etiology: Central dopamine receptor blockade
                                                                with severe extrapyramidal reactions rang-
  • Cardiac:     Quinidine-like (IA) effects = block            ing from dystonia to lead-pipe rigidity and
      cardiac Na channels, reduced conduction and               choreoathetosis.
      prolong QRS; anticholinergic effects = tachy-         •   Treatment: DC neuroleptics, cool in ice, BZs,
      dysrhythmias; direct myocardial depression due            consider dantrolene; usually occurs within first
      to Na and K channel blockade.                             week of treatment — if neuroleptics indicated,
  •   CNS: NE and dopamine reuptake inhibitor,                  select one from another class.
      agitation, hallucinations, confusion, sedation,
      coma, seizures, central and peripheral anticho-      Diagnosis and Management
      linergic effects.
  •   Peripheral vascular: α -Adrenergic blockers =
  •   Serotonin syndrome: Clomipramine only.
                                                            • Diagnosis:     ECG-increased QT, QRS > 100
                                                                msec, sinus tachycardia, R wave — aVR; serum
                                                                levels > 1000 ng/mL.
SSrIs                                                       •   Initial management: No ipecac due to seizures;
                                                                orogastric lavage; AC, 1 g/kg and sorbitol, sec-
  • Cardiovascular:      No cardiotoxicity or alpha             ond dose AC — no cathartic.
      blockade.                                             •   Specific management: Na and hypervent low
  • CNS:     Jitteriness, dizziness, blurred vision,            TCA binding to Na channels; NaHCO3 1–2
      depressed mental status, and rarely seizures.             mEq/kg bolus, then 3 amp/L D5W infusion
  •   Gastrointestinal: Anorexia, nausea and vomiting.          every 4–6 hours = art pH 7.50–7.55. Seizures:
  •   Serotonin syndrome: All SSRIs can cause the               IV BZs. Hypotension: LR-NS load, direct vaso-
      serotonin syndrome.                                       pressors (NE), dopamine contraindicated due
                                                                to vasodilation.
SSRIs vs. Neuroleptics
Serotonin Syndrome

                                                            • Diagnosis: Clinical = nausea, vomiting, dizzi-
  • Definition: An acute idiosyncratic reaction due             ness, blurred vision, tachycardia, rarely seizures
      to hyperstimulation of central serotonin recep-           in massive overdose. No specific ECG changes.
      tors by increased synaptic serotonin levels; char-    •   Treatment: Ipecac contraindicated due to men-
      acterized by agitation, mental status changes,            tal status depression and low risk of seizures;
      diaphoresis, tremor, rigidity, myoclonus, hyper-          dextrose and thiamine bolus; oral AC, 1 g/kg
      reflexia, incoordination, and seizures.                   and sorbitol, 1 g/kg; consider MDAC for co-
  •   Etiology: (1) 5-HT breakdown inhibitors                   ingestions. SSRI overdoses are rarely life-threat-
      — MAOIs; (2) 5-HT RIs — SSRIs and trama-                  ening, unless there are co-ingestions.
      dol; (3) 5-HT agonists or precursors — lithium
      and buspirone; (4) 5-HT releasers — MDMA
      (Ecstasy), meperidine, and dextromethorphan.
  •   Treatment: External cooling, muscle relaxants
      — BZs and NMBs; self-limited and resolves
      within 4 hours.

Neuroleptic Malignant Syndrome

  • Definition:   A subacute idiosyncratic reaction
      that develops during early tx with neurolep-
      tics from three classes (phenothiazines, thio-
      xanthenes, butyrophenones); characterized by
      mental status changes, hyperthermia, muscular

162 | Color Atlas of Human Poisoning and enenoming
   Monoamine Oxidase Inhibitors
Pharmacology                                             MAOIs and Amines
                                                         Safe = Direct-acting Sympathomimetics
  • Mechanism: A class of ADs that inhibit both
      hepatic (gastrointestinal) MAO-A and CNS
      MAO-B to cause mood elevation by an increase
                                                           • Epinephrine
      in all CNS monoamines: NE, epinephrine,
                                                           • Norepinephrine
      Dopamine and 5-HT (Serotonin).
                                                           • Isoproterenol
  •   Types (all orally): (1) Old irreversible MAOIs
                                                           • Methoxamine
      = phenelzine, tranylcypromine, selegiline
                                                           • Phenylephrine
      (anti-Parkinson drug); and (2) new reversible
      MAOIs.                                             Unsafe = Indirect-acting and Combined
                                                           • Indirect-acting:
  • Mechanism: Increased norepinephrine and epi-             − Amphetamines
      nephrine effects = tachycardia and hyperten-
                                                             − Phenylpropanolamine
      sion, headache, angina, myocardial infarction
                                                             − Fenfluramine
      (MI), cerebrovascular accident (CVA), cardio-
                                                             − Phentermine
      vascular collapse. Increased 5-HT and Dopa-
                                                             − Tyramine
      mine effects = agitation, delirium, obtundation,
                                                           • Combined direct–indirect:
      nystagmus, hyperreflexia, tremors, myoclonus,
                                                             − Dopamine
      muscle rigidity, hyperthermia, diaphoresis, sei-
                                                             − Metaraminol
      zures, respiratory depression.
                                                             − Ephedrine
  •   Interactions: (1) Drug interactions: all sympa-
                                                             − Mephentermine
      thomimetic drugs, SSRIs, cocaine some opioids
      (codeine, meperidine, and dextromethorphan);
      (2) foods high in tyramine = aged cheeses, red
      wines, pickled or smoked meats and fish.

  tABLe 9.3 MAOIs and Drugs
  Interacting Drugs                                      Manifestations of Interactions
  Indirect sympathomimetics                              Hypertensive crisis and death
  l-dopa and tryptophan                                  Hypertension, not deadly
  antidepressants (tCas, SSrIs)                          Disorientation, seizures, death
  Opioids (meperidine, dextromethorphan)                 Hyperthermia, death
  Cocaine                                                Hyperthermia, death
  theophylline > caffeine                                Hyperthermia, potentially deadly
  Codeine and barbiturates                               Sedation potentiation
  Hypoglycemic agents                                    Hypoglycemia potentiation

         Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 163
MAOIs and Foods                                       Diagnosis
Foods to avoid
                                                        • Delayed onset: Consistently delayed (12 hours)
                                                            onset of symptoms or few symptoms post
  • High tyramine foods:                                    overdose.
    − Aged cheeses                                      •   Early symptoms: NE/Epi = tachycardia, hyper-
    − Red wines                                             tension, headache; 5-HT and Dopa = agitation,
    − Yeast                                                 delirium, obtundation, nystagmus, tremors,
    − Smoked and pickled meats and fish                     and hyperthermia.
                                                        •   Late symptoms: NE/Epi = angina, MI, CVA;
                                                            5-HT and Dopa = muscular rigidity, seizures,
Foods to Beware of and Safe Foods
                                                            rhabdomyolysis, myoglobinuria, renal failure,
                                                            DIC, and ARDS.
  • Beware: moderate tyramine:
    − Avocados
    − Beer                                            Management
    − Meat extracts
  • Low tyramine safe foods:                            • General:      Syrup of ipecac contraindicated due
    − Cottage and cream cheeses                             to seizures; orogastric lavage and AC; seizure
    − Chocolate and caffeine                                control and muscle relaxation with benzodiaz-
    − Distilled alcohols                                    epines; aggressive cooling for hyperthermia.
    − Fruits                                            •   Specific: For hypertension, use short-acting
    − Soy sauce                                             vasodilators (SCN); and for hypotension, use
    − Yogurt and sour cream                                 only direct-acting vasopressors (NE and phen-
                                                            ylephrine). Bretylium is contraindicated due to
                                                            its initial release of NE.

164 | Color Atlas of Human Poisoning and enenoming
Classification                                             • Chronic     dopamine receptor blockade caus-
                                                               ing increased synaptic dopamine = tardive
First Generation (all Cause NMS)                               dyskinesias.
                                                           •   Neuroleptic malignant syndrome = increased T
  • Phenothiazines:                                            and EPS.
    − Chlorpromazine (Thorazine )           ®

    − Prochlorperazine (Compazine )             ®

    − Fluphenazine (Prolixin )          ®               toxicology
  • Thioxanthenes:                                      toxicities
    − Thiothixine (Navane )         ®

  • Butyrophenones:
    − Droperidol (Inapsine )        ®                      • Cardiovascular:    Quinidine-like effects = pro-
    − Haloperidol (Haldol )         ®                          longed QT, PR, and QRS complex; direct
                                                               myocardial depression; alpha blockade with
Second Generation (No NMS, except                          •   CNS: Anticholinergic and antidopaminer-
Loxipine)                                                      gic = parkinsonism, rabbit syndrome, tardive
  • Indoles                                                •   Gastrointestinal: Anticholinergic = decreased
                                                               secretions and gastrointestinal motility, leads to
  • Dibenzoxapines                                             pseudo-obstruction from concretions.
  • Loxipine (Loxitane)                                    •   GU: Priapism, urinary retention.
  • Dibenzodiazepines
  • Diphenylbutylpiperidines
  • Benzisoxazoles                                      adverse Effects
  • Risperidone (Risperdal )    ®

                                                           • Acute     dystonia: Oculogyric crisis, torticollis,
Mechanisms of action                                       •   Akathisia: Restlessness.
                                                           •   Parkinsonism: Classical and rabbit syndrome =
                                                               perioral tremors.
  • Dopamine receptor blockade peripherally and            •   Neuroleptic malignant syndrome: Lead-pipe
      centrally within the limbic system
                                                               rigidity, hyperthermia, choreoathetosis.
  •   Alpha-adrenergic blockade
                                                           •   Tardive dyskinesia: Choreoathetosis without
  •   Central and peripheral cholinergic blockade
                                                               hyperthermia and rigidity.
  •   Serotonin reuptake inhibition centrally

Metabolism and Major Side Effects
                                                        Diagnosis and General Management
  • Extensive hepatic metabolism to active metabo-
      lites, increased half-life.                          • Diagnosis:  Positive urine ferric chloride test;
  • Acute dopamine inhibition = parkinsonism syn-              radiopaque phenothiazine concretions on
      drome of extrapyramidal effects, treatment =             abdominal x-ray; serum levels unhelpful.
      anticholinergics (Benzotropin [Cogentin®] and
      trihexyphenidyl [Artane®]) or antihistamines
      (diphenhydramine [Benadryl®]).

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 165
  • General management: Orogastric lavage > ipe-      Specific Syndrome Management
     cac emesis due to CNS effects; consider MDAC;
     HP and HD useless due to increased VD; car-
     diovascular support with α-agonists only, as
                                                       • Acute dystonia: Mechanism = unknown; treat-
                                                           ment = diphenhydramine, BZs.
     β-agonists cause vasodilation; NaHCO3 for
     conduction block and prolonged QRS complex;
                                                       • Akathisia: Mechanism = unknown; treatment =
                                                           same at reduced doses.
     physostigmine for central anticholinergic syn-
     drome could exacerbate conduction blockade.
                                                       • Parkinsonism: Mechanism = dopamine antag-
                                                           onism; treatment = anticholinergics at low
                                                       •   NMS: Mechanism = dopamine antagonism;
                                                           treatment = cooling, BZs, consider dantrolene.
                                                       •   Tardive dyskinesias: Mechanism = excess
                                                           dopamine activity; treatment = consider

166 | Color Atlas of Human Poisoning and enenoming
History                                                   Chronic Li toxicity

  • An     early “picker-upper” and ingredient of           • Action level: >1.5 mEq/L
      Seven-Up®.                                            • CNS > renal > endocrine:
  •   Lightest metal known that behaves like its peri-        − CNS: Mild = same; moderate = same; severe
      odic table neighbors, Na and K.                               = memory loss, psychosis, parkinsonism.
  •   A salt substitute for hypertensives prior to              −   Gastrointestinal: None.
      antihypertensives.                                        −   Cardiovascular: Myocarditis.
  •   Exhibits a very narrow therapeutic:toxic ratio.           −   Renal: Interstitial nephritis, diabetes insipi-
  •   Uses: Bipolar disorders and cluster headaches.                dus, renal failure.
                                                                −   Endocrine: Hypothyroidism, cretinism.
                                                                −   Dermal: Edema, dermatitis, ulcers.

  • Li    is rapidly absorbed and peaks in serum
      within hours.
  •   Therapeutic level = 0.6–1.2 mEq/L; acute toxic-       • Ipecac      contraindicated due to prominent
      ity >4.0 mEq/L (HD indicated); chronic toxicity           neurotoxicity.
      >1.5 mEq/L.                                           •   Orogastric lavage for retained pills.
  •   Low Vd, no protein binding, not metabolized,          •   Li is not adsorbed to AC. AC is contraindicated
      90% renally excreted, and easily dialyzable.              unless there is co-ingestion.
  •   Mechanism unknown.                                    •   Volume (NS) hydration to promote diuresis and
  •   Primary toxicity neurologic: Mental status                renal excretion.
      depression, tremor, clonus, choreoathetosis, sei-     •   WBI with PEG-ELS for sustained-release lith-
      zures, coma, parkinsonism (chronic toxicity).             ium (Lithobid®).

toxicity                                                  enhanced elimination
acute Li toxicity
                                                            • Peritoneal dialysis is contraindicated.
  • Action level: >4.0 mEq/L.                               • Hemodialysis is best, especially for high Li lev-
                                                                els (>4.0 mEq/L) and patients with CHF, pul-
  • CNS > Gastrointestinal > cardiovascular:                    monary edema, or CRF. Li rebound occurs
    − CNS: Mild-lightheadedness and tremor;                     post-dialysis.
         moderate drowsiness, tinnitus, muscle
         twitching, hyperreflexia; severe clonus, cho-
                                                            •   CAVH and CVVH are both good for slow Li
                                                                removal in mild-moderate overdoses without
         reoathetosis, seizure, coma.
                                                                rebound high [Li] with HD.
      − Gastrointestinal: Nausea and vomiting.
      − Cardiovascular: Prolonged QT, ST, T wave
  •   Renal, endocrine, Dermal: None.

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 167
Classification                                            • Side    effects: Nausea, vomiting, gingival
  • Prolonged Na-channel inactivators:                    •   Treatment: AC, MDAC, BZs for seizures, HD
                                                              and HP ineffective.
    − Carbamazepine
    − Tegretol   ®

    − Phenytoin (Dilantin )  ®
                                                        GABA Inhibition enhancers
  • GABA enhancers:
    − Barbiturates                                      Gabapentin
    − Benzodiazepines
    − Gabapentin (Neurontin )    ®
                                                          • Acute toxicity: CNS > gastrointestinal; very safe
    − Vigabatrin                                              due to lack of protein binding, no metabolic
  • Na channel blockers and GABA enhancers                    biotransformation, and 100% renal excretion.
    − Felbamate                                               − CNS: Somnolence, sedation, dizziness,
    − Lamotrigine                                                ataxia.
    − Valproic acid                                       •   Treatment: AC, all symptoms will resolve in 48
Sodium Channel Blockers
Carbamazepine                                           Vigabatrin

  • Acute toxicity: CNS > cardiovascular:                 • Acute     toxicity: CNS only,          similar   to
    − CNS: Ataxia, dysarthria, dystonia, clonus,              gabapentin.
          choreoathetosis, seizures, stupor.                  − CNS: Acute psychosis.
      −   Cardiovascular: Prolongs QT, widens QRS,        •   Chronic toxicity: Psychosis.
          torsades de pointes, VT.                        •   Treatment: Supportive.
  •   Chronic toxicity: Headache, diplopia, ataxia.
  •   Side effects: Aplastic anemia, Stevens-Johnson
      syndrome.                                         Combined Sodium Channel
  •   Treatment: AC, MDAC, abdominal x-ray for          Blockers and GABA enhancers
      concretions, NaHCO3 for wide QRS, BZs for         Felbamate
      seizures, hemodialysis ineffective.

                                                          • Acute     toxicity: Mild gastrointestinal symp-
Phenytoin                                                     toms.
                                                          •   Chronic toxicity: psychosis.
  • Acute toxicity: CNS > Gastrointestinal > endo-        •   Side effects: Nausea, vomiting, pancreatitis, ful-
                                                              minant hepatic failure (20%), aplastic anemia.
      crine > cardiovascular:
      − CNS: Ataxia, nystagmus, ophthalmoplegia,          •   Treatment: AC.
          dysarthria, hyperreflexia, depressed mental
          status, hallucinations, rarely seizures, no   Lamotrigine
          ECG changes (Class IB antidysrhythmic)
          and hypotension.
  •   Chronic toxicity: Megaloblastic anemia, aplas-      • Acute toxicity: CNS > cardiovascular:
      tic anemia, hypothyroidism, teratogenicity.           − CNS: Ataxia, nystagmus.
                                                            − Cardiovascular: Prolongs QRS complex.

168 | Color Atlas of Human Poisoning and enenoming
  • Chronic     toxicity: Nausea, headache, blurred
      vision, diplopia, dizziness, ataxia.
  •   Side effects: Stevens-Johnson syndrome, toxic
      epidermal necrolysis.

Valproic acid

  • Acute        toxicity:   Produces     hepatotoxic
  •   CNS: Lethargy, cerebral edema due to hyper-
      ammonemia from metabolite that inhibits NH3
  •   Gastrointestinal: High LFTs and high NH3.
  •   Hemetologic: Low white blood cells and
  •   Side effects: Sedation, ataxia, tremor, Reye’s-
      like fulminant hepatitis.
  •   Treatment: AC, MDAC, carnitine for high NH3,
      HD and HP ineffective.

         Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 169
Definitions                                                • Lipid-soluble barbiturates and BZs are highly
                                                               protein bound, poorly filtered renally, and not
                                                               dialyzable. BZs are hepatically biotransformed
  • Sedatives: Drugs that reduce activity, moderate            to active metabolites (oxazepam); barb met
      excitement, and exert a calming effect.
                                                               yields few active intermediates.
  • Hypnotics: Drugs that produce drowsiness and
      facilitate sleep.
  • Anxiolytics: Sedative-hypnotics that also have       Diagnosis
      anti-anxiety properties (e.g., BZs, zolpidem,
      and buspirone).                                    Physical Findings

                                                           • CNS:       Mydriasis, mild-mod ataxia, slurred
                                                               speech, incoordination leads to increased
                                                               CNS depression, stupor, coma; rarely eupho-
  • Barbiturates:   Ultra-short acting, short acting,          ria-excitation (methaqualone), toxic psycho-
      intermediate acting, long acting.                        sis (triazolam, flurazepam, glutethimide), and
  •   Non-barbiturates: BZs, alcohols, piperidinedio-          extrapyramidal effects (methaqualone).
      nes, paraldehyde, meprobamate, new anxiolyt-         •   Cardiovascular: Myocardial depression due to
      ics-zolpidem, buspirone.                                 hypotension and heart rate and smooth mus-
                                                               cle vasodilation; rarely AT and SVT (alcohols,
                                                               chloral hydrate, meprobamate).
Mechanism                                                  •   Pulmonary: Respiratory depression and arrest.
                                                           •   Metabolic: Hypothermia (barbiturates, BZs,
  • Barbiturates     and BZs: Enhance inhibitory               and bromides).
      GABA-mediated chloride currents in CNS by
      binding at different receptor sites on the GABA
                                                         Lab and X-ray Findings
      receptor–Cl ionophore complex.
  •   Barbiturates and BZs: Potentiate each other’s
      sedative, hypnotic, and anticonvulsant effects.      • Labs — to rule out other causes of stupor and
  •   BZs also exert muscle relaxant effects centrally         coma (especially metabolic and neurologic
      and peripherally.                                        causes): Electrolytes, BUN, creatinine, glucose,
  •   Antidote for BZs: Flumazanil, a pure BZ-recep-           serum alcohol and phenobarbital, LFTs, ABGs.
      tor antagonist.                                      •   Abdominal x-ray: Gastric concretions with bar-
                                                               biturates and meprobamate.
                                                           •   Endoscopy: To break up and/or remove
Pharmacology                                                   concretions.

  • SHs     induce sleep by reducing time to sleep
                                                         Pathognomonic Signs
      onset, reducing REM sleep, increasing stage 2
      non-REM sleep. In overdose, SHs depress CNS
      to stage III anesthesia.                             • Breath odor: Chloral hydrate and paraldehyde
  •   Tolerance to sedation in 1 week.                         = pear-like; ethchlorvynol (Placidyl®) = pungent
  •   Barbiturates and BZs are rapidly absorbed in SI;         plastic or vinyl smell.
      as their lipid solubility increases, blood-brain     •   Skin: (1) Barbiturate (6.0–6.5 %) (and ethchlor-
      barrier penetration increases, and CNS depres-           vynol) blisters = bullous lesions on hands, but-
      sion increases.                                          tocks, knees; (2) bromoderma = bromide acne =

170 | Color Atlas of Human Poisoning and enenoming
      ulcerating acneiform eruption starts on face and      Bromides
      spreads over body.
  •   Gastrointestinal: Hemorrhagic gastritis unique
                                                              • Use:    Old nerve-headache tonics and sedatives
      to chloral hydrate overdose.
                                                                  (Bromo-Seltzer®); gas fumigant for soil, fruits
                                                                  and vegetables; vehicle for some drugs (bromo-
                                                                  pheniramine and dextromethorphan).
Oerdose Management
                                                              •   Toxicity: Severe gastrointestinal mucosal irri-
Basic Management                                                  tant, brown-stained tongue, progressive CNS
                                                                  depression = Bromism: headache, apathy, irri-
                                                                  tability leads to confusion, ataxia, tremor,
  • Airway protection: ETT.                                       dysarthria, psychosis leads to coma. Later Bro-
  • Orogastric lavage: Reduced gastric motility and               moderma = like ioderma with ulcerating facial
      concretion potential.
                                                                  acne; treatment = antibiotics and Retin-A®.
  •   Initial AC slurry: 1 g/kg and cathartic.
                                                              •   Treatment: Lavage and AC, hemodialysis.
  •   MDAC: q 2–4 h, 0.5 g/kg, no additional cathar-
                                                              •   Bromoderma acne resembles ioderma acne,
      tic, especially for phenobarbital, meprobamate,
                                                                  with weeping and ulcerating facial pustules and
      and glutethimide.
                                                                  indicates long-term exposure to brominated or
  •   WBI-PEG/ELS: For gastrointestinal concretions
                                                                  iodinated products.
      on x-ray (meprobamate) and overdoses with
      sustained-release SHs (diazepam CR).
Enhanced Elimination                                        Barbiturate Classification

  • Acid-base manipulation: Urinary alkalinization            • Ultra-short      acting    (redistribution, then
      only for phenobarbital (pKa = 7.21), NaHCO3                 hepatic elimination): Methohexital, thiamylal,
      1–2 mEq/kg iv bolus, then 150 mEq/L D5W to                  thiopental.
      keep arterial pH 7.45–7.50 and urine pH 7.5–            •   Short acting (hepatic > renal): Hexobarbital,
      8.0; replace K losses.                                      pentobarbital, secobarbital.
  •   Hemoperfusion: Preferred over HD for all SH             •   Intermediate acting (hepatic > renal): Amobar-
      overdoses, except bromides (HD only); due to                bital, aprobarbital, butabarbital.
      low Vd, increased lipid solubility, increased water     •   Long acting (mostly renal elimination): Barbi-
      solubility, increased protein binding. HP very              tal, phenobarbital, primidone.
      effective for phenobarbital and meprobamate.
  •   Antidote: Flumazenil for all BZs and zolpidem,
      can precipitate BZ-withdrawal reactions.              Barbiturate Pharmacology

                                                            Short and Intermediate Acting
Bromates s. Bromides
                                                              • High pKa, very alkaline
Bromates                                                      • More lipid soluble
                                                              • More protein bound
  • Use: Hair neutralizers and straighteners, bread           • Rapid onset, short duration
      preservatives.                                          • Almost completely metabolized hepatically
  • Toxicity: Like aminoglycosides, bromates target           • Alkaline diuresis ineffective
      the hair cells of the cochlea and the renal tubules     • Enhanced elimination by hemoperfusion only
      impairing their unique abilities to regulate elec-
      trochemical gradients. Bromate ototoxicity is
      permanent, but renal failure is reversible.           Long acting
  •   Treatment: Lavage and AC.
                                                              • Lower pKa, weak acids
                                                              • Less lipid soluble
                                                              • Less protein bound

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 171
  • Slow onset, long duration                              Benzodiazepines (BZ)
  • Almost completely renally eliminated                   BZ Classification
  • Enhanced elimination by MDAC,          alkaline
      diuresis, and hemoperfusion > hemodialysis           Short Acting (Half-life < 24 hours)

Barbiturate toxicity
                                                             • Alprazolam (Xanax )  ®

                                                             • Flurazepam (Dalmane )        ®

                                                             • Lorazepam (Ativan ) ®

  • CNS: Slurred speech, ataxia, lethargy, confu-            • Midazolam (Versed )  ®

      sion, headache progressing to anesthesia, coma,        • Temazepam (Restoril )    ®

      respiratory arrest, cerebral edema.                    • Triazolam (Halcion ) ®

  •   Cardiovascular: Direct myocardial depression,          • Flunitrazepam (Rohypnol              ®
                                                                                                        ,   date-rape,   not
      peripheral vasodilation, pulmonary edema, car-             FDA-approved)
      diac arrest.
  •   Dermal: Barbiturate blisters = cutaneous bullae
      (6.5%).                                              Long Acting (Half-life > 24 hours)
  •   Metabolic: Hypothermia.
  •   Miscellaneous: CYP-450 inducers, increase δ -          • Chlordiazepoxide (Librium )          ®

      ALA and contraindicated in porphyrias.                 • Clonazepam (Klonopin ) — only BZ used as a

                                                                 chronic anticonvulsant
                                                             •   Diazepam (Valium®)
Drug–Drug Interactions                                       •   Oxazepam (Serax®)

  • Hepatic enzyme induction: Increased metabo-            BZ toxicity
      lism of drugs.
  •   Synergistic CNS depression: With other SHs
      and all CNS depressants (especially alcohol).          • General:   Weakness, nausea, diarrhea, chest
  •   Increased production of δ -ALA: Contraindi-                pain.
      cated in porphyrias.                                   • CNS: Headache, vertigo, blurred vision, obtun-
  •   ASA and warfarin: Displace barbiturates from               dation, stupor, coma — all potentiated by co-
      their protein binding sites.                               ingestions, especially with alcohol.
                                                             •   Cardiovascular: VS well-maintained, not
                                                             •   Tolerance: Occurs rapidly, within 1 week.
                                                             •   Withdrawal: Headache, tremor, weight loss,
                                                                 paresthesias, perceptual losses.

                                                           Miscellaneous and Drug–Drug Interactions

                                                             • Miscellaneous:      Triazolam (Halcion®) = toxic
                                                                 psychosis; flurazepam (Dalmane®) = nightmares
                                                                 and hallucinations.
                                                             •   Synergistic CNS depression: Potentiate the
                                                                 actions of all other CNS depressants.
                                                             •   Cimetidine: Inhibits hepatic microsomal
                                                                 enzymes and increased half-lives of all BZs,
                                                                 especially those with active metabolites
Figure 9.3 Mydriasis, Right Eye. Pupillary dilation or
mydriasis characteristic of an anticholinergic toxidrome
and overdoses with alcohol and barbiturates.

172 | Color Atlas of Human Poisoning and enenoming
“Date-Rape” Drugs                                            • Short-acting    benzodiazepine: 7–10 times as
                                                                 potent as diazepam.
  • Gamma-hydroxybutyrate           (GHB,      gamma-
                                                             •   Rapid oral absorption: Peak onset in 15–20
                                                                 minutes; duration 4–6 hours.
      hydroxybutyric acid) and its precursors: gamma-
      butyrolactone (GBL) and 1, 4-butanediol.
  •   Flunitrazepam (Rohypnol®).
                                                           Clinical Manifestations and Management
  •   “Date-Rape”: GHB.
                                                             • Profound CNS depression with maintenance of
toxicology                                                       stable VS.
                                                             • Anterograde amnesia common.
  Street names: Liquid Ecstasy, Easy Lay.
  • GABA metabolite: A naturally occurring CNS               • General overdose management:          Support-
                                                                 ive, protect airway, monitor oxygenation and
     (brain) metabolite of GABA, the inhibitory                  ventilation.
  • Rapid oral absorption: Peak onset in 15 min-             •   Antidote: Flumazenil.
     utes; duration 1.5–2 hours.
Clinical Manifestations                                    Chloral Hydrate (Noctec ®)

  • CNS:     Initial relaxation, tranquility, disinhibi-     • Pharmacology: Severe gastrointestinal irritant,
      tion; followed rapidly by loss of consciousness,           rapidly absorbed, first-pass active metabolite
      delirium, amnesia; rarely seizures.                        = trichloroethanol; “Mickey Finn” = chloral
  •   Cardiopulmonary: Bradycardia, mild hypoten-                hydrate and ethanol.
      sion, transient respiratory depression.                •   CNS: Mimics barbiturate overdose with stu-
  •   Gastrointestinal: Vomiting.                                por and coma; pathognomonic pear-like breath
Use/abuse and Management                                     •   Gastrointestinal: Nausea, vomiting, hemor-
                                                                 rhagic gastritis with gastric and SI necrosis
Methods of Use and Abuse                                         and gastrointestinal perforation; esophageal
  • Licit use: Narcolepsy, not FDA-approved in the           •   Cardiovascular: Myocardial sensitization leads
      United States.                                             to depression, ventricular arrhythmias = VT,
  •   Ineffective use: By body builders to promote               VF, torsades. Treatment: β -blockers.
      rest, fasting, fat metabolism, muscle mass and         •   Miscellaneous: Genotoxic, animal carcinogen.
      high growth hormone levels.
  •   Illicit use: “Date-rape.”
                                                           ethchlorynol (Placidyl®)

General Management of Overdose
                                                             • Pharmacology: Rapidly absorbed, 90% hepati-
                                                                 cally metabolized.
  • Airway     protection: Monitor oxygenation and
                                                             • CNS:     Central respiratory depression, stupor
                                                                 progressing to prolonged deep coma; pathogno-
  •   Consider coma cocktail with thiamine and
                                                                 monic plastic- or vinyl-smelling breath.
      D50W: Flumazenil and naloxone ineffective.
  •   Atropine: For bradycardia.
                                                             •   Cardiovascular: Myocardial depression = hypo-
                                                                 tension and bradycardia.
  •   Consider physostigmine.
                                                             •   Pulmonary: Respiratory depression, pulmonary
                                                                 edema, especially after IV overdose.
Flunitrazepam                                                •   Dermal: “Barbiturate blisters” on hands, knees,
Toxicokinetics                                                   and buttocks.
  • Rohypnol®: Foreign trade name, U.S. street               •   Treatment: Hemoperfusion.

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 173
Piperidinediones                                          Withdrawn Sedaties-Hypnotics
Glutethimide (Doriden®)                                   Methaqualone (Quaalude®)

  • Acute     overdose: Similar to barbiturate over-
                                                            • Overdose:     CNS = euphoria (cause for abuse),
                                                                fatigue, delirium, hypertonia, myoclonus,
      dose, profound and prolonged coma like eth-
                                                                hyperreflexia, stupor-coma, respiratory arrest.
      chlorvynol, sudden apnea, and seizures.
  •   Chronic overdose: Toxic psychosis, ataxia, sei-
                                                            •   Miscellaneous: Withdrawal syndrome with agi-
                                                                tation, delirium, seizures.
      zures, peripheral neuropathy.
  •   Miscellaneous: Anticholinergic, thick bronchial
      secretions block major airways.                     Paraldehyde (Paral®)

                                                            • Overdose: An alcohol metabolite, overdose mim-
Methyprylon (Noludar )    ®                                     ics ethanol intoxication, pear-smelling breath;
                                                                formerly used to cover ethanol detoxification;
  • Overdose: Stupor, coma, hypotension, pulmo-                 causes a high anion gap metabolic acidosis.
      nary edema, shock.                                    •   Anion gap = Na+ − (Cl− + HCO3 −) = 12 ± 4 mEq/
  •   Miscellaneous: Cytochrome P-450 inducer,                  L = 8–16 mEq/L.
      increases δ -ALA synthetase and contraindi-           •   MUDPPIILES: Methanol, Uremia, Diabetic keto-
      cated in porphyrias.                                      acidosis, Paraldehyde, Phenformin, INH, Iron,
                                                                Lactic acidosis, Ethylene glycol, Salicylates.

Carbamates and Bromides
                                                          New Anxiolytics
Meprobamate (Miltown®)
                                                          Buspirone (Buspar ®)

  • Overdose: Can cause euphoria, seizures, coma,           • Pharmacology: Central serotonin and dopamine
      hypotension, respiratory depression, pulmonary            reuptake inhibitor.
      edema, arrhythmias.                                   • Overdose: Gastrointestinal symptoms, drowsi-
  •   Miscellaneous: Forms large masses or bezoars              ness, dizziness, miosis, rarely dysphoria and
      of pills that can become concretions.                     extrapyramidal reactions, no cardiovascular
  •   Treatment: Lavage and endoscopy to remove                 and respiratory depressant effects.
      concretions, WBI with PEG-ELS if concretions
      detected in gastrointestinal tract on abdominal
      x-ray.                                              Zolpidem (ambien®)

                                                            • Pharmacology:        A non-BZ that has its own
Bromides                                                        unique BZ receptor binding sites; unlike BZs,
                                                                has little effect on the stages of sleep.
  • Overdose:     Old nerve tonics (Bromo-seltzer)          •   Overdose: Drowsiness, sensory distortion, psy-
      and nematocidal fumigants; very irritating to             chotic reactions, rarely respiratory depression
      the gastrointestinal tract = increased vomiting;          and coma; high CFR with co-ingestions (alco-
      increased sedation leads to stupor and coma;              hol, SSRIs).
      bizarre neurologic and psychologic effects            •   Antidote: Flumazinil.
  •   Bromism: Bizarre behavior, delusions, hallucina-
      tions, headache, apathy, irritability, confusion,   Short-term Anesthetics
      dysarthria, tremors, ataxia, anorexia-weight
      loss, bromoderma.                                   Propofol (Diprivan®)
  •   Miscellaneous: Spurious hyperchloridemia.
                                                            • Pharmacology: GABA enhancer.
                                                            • Overdose: Transient apnea,        dose-related
                                                                respiratory depression and hypotension, not

174 | Color Atlas of Human Poisoning and enenoming
• Miscellaneous: Lipemic serum due to high TGs;     Etomidate (amidate®)
  histamine and anaphylactoid reactions to soy-
  bean-egg emulsion formulation, rarely true           • Pharmacology: GABA enhancer.
  anaphylaxis; supports bacterial overgrowth.          • Overdose: Same as propofol and       involuntary
                                                           muscle movements, rarely severe cardiovascular
                                                           and respiratory depression.
                                                       •   Miscellaneous: Suppresses adrenal steroid hor-
                                                           mone production — cortisol and aldosterone;
                                                           no longer recommended for prolonged ICU

      Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 175
                                                                                        Part 2:

                   Illicit Substances: Outline
                                              Methods of abuse
                                              Clinical manifestations
                                              General overdose management
                                              Specific overdose management
                                              Management: body packers vs. stuffers

                                              Prescription v. designer
                                              Acute vs. chronic amphetamine toxicity
                                              Overdose management

                                            Phencyclidine (PCP)
                                              History of PCP
                                              Pharmacology of PCP
                                              Clinical manifestations
                                              Lab findings
                                              Management of PCP overdose

                                            Lysergic acid diethylamide (LSD)
                                              Common hallucinogens
                                              LSD Pharmacology
                                              Clinical manifestations
                                              LSD intoxication

                                              Acute vs. chronic marijuana toxicity
                                              Management of marijuana intoxication

                                            “Date-rape” drugs
                                              “Date-rape”: GHB
                                              Miscellaneous date-rape drugs

Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 177
History                                                        dium, a quinidine (Type IA antiarrhythmic)
 • Cocaine is a natural plant alkaloid of the Cen-         •   Vasoconstriction: Results from catecholamine
                                                               reuptake inhibition with intense cerebral, coro-
     tral and South American cocoa plant.
                                                               nary, and mesenteric vasoconstriction.
 • Peruvian    Incas first used cocaine-filled saliva
                                                           •   Rostral-caudal CNS stimulation: Euphoria,
     as a local anesthetic for ritual and war wound
                                                               excitement, restlessness, hyperthermia, tonic-
                                                               clonic seizures, all resulting from reuptake
 •   Cocaine was an early ingredient of Coca-Cola.
                                                           •   Alcohol and cocaine: Results in the hepatic
                                                               formation of a long-acting, more cardiotoxic
                                                               metabolite — coca-ethylene.

 • Cocaine abuse is the most frequent drug-related
     cause of emergency department visits in the        Methods of Abuse
     United States.
 •   More than 25 million Americans have tried
                                                           • Snorting:     Nasally insufflated; using “head
     cocaine at least once.
                                                               shop” paraphernalia = spoons, dollar bills, and
 •   More than 5 million Americans use cocaine one
     or more times a month.
                                                           •   Free-basing: Home conversion of hydrochlo-
                                                               ride salt to pure cocaine base for inhalation or
                                                               IV use by flame processing in volatile solvents
                                                               (ether, benzene, alcohol) (e.g., Richard Pryor).
                                                           •   Crack: A highly purified and dry-processed
 • Ester-type LA: Rapid onset = inhalation: onset              smokeable form of cocaine, available in small,
     1–3 minutes and peaks 20–30 minutes; IV:                  inexpensive packages of “chips” or “rocks.”
     onset within seconds and peaks 3–5 minutes.
 •   Three routes of metabolism: (1) hydrolysis by
     plasma pseudocholinesterases to ecgonine           Clinical Manifestations
     methyl ester (EME), major metabolite (50%);
     (2) nonenzymatic hydrolysis to longest active
     metabolite, benzoylecgonine (40%, used as the
                                                           • Hyperthermia:       Resulting from serotonin-
                                                               induced high psychomotor hyperactivity
     preferred cocaine urine drug screen marker due
                                                               and low heat dissipation from peripheral
     to its long half-life); (3) hepatic N-demethyl-
     ation to norcocaine (10%).
                                                           •   CNS: Mydriasis, seizures, greater risk of cere-
                                                               brovascular accidents (CVAs) = subarachnoid
                                                               hemorrhage, intracranial hemorrhage, transient
                                                               ischemic attacks.
                                                           •   Acute cardiovascular: Tachycardia, hyperten-
 • Pseudocholinesterase deficiency: Predisposes to             sion, tachyarrhythmias, myocardial infarction
     high toxicity due to hereditary ineffectiveness           (MI), vascular endothelial damage and platelet
     of cocaine’s primary metabolic pathway via                aggregation and adhesion, subacute bacterial
     plasma pseudocholinesterases.                             endocarditis (SBE) from septic emboli.
 •   LA effect (IB): Produced by Na channel block-         •   Chronic cardiovascular: Coronary artery dis-
     ade centrally, peripherally, and in the myocar-           ease (CAD) and left ventricular hypertrophy

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 179
      (LVH) = dilated cardiomyopathy, peripheral
      vascular disease, and acute aortic dissection.
  •   Pulmonary: Pneumomediastinum from deep
      inhalation with breath-holding, noncardiogenic
      pulmonary edema (NCPE) may result from
      adrenergic tone, pulmonary capillary leak, and
      pulmonary hypertension.
  •   Skeletal muscle: Muscular hyperactivity and
      rigidity leading to muscle damage, high creatine
      phosphokinase (CPK) levels, rhabdomyolysis;
      myoglobinuria may lead to acute tubular necro-
      sis (ATN) and acute renal failure (ARF).
  •   Gastrointestinal vasoconstriction: Gut ischemia
      and mesenteric thrombosis may lead to bowel         Figure 9.4 Noncardiogenic Pulmonary Edema: Crack
      necrosis with pneumatosis intestinalis.             Cocaine Injection. Frontal chest radiograph that dem-
  •   Uteroplacental and fetal: Spontaneous abortion,     onstrates normal size and configuration of the cardio-
      abruptio placenta, intrauterine growth retarda-     mediastinal silhouette and bilateral diffuse pulmonary
      tion (IUGR), limb autoamputation, microceph-        edema following the intravenous injection of crack
      aly, and low birth weight.                          cocaine. Noncardiogenic pulmonary edema may also
                                                          follow opioid overdoses with the same radiographic
                                                          patterns. (Courtesy of Carlos R. Gimenez, M.D., Pro-
Differential Diagnosis of Sympathetic                     fessor of Radiology, LSU School of Medicine, New
toxidromes                                                Orleans, LA.)

  • Toxins:      Cocaine, phenycyclidine (PCP),
      amphetamines, caffeine, hallucinogens, phenyl-
      propanolamine (PPA), theophylline, ephedrine,
      pseudoephedrine, tyramine, monoamine oxi-
      dase inhibitors (MAOIs).
  •   Metabolic: Thyrotoxicosis, pheochromocy-
      toma, hypoglycemia, serotonin syndrome, neu-
      roleptic malignant syndrome.
  •   Withdrawal: Ethanol, sedative-hypnotics.
  •   Neuropsychiatric: Status epilepticus, mania,
      psychosis, schizophrenia.

Diagnostic tests

  • Labs:    Hyperglycemia, hypokalemia, increased
      CPK, and increased CPK-MB.
  •   Electrocardiogram (ECG): All tachydysrhyth-
      mias increased, ischemia, MI.                       Figure 9.5 Intracranial Aneurysm: Crack Cocaine
  •   Head CT: All CVAs increased = subarach-             Inhalation. Cranial computerized axial tomogram (CT)
      noid hemorrhage (SAH), intracranial (ICH),          at the level of the pons and the superior fourth ventri-
      interventricular hemorrhage (IVH), ischemic         cle in a crack cocaine abuser that demonstrates a right
      cerebral infarcts, septic cerebral emboli, brain    parasellar hyperdense rounded area consistent with
      abscesses.                                          a saccular aneurysm of the right posterior communi-
  •   Abdominal x-rays: Body packing mules vs.            cating artery. (Courtesy of Carlos R. Gimenez, M.D.,
      body stuffers; free air from perforated, necrotic   Professor of Radiology, LSU School of Medicine, New
      bowel.                                              Orleans, LA.)

180 | Color Atlas of Human Poisoning and enenoming
Figure 9.6 Intracranial Aneurysm: Crack Cocaine              Figure 9.8 Septic Cerebral Emboli with Brain
Abuser. Digital subtraction arteriogram in a lateral pro-    Abscess. Axial T1-weighted magnetic resonance
jection following radiographic contrast injection into       image (MRI) of the brain at the level of the centrum
the left internal carotid artery of a crack cocaine abuser   semiovale that demonstrates a large cystic lesion with
that demonstrates a saccular aneurysm of the left pos-       surrounding halos of vasogenic edema consistent with
terior communicating artery. (Courtesy of Carlos R.          multiple septic emboli and resulting cerebral abscess
Gimenez, M.D., Professor of Radiology, LSU School of         in an intravenous crack cocaine abuser. (Courtesy of
Medicine, New Orleans, LA.)                                  Carlos R. Gimenez, M.D., Professor of Radiology, LSU
                                                             School of Medicine, New Orleans, LA.)

Figure 9.7 Intracranial and Interventricular Hemor-          Figure 9.9a Pneumomediastinum Following Crack
rhage: Crack Cocaine Inhalation. Noncontrast comput-         Cocaine Inhalation. Frontal (9.9a) and lateral (9.9b)
erized axial tomogram (CT) of the brain at the level of      chest radiographs that demonstrate radiolucencies
the third ventricle in a crack cocaine abuser that dem-      throughout the left lung interstitium, mediastinum, and
onstrates a hyperdense lesion in the left basal ganglia,     base of the neck consistent with pulmonary interstitial
asymmetry of the left frontal ventricular horn, and          emphysema, pneumomediastinum, and subcutaneous
interventricular hemorrhage in the right ventricular horn    soft tissue emphysema following crack cocaine inhala-
consistent with hypertensive intracranial hemorrhage         tion. (Courtesy of Carlos R. Gimenez, M.D., Professor
with disruption into the ventricular system. (Courtesy       of Radiology, LSU School of Medicine, New Orleans,
of Carlos R. Gimenez, M.D., Professor of Radiology,          LA.)
LSU School of Medicine, New Orleans, LA.)

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 181
Figure 9.9b Pneumomediastinum Following Crack             Figure 9.11 Fatal Mesenteric Infarction with Small
Cocaine Inhalation. Frontal (9.9a) and lateral (9.9b)     Bowel Perforation. Noncontrast, computerized axial
chest radiographs that demonstrate radiolucencies         tomogram (CT) of the abdomen at the level of the
throughout the left lung interstitium, mediastinum, and   uncinate process of the pancreas that demonstrates
base of the neck consistent with pulmonary interstitial   bowel gas in the main portal vein and its intrahepatic
emphysema, pneumomediastinum, and subcutaneous            branches, extraperitoneal emphysema in the pro-
soft tissue emphysema following crack cocaine inhala-     peritoneal fat space and posterior pararenal space,
tion. (Courtesy of Carlos R. Gimenez, M.D., Professor     pneumoperitoneum, and subcutaneous soft tissue
of Radiology, LSU School of Medicine, New Orleans,        emphysema following acute mesenteric infarction and
LA.)                                                      subsequent small bowel perforation in an intravenous
                                                          cocaine abuser. (Courtesy of Carlos R. Gimenez, M.D.,
                                                          Professor of Radiology, LSU School of Medicine, New
                                                          Orleans, LA.)

                                                            • MRI: Dissecting aortic aneurysm, pneumatosis
                                                                intestinalis, portal and mesenteric venous air

                                                          Clinical Findings: Ct, radiographic, and MrI

                                                            • Crack     cocaine inhalation: intracranial and
                                                                interventricular hemorrhage.
                                                            •   Intravenous crack cocaine abuse: septic cerebral
                                                                emboli with multiple brain abscesses.
                                                            •   Crack cocaine inhalation: radiolucencies
                                                                throughout the left lung interstitium.
                                                            •   Intravenous crack cocaine abuse: dissecting
                                                                thoracic aneurysm.
                                                            •   Intravenous cocaine abuse: fatal mesenteric
                                                                infarction with small bowel perforation.

Figure 9.10 Dissecting Thoracic Aneurysm. Contrast-
enhanced, T1-weighted, sagittal-oblique, computerized     General Oerdose Management
axial tomogram (CT) of the chest that demonstrates
                                                          General Principles
an intimal flap dividing the descending thoracic aorta
into true and false lumens consistent with dissecting
thoracic aneurysm Type B in an intravenous cocaine          • Secure airway and control motor hyperactivity
abuser. (Courtesy of Carlos R. Gimenez, M.D., Pro-              and seizures with benzodiazepines; barbiturates
fessor of Radiology, LSU School of Medicine, New                and neuromuscular paralysis with non-depolar-
Orleans, LA.)

182 | Color Atlas of Human Poisoning and enenoming
      izers (avoid succinylcholine — hyperkalemia,       CNS toxicity
      rhabdomyolysis unopposed).
  •   Coma cocktail: 1 g/kg D50W and 100 mg thia-
                                                           • Hyperthermia: O , ice water baths, BZs (loraz-
      mine IV.                                                                          2
                                                                epam > diazepam), vasodilators, nondepolariz-
  •   Externally cool: Ice-water baths.
                                                                ing muscle relaxants, dantolene.
  •   Avoid all neuroleptics, especially phenothi-
                                                           •    Agitation: Sedation with BZs and barbiturates,
      azines and succinylcholine, which could exacer-
                                                                if indicated.
      bate rhabdomyolysis and increase K.
  •   Treat SVTs with calcium channel blockers
                                                           •    Rhabdomyolysis: Hydrate while monitoring
                                                                CVP-PAP, alkalinize urine with NaHCO3,
      (CCBs); treat QRS widening with NaHCO3;
                                                                institute osmotic diuresis with mannitol, con-
      and treat torsades de pointes with Mg.
                                                                sider hemodialysis if ATN imminent.
  •   Avoid beta-blockers, which could precipitate
      unopposed alpha-agonist effects.
                                                         Management: Body Packers s. Stuffers
Enhanced elimination                                     Body Packers

  • Initial AC and sorbitol, both at 1 g/kg, followed      • Confirm cocaine packs by abdominal x-ray.
      by MDAC for both body packers and body               • Institute ECG monitoring.
      stuffers; monitor packers for packet rupture         • Activated charcoal (AC) and cathartic, then
      and need for surgical exploration.                        multi-dose activated charcoal (MDAC) to
  •   Consider whole-bowel irrigation (WBI) with                reduce absorption and enhance elimination.
      polyethylene glycol electrolyte solution (PEG-       •    Whole-bowel irrigation (WBI) with polyeth-
      ELS) for hemodynamically stable packers and               ylene glycol electrolyte solution (PEG-ELS) to
      stuffers.                                                 reduce gastrointestinal mucosal contact time,
  •   Hydrate while monitoring central venous pres-             speed transit, and increase elimination.
      sure (CVP)–pulmonary artery pressure (PAP)           •    Surgical removal for symptomatic patients with
      and alkalinize urine with NaHCO3 drip to                  packet rupture or intestinal obstruction.
      protect kidneys from rhabdomyolysis-induced          •    Follow-up imaging with abdominal x-rays; con-
      myoglobinuria and high risk of acute tubular              sider barium enema.
      necrosis (ATN).                                                                          Yes     Are the symptoms consistent
                                                                 Is the patient symptomatic?
                                                                                                              with cocaine?
                                                                                                                 No                Yes
Specific Oerdose Management                                                    No                     Are the symptoms
                                                                                                        consistent with         Sedate
Cardiovascular toxicity                                                                                    an opioid?          intubate
                                                                 Order abdominal radiograph                                    Operate

  • Hypertension:      O2 , benzodiazepines for seda-                                                  Bolus with naloxone
                                                                                                       and start iv unfusion
      tion, vasodilatation with rapidly acting periph-
      eral vasodilators–phentolamine, nitrogylcerine              Does the radiograph show     Yes
                                                                     bowel obstruction
      (NTG), and sodium nitroprusside (SCN).
  •   Pulmonary edema: O2 , furosemide, morphine                                No

      sulfate (MS), NTG.                                            Begin multiple dose activated

  •   Angina: O2 , benzodiazepines (BZs), MS, acetyl-
                                                                 charcoal and whole bowel irrigation

      salicylic acid (ASA), NTG, CCBs, (verapamil >
                                                                     Is the radiograph clear and have the
      diltiazem), avoid beta-blockers.                     No    expected number of packets been retrieved?
  •   ST and SVT: O2 , BZs, CCBs, adenosine.
  •   VT and VF: O2 , BZs, NaHCO3, cardioversion,
                                                                 Obtain contrast radiography
      defibrillation, consider lidocaine (avoid brety-               prior to discharge
      lium due to its initial adrenergic response).      Figure 9.12 Management: Cocaine v. Heroin Body
                                                         Packers. A flow chart outlining the clinical practice
                                                         management strategies for body packers of cocaine
                                                         or heroin.

         Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 183
Figure 9.13 Phentermine-Fenfluramine (Amphet-
amine) Cardiomyopathy. Digital subtraction frontal
chest radiograph that demonstrates diffuse dilated
cardiomegaly, predominantly of the left-sided cardiac
chambers consistent with amphetamine-induced
dilated cardiomyopathy in an obese patient taking an
oral phentermine-fenfluramine combination for weight
loss. (Courtesy of Carlos R. Gimenez, M.D., Professor     Figure 9.14 Phentermine-Fenfluramine (Amphet-
of Radiology, LSU School of Medicine, New Orleans,        amine) Cardiomyopathy with Mitral Valve Prolapse.
LA.)                                                      A cardiac ultrasound examination that demonstrates
                                                          diffuse cardiomegaly predominantly of the left-sided
Body Stuffers                                             cardiac chambers with mitral valve prolapse in an
                                                          obese patient taking an oral phentermine-fenfluramine
                                                          combination for weight loss. (Courtesy of Carlos R.
  • Confirm by abdominal x-ray.                           Gimenez, M.D., Professor of Radiology, LSU School of
  • Immediate orogastric lavage           for recent      Medicine, New Orleans, LA.)
  •   Institute ECG monitoring.
  •   AC and cathartic, MDAC to reduce absorption
      and increase elimination.
  •   WBI with PEG-ELS to reduce gastrointesti-
      nal mucosal contact time, speed transit, and
      increase elimination.
  •   Surgical removal for obstructed patients (ileoce-
      cal valve).
  •   Follow-up imaging with abdominal x-rays.

184 | Color Atlas of Human Poisoning and enenoming
Pharmacology                                                       dextroamphetamine,           methamphetamine,
                                                                   methylphenidate (Ritalin® = most popular
                                                                   prescribed drug for preteens with ADHD),
  • Mechanism: (1) Direct central release of cate-                 pemoline.
      cholamines, particularly norepinepherine (NE)
      and dopamine, from presynaptic terminals;
                                                                − Weight reduction: Amphetamine, dexto-
                                                                   amphetamine, methamphetamine, dexfen-
      (2) competitive inhibition of catechol reuptake
                                                                   fluramine, phentermine and fenfluramine
      at adrenergic terminals; (3) central serotonin
                                                                   (phen-fen combination: withdrawn by the
      5-hydroxytryptamine (HT) release at higher
                                                                   FDA due to increased risks of pulmonary
                                                                   hypertension and valvular heart disease).
  •   NE effects: α - and β -adrenergic stimulation
                                                                − Pure methamphetamine = ice or speed,
      produce anorexia and alerting effects.
  •   5-HT effects: Altered perception, psychosis,
                                                            •   Designer amphetamines:
      agitation, hallucinations, seizures.
  •   Metabolic: Lipid-soluble, high volume of dis-
                                                                − All designer amphetamines are potent
                                                                   central serotonin releasers; popular at all-
      tribution (Vd), increased active metabolites,
                                                                   night Rave Parties, often combined with
      no     catechol-o-methyltranferase     (COMT)
                                                                − Dimethoxyamphetamine: DOM or STP.
                                                                − Methylene-dioxyamphetamine: MDA, love
                                                                − M e t hyl e n e - d iox y m e t h a mp h e t a m i n e :
                                                                   MDMA, Ecstasy, or Adam.
  • Prescription: Used for attention deficit hyperac-           − Methylene-dioxyethamphetamine: MDEA,
      tive disorder (ADHD), narcolepsy, and weight                 Eve.
  •   Illicit: Methamphetamine (ice, speed) — most
      common illicit drug produced by clandestine          Acute s. Chronic Amphetamine toxicity
      drug labs; primary ingredient = ephedrine,
      adulterants = Pb and Hg.
  •   Designer: Methylene-dioxymethamphetamine
                                                            • Acute toxicity:
      (MDMA) (Ecstasy, Adam) and methylene
                                                              − CNS > cardiovascular > pulmonary:
      dioxyethamphetamine (MDEA, Eve).
                                                                 − CNS: Mydriasis, anorexia, euphoria,
                                                                         psychosis, hyperthermia → diaphore-
  •   International: (1) khat: active agent = cathinone,
                                                                         sis, headache, agitation-hyperactivity
      Arabia and East Africa (Somalia) = euphoria,
                                                                         → tremor, seizures → muscle rigidity →
      alertness, anxiety, hyperactivity; (2) ma-huang:
                                                                         choreoathetosis → rhabdomyolysis →
      Chinese ephedrine used as a bronchodila-
                                                                         myoglobinuria → acute tubular necrosis
      tor for asthmatics and COPD patients and for
                                                                         → acute renal failure.
      sports performance enhancement. Banned by
                                                                    −   Cardiovascular: Hypertension, tachy-
                                                                         cardia, tachydysrhythmias, vasospasm,
                                                                         angina, myocarditis, and myocardial
                                                                         infarction (MI).
Prescription s. Designer
                                                                    −   Pulmonary: Tachypnea, pulmonary
                                                                         vasoconstriction,    and   pulmonary
  • Prescription amphetamines:                                           hypertension.
    − Attention deficit-hyperactivity
         (ADHD) and narcolepsy: Amphetamine,

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 185
  • Chronic toxicity:                                         −  Administer coma cocktail, without nalox-
    − Cardiovascular       and pulmonary: Catechol-              one: 1 g/kg D50W and thiamine 100 mg IV.
         amine-induced dilated and valvular cardio-           − Avoid all neuroleptics, which may exacerbate
         myopathies, mitral regurgitation (phen-fen),            hyperthermia and lower seizure thresholds;
         pulmonary hypertension (phen-fen), necro-               cause dystonia and choreoathetosis with
         tizing vasculitis with ischemic colitis.                neuroleptic malignant syndrome; and may
     −   CNS: Permanent dopaminergic and seroto-                 precipitate tachydysrhythmias due to quini-
         nergic neurotransmitter depletion-induced               dine (Type IA) effects. Avoid beta-blockers,
         encephalopathy.                                         which could precipitate unopposed alpha-
     −   Labs: Hyperglycemia, leukocytosis, elevated             agonist activity.
         liver function tests (LFTs), elevated creatine       − Monitor for rhabdomyolysis with serum
         phosphokinase (CPK) from rhabdomyolysis                 CPK levels and urinary myoglobin levels.
         with myoglobinuria. False-positive urine         •   Specific treatment:
         drug screens may result from ephedrine,              − Agitation and restlessness: BZs, such as IV
         pseudoephedrine, or phenylpropanolamine                 diazepam.
         (PPA), often found in over-the-counter               − Seizures: BZs > barbiturates > muscle relax-
         (OTC) cold medications.                                 ants (often, patients continue to manifest
                                                                 seizure activity on EEG and require pro-
                                                                 longed anticonvulsant therapy).
Oerdose Management                                           − Hyperthermia: Sedation and external
  • General management:                                       − Oral ingestions: AC and sorbitol, both 1
    − Restrain and sedate with BZs.                              g/kg.
                                                              − Hypertension: Initially sedate with BZs,
    − Rapid external cooling with ice-water baths;
         consider dantrolene IV.                                 consider peripheral vasodilators for ease
     −   AC for recent oral ingestions.                          of titration — phentolamine, nitroglycerin,
                                                                 and sodium nitroprusside.

186 | Color Atlas of Human Poisoning and enenoming
   Phencyclidine (PCP)
History of PCP                                              • Cardiorespiratory: Hypertension, sinus tachy-
                                                                cardia, no cardiorespiratory depression,
  • Developed in the 1950s as a dissociative anes-          •   Renal: ATN, ARF.
      thetic for painful diagnostic procedures;
      associated with post-operative psychomi-
      mesis, including hallucinations and sleep
                                                          Lab Findings
  •   Some of the early congeners of PCP are still in
      use today as dissociative anesthetics, primarily      • WBC: Leukocytosis.
      ketamine.                                             • Lytes: Hyperkalemia.
  •   PCP was introduced to the San Francisco drug          • Glucose: Hypoglycemia.
      scene in the 1960s as the PeaCePill, hence the        • Arterial Blood Gases          (ABGs): Metabolic
      abbreviation “PCP.”                                       acidosis.
                                                            •   Enzymes: Elevated muscle enzymes from rhab-
                                                                domyolysis, LDH, and CPK, often associated
Pharmacology of PCP                                             with myoglobinemia and myoglobinuria.
                                                            •   Urine: False-positive urine PCP toxicity screens
                                                                may result from co-ingestions with ketamine
  • Pharmacology: Highly lipid-soluble weak base;               and dextromethorphan; both are also NMDA
      65% plasma protein-bound; large volume of
      distribution of 6.2 L/kg; hepatically metabo-
      lized to inactive metabolites; renal excretion.
      − Mechanism: n-methyl-d-aspartate (NMDA)            Management of PCP Oerdose
          receptor antagonist, like ketamine and dex-
          tromethorphan, which inhibits the binding       General Management
          of glutamate to NMDA receptors centrally.
  •   Street use: Sold as tabs, caps, or rock salt-like     • Restrain and sedate with BZs.
      crystals and abused by smoking, insufflation,
      and ingestion.
                                                            • Administer 100 ml D W and 100 mg thiamine
                                                            •   Avoid syrup of ipecac (epileptogenic) and seda-
                                                                tion with neuroleptics (increased temperature,
Clinical Manifestations                                         decreased seizure threshold, can induce dysto-
                                                                nias and neuroleptic malignant syndrome).
  • Ophthalmic: Exception: PCP is the only NIDA-            •   Orogastric lavage followed by AC (1 g/kg) and
      5 drug of abuse to cause miosis (all the rest             sorbitol (1 g/kg).
      cause mydriasis) — with blank stare, dysconju-        •   MDAC preferred over continuous NG suction.
      gate gaze, and nystagmus-horizontal, vertical,
      and rotatory; nystagmus is pathognomonic of
      PCP abuse.                                          Specific treatment
  •   CNS: Disorientation, dysphoria, paranoia,
      dysarthria, jargonaphasia, auditory and visual        • Monitor for elevated CPK and myoglobinuria,
      hallucinations, agitation, hyperactivity, tremor,         as rhabdomyolysis is associated with high case
      seizures, dystonia, torticollis, choreoathetosis,         fatality rates (CFRs).
      facial grimacing, opisthotonos, rhabdomyoly-          •   If myoglobinuria occurs, protect kidneys with
      sis, myoglobinuria, ATN, ARF.                             hydration, osmotic diuretics (mannitol), and
                                                                urinary alkalinization with NaHCO3.

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 187
   Lysergic Acid Diethylamide (LSD)
Common Hallucinogens                                      Chronic Hallucinogen toxicity

  • Lysergamides: All natural and synthetic ergot           • Preexisting    psychiatric illnesses predispose to
      alkaloid derivatives (Claviceps purpurea), like           chronic mental disturbances.
      LSD, and morning glory seeds.                         •   Extended psychoses possible: Schizophrenia.
  •   Indolealkylamines: Mushroom psilocybin and            •   Recurring panic reactions: Best managed by
      psilocin; bufotenine but more likely, methoxy-            reassurance and support.
      dimethyltryptamine from Bufo alvarius toads.          •   Hallucinogen persisting perceptual disorder
  •   Phenylethylamines: Mescaline from peyote cac-             (HPPD): aka “purple haze” = recurrence of
      tus, all amphetamines (especially the serotonin           flashbacks of earlier “bad trips,” triggered by
      [5-HT] releasers, MDMA and MDEA).                         exercise, stress, or illness.
  •   Cannabinols:      Delta-9-tetrahydrocannabinol
      (THC) in marijuana and hashish.                     LSD Intoxication
                                                          General Management
LSD Pharmacology

  • Pharmacology: Colorless, tasteless, and odorless        •    “Coma cocktail” IV: 100 mL D50W and 100 mg
                                                                thiamine and 2 mg naloxone; secure airway.
      powders that are rapidly absorbed mucosally;
      80% protein bound; hepatically metabolized
                                                            •   AC and sorbitol (both 1 g/kg): For recent inges-
                                                                tions; ineffective once hallucinations begin.
      with no active metabolites and short durations
      of action; terminated by renal excretion.
                                                            •   Acute panic reactions: Quiet room, no stimuli,
                                                                reassurance by nonjudgmental advocate.
  •   Mechanism: All act as serotonin releasers and
                                                            •   “Bad trip” dysphoria: Sedation with BZs.
      agonists, usually by promoting presynaptic
      serotonin release in the limbic system.
                                                            •   Avoid excessive physical restraint: Secondary
                                                                to rhabdomyolysis risks with high case fatality
                                                                rates (CFRs).
Clinical Manifestations
acute Hallucinogen toxicity                               Specific treatment

  • Initial    autonomic effects: Sympathomimetic           • Hypertension:      BZs initially, then vasodila-
      with LSD (anxiety, tachycardia, hypertension,             tors = phentolamine, nifedipine, sodium
      mydraiasis, tremor, nausea, flushing, chills),            nitroprusside.
      but gastrointestinal (nausea and vomiting) with       •   Avoid all neuroleptics: May produce α -block
      peyote; then a constellation of mydriasis, diz-           with hypotension, hyperthermia, and reduced
      ziness, diaphoresis, piloerection, ataxia, tachy-         seizure threshold with convulsions, or precipi-
      pnea, hypetension, and tachycardia.                       tate neuroleptic malignant syndrome.
  •   Later psychological effects: Emotional lability       •   Avoid β - and mixed α - and β -blockers: Because
      = euphoria–dysphoria, perceptual distortions,             of risks of unopposed α -adrenergic-mediated
      visual (“psychedelic” colors) > auditory (sounds          hypertension.
      magnified) > tactile > olfactory hallucinations.      •   Hyperthermia: Aggressive external cooling, IV
                                                                hydration, BZs and skeletal muscle relaxants
                                                                (MRs); consider dantrolene.
                                                            •   Monitor for rhabdomyolysis: Elevated CPK,
                                                                myoglobinuria, protect renal function with
                                                                hydration, osmotic diuresis, and urinary

188 | Color Atlas of Human Poisoning and enenoming
epidemiology                                              Chronic Marijuana toxicity

  • Marijuana     is an oily, dried fibrous material        • Tolerance    and dependence: Resulting from
      obtained from the Indian hemp plant, Canna-               repeated use.
      bis sativa.                                           •   Withdrawal syndrome: Irritability, restlessness,
  •   The most commonly used illegal substance in               insomnia, and appetite loss.
      the United States.                                    •   COPD,       oral     and      lung       cancer:
  •   The most commonly abused substance in the                 Smoking-induced.
      world after nicotine, alcohol, and caffeine.          •   Congenital toxicity: Neonatal and early child-
  •   Considered a “gateway drug” by the DEA,                   hood neurobehavioral and developmental
      NIDA, and the Substance Abuse and Mental                  disturbances.
      Health Services Administration (SAMHSA).              •   Male infertility: The result of combinations
                                                                of low testosterone levels, low sperm counts,
                                                                reduced sperm motility, and greater abnormal
Pharmacology                                                    sperm morphology.

  • Delta-9-THC is the psychoactive component.            Management of Marijuana Intoxication
  • Hashish (smoked in pipes) and hashish oil
      (mixed with tobacco and smoked): All are Can-
      nabis derivatives that contain higher concentra-      • Motor vehicle and other transportation-related
      tions of THC.                                             accidents: Marijuana is detected in 11–33%
  •   THC is transported to the brain within 15 sec-            of cases (including mass transit and train acci-
      onds of smoking to occupy specific cannabinoid            dents) and associated with a prolonged (≥24
      receptors in the cerebral cortex.                         hours) loss of judgment and motor skills needed
                                                                for safe vehicular operation.
                                                            •   Acute psychotic reactions: Sedation with BZs.
Acute s. Chronic Marijuana toxicity                        •   Pneumomediastinum: Rare and the result of
                                                                deep inhalation with alveolar overdistension
acute Marijuana toxicity
                                                                and rupture; supportive management with O2 .

  • Physiological effects: Dose-related tachycardia,
      blood pressure remains stable, increased appe-
      tite, dry (cotton) mouth, conjunctival injection,
      reduced intra-ocular pressure, bronchodilation,
      weakness, muscle tremors, urinary retention,
      low testosterone levels — impotence.
  •   Psychological effects: Dose-related euphoria,
      relaxation, sensory alterations. Preexisting
      psychopathology may predispose to transient,
      acute psychotic reactions with paranoid delu-
      sions and hallucinations.

          Poisonings with Analgesic Adjuants, Psychotropics, Sedatie-Hypnotics, and Illicit Substances | 189
      “Date-Rape” Drugs
“Date-Rape”: GHB                                           Flunitrazepam
toxicokinetics                                             toxicokinetics

  • Street names: Liquid Ecstasy, Easy Lay.                  • Rohypnol    ®
                                                                            : Foreign trade name, not FDA-
  • GHB is an active GABA metabolite: GHB is a                   approved; U.S. street drug; a tasteless, odorless
      naturally occurring CNS (brain) metabolite of              powder that dissolves rapidly in alcohol.
      GABA, the central inhibitory neurotransmitter.         •   Short-acting benzodiazepine: ≥ 10 times more
  •   Rapid oral absorption: Peak onset in 15 min-               than potent as diazepam.
      utes; duration 1.5–2 hours.                            •   Rapid oral absorption: Peak onset in 15–20
  •   Gamma-butyrolactone (GBL): An active hepatic               minutes; duration 4–6 hours.
      (tricarboxylic acid cycle) metabolite of GHB.

                                                           Clinical Manifestations and Management
Clinical Manifestations
                                                             • Profound CNS depression with maintenance of
  • CNS:     Initial relaxation, tranquility, disinhibi-         stable vital signs; characteristic of BZs.
      tion; followed rapidly by loss of consciousness,       •   Antero-grade amnesia common.
      drowsiness, dizziness, disorientation, delirium,       •   General overdose management: Support-
      amnesia, rarely seizures.                                  ive, protect airway, monitor oxygenation and
  •   Cardiopulmonary: Bradycardia, mild hypoten-                ventilation.
      sion, transient respiratory depression.                •   Antidote: Flumazenil.
  •   Gastrointestinal: Vomiting.

                                                           Miscellaneous Date-Rape Drugs
Methods of Use and abuse
                                                             • Ketamine:     A sympathomimetic amine similar
  • Licit use: Narcolepsy, not FDA-approved in the               to phencyclidine (PCP) that rapidly induces dis-
      United States.                                             sociative anesthesia with sedation, delirium,
  • Ineffective use: Thought to potentiate the ana-              hallucinations, and respiratory depression.
      bolic effects of growth hormone and often                  Seizures, tachyarrhythmias, and cardiac arrest
      abused by body builders to promote rest, fast-             are possible. Therapy requires supportive care,
      ing, fat metabolism, muscle mass, and high                 ECG monitoring, and quiet recovery, often with
      growth hormone levels.                                     BZ sedation.
  •   Illicit use: “Date-rape.”                              •   Chloral hydrate: A halogenated hydrocarbon
                                                                 alcohol hepatically metabolized by alcohol
                                                                 dehydrogenate to trichloroethanol that has a
General Management of Overdose                                   prolonged half-life of 4–14 hours and potenti-
                                                                 ates alcohol intoxication. Also known as knock-
  • Airway     protection: Monitor oxygenation and               out drops or a “Mickey Finn.”
  •   Consider coma cocktail: Flumazenil and nalox-
      one ineffective.
  •   Atropine: For bradycardia.
  •   Consider physostigmine: For reversal of CNS

190 | Color Atlas of Human Poisoning and enenoming
                                          Chapter 10

Poisonings with Cardioascular

              Poisonings with Cardioascular Medications | 191
Chapter Outline
              Cardiac glycosides
                  Toxic effects: adults vs. children
                  Lab diagnosis
                  General management
                  Specific management
                  Digoxin-specific Fabs

                  Overdose epidemiology
                  β -Adrenergic physiology
                  Classification (mean half-life = 5 hours)
                  Differential diagnosis: Drug-induced bradycardia
                  General overdose management
                  Specific management of severe toxicity

              Calcium channel blockers
                  Epidemiology of CCB overdose
                  CCB physiology
                  CCB pharmacology
                  CCB classification
                  CCB indications
                  Clinical manifestations
                  General overdose management
                  Specific management

              Miscellaneous antihypertensies
                  Angiotensin classification blockers

                     Poisonings with Cardioascular Medications | 193
   Cardiac Glycosides
etiology                                                    • Half-life: 1.6 days.
                                                            • Limited hepatic metabolism and enterohepatic
  • Digoxin is most often implicated.                           circulation.
  • Rarely implicated cardiac glycosides: Digitoxin,        • 60–80% renal excretion.
      ouabain, lanatoside C (now used infrequently).        • Narrow therapeutic index: 0.5–2.0 ng/mL.
  • Plant glycoside ingestions: Foxglove, oleander,
      lily-of-the-valley, red squill.
  • Toad       skin venom: Presumed aphrodisiacs          Pathophysiology
      secreted by Bufo toads (Family Bufonidae) that
      contain bufotoxins, especially from the bufadi-       • At    toxic doses, digoxin suppresses the sino-
      enolide class. Common U.S. species include                atrial (SA) node, increasing atrial and ven-
      Colorado River toad (Bufo Alvariusi), cane toad           tricular automaticity causing extrasystoles and
      (Bufo marinus), and the American toad.                    tachydysrhythmias: junctional tachycardia,
                                                                atrial fibrillation, atrial flutter, and ventricular
                                                                tachycardia — ventricular fibrillation, pathog-
Mechanisms                                                      nomonic bidirectional ventricular tachycardia
                                                                (torsades de pointes).
  • Inhibition of the Na-K ATPase-dependent myo-            •   Reduces conduction velocity in atria, ventricles,
      cardial sarcolemmal pump.                                 and atrioventricular node = increased PR inter-
  •   Positive inotropic effect from elevated intracel-         val, sinus bradycardia, sinoatrial (SA) and junc-
      lular (cytosolic) Ca during systole.                      tional blocks, and atrioventricular blocks.
  •   Direct and indirect vagomimetic effects = cause       •   Noncardiac: Anorexia, nausea, vomiting,
      the most common side effects: nausea, vomit-              cramps, confusion, hyperkalemia (blocks cyto-
      ing, bradycardia, heart block.                            solic K entry), hypomagnesemia.
  •   Peripheral vasodilation and reduced afterload.

                                                          toxicity effects: Adults s. Children
Plant Glycosides

  • Foxglove (Digitalis purpurea)                           • Cardiac:     Sinus bradycardia, atrioventricular
  • Oleander (Nerium oleander)                                  (AV) block, nonparoxysmal atrial tachycardia,
                                                                premature ventricular contractions (PVCs),
Natural Glycosides                                              bigeminy, bidirectional ventricular tachycardia
                                                                (torsades de pointes), ventricular fibrillation.
                                                            •   Noncardiac: Anorexia, crampy abdominal
  • Lily-of-the-Valley (Convallaria majalis)                    pain, nausea and vomiting, confusion, dizzi-
  • Cane toad (Bufo marinus)                                    ness, fatigue, lethargy, delirium. Unique visual
                                                                disturbances: halos, yellow and green flashes
                                                                and objects, darkened and blurred vision.

  • Slow absorption and onset: IV 5–30 minutes;           Children
      orally 1.5–6 hours.
  •   25% protein binding.
  •   High volume of distribution (Vd): 6–7 L/kg            • Cardiac:     Bradycardia, 1st–2nd degree AV
      adults, even greater in children.                         blocks, junctional rhythm, SA arrest, SA blocks,

                                                            Poisonings with Cardioascular Medications | 195
      AV junctional tachycardia, rarely ventricular        • Hemoperfusion      and hemodialysis ineffective
      fibrillation.                                            due to high molecular weight and increased vol-
  •   Noncardiac: Lethargy and vomiting.                       ume of distribution.

Lab Diagnosis                                            Specific Management
Serum Digoxin Levels
                                                           • Digoxin-specific     antibody fragments — Fabs
                                                               (DigiBind®): Will decrease free digoxin but ele-
  • Very narrow therapeutic index: 0.5-2.0 ng/mL.              vate total serum digoxin levels; Fabs will also
  • Heightened toxicity caused by electrolyte                  decrease levels of K and increase excretion of
      changes and certain drugs: Decreased levels
                                                               Fab-bound digoxin.
      of K-Mg-Ca, elevated Na, alkalosis, hypothy-
      roidism, decreased level of O2 , catecholamines,
                                                           •   K > 5 mEq/L: Fab > insulin and glucose >
                                                               NaHCO3 > sodium polystyrene sulfonate.
      calcium channel blockers (CCBs), quinidine,
      amiodarone, diuretics (via hypokalemia),
                                                           •   Supraventricular tachycardia (SVT): Fab pre-
                                                               ferred over β -blockers.
      enzyme inhibition by cimetidine.
  •   Increased by digoxin-like immunoreactive sub-
                                                           •   Atrioventricular (AV) block: Fab preferred over
      stances (DLIS) and digoxin-Fabs.
  •   Polyclonal digoxin radioimmunoassays (RIAs):
                                                           •   Ventricular tachycardia (VT)/ventricular fibril-
                                                               lation (VF): Cardioversion/defibrillation pre-
      To clarify true increase [digoxin].
                                                               ferred over Fab, phenytoin, and lidocaine.
                                                           •   Contraindicated medications: Isoproterenol
Endogenous Digoxin-Like Immunoreactive                         and, especially, calcium, due to increased intra-
                                                               cellular calcium stores.
Substances (DLIS) are associated with:

  • Renal insufficiency.                                 Digoxin-Specific Fabs
  • Pregnancy.                                           Indications
  • Liver disease.
  • Heart disease: Congestive heart failure (CHF).
  • CNS insults: Subarachnoid hemorrhage (SAH).            • Rising K or K > 5 mEq/L at any time.
  • Endocrinopathies: Insulin dependent diabetes           • Severe ventricular dysrhythmias: VT, VF, tors-
      mellitus (IDDM) and acromegaly.                          ades de pointes.
  • Neonates: Stress and elevated serum bilirubin          • Progressive    bradydysrhythmias refractory to
      levels.                                                  atropine.
  • Adults: Stress and drugs = spironolactone (via         •   Serum [dig] > 10–15 ng/mL anytime.
      hyperkalemia).                                       •   Ingestion of > 4 mg of digoxin by a child; and
                                                               > 10 mg by adult.

General Management
                                                         Dose Calculations for Digoxin Fab therapy
  • Discontinue      digoxin, gastrointestinal decon-
      tamination, especially with AC.                      • Each vial of DigiBind   ®
                                                                                       contains 38 mg purified
  •   Orogastric lavage preferred to emesis in a               digoxin-specific Fabs that will bind exactly 0.5
      digoxin-toxic patient already vomiting.                  mg digoxin.
  •   AC and sorbitol, then MDAC up to 1 g/kg every        •   Assume 80% bioavailability on absorption of
      2–4 hours. Slow absorption and an enterohe-              ingested digoxin.
      patic circulation make digoxin very amenable to      •   Example: Adult 70 kg ingests 50 0.25-mg tabs;
      decontamination, with both AC and MDAC.                  0.25 × 50 = 12.5 mg digoxin ingested; 12.5 ×
  •   Steroid-binding resins: Cholestyramine and               0.80 = 10 mg digoxin absorbed; 10/0.5 = 20
      colestipol to bind digoxin and interrupt entero-         vials DigiBind® are indicated.
      hepatic circulation along with MDAC.                 •   Give at least 5–20 vials of DigiBind® whenever
                                                               treatment of digoxin toxicity is indicated.

196 | Color Atlas of Human Poisoning and enenoming

Oerdose epidemiology                                                                          • There are three (3) types of β -receptors: β , β ,                        1   2
                                                                                                   and β3, with β1 subserving the cardiovascular
                                                                                                   effects of increasing cardiac contractility, intra-
   • During 1989–1995, 5000 β -blocker overdoses                                                   cardiac conduction velocity, cardiac automatic-
       were reported to the American Association
                                                                                                   ity, and renal renin secretion.
       of Poison Control Centers (AAPCC), with 15
       adult deaths and no pediatric deaths.
                                                                                               •   Specific β1-receptor stimulation causes the car-
                                                                                                   diovascular effects of increased cardiac contrac-
   •   Children <6 years old accounted for 1/3 of all
                                                                                                   tility, intracardiac conduction velocity, cardiac
       exposures, but no deaths.
                                                                                                   automaticity, and renal renin secretion.
   •   Intentional β -blocker overdose occurred most
                                                                                               •   Specific β2-receptor stimulation causes periph-
       commonly with propranolol, frequently pre-
                                                                                                   eral arteriolar vasodilation, pulmonary bron-
       scribed to patients with suicidal ideations =
                                                                                                   chodilation, hepatic gluconeogenesis, and
       anxious, nervous, hyperactive, stressed out,
                                                                                                   glycogenolysis, increased insulin secretion with
       often with migraine headaches and chronic pain
                                                                                                   hypoglycemia, and increased uptake by muscle
       syndromes or tremors.
                                                                                                   resulting in serum hypokalemia.
                                                                                               •   β3 -receptor stimulation probably mediates ther-
                                                                                                   mogenesis and lipolysis.
β -Adrenergic Physiology
                                                                                               •   Even the most selective β -blockers will lose their
                                                                                                   selectivity in overdose.
   • Catecholamines      (norepinephrine, epinephrine)
       stimulate their β -adrenergic receptors that are
       coupled to G proteins on myocardial, pulmo-                                       Classification (mean half-life = 5 hours)
       nary, and vascular membrane surfaces.
   •   This stimulation increases intracellular cAMP,                                    Nonselective β -Blockers (β1 and β2)
       which in turn activates protein kinases, the ulti-
       mate end mediators of the cellular effects of β -                                       • Labetolol (increased also an α -blocker)
                                                                                               • Nadolol (half-life = 10 hours)
       receptor stimulation.

                                            Catecholamines                                                                             (2)
                                                          receptor                                                                    Catecholamines
                                                      1                                                                 Glucagon
                             Adenylate       Gs                                                                                                 1   receptor
                              cyclase      protein              Calcium                                                 Adenylate
            ATP                                                                                                                         Gs
       5 AMP                                                              Ca2+                                           cyclase      protein             Calcium
                                                                Channel                                 ATP                                                         Ca2+
                                                                                                   5 AMP                                                  Channel
                                             Protein                                     (3)
Amrinone                      c-AMP                                  Voltage-sensitive
               PDE                          Kinase A                                                                                   Protein
                                                                     calcium channel                                     c-AMP                                 Voltage-sensitive
                                                                                         Amrinone        PDE                          Kinase A
                      Ca2+                                                                                                                                     calcium channel

                                 Sarcoplasmic                   Calcium                                          Ca2+
           Troponin                                  Ca2+                  Ca2+
                                  reticulum                     Channel                                                     Sarcoplasmic                  Calcium
                                                                                                     Troponin                                   Ca2+                Ca2+
                                                                                                                             reticulum                    Channel
                                          Membrane                        (1)
    Actin-myosin complex                  potential                                                                                  Membrane
                                                                                                Actin-myosin complex                 potential

Figure 10.1 Cardiovascular adrenergic physiology and pharmacology. The cardiovascular molecular receptors
and ionic channels and the mechanisms and sites of action of (1) calcium channel blockers, (2) beta-receptor
blockers, and (3) phosphodiesterase inhibitors.

                                                                                               Poisonings with Cardioascular Medications | 197
  • Oxprenolol       (exhibits intrinsic sympathetic      toxicity
      activity [ISA])
  •   Pindolol (exhibits ISA)
                                                            • Asymptomatic: 1/3 of all β -blocker overdoses.
  •   Propranolol (increased lipid solubility)
                                                            • Mild toxicity: Bradycardia, mild hypotension,
  •   Sotolol (increased half-life = 10 hours)
                                                                ECG — increased PR interval and widened
  •   Timolol
                                                            •   Moderate toxicity: Sinus arrest, atrioventricular
β1-Selective Blockers                                           (AV) block, severe hypotension, hypoglycemia.
                                                            •   Severe toxicity: All of the above and cardiovas-
                                                                cular collapse, delirium, coma, seizures (espe-
  • Acebutalol (ISA)                                            cially with propranolol overdose), respiratory
  • Atenolol (increased H O solubility)                         depression, bronchospasm in COPD patients,
  • Esmolol (very short-acting)
                                                                and possibly, asthmatics.
  • Metoprolol
                                                          Differential Diagnosis: Drug-
Indications                                               Induced Bradycardia

  • Hypertension:      β1-selective > nonselectives,        • β -Blockers: Hypotension, depressed mental sta-
      which also block bronchodilation and periph-              tus, slightly elevated K, ECG — prolonged PR
      eral vasodilation and could exacerbate bron-              interval and widened QRS.
      chospasm in obstructive pulmonary disease             •   CCBs: Hypotension, preserved mental status,
      and lower extremity claudication in peripheral            ECG — PR prolonged interval and widened
      vascular disease.                                         QRS complex.
  •   Angina: Reduce anginal attacks and decrease           •   Digoxin: Nausea and vomiting, hyperkalemia,
      post-myocardial infarction mortality.                     hypertension, and mental status preserved;
  •   Tachydysrhythmias: Used in theophylline over-             ECG — prolonged PR, ST changes, atrial then
      dose, butadenosine preferred over β -blockers.            ventricular dysrhythmias.
  •   Tremor: Propanolol over prescribed agitation,         •   Na-channel blockers: Seizures, hypotension,
      stage fright, and panic attacks (“shakes”).               depressed mental status, ECG — widened QRS
  •   Migraine headaches.                                       complex.
  •   Hyperthyroidism: β -blockers moderate the             •   Cholinergics: SLUDE, DUMBBELS, ECG —
      sympathetic, hyperdynamic effects of thyroid              sinus tachycardia or paradoxical bradycardia.
      storm.                                                •   α -agonists: α1 = phenylpropanolamine (PPA):
                                                                Severe hypertension, intracranial hemorrhage
                                                                (ICH), sinus bradycardia; α2 = clonidine, imid-
Side Effects                                                    azolines: cause an opioid toxidrome, with pin-
                                                                point miosis and sinus bradycardia.
  • Bronchospasm:        Nonselectives prevent bron-
      chodilation and promote bronchospasm in
      chronic obstructive pulmonary disease (COPD)        General Oerdose Management
  •   High anaphylaxis risk: Nonselectives block cat-       • Asymptomatic:      No ipecac, AC preferred over
      echol’s ability to reduce mast cell degranulation         lavage with vagomimetic effects, WBI for sus-
      in patients with atopic allergies.                        tained-release preps.
  •   Hypoglycemia: All β -blockers mask sympa-             •   Mild toxicity: All of the above and atropine for
      thetic response to hypoglycemia and interfere             bradycardia and fluid bolus for hypotension.
      with gluconeogenesis/glycogenolysis.
  •   Withdrawal: Rebound increased heart rate and
      elevated blood pressure on abrupt withdrawal
      can precipitate MI and CVA.

198 | Color Atlas of Human Poisoning and enenoming
• Moderate   toxicity: All of the above and glu-    Specific Management of Seere toxicity
  cagon (hormone secreted by pancreatic α cells
  in response to decreased levels of glucose and
  elevated catechols); administer 2–5 mg bolus of
                                                     • General management and invasive monitoring.
  glucagon IV push to bypass β -receptors and to
                                                     • Catecholamine infusion: Dobutamine (β ) pre-
                                                         ferred over norepinephrine (NE) (α and β) and
  increase intracellular cAMP; CaCl2 IV up to 1
  g; consider more atropine, up to 3 mg IV.
                                                     •   Isoproterenol is the least preferred catechol-
                                                         amine due to peripheral vasodilation with hypo-
                                                         tension (from β2 stimulation).
                                                     •   Add a phosphodiesterase inhibitor: Amri-
                                                         none or milrinone to bypass β -receptors and
                                                         increase intracellular cAMP restoring cardiac
                                                     •   Consider IV insulin and glucose therapy.
                                                     •   Consider ventricular pacing.
                                                     •   Hemodialysis rarely indicated.

                                                      Poisonings with Cardioascular Medications | 199
   Calcium Channel Blockers

epidemiology of CCB Oerdose                               • CCBs     are well absorbed orally, hepatically
                                                               metabolized and highly protein bound, and
                                                               have increased volumes of distribution (not
  • In 1995, there were over 8300 CCB overdoses,               dialyzable).
      >1000 caused moderate to major toxicity,
      with 69 deaths, mostly from sustained-release
                                                         CCB Classification
  •   CCBs are No. 3 in prescribed drug overdoses,
      after No. 1 TCAs/SSRIs and No. 2 opioids.
  •   In 1989, verapamil, diltiazem, and nifedipine        • Phenylalkylamines: Exert the greatest effects on
      were among the top-20 prescribed drugs.                  SA and AV normal conduction and cause pro-
                                                               found negative inotropic effects in overdose:
                                                               − Verapamil (Calan®)
CCB Physiology                                             •   Benzothiazepines:
                                                               − Diltiazem (Cardizem®)
  • Cardiac and smooth muscle cells (GI and vascu-         •   Dihydropyridines: The largest, safest, and most
                                                               frequently prescribed class of CCBs:
      lar) require active influx of Ca through L-type,
      voltage-sensitive Ca channels for excitation-
                                                               − Nifedipine (Procardia®)
      contraction coupling (ECC) and cardiac, vas-
                                                               − Nimodopine (Nimotop®)
      cular, and intestinal muscle conduction and
                                                               − Nicardipine (Cardene®)
  •   Skeletal muscle depends on its own intracellular
                                                         CCB Indications
      Ca stores for ECC and is unaffected by CCBs.
  •   Ca influx also modulates myocardial conduc-
      tion by stimulating spontaneous depolarization       • Severe hypertension
      (phase 4) in SA node and propagating conduc-         • Tachycardias: atrial    fibrillation, atrial flutter,
      tion from the SA node and through the AV                 reentrant supraventricular tachycardia (SVT)
      node.                                                •   High peripheral vascular resistance (PVR) with
                                                               hypertension and/or vasospastic conditions:
                                                               Raynaud’s phenomenon, Prinzmetal’s angina,
CCB Pharmacology                                               cardioesophageal spasm, vascular headaches,
                                                               post-subarachnoid hemorrhage (SAH), cerebral
  • CCBs block L-type, slow Ca channels in car-
      diac and smooth muscle cells.
  • CCBs limit Ca entry into cardiac and smooth          Clinical Manifestations
      muscle cells, reducing excitation-contraction
      coupling and slowing intracardiac electrical       Onset and Severity of Poisoning
  •   Myocardial force of contraction and inotropy         • Toxicity presents within 2–3 hours post inges-
      are decreased; conduction through the SA and             tion with regular-release preparations.
      AV nodes is reduced; vascular smooth muscle
      relaxes, causing peripheral vasodilation and
                                                           • Toxicity may be delayed 6–8 to 15 hours with
                                                               sustained-release preparations with half-lives
      lowered blood pressure.                                  >48 hours.

200 | Color Atlas of Human Poisoning and enenoming
  • Co-morbidities: Congestive heart failure (CHF)        Specific Management
      and advancing age magnify predisposition to
      and severity of toxicity from CCB overdoses.
                                                           • Atropine: 0.5 mg IV every 2–3 minutes, to 3
Forme Fruste Clinical Presentation                         • 10% CaCl : 3 times more ionic calcium activity
                                                               than calcium gluconate, dose = calcium chlo-
                                                               ride: 1 gram IV (20 mg/kg); calcium gluconate:
  • Cardiovascular:    Myocardial depression with              3 grams IV (60 mg/kg).
      bradycardia and peripheral vasodilation = hypo-      •   Vasopressor support: Epinephrine > norepi-
      tension, decreased myocardial conduction = AV            nephrine > phenylephrine > dopamine > dobu-
      block may progress to complete heart block.              tamine (β2) > isoproterenol (β2).
  •   CNS: Lightheadedness, dizziness, fatigue, leth-      •   Glucagon: Bypasses β -receptor to increase
      argy, syncope, and rarely, coma. Severe CNS              cAMP; administer 2–5 mg IV push over 1 min-
      depression uncommon. As opposed to β -blocker            ute, infuse at 4 mg/hour.
      toxicity with heart block and profound CNS           •   Phosphodiesterase inhibitor: Amrinone > milri-
      depression.                                              none to bypass β -receptor and to increase intra-
  •   Reduced insulin release = hyperglycemia.                 cellular cAMP.
  •   Pulmonary: Noncardiogenic pulmonary edema            •   Intra-aortic balloon pump > cardiopulmonary
      (NCPE) from increased transcapillary hydro-              bypass > extracorporeal membrane oxygen-
      static pressure.                                         ation > pacemaker.
                                                           •   Consider insulin and glucose therapy.

General Oerdose Management

  • Gastrointestinal     decontamination: No ipecac
      due to rapid deterioration in level of conscious-
      ness; immediate orogastric lavage within 1–2
  •   AC: 1 g/kg and cathartic, then MDAC, 0.5 g/kg,
      especially for sustained-release preparations.
  •   WBI: WBI with PEG-ELS for sustained-release
      preparations, 1–2 L via NG and antiemetic.
  •   Monitoring: ECG, good IV access.

                                                            Poisonings with Cardioascular Medications | 201
   Miscellaneous Antihypertensies
Sympatholytics                                            Management
                                                            • No ipecac, AC, whole-bowel irrigation (WBI)
                                                                for clonidine patch ingestions, naloxone drip,
  • Central α -agonists: Clonidine (Catapress
                                                 ), α -
                                                                IV fluids, sodium nitroprusside (SCN) for ini-
      methyldopa (Aldomet® a prodrug that induces
                                                                tial hypertension.
      central α2-agonist activity), imidazolines (eye/
      nose drops).
                                                            •   Crystalloid fluid boluses, direct-acting vaso-
                                                                pressors — NE > phenylephrine.
  •   Ganglionic blockers: Trimethaphan (Arfonad®)
                                                            •   Crystalloid fluid boluses and vasopressors
  •   Peripheral adrenergic blockers: Guanethidine
      (Ismelin®), reserpine
  •   Peripheral α1-blockers: Prazosin (Minipress®)
Mechanisms, Indications, and Side Effects                 Classification

  • Reduce central sympathetic outflow: Indicated           • Thiazides:    HCTZ (Hydrodiuril®), chlorthali-
      for hypertension, migraine, opioid/EtOH with-             done (Hygroton®).
      drawal, as nasal decongestants; side effects          •   Loop diuretics: Furosemide (Lasix®), bumetanide
      include withdrawal, rebound hypertension,                 (Bumex®), ethacrynic acid (Edecrin®).
      α -methyldopa causes a Coomb and hemolytic            •   K-sparing diuretics: Triamterene (Maxzide®),
      anemia.                                                   spironolactone (Aldactone®).
  •   Reduce postganglionic autonomic transmission:
      Often used for deliberate hypotension to limit
      surgical blood loss.                                Mechanisms, Indications, and Side Effects
  •   Reduce NE release from distal nerve terminals:
      Initially used to treat hypertension, prior to        • Limit    Na and Cl reabsorption in distal con-
      newer antihypertensives.                                  voluted tubule: Indicated for hypertension,
  •   Block postsynaptic α1-receptors in vascular               diuresis.
      smooth muscle.                                        •   Limit K-Na-Mg reabsorption: Indicated for
                                                                digoxin toxicity.
                                                            •   Limit Na-K-Cl reabsorption in ascending loop:
                                                                Indicated for diuresis.
                                                            •   Limit Na and Cl reabsorption in distal convo-
  • α -agonists: Opioid toxidrome = miosis, brady-
                                                                luted tubule and collecting ducts, aldosterone
      cardia; hypotension and CNS depression may                antagonists: Indicated for diuresis.
      follow initial paradoxical hypertension, and          •   Side effects: Hyperuricemia (gout), hypona-
      hypothermia; CNS depression = lethargy, som-              tremia, hypokalemia, ototoxicity; aldosterone
      nolence, stupor.                                          antagonist may cause hyperkalemia and pre-
  •   Ganglionic blockers: Hypotension, constipa-               cipitate digitalis toxicity.
      tion, urinary retention.
  •   Peripheral blockers: Hypotension, orthostasis,
      drowsiness, diarrhea.
  •   Peripheral α1-blockers: Hypotension, syncope,
      orthostasis, CNS depression.

202 | Color Atlas of Human Poisoning and enenoming
toxicity                                                 Angiotensin Blockers
  • Hypovolemia: From brisk diuresis.
  • Electrolyte disturbances: Low serum Na, K, Cl,         • Angiotensin      converting enzyme (ACE) inhibi-
      and Mg levels may be associated with altered             tors: Captopril (Capoten®), enalapril (Vasotec®),
      mental status, muscle weakness, and digoxin              lisinopril (Prinivil®), quinapril (Accupril®).
      toxicity.                                            •   Angiotensin II receptor blockers: Losartan
                                                               (Cozaar®), valsartan.

                                                         Mechanisms, Indications, and Side Effects
  • Fluid replacement.
  • Electrolyte replacement: Restore normal Na, Cl,        • Angiotensin      converting enzyme inhibitors:
      K, and Mg levels; consider sodium polystyrene            Block conversion of angiotensin I to II in lungs
      sulfonate binding agent for hyperkalemia from            and vascular endothelium, reduced peripheral
      K-sparing diuretics; monitor digoxin levels.             vascular resistance (PVR), lower blood pres-
                                                               sure; indications — hypertension; side effects:
                                                               reduced bradykinin breakdown in lungs, caus-
Vasodilators                                                   ing angioedema and cough.
                                                           •   Management of toxicity: Epinephrine, H1-
  • Direct smooth muscle vasodilators:                         blockers, steroids.
    − Hydralazine (Apresoline )      ®                     •   Angiotensin receptor blockers: Decrease forma-
    − Minoxidil (Rogaine )   ®                                 tion of angiotensin II at vascular receptor sites;
    − Diazoxide (Hyperstat )     ®                             indications — hypertension; side effects: few,
    − Sodium nitroprusside (Nipride )    ®                     bradykinin metabolism unaffected, no angio-
                                                               edema and cough so common with ACE inhibi-
                                                               tor therapy.
Mechanisms, Indications, and Side Effects

  • All: Produce vascular smooth muscle relaxation                      Angiotensinogen
      with peripheral vasodilation and triggering of                                Renin       converting enzyme
      baroreceptor-mediated tachycardia; main uses                                               inhibitors (ACEI)    Inactived
                                                                             Angiotensin I                           bradykinin
      — hypertension.
  •   Management of toxicity: Fluids, α -pressors.
  •   Hydralazine: Same indications, and lupus

      syndrome possible as a side effect, as with                           Angiotensin II                           Bradykinin
      procaineamide.                                                          Angiotensin
  •   Minoxidil: Same indications, and hair growth.                             receptor
  •   Diazoxide: Same, and immediate increase in         Vasoconstriction
                                                                            blockers (ARBs)
      glucose in management of insulin and oral                                                secretion

      hypoglycemic overdoses.
  •   Sodium nitroprusside: Vasodilation via nitric
                                                                                              Na+ and water
      oxide mechanism; cyanide (CN) toxicity pos-          resistance
      sible (Lilly CN kit — sodium nitrite first, then                             Blood                              and cough
      sodium thiosulfate).                                                        pressure

                                                         Figure 10.2 The renin-angiotensin-aldosterone path-
                                                         way and mechanisms of action. Flow chart demonstrat-
                                                         ing the rennin-angiotensin-aldosterone (RAA) system
                                                         and mechanisms of action and the sites of action of
                                                         angiotensin-converting enzyme (ACE) inhibitors and
                                                         angiotensin receptor blockers (ARBs).

                                                            Poisonings with Cardioascular Medications | 203
  tABLe 10.1 Vaughan-Williams Classification of Antiarrhythmics
  Class                     Mechanisms                     toxicity                      examples
  Class Ia                  Short-acting, open-state,      Widened QrS; prolonged        Quindine
                             Na channel block >             Qt, Sa, and aV blocks;       Procainamide
                             K channel block                torsades                     Disopyramide
  Class IB                  Increased effective            Biphasic CNS —                Lidocaine
                             refractory period; short-      cardiovascular toxicity      Mexilitene
                             acting Na channel block        — CNS > CV; little           tocanide
                                                            change in QrS and Qt;        Phenytoin
                                                            sinus arrest; aV block       Propafenone
  Class IC                  Prolonged Na, K, and Ca        Widened QrS, prolonged        Ecainide
                             channel blocks                 Qt, Sa, and aV blocks,       Flecanide
  Class II                  β1 and 2-blockers,             Prolonged Pr, widened         Esmolol (β1)
                             selective (β1) and             QrS, bradycardia, aV         Labetolol (β1, 2)
                             nonselective (β1 and 2)        block, bronchospasm,         Propranolol (β1, 2)
                                                            hyperglycemia, and
  Class III                 K channel blockers,            Sinus bradycardia,            amiodarone
                             prolonged                      profound negative             (hypothyroidism,
                             depolarization and             inotropism, severe            pulmonary fibrosis,
                             repolarization                 hypotension                   corneal micro-deposits)
                                                                                         Bretylium (intial
  Class IV                     L-type Ca channel             Bradycardia and             Verapamil
                                blockers                      hypotension, aV blocks,    Diltiazem
                                                              lethargy and vertigo,      Nifedipine
                                                              little CNS depression
  Unclassified:                Purine (adenosine)            Sinus arrest, asystole,     adenosine
  adenosine                     receptor agonist, very        bronchospasm,
                                short half-life               hypotension,
                                                              SVts require larger
                                                              doses due to adenosine
                                                              receptor antagonism

Unclassified: adenosine                                      Class Ia: Quinidine

  •A     naturally occurring nucleoside and G-pro-             • Mechanism: Na, K, and Ca channel blocker.
      tein with its own specific adenosine receptors;          • Pharmacology: An amide local anesthetic, with
      IV boluses of adenosine are indicated to rapidly             excellent mucosal absorption, d-isomer of qui-
      terminate reentrant and theophylline-induced                 nine, the antimalarial from cinchona bark; rap-
      SVTs.                                                        idly absorbed orally; high volume of distribution
  •   Mechanisms: Provides an evanescent (10 sec)                  and protein binding.
      calcium entry block and increases AV nodal               •   Toxicity: Prolonged QT interval and widened
      refractory period; reduces action potentials and             QRS complex, ventricular tachycardia, ventric-
      reduces automaticity.                                        ular fibrillation, torsades, hypotension, seizures,
  •   Toxicities: Transient asystole, atrial fibrillation,         noncardiogenic pulmonary edema, cinchonism.
      hypotension, bronchospasm. All toxicities are            •   Treatment: Decontamination — no ipecac, oro-
      potentiated by the antiplatelet agent, dipyri-               gastric lavage; IV fluids and vasoMech (a car-
      damole, an adenosine uptake inhibitor. Higher                diac and peripheral Na channel blocker).
      doses are required for methylxanthine over-
      doses due to adenosine receptor blockade.
  •   Treatment of toxicity: Supportive.

204 | Color Atlas of Human Poisoning and enenoming
                                               Chapter 11

 Miscellaneous Poisonings
with Commonly Prescribed
 Drugs: Antibiotics, Cancer
       and Hypoglycemics

      Miscellaneous Poisonings with Commonly Prescribed Drugs | 205
Chapter Outline

                   Cancer chemotherapeutics


            Miscellaneous Poisonings with Commonly Prescribed Drugs | 207
                                                  Part 1

  Antibiotics: Outline

       Antituberculosis agent toxicity
          TB and isoniazid (INH) epidemiology
          INH pharmacokinetics
          INH mechanisms and toxicity
          INH overdose management
          Chronic INH toxicity
          Other antituberculosis agents

       Antimalarial agent toxicity
          Current antimalarials
          Quinine and cinchonism
          Quinine and quinidine overdose
          Chloroquine toxicity
          Other antimalarials

Miscellaneous Poisonings with Commonly Prescribed Drugs | 209
Penicillins                                               Unique toxicities
Mechanism and toxicity
                                                            • n-Methylthiotetrazole (nMTT) side-chain reac-
                                                                tions: Disulfiram-like reactions due to inhibition
  • Mechanism: Penicillins are β -lactams that erode            of aldehyde dehydrogenase = nausea, vomiting,
      bacterial cell walls by inhibiting mucopeptide
                                                                and flushing following ethanol consumption.
  •   Toxicity: Gastrointestinal (nausea, vomiting,
                                                            •   n-MTT-mediated hypoprothrombinemia: Due
                                                                to inhibition of active vitamin K formation.
      diarrhea) > allergic manifestations > CNS:
      − Allergy: 5% manifest penicillin sensitivities       •   n-MTT representatives: Cefazolin, cefotetan,
                                                                cefamandole, moxalactam.
         = local pruritus, asthma; 1% develop ana-
         phylaxis. Treatment: O2 , epinepherine-nor-
         epinepherine, β2-agonists, steroids, H1- and     Aminoglycosides
         H 2-blockers, theophylline, fluids. Consider
         glucagon for severe hypotension.                 Mechanism and toxicity
      − CNS: Seizures due to inhibition of GABA-
         to-receptor binding. Treatment: benzodi-           • Mechanism: Aminoglycosides inhibit bacterial
         azapines > barbiturates.                               protein synthesis by blocking 30s RNA ribo-
                                                                somal subunit.
Unique toxicities                                           •   Representatives: Kanamycin, streptomycin,
                                                                neomycin, gentamicin, tobramycin, amikacin.
  • Jarisch-Herxheimer      reaction: Acute febrile
                                                            •   Toxicity: Ototoxicity > renal toxicity > neuro-
                                                                muscular junction blockade:
      response to antigens released from lysed spiro-
      chetes = myalgias, chills, fever, headache, rash.
                                                                − Ototoxicity: 0.5-5%: (1) cochlear dysfunc-
                                                                   tion = deafness; (2) vestibular toxicity =
  •   Hoigne syndrome: Local anesthetic toxicity                   permanent tinnitus–vertigo from cochlear
      reaction due to the procaine contained in pro-               and vestibular hair cell damage, same as
      caine–penicillin G = seizures, hallucinations,               bromates.
      tachycardia, and hypertension.
  •   Hyperkalemia: Due to potassium–penicillin G
      administration in chronic renal failure (CRF)       Unique toxicities

                                                            • Ototoxicity and vestibular toxicity
Cephalosporins                                              • Permanent: (1) Cochlear and (2) vestibular hair
                                                                cell degeneration (G2):
Mechanism and toxicity                                          − Gentamicin: Causes both cochlear and ves-
                                                                    tibular that may be permanent ototoxicity
  • Mechanism:       β -lactams, like penicillins, that         − Tobramycin: and vestibular ototixicity that
      interfere with bacterial cell wall integrity.                 may be permanent
  •   Toxicity: Allergy > hematological manifestations:         − Cochlear toxicity alone that may be
      − Allergy: 4% in general population, but                      permanent:
          increases to 8% in those with a preexisting               − Amikacin
          penicillin allergy.                                       − Kanamycin
      − Hematological: Acute hemolysis.                             − Neomycin
  •   Acute overdose: Same as penicillin, but not as        •   Permanent vestibular hair cell degeneration
      life-threatening.                                         alone

                                             Miscellaneous Poisonings wiht Commonly Prescribed Drugs | 211
      −  Streptomycin:       Antituberculosis    (TB)    Fluoroquinolones
  •   Nephrotoxicity: Acute tubular necrosis (ATN)
                                                          • Representatives:      Ciprofloxacin, oxfloxacin,
      possibly during first week of treatment. Unique
                                                              norfloxacin, levofloxacin.
      antidote: ticarcillin — complexes with and
      binds aminoglycosides to inactivate both anti-
                                                          •   Mechanism: Quinolones inhibit bacterial DNA
      microbial and nephrotoxic effects; removes
      50% more drug than hemodialysis (HD).
                                                          •   Toxicity: Soft tissue > CNS > renal:
  •   Neuromuscular blockade: Due to reduced pre-
                                                              − Soft tissue: Target and damage developing
                                                                 articular cartilage, especially in children
      synaptic acetylcholine (Ach) release, especially
                                                                 and pregnancy.
      in those on neuromuscular blockers (NMBs)
      or with preexisting myasthenia gravis or
                                                              − CNS: Rarely, seizures due to GABA inhibi-
                                                                 tion, especially during concomitant theoph-
                                                                 ylline treatment.
                                                              − Renal: Rarely, renal failure.
  • Mechanism: Inhibits bacterial protein synthesis
      by blocking 50s ribosomal subunit.
  • Toxicity:    Cardiovascular and gray baby syn-
                                                          • Mechanism:      Macrolides reduce bacterial pro-
                                                              tein synthesis by inhibiting 50s RNS ribosomal
      drome > hematological:
      − Cardiovascular: (1) Acute cardiovascular          •   Representatives: Erythromycin estolate-lactobi-
         collapse in overdose. Treatment: orogastric
                                                              onate-stearate, clarithromycin, azithromycin.
         lavage, activated charcoal, exchange trans-
         fusion in neonates. (2) Gray baby syndrome:
                                                          •   Toxicity: Cardiovascular > drug–drug interac-
                                                              tions > hepatotoxicity > ototoxicity:
         hypotension, gray color, vomiting, respira-
         tory distress, hypoglycemia; all due to low
                                                              − Cardiovascular: Lactobionate causes pro-
                                                                  longed QT and torsades due to K-channel
         hepatic conjugation and reduced renal abil-
         ity to excrete free drug.
      − Hematological: Dose-dependent bone mar-               − Drug–drug interactions: Erythromycins
                                                                  inhibit P-450 = torsades when co-adminis-
         row (BM) suppression and potentially fatal
                                                                  tered with the nonsedating antihistamines,
         aplastic anemia.
                                                                  astemizole or terfenadine.
                                                              − Hepatic: Estolate causes cholestatic hepatitis
                                                                  with chronic use.
                                                              − Ototoxicity: Reversible high-frequency hear-
                                                                  ing loss.
  • Mechanism:       Reduced bacterial glycopeptide
      polymerization with cell wall instability.
  •   Toxicity: Dermatitis/allergy > renal > hemato-     Sulfonamides
      − Dermal: 3.4% will develop red man syn-            • Mechanism:       Sulfonamides inhibit bacterial
          drome, a glycopeptide-induced anaphylac-
                                                              para-aminobenzoic acid (PABA) metabolism
          toid reaction with pruritus–urticaria–angio-
                                                              required for folic acid synthesis.
          edema, hypotension, angina, cardiovascular
          collapse, seizures.
                                                          •   Toxicity: Gastrointestinal (nausea and vomiting)
                                                              > dermal > hematological > renal > metabolic:
      − Treatment: slow IV administration, H1-                − Dermal: Skin hypersensitivity.
      − Renal: Nephrotoxicity due to chronic use.             − Hematological: BM suppression and aplas-
                                                                 tic anemia, especially with folic acid or B12
      − Hemotoxicity: Rarely neutropenia and                     deficiency.
                                                              − Renal: Nephrolithiasis.
                                                              − Metabolic: Hypoglycemia.

212 | Color Atlas of Human Poisonings and enenoming
  • CRANK:      Crystalluria, rash, aplastic anemia,          −   Febrile Syndrome: Fever, headache, rigors,
      nausea, kernicterus (neonatal jaundice).                    nausea, vomiting, dyspnea, hypotension
                                                                  and bradycardia, IV phlebitis. Pretreat-
                                                                  ment: acetaminophen (APAP), steroids,
tetracyclines                                                     H1-blockers.
                                                              −   Renal: 80% develop minor renal insuf-
  • Mechanism: Tetracyclines reduce bacterial pro-                ficiency; later azotemia possible due to
      tein synthesis by binding to the 30s RNA ribo-              renal tubular damage and renal artery
      somal subunits.                                             vasoconstriction.
  •   Representatives: Tetracycline, oxytetracycline,         −   Hematological: BM suppression = aplastic
      doxycycline, minocycline.                                   anemia, leukopenia, thrombocytopenia.
  •   Toxicity: Dermal > bone > gastrointestinal:
      − Dermal: Sun-exposed skin develops hyper-        azoles
          sensitivity and hyperpigmentation.
      − Bone: Discolors teeth in children <6–8 years
          old and in fetuses >12 weeks.                   • Mechanism: Azoles alter fungal cell membranes
      − Gastrointestinal: Nausea, vomiting, epigas-           to increase permeability.
          tric pain, esophageal ulceration.               •   Representatives:
                                                              − Triazoles: Fluconazole, itraconazole.
                                                              − Imidazoles: Miconazole, clotrimazole.
Antifungals                                               •   Toxicity: Increased drug–drug interactions:
amphotericin B
                                                              − Drug–drug interactions: Azoles inhibit
                                                                  CYP3A4, responsible for metabolizing
                                                                  many drugs, including statins, H1-blockers,
  • Mechanism:      Combines with ergosterol in the               steroids, benzodiazepines, calcium channel
      fungal cytoplasmic cell membrane to reduce cell             blockers (CCBs).
      wall integrity and increase porosity with leak-
      age of cellular organelles.
  •   Toxicity: Febrile syndrome > renal > hemato-

                                             Miscellaneous Poisonings with Commonly Prescribed Drugs | 213
     Antituberculous Agent toxicity
tB and Isoniazid (INH) epidemiology                                                       INH Pharmacokinetics
                                                                                          INH Pharmacology
   • TB is epidemic among high-risk populations of
       Asian, African, and Eastern European immi-
       grants; Native Americans and Inuits; alcohol-
                                                                                             • Absorption:       Rapid following oral ingestion
                                                                                                   from gastrointestinal tract, peak levels in 1–2
       ics; prisoners; homeless; refugees; intravenous
       drug users (IVDUs), and HIV/AIDS patients.
   •   Approximately 2 billion people worldwide are
                                                                                             •     Very low Vd: 0.6 L/kg.
       infected with TB, with 10 million new cases per
                                                                                             •     Low protein binding: 10%.
       year, and 1 million deaths per year.
                                                                                             •     Mostly renally excreted: 75–95%.
   •   Isonicotinyl hydrazide (INH) or isoniazid
                                                                                             •     Easily dialyzable: Due to low Vd, reduced pro-
                                                                                                   tein binding, and increased renal excretion.
       is among the most common causes of drug-
       induced seizures in the United States.
   •   10–20% of patients taking INH will develop                                         INH Metabolism
       asymptomatic high ALT and AST (2–3 times
       normal serum levels); 10% of these will develop
       INH hepatitis (1% total) with a 10% case fatal-                                       • Hepatic metabolism: Two pathways, (1) acety-
       ity rate (CFR = 0.1).                                                                       lation > (2) dehydrazination.
   •   INH toxic risk factors: rapid acetylators of INH;                                     • Rapid acetylators of INH: An autosomal domi-
       the elderly or malnourished; alcoholics; patients                                           nant trait present in 50% of U.S. population
       with preexisting liver disease; synergistic drug                                            and 95% of Inuits, Chinese, Japanese, and Afri-
       toxicity: INH and concomitant rifampin or pyr-                                              cans — who will distribute 30–50% less free
       azinamide antituberculosis treatment.                                                       INH than slow acetylators (most whites) with
                                                                                                   reduced half-life and less drug efficacy. Slow
                                                                                                   acetylators = higher INH toxicity, especially
                                                                                                   slow acetylators on concomitant rifampin.
                                                                                             •     Who are the slow acetylators? 60% of Cauca-
                                                                                                   sian Americans, 60% of Jews, 50% of African
                                                                                                   Americans — all groups are at greater risk of
                                                                                                   INH toxicity.
                       Acetylation                                   Dehydrazination
                                                            Hydrolysis (P450
                               Methylation                    microsomal
                                                               enzyme               Ketoglutaric
                                                               system)              and pyruvic
                              n-Methyl isoniazid                                    hydrazones
         Acetyl isoniazid

                                                                 Hydrazine      Isonicotinic
                    Hydrolysis                                   derivative and     acid

Isonicotinic                  Monoacetyl           system
    acid                      hydrazine                         Toxic intermediate


               Isonicotinyl                                      Hepatic necrosis                      FIGURe 11.1 Isoniazid (INH) metabolism.
                  glycine                                                                              The intrahepatic biotransformation pathways
Isonicotinyl                    Diacetyl                                                               of isoniazid (INH) and the production of non-
 hydrazone                     hydrazine
                                                                                                       toxic and toxic intermediate metabolites.

214 | Color Atlas of Human Poisonings and enenoming
INH Mechanisms and toxicity                                  • Sodium bicarbonate (NaHCO ): Correct meta-   3
                                                                 bolic acidosis.
INH Mechanisms                                               •   Dialysis: Reserve hemodialysis (HD) and
                                                                 hemoperfusion (HP) for those with renal
  • Pyridoxine (or B    6
                          = cofactor for GABA synthe-            insufficiency.
      sis) antagonism via three mechanisms:
      − B6 complex: INH complexes directly with B6
           to form a large complex, not activated and     Specific Management of INH Overdose
           excreted in urine.
      − INH hydrazones: Dehydrazinization pro-               • Pyridoxine (B ): For seizure control; use 1 g per
           duces hydrazone metabolites that inhibit              gram of INH ingested, to a maximum of 5 g at
           pyridoxine phosphokinase, the enzyme                  1 g every 2–3 minutes.
           catalyzing activation of B6 to active form,       •   Repeat pyridoxine: For refractory seizures and
           pyridoxyl-5′-phosphate.                               status epilepticus.
      − INH inhibits pyridoxyl phosphate: The                •   Add diazepam: Diazepam and pyridoxine (B6)
           active form of B6 and the final required              act synergistically to enhance GABA’s seizure-
           cofactor for the synthesis of the inhibitory          inhibition activity.
           neurotransmitter, GABA = reduced CNS                              Dehydrazination
           GABA levels = seizures.                               Isoniazid                      Isoniazid

INH toxicity                                                 and
                                                          hydrolysis                                  Inhibition

  • Acute     toxicity: CNS > metabolic > gastro-
                                                               Hydrazines                                              Pyridoxine
      intestinal                                                  and                         Pyridoxine
  •   INH triad = (1) refractory seizures, (2) meta-           Hydrazides                   phosphokinase
      bolic acidosis (really lactic acidosis because                                                                    Pyridoxal 5′
      INH also inhibits the metabolism of lactate to                                                                    phosphate
      pyruvate), and (3) persistent coma.
  •   Initial gastrointestinal: Nausea and vomiting;
                                                                        Complexation Pyridoxine                   Urinary
      then dizziness, hyperthermia, and hypotension.                       with                                 elimination
  •   CNS: Tonic-clonic seizure, refractory status
      epilepticus (CFR 20%).                              FIGURe 11.2 Isoniazid (INH) toxicity 1. The mecha-
  •   Metabolic: High anion gap metabolic acidosis        nisms and sites of action of isoniazid (INH)-mediated
                                                          epileptogenic neurotoxicity.
      mimicking diabetic ketoacidosis due to seizures
      and increased lactate levels.
  •   Toxic doses: Seizures >20 mg/kg; death >50 mg/                    Glutamine

      kg; LD50 >80–150 mg/kg.                                                −NH3 groups

                                                                 Glutamic acid (brain)
INH Oerdose Management
General Management of INH Overdose
                                                                            Glutamic acid
  • No ipecac: Due to unprotected airway during                         CO2 decarboxylase

      seizures, airway loss, and aspiration risk.                            Pyridoxal 5′-phosphate
  •   Secure airway: Endotracheal intubation; insert                                cofactor
  •   Immediate orogastric lavage: Then AC and                       GABA
                                                             (gamma aminobutyric acid)
  •   Multi-dose activated charcoal (MDAC): No            FIGURe 11.3 Isoniazid (INH) toxicity 2. Additional
      additional cathartic.                               mechanisms and sites of action of isoniazid (INH)-
                                                          mediated epileptogenic neurotoxicity.

                                              Miscellaneous Poisonings with Commonly Prescribed Drugs | 215
Chronic INH toxicity                                       Ethambutol
Common Side Effects: #1 Hepatic
                                                             • Mechanism: Antimetabolite that inhibits bacte-
                                                                 rial RNA synthesis.
  • Adverse reactions: 5.4% will develop fever, rash,        • Pharmacology: Well absorbed orally, peaks IV
      peripheral and/or optic neuritis, or jaundice.
                                                                 2–4 hours, 20% metabolized, 50% excreted.
  • Liver function tests: 10% develop asymptom-              • Toxicity: Eye > initial gastrointestinal and CNS
      atic hepatitis with high liver function tests.
                                                                 > metabolic:
  • INH hepatitis: 1% will develop nausea, vomit-                − Ocular: Optic neuritis, reduced visual acu-
      ing, fever, fatigue, RUQ pain due to hydrazine
                                                                    ity, reduced red-green color perception; all
      intermediates that covalently bind to hepato-
                                                                    dose-related and reversible.
      cytes; hepatic necrosis, may occur, especially in
      slow acetylators also taking rifampin (APAP-
                                                                 − Gastrointestinal, then CNS: Initial nau-
                                                                    sea and crampy pain, then confusion and
      like mechanism of toxicity).
                                                                 − Metabolic: Inhibits renal uric acid excretion
                                                                    and causes acute gout.
Less Common Side Effects: #1 CNS

  • Optic     neuritis: INH can cause optic neuritis       Pyrazinamide
      and optic atrophy.
  •   Peripheral neuropathy: Up to 20% of patients           • Mechanism:       Bactericidal analog of nicotinic
      on INH therapy may develop distal sensory and              acid.
      motor axonopathy.                                      •   Pharmacology: Well absorbed orally, peaks
  •   Pellagra-like skin syndrome: Triad of dermati-             in 2 hours, partially metabolized, excreted by
      tis, diarrhea, and dementia due to inability of            filtration.
      pyridoxyl-5′-phosphate to serve as a required          •   Toxicity: Hepatic > metabolic:
      cofactor in niacin synthesis = niacin deficiency           − Hepatic: 15% will develop acute hepati-
      results in pellagra, the 3-D syndrome.                          tis with CFR 2–3% due to acute hepatic
                                                                 − Metabolic: Inhibits renal uric acid excretion
Other Antituberculosis Agents                                         and causes acute gout.
  • Mechanism: Special antibiotic that inhibits bac-
      terial DNA-dependent RNA polymerase.
  • Pharmacology:        Well absorbed orally, peaks
                                                             • Mechanism: An aminoglycoside antibiotic that
                                                                 inhibits bacterial protein synthesis by binding
      IV 2–4 hours, high Vd (1.6 L/kg), 75% pro-
                                                                 to 30s subunit of bacterial ribosomal RNA.
      tein bound, enterohepatic recirculation, 30%
      excreted, potent P-450 inducer.
                                                             •   Pharmacology: Intramuscular (IM) administra-
                                                                 tion only, peaks in 1 hour, 34% protein bound,
  •   Toxicity: 6% gastrointestinal (nausea, vomit-
                                                                 half-life of 2–5 hours, 89% excreted.
      ing) > dermal > hepatic:
      − Dermal toxicity: red-orange staining of skin,        •   Toxicity: Ototoxicity > neuromuscular junction
                                                                 blockade > hemotoxicity > renal:
          fluids (urine, tears, sweat, breast milk) and
          tissues, flushing, rash, pruritus.
                                                                 − Ototoxicity: Tinnitus, vertigo, dizziness,
                                                                     ataxia, deafness, congenital CN VIII
      − Hepatic: 33% manifest increased liver func-                  damage.
          tion tests (LFTs) and 1% will develop hepati-
          tis with jaundice, especially in slow rifampin
                                                                 − Neuromuscular block: Reduces presynap-
                                                                     tic Ach release; reversed by calcium, not
          inactivators, patients with history of liver
          disease, and patients on INH co-treatment.
      Treatment: Orogastric lavage, AC, MDAC,
                                                                 − Hemotoxicity: Hemolytic anemia, IgG-
                                                                     mediated factor V inhibition with bleeding.
      hemodialysis — hemoperfusion (HD-HP)
                                                                 − Renal: Aminoglycoside nephrotoxicity; no

216 | Color Atlas of Human Poisonings and enenoming
   Antimalarial Agent toxicity
Current Antimalarials                                           −   Gastrointestinal/endocrine: Increased nau-
                                                                    sea and vomiting, increased insulin release
                                                                    — hypoglycemia (similar to sulfonylureas).
  • Quinolines:    Quinine, quinidine, chloroquine,
                                                                −   Dermatology: Flushing, rash, angioedema.
  •   Dihydrofolate reductase inhibitors (folic acid
                                                                −   Hemotoxicity: Hemolysis in G-6-PD defi-
                                                                    ciency, thrombocytopenia.
      inhibitors): Proguanil, pyrimethamine, pyri-
      methamine + dapsone (Maloprim®), pyrimeth-
                                                                −   Miscellaneous: Oxytocic properties may
                                                                    precipitate premature labor.
      amine + sulfadoxine (Fansidar®).
  •   Sulfonamides/sulfones: Sulfonamides — sulfa-
      doxine/sulfones — dapsone.
                                                          Quinine and Quinidine Oerdose
  •   Antibiotics:     Tetracycline,   doxycycline,
      azithromycin.                                       General Overdose Management
  •   Miscellaneous: Halofantrin, artemisinins.
                                                            • No ipecac: Due to emesis, seizures, aspiration
Quinine and Cinchonism                                      • Orogastric   lavage: Only for ingestions of <1
Pharmacology: Quinine and Quinidine                         •   AC + cathartic: 1 g/kg.
                                                            •   MDAC: 0.5 g/kg, no cathartic, every 2–4
  • Source: The optical isomers, quinine and quini-             hours.
      dine, are extracts from the bark (Jesuit bark) of
      the South African Cinchona tree.
                                                          Specific Overdose Management
  •   Absorption: Rapid and complete orally, peaks
      in 3 hours.
  •   Protein binding: 95%.                                 • Serum      alkalinization to pH 7.45–7.50, espe-
  •   Vd: 1.8 L/kg.                                             cially for widened QRS complex with myocar-
  •   Half-life: 6–8 hours.                                     dial depression.
  •   Metabolism: 80%.                                      •   Avoid IA and IC antidysrhythmics with qui-
  •   Renal excretion: 20%.                                     nine/quinidine additive toxicities.
                                                            •   Large Vd renders HP and HD ineffective.
                                                            •   Eye: Monitor for retinal toxicity with baseline
Cinchonism                                                      fundoscopy, visual fields, and color testing.

  • Toxicity: CNS > gastrointestinal > dermatologi-       Chloroquine toxicity
      cal > hematological:
      − CNS: Headache, dizzy–vertigo, confusion,          Chloroquine Pharmacology
          syncope, delirium, seizures, coma.                     and Mechanisms
      − Eye: Mydriasis, scotomata, diplopia, blurred
          vision, photophobia, visual field cuts,
          reduced color vision.
                                                            • Epidemiology:      Highest overdose case fatality
      − Ototoxicity: Tinnitus, deafness.                        rate (CFR) of all antimalarials; narrow thera-
      − Cardiovascular: A Class IA antiarrhyth-             •
                                                                peutic index.
                                                                Pharmacology: Rapidly absorbed orally, peaks
          mic = prolonged PR-QRS-QT; torsades de
                                                                in 1–3 hours, highly protein bound 70%, very
          pointes, ventricular tachycardia, ventricular
                                                                long half-life (40+ days), not dialyzable.
          fibrillation, vasodilation, then hypotension.

                                              Miscellaneous Poisonings with Commonly Prescribed Drugs | 217
  • Binds to tissues: Liver, lungs, kidneys.           Other Antimalarials
  • Less ocular toxicity than quinine/quinidine.       Mefloquine

Chloroquine toxicity and Management                      • Use:       Chloroquine-resistant    Plasmodium
  • Toxicity: Cardiovascular and CNS > pulmonary         •   Pharmacology: Long half-life of 20 days.
      > metabolic:                                       •   Toxicity: CNS > cardiovascular > hepatic:
      − Cardiovascular: Wide QRS, peripheral                 − CNS: Hallucinations, nightmares, seizures,
         vasodilation, direct myocardial depres-                 diffuse encephalopathy.
         sion, severe hypotension, cardiovascular            − Cardiovascular: Hypotension, dysrhythmias.
      − CNS: CNS depression, headache, dizziness,      Primaquine
      − Pulmonary: Respiratory depression and sud-
         den apnea possible.                             • Uses: Relapsing malaria due to P. vivax and P.
      − Metabolic: Severe hypokalemia, flattened T           ovale.
         waves, U waves, shortened ST segments.          •   Toxicity: Less CNS toxicity than mefloquine.
  •   Management: Combined epinephrine and               •   Methemoglobinemia: Especially in G-6-PD
      diazepam = best overdose management                    deficient patients.

218 | Color Atlas of Human Poisonings and enenoming
                                                Part 2:

Cancer Chemotherapeutics:
         Human Carcinogens



         Methotrexate (MtX)
           MTX mechanisms, indications, and toxicities
           General management of MTX overdose
           Specific management of MTX overdose
           General management of intrathecal MTX overdose
           Specific management of intrathecal MTX overdose

         Vincristine (VCR)
           VCR mechanisms, indications, and toxicities
           General management of VCR overdose
           Specific management of VCR overdose
           VCR intrathecal overdose and VCR extravasation

         Anthracycline\ Antibiotics
           Antibiotic toxicities
           Anthracycline extravasation

         Nitrogen Mustards
           Toxicities and management
           Mustard extravasation

           Platinoid mechanism and toxicity
           Platinoid overdose management
 Human Carcinogens

Alkylating chemotherapy agents: Cyclophospha-       Hormones: Estrogens (diethyl stilbesterol), ana-
   mide, melphalan.                                    bolic steroids.
Aromatics: Aromatic amines, benzene, benzidene,     Plastics: Vinyl chloride monomer, aryl acrylates.
   polycyclic aromatic hydrocarbons (PAHs).         Heavy metals: Arsenic, chromium, nickel.
Environmental toxins: Aflatoxins, tobacco smoke,    Ionizing radiation: Radon, x-rays.
   tars, soots, hydrocarbon, dry cleaning and       Nonionizing radiation: Ultraviolet light.
   degreasing solvents = carbon tetrachloride       Miscellaneous drugs: Chloramphenicol, phenytoin.
   (CCl4), perchloroethylene, trichloroethylene,    Industrial exposures: Arsenic, asbestos, cadmium,
   trichloroethane.                                    chromium, nickel, silica.

                                        Miscellaneous Poisonings with Commonly Prescribed Drugs | 221
  • Antimetabolites:      Example = methotrexate                     • Antibiotics:    Two main classes = (1) the true
      (MTX), a dihydrofolate reductase (DHFR)                            anthracyclines = daunorubicin, doxorubicin,
      and thymidine synthetase inhibitor that pre-                       and (2) the mycins = adriamycin, bleomycin,
      vents activated, reduced folate from serving as                    mithramycin, mitomycin. Most antineoplastic
      a cofactor for DNA and RNA synthesis. Over-                        antibiotics are derived from the Streptomyces
      dose causes diffuse mucositis, myelosuppres-                       bacterium and release oxygen (O -) free radicals
      sion, acute renal failure, and death, usually                      (similar to paraquat), causing severe cardiotox-
      from sepsis.                                                       icity, parenchymal pulmonary toxicity, mucosi-
  •   Antimitotics: Examples = vincristine (VCR) and                     tis, and myelosuppression.
      vinblastine (VB), both vinca plant alkaloids                   •   Alkylating agents: Two main classes = (1) nitro-
      that inhibit microtubular polymerization and                       gen mustards, like cyclophosphamide and chlor-
      arrest mitosis at metaphase, limiting cell move-                   ambucil, can cause hemorrhagic cystitis and
      ment and cell division. Overdoses cause sei-                       myelosuppression on overdose; and (2) heavy
      zures, encephalopathy, autonomic dysfunction,                      metal platinoids, like cisplatin and carboplatin,
      myelosuppression, and inappropriate secretion                      can cause seizures, encephalopathy, retinal tox-
      of antidiuretic hormone.                                           icity, ototoxicity, and peripheral neuropathy on

 tABLe 11.1     Classification of Anti-Cancer Agents and Their Toxicities
 Class                 Agent                     toxicity                   Oerdose              Antidote
 alkylating            Mustards                  Hemorrhagic                Seizures,             Benzodiazepines
  agents               Chlorambucil               cystitis,                  myocardial
                       Cyclophosphamide           encephalopathy,            necrosis
                       Platinoids                Peripheral                 Seizures,             Diethyldithiocarbamate
                       Cisplatin                  neuropathy,                encephalopathy,       (chelates platinum)
                       Carboplatin                ototoxicity, retinal       ototoxicity, renal
                                                  toxicity, distal           toxicity
                                                  tubular necrosis,
                                                  acute renal failure,
 antimetabolites       Methotrexate              Mucosities, acute          Myelosuppression      Folinic acid (to block
                                                 renal failure,                                    DHFr inhibition)
 antimitotics          Vinblastine               Peripheral                 Seizures,             Glutamic acid (to
                       Vincristine                neuropathy,                encephalopathy,       stabilize tubulin)
                                                  autonomic                  paralytic ileus,
                                                  neuropathy                 myelosuppression,
 antibiotics           anthrcyclines             Direct                     Dysrhythmias,         Digoxin
                       Doxorubicin                cardiotoxicity,            congestive heart
                                                  congestive                 failure
                       Mycins                    Pulmonary fibrosis         respiratory failure   None, avoid high FO2
 Note: DHFr = dihydrofolate reductase; SIaDH = syndrome of inappropriate secretion of antidiuretic hormone.

222 | Color Atlas of Human Poisonings and enenoming
• Antineoplastic     agents have a very narrow       • Anthracycline     and mycin antibiotics (doxo-
    therapeutic index; 90% of overdoses are unin-       rubicin, bleomycin) are the most toxic cancer
    tentional and iatrogenic; and 20% result in         chemotherapeutics and can cause oxygen-free-
    moderate-to-severe toxicity.                        radical-induced cardiomyopathy with irrevers-
•   Antineoplastic agent overdose has increased         ible congestive heart failure (CHF) and a high
    threefold over the past 10 years.                   case fatality rate (CFR) of 48%+.
•   Vincristine overdose is the most frequently
    reported antineoplastic agent overdose.

                                         Miscellaneous Poisonings with Commonly Prescribed Drugs | 223
    Methotrexate (MtX)
MtX Mechanisms, Indications,                                            General Management of MtX Oerdose
and toxicities
                                                                         • Immediate gastric emptying: Ipecac only if wit-
  • Mechanisms: Inhibits both dihydrofolate reduc-                           nessed ingestion.
      tase (DHFR) and thymidine (thymidylate) syn-                       • Orogastric lavage: Then AC, no cathartic.
      thetase, making reduced folate (folic acid)                        • MDAC: No cathartic.
      unavailable for DNA and RNA synthesis.                             • Cholestyramine: Synergistic with MDAC         in
  •   Indications: Lymphoma, lymphocytic leukemia,                           interrupting enterohepatic circulation of MTX.
      breast cancer, small cell carcinomas, gesta-                       •   Fluid loading: For diuresis.
      tional trophoblastic disease, rheumatoid arthri-                   •   Urinary alkalinization: Using intravenous
      tis, psoriasis, suppression of organ transplant                        sodium bicarbonate (NaHCO3) to maintain
      rejection.                                                             urine at pH 7–8.
  •   Toxicities: Gastrointestinal > renal > bone mar-
      row > CNS > pulmonary:
      − Gastrointestinal: Nausea, vomiting, mucosi-                     Specific Management of MtX Oerdose
          tis = stomatitis, esophagitis, diarrhea; hepa-
          totoxicity = increased hepatic transaminases                   • Antidote: Leucovorin (folinic acid) — restores
          (AST/ALT).                                                         reduced folate; monitor efficacy of folinic acid
      − Renal: Oliguria and azotemia = acute renal                           therapy with decreasing MTX levels. Folic acid
          failure.                                                           is ineffective as a specific antidote; only folinic
      − Bone marrow: Pancytopenia.                                           acid is effective.
      − CNS: Seizures, hemiparesis.                                      •   Enhanced elimination: Hemoperfusion (HP)
      − Pulmonary: Delayed (by 12–17 years) hyper-                           best: HP > HP and hemodialysis (HD) > HD
          sensitivity pneumonitis.                                           (removes both folic and folinic acids).
                                                                         •   Specific granulocyte colony stimulating factors
                                                                             (G-CSF): For bone marrow suppression with
              MTX inhibits both dihydrofolate reductase                      pancytopenia; will restore granulocytes and
                     & thymidylate synthetase
                                                                             reduce risk of sepsis.
    2-Deoxyuridine               Folate
    monophosphate                                   ∗ Dihydrofolate
                                                    reductase (DHFR)    General Management of
                                                                        Intrathecal MtX Oerdose
                       n5, 10, 10 - Methylene Fh4
  ymidylate                                                              • Maintain upright, sitting posture.
synthetase                                                               • Spinal tap for cerebrospinal fluid (CSF) drain-
                                                      n5 - Formyl FH4        age: Use same lumbar puncture (LP) site, if
                           n10 - Formyl FH4            (Leucovorin)
                                Purines                                  •   Perform CSF exchange: 2–3 exchanges replac-
                                                                             ing CSF with equal parts (30 mL) of lactated
                                                                             Ringer’s solution (LR) to CSF.
                                                                         •   Consider CSF perfusion: Perform ventriculos-
FIGURe 11.4 The mechanisms of action of metho-                               tomy for spinal subarachnoid space irrigation
trexate (MTX). The anti-neoplastic activities and sites                      with LR and 25 mL fresh frozen plasma (FFP)/
of action of the commonly prescribed cancer chemo-                           L of LR at 150 mL/hour for 24 hours.
therapeutic agent, methotrexate (MTX).

224 | Color Atlas of Human Poisonings and enenoming
Specific Management of
Intrathecal MtX Oerdose
                                                                             10−3                  Leucovorin dose
 • High dose leucovorin (folinic acid) rescue: IV

                                                     concentration (molar)
                                                     Plasma methotrexate
                                                                                               1000 mg/m2 every 6 hours
   only; CNS toxic if given intrathecally (IT).
 • Overhydration: To promote renal excretion.                                10−5
 • Urinary alkalinization.                                                   10−6
                                                                                                         100               C
 • Dexamethasone IV: To limit meningeal                                                                  10                B
   inflammation.                                                             10−7
                                                                                                         10                A
                                                                             10−8       No leucovorin

                                                                                    0          24          48             72
                                                                                         Hours post methotrexate

                                                     FIGURe 11.5 The management of methotrexate
                                                     (MTX) overdose with leucovorin. A clearance graph of
                                                     the efficacy of leucovorin in the management of meth-
                                                     otrexate (MTX) overdose.

                                           Miscellaneous Poisonings with Commonly Prescribed Drugs | 225
   Vincristine (VCR)

VCR Mechanisms, Indications,                                    tion and propagation, and improving peripheral
and toxicities                                                  neuropathy.
                                                            •   Leucovorin (folinic acid): May limit neuropa-
                                                                thy and myelosuppression by blocking VCR’s
  • Mechanisms:       VCR and vinblastine (VB) are
                                                                inhibition of both DHFR and thymidylate
      periwinkle plant alkaloids that, like colchicine
      (from crocus plants) and podophyllin from
      mayapple plant, bind to tubulin to prevent its
      polymerization into microtubules, arresting
                                                          VCR Intrathecal Oerdose
      mitosis at metaphase, and inhibiting cell move-
                                                          and extraasation
      ments and cell division.
  •   Indicications: Leukemias, lymphomas, solid          Intrathecal Overdose of VCr
  •   Toxicities: CNS > bone marrow > cardio-               • High CFR: Secondary to chemical arachnoidi-
      vascular:                                                 tis, ascending neuropathy, encephalopathy, and
      − CNS: ascending peripheral neuropathy (axo-              seizures.
          nopathy), seizures, encephalopathy, auto-
          nomic dysfunction = paralytic ileus, atonic
                                                            •   Posture: Maintain upright for gravitational pro-
                                                                tection of brain.
          bladder; hypothalamic stimulation = fever         •   CSF drainage: Use same LP.
          and syndrome of inappropriate antidiuretic
          hormone secretion (SIADH) with hyponatre-
                                                            •   CSF exchange: 30 mL lactated Ringer’s solution
                                                                per 30 mL CSF every 3 exchanges.
          mia and intravascular volume overloading.
      − Bone marrow: Myelosuppression, VB >                 •   CSF perfusion: Lactated Ringer’s solution + FFP
                                                                25 mL/L as for intrathecal overdose of MTX.
      − Cardiovascular: Necrotic myocardial infarc-
          tion as a result of alkaloid-induced coronary   VCr Subcutaneous Extravasation
          vasospasm and platelet aggregation.

General Management of VCR Oerdose                          • Aspirate infusate: From infiltrated IV site.
                                                            • Consider dilution: Use normal saline to dilute
                                                                VCR in subcutaneous tissues.
  • Oral overdose: Ipecac only if witnessed inges-          •   Hyaluronidase: Inject intradermally or subcu-
      tion, then orogastric lavage and AC.                      taneously to promote systemic absorption of
  •   IV overdose: Most common, provide seizure                 VCR.
      management with benzodiazepines (BZs)                 •   Warm dry compresses: To promote vasodilation
      preferred over barbiturates (respiratory and              and systemic absorption of VCR.
      cardiovascular depressants), secure airway            •   Extremity elevation: To limit further progres-
      immediately.                                              sion of extravasation.

Specific Management of VCR Oerdose

  • Antidote = Glutamic acid: May assist in stabili-
      zation of tubulin promoting polymerization into
      microtubules, restoring granulocyte locomo-

226 | Color Atlas of Human Poisonings and enenoming
Antibiotic toxicities                                   Anthracycline extraasation

  • Representatives: (1) Doxorubicin group, includ-      • Consider dimethylsulfoxide (DMSO) as a free
      ing all Streptomyces-derived antibiotics, are        radical scavenger.
      cardiotoxic (increased risk of CHF) free radi-     • Cold compresses to reduce swelling and limit
      cal formers; (2) mycins: adriamycin, bleomycin,      absorption.
      mitomycin.                                         • Extremity elevation.
  •   Antidotes: None.
  •   Cardiotoxicity: Monitor for 10% drop in ejec-
      tion fraction.
  •   Cardioprotectants: Consider digoxin to increase
      ejection fraction.
  •   Pulmonary toxicity: Maintain adequate oxygen
      saturation with the lowest inspired concentra-
      tions of oxygen to limit oxygen toxicity with
      enhanced pulmonary parenchymal damage.
  •   Myelosuppression: Monitor CBC and platelets.
  •   Enhanced elimination: Hemoperfusion (HP)

                                            Miscellaneous Poisonings with Commonly Prescribed Drugs | 227
   Nitrogen Mustards
toxicities and Management                                  Mustard extraasation

  • Representatives:    Cyclophosphamide, chloram-          • Sodium     thiosulfate: Administer intradermally
      bucil, mechlorethamine.                                   or subcutaneously to dilute extravasation and
  •   Mechanism: Form reactive intermediates that               inhibit subcutaneous tissue alkylation by blis-
      bind to nucleophilic moieties on DNA.                     tering mustards through sulfhydryl group
  •   Toxicities: Chlorambucil — seizures, CNS                  donation.
      depression; cyclophosphamide — hemorrhagic            •   Cool compresses.
      cystitis in 10% of cases and cardiotoxicity =         •   Extremity elevation.
      arrhythmias and myocarditis.
  •   Management: Benzodiazepines (BZs) for sei-
      zures, secure the airway, orogastric lavage, acti-
      vated charcoal (AC).

228 | Color Atlas of Human Poisonings and enenoming
Platinoid Mechanism and toxicity                        Platinoid Oerdose Management

 • Representatives:     Platinum-containing cisplatin    • Renal    protection: By (1) chloride diuresis —
     and carboplatin.                                        intravenous administration of 0.9% NaCl +
 •   Mechanism: Platinoids form intra- and inter-            mannitol to maintain high chloride (Cl) diure-
     strand crosslinks with DNA molecules when               sis and increased platinum excretion; and (2)
     hydrolytically activated upon entering low chlo-        nephroprotection with two specific antidotes:
     ride intracellular environments.                        diethyldithiocarbamate (DDTC) or its precur-
 •   Toxicities: CNS > renal > bone marrow:                  sor disulfiram and sodium thiosulfate, both of
     − CNS: Seizures, encephalopathy, heavy-metal            which chelate free platinum.
         induced sensory peripheral neuropathy-          •   Enhanced       elimination:     Plasmapheresis
         axonopathy, retinal toxicity, reduced color         only, especially for chelated platinum; HD
         vision, ototoxicity (high-frequency).               ineffective.
     − Renal: Distal tubular necrosis with subse-
         quent acute renal failure (ARF).
     − Bone marrow: Myelosuppression: anemia,

                                            Miscellaneous Poisonings with Commonly Prescribed Drugs | 229
                                                    Part 3:

Hypoglycemics: Outline


          etiologies of hypoglycemia

          Clinical manifestations of hypoglycemia

          Orally administered hypoglycemic agents

          General and specific management
          of toxic hypoglycemia

          Surreptitious hypoglycemia

   Miscellaneous Poisonings with Commonly Prescribed Drugs | 231
Definitions                                               Clinical Manifestations of Hypoglycemia
                                                          Manifestations Caused by Catecholamine
  • Hypoglycemia: Failure to maintain serum glu-                release
      cose >60 mg/dL.
  • Euglycemia:    Serum glucose level of 70–110
                                                            • Cardiovascular      effects: Arrhythmias (SVT,
                                                                PVCs, atrial fibrilation); hypertension — head-
  •   Therapeutic euglycemia maintenance: 100–250
                                                                ache; angina from cardiac ischemia, myocardial
                                                            •   Autonomic effects: Anxiety, diaphoresis, dry
epidemiology                                                    mouth, pallor, piloerection.
                                                            •   Gastrointestinal effects: Hunger, nausea.

  • Accidental     insulin overdose: Most common
      cause of hypoglycemia due to combinations of        Manifestations Due to Cerebral Glucose
      insulin dose miscalculations, reduced caloric       Depletion
      intake, increased exercise level or intercurrent
      infections or other illnesses.
  •   Long-acting (LA) sulfonylureas: Most common
                                                            • Acute     delirium: Confusion, bizarre behavior,
      cause of non-insulin, drug-induced hypoglyce-
      mia, especially chlorpropamide LA and glybu-
                                                            •   Coma: Posturing, CNS and respiratory depres-
                                                                sion, hypothermia, preserved brainstem reflexes
      ride LA.
                                                                (doll’s eyes, oculocephalic, oculovestibular, and
  •   Market withdrawals: (1) The biguanide, phen-
                                                                papillary light reflexes).
      formin, was withdrawn in 1976, due to fatal
      lactic acidosis; (2) troglitazone (Rezulin®), a
                                                            •   Focal neurologic deficits: Mimics cerebrovascu-
                                                                lar accident (CVA) or stroke, ataxia, weakness,
      thiazolidinedione, was withdrawn in the 1990s,
                                                                hemiparesis, hemiplegia.
      due to fatal hepatotoxicity.
                                                            •   Solitary or refractory seizures: No postictal
etiologies of Hypoglycemia
                                                          Orally Administered Hypoglycemic
  • Pathophysiological:        Endocrinopathy (Addi-      Agents
      son’s disease, Sheehan’s syndrome); neoplasms
      (insulinomas, multiple endocrine adenomatosis       Sulfonylureas
      [MEA] type I); liver disease (alcoholism, cirrho-
      sis); chronic renal failure (CRF) and hemodialy-      • First-    vs. second-generation sulfonylureas are
      sis; miscellaneous (AIDS, autoimmune diseases,            derivatives of the sulfonamide antibiotics that
      pregnancy).                                               stimulate insulin release from pancreatic beta
  •   Drug-induced: Oral hypoglycemic agents, par-              islet cells by blocking K channels and opening
      enteral insulin preparations.                             Na channels to cause depolarization and release
  •   Food or drug potentiation of hypoglycemic                 of endogenous insulin. Sulfonamides also
      agents: Foods (unripe Jamaican ackee fruit-               decrease hepatic gluconeogenesis and increase
      hypoglycin [vomiting, hypoglycemia, CNS                   peripheral tissue sensitivity to insulin.
      depression, seizures], ethanol); drugs (ACE
      inhibitors, β -blockers, chloramphenicol, diso-     Intestinal alpha-Glucosidase inhibitor
      pyramide, MAOIs, quinine-quinidine, salicy-
      lates, sulfonamides).                                 • Acarbose (Precose    ®
                                                                                    ); reduces sugar absorption
                                                                from gut, does not cause hypoglycemia, must be
                                                                used concomitantly with sulfonylureas.

                                              Miscellaneous Poisonings with Commonly Prescribed Drugs | 233
thiazolidinediones                                               • Type I IDDM: Ineffective.
                                                                 • Type II NIDDM: Effective.
  • Troglitazone    (Rezulin®); recently withdrawn               • Non-diabetics: Can cause severe hypoglycemia,
     due to fatal hepatotoxicity.                                   especially long-acting chlorpropamide and all
                                                                    second-generation sulfonylureas, glypizide and
First generation: Few hypoglycemic events, but can                  glyburide.
act up to 72 hours

  • Acetohexamide (Dymelor )       ®                          Biguanides
  • Chlorpropamide (Diabenese          ), long-acting (LA)

  • Tolazamide (Tolinase )     ®                              Metformin (Glucophage®); phenformin withdrawn
  • Tolbutamide (Orinase )     ®                              in 1976 due to fatal lactic acidosis. The biguamides
                                                              increase peripheral glucose uptake and decrease
                                                              hepatic gluconeogenesis.
Second generation: All LA preparations increase
hypoglycemic events                                           Mechanism: Biguanides do not stimulate insulin
                                                              secretion, but do inhibit gluconeogenesis, and pro-
  • Glipizide (Glucotrol ) LA
                                                              mote peripheral tissue, especially muscle tissue,
  • Glyburide (Diabeta , Micronase
                           ®               ®
                                            ) LA              glucose uptake.

                                                                 • Type I IDDM: Ineffective.
Mechanisms: Sulfonylureas stimulate pancreatic                   • Type II NIDDM: Effective.
beta cells to release preformed endogenous insulin               • Non-diabetics: Do not lower blood glucose.

Characteristics of Routinely Administered Insulin Preparations

   table 11.2 Insulin Pharmacoknetics. Common classes and examples of routinely administered insulin
   preparations that are often mixed on individual daily dosing schedules to permit the most precise therapeutic
   maintenance of euglycemia in Type ! (juvenile diabetes) and Type II (adult-onset diabetes) insulin-dependent
        Class of Insulin
         Preparations              Short (rapid)-acting         Intermediate-acting           Long (ultra)-acting
       Duration (hours)                        3-6                      10-18                        18-36
     Examples of routinely           regular insulin                 NPH insulin                       PZI
      administered insulin         (Humulin®, Novolin®)              Lente insulin             Ultralente insulin
         preparations                 Insulin aspart                                            Insulin glargine
                                        (Novolog®)                                                 (Lantus®)
                                      Insulin lispro
          Metabolism                       Hepaticq                    Hepatic                  Not metabolized
           Excretion                        renal                       renal                renal excretion only
   NPH: Neutral Protamine Hagedorn Insulin.
   PZI: Protamine Zinc Insulin.

234 | Color Atlas of Human Poisonings and enenoming
General and Specific Management                             • Octreotide (sandostatin): A semisynthetic, long-
of toxic Hypoglycemia                                           acting analog of somatostatin that also inhibits
                                                                insulin release in insulinomas, quinine-quini-
Immediate General Management                                    dine overdoses, and sulfonylurea overdoses
  • Contraindicated treatments: No ipecac due to
      seizures; no glucagon.
  • Secure     airway: Then left lateral decubitus        Surreptitious Hypoglycemia
  •   Labs: Glucose, BUN-creatinine, electrolytes,        Epidemiology
      Ca, Mg, CBC, ethanol level.
  •   Coma cocktail: D50W, 1 g/kg, + thiamine, 100          • IDDM      patients: High risk for unintentional
      mg.                                                       insulin overdoses.
  •   Initial orogastric lavage: Then AC and                •   Health-care workers: High-risk intentional
      cathartic.                                                insulin overdoses; suicides, homicides, child
  •   MDAC: For long-acting (chlorpropamide) and                abuse, and elder abuse (Example: Klaus von
      enterohepatic recirculating (glipizide) agents.           Bulow case, Newport, RI).
  •   D10W maintenance: Maintain relative euglyce-
      mia, 100–250 mg/dL.
                                                          Differential Lab Evaluation
Specific Drug Overdose Management                           • Insulin   induced: High insulin levels, insulin
                                                                antibodies present, and low C-peptide lev-
  • Urinary      alkalinization: Only for chlorprop-            els (a useful biomarker of exogenous insulin
      amide, a weak acid; maintain urine pH                     administration).
      7.0–8.0.                                              •   Sulfonylurea induced: High insulin levels, no
  •   Diazoxide (Hyperstat ®): Directly inhibits insu-          insulin antibodies, high C-peptide levels, and
      lin secretion from insulinomas and sulfonylurea           urinary sulfonylurea metabolites present.
      overdoses; administer 300 mg slow IV over 30
      minutes in D10W every 4 hours to avoid hypo-
      tension. Diazoxide is a true antidote for sul-
      fonylurea-induced hypoglycemia and blocks
      insulin release by closing the beta islet cell Na
      channels, opening their K channels, and stop-
      ping beta islet cell depolarization.

                                              Miscellaneous Poisonings with Commonly Prescribed Drugs | 235
         Chapter 12

Food Poisonings

        Food Poisonings | 237
   Chapter Outline
Introduction                                      Parasitic Diseases
                                                    Trichinella spiralis
Clinical manifestations
                                                  Cruise Ship Diarrhea
etiologic agents                                    Prevention and control
  Potential etiologic agents
  Bioterrorism (BW) agents and categories of BW
     agents                                         Final recommendations

top etiologic agents

Bacterial diseases
  Bacillus anthracis
  Bacillus cereus (d-toxin)
  B. Cereus (enterotoxin)
  Brucella spp.
  Campylobacter jejuni
  Clostridium botulinum
  Clostridium perfringens
  Escherichia coli
  Listeria monocytogenes
  Salmonella spp.
  Shigella sonnei
  Staphylococcus aureus
  Vibrio cholerae
  Non-cholera vibrios
  Yersinia enterocolitica

Viral diseases
  Hepatitis A virus (HAV)
  Hepatitis E virus (HEV)
  Norwalk-like viruses

Protozoal diseases
  Entamoeba histolytica
  Giardia lamblia
  Coccidial protozoan: Cryptosporidium parvum
  Coccidial protozoan: Cyclospora cayatenesis
  Coccidial protozoan: Isospora belli
  Coccidial protozoan: Toxoplasma gondii

                                                                             Food Poisonings | 239
                           Incidence∗ of diagnosed infections, by pathogen and site - foodborne
                                 diseases active surveillance network†, United States 2000
           30                                                                   Shigella
                                                                                Escherichia coli O157

                CaliforniaConnecticut Georgia Maryland Minnesota New York Oregon Tennessee
                ∗Per   100,000 population

    FIGURe 12.1 Active surveillance for foodborne infectious diseases by
    pathogen and site, U.S., 2002. The incidence of diagnosed foodborne
    infectious diseases by causative pathogen and state of occurrence in
    the U.S. in 2002. (Source: U.S. Government Document, CDC, FoodNet,
    U.S. Foodborne Diseases Active Surveillance Network, 2002.)

                                              Bacterial: Cholera pandemics

                                     1887                            1960s 1817

                              1991                                       1822

                                                   I. Classic (pandemics 1-6: 1817–1923)
                                                   II. EI Tor (7th pandemic: 1961–present)
                                                   III. 0139-Bengal (8th pandemic: 1992–present)

    FIGURe 12.2 The historical global cholera pandemics. A world map
    indicating the major pandemics and the pandemic spreading routes of
    historical global cholera pandemics of the nineteenth and twentieth

                                                                                                        Food Poisonings | 241
   Clinical Manifestations
  • Acute gastroenteritis: Vomiting is the primary       • Neurologic       manifestations: Gastroenteritis
      symptom; diarrhea may also be present.                 and/or diarrhea with paresthesias, respiratory
  •   Noninflammatory diarrhea: Watery diarrhea              depression, weakness, or any other peripheral
      without high fever or dysentery; low-grade fever       or central neurologic manifestation.
      possible.                                          •   Systemic illness: A multisystem disease of the
  •   Inflammatory diarrhea: Grossly bloody diar-            gastrointestinal (GI) tract and other systems,
      rhea with mucus and pus; often high fever.             particularly the circulatory, nervous, and renal
  •   Persistent diarrhea: Diarrhea lasting more than        systems.
      14 days.

242 | Color Atlas of Human Poisonings and enenoming
   etiologic Agents
Potential etiologic Agents                                 • Neurologic      manifestations: Botulinum tox-
                                                               inbw, OP pesticidescw, thallium, scombrotoxin,
  • BW:     Potential biological warfare agent; and
                                                               ciguatoxin, tetrodotoxin, brevitoxin, saxitoxin,
      CW: potential chemical warfare agent.
                                                               domoic acid, mushroom toxins, post-Campylo-
  •   Acute gastroenteritis: Norwalk-like virus (vom-
                                                               bacter Guillain-Barré syndrome.
      itoxin), Staphylococcus aureus toxinbw, Bacillus
      cereus toxin, all heavy metals (Hg, As).
                                                           •   Systemic illness: Listeria monocytogenes, Bru-
                                                               cella Trichinella spiralis, Toxoplasma
  •   Noninflammatory diarrhea: Enterotoxigenic E.
                                                               gondii, Vibrio vulnificus, hepatitis A virus.
      coli (ETEC), Vibrio cholerae, astroviruses, cali-
      civiruses (genus Norovirus), rotaviruses, adeno-
      viruses, Cryptosporidium parvum, Cyclospora         Bioterrorism (BW) Agents and
                                                          Categories of BW Agents
  •   Inflammatory dysentery: Shigella, Cam-
      pylobacter spp., Salmonella spp., Enteroinva-
      sive E. coli (EIEC), Enterohemorrhagic E. coli       • Bacillus anthracis (BW-A list)
      (EHEC), Vibrio parahemolyticus, Entamoeba            • Botulinum toxin (BW-A list)
      histolytica, Yersinia enterocolitica.                • Brucella species (BW-B list, Greece-WWII)
  •   Persistent diarrhea: Cyclospora cayetanensis,        • Shigella species (BW-B list, N. Africa — World
      Cryptosporidium parvum, Entamoeba histo-                 War II, Oregon salad bar)
      lytica, Giardia lamblia.                             • Staph aureus toxin (BW-B list)

                                                                                        Food Poisonings | 243
   top etiologic Agents
  • Acute gastroenteritis: Norwalk-like virus > S.           • Persistent diarrhea: Cryptosporidium parvum >
      aureus > B. cereus.                                        Cyclospora cayetanensis.
  •   Noninflammatory diarrhea: ETEC (traveler’s             • Neurologic      manifestations: Botulismbw, OP
      diarrhea) > Vibrio cholerae.                               poisoningcw.
  •   Inflammatory diarrhea: Campylobacter spp. >            •   Systemic illness: Listeria monocytogenes > Bru-
      Shigella spp.                                              cella

 tABLe 12.1 Differential Diagnosis
        Acute Onset                                             Unpasteurized
        <6 h = toxin          Fecal wbc’s = Dysentery            Milk/Cheese            Dysentery + High Feer
 Staph aureus                Shigella                   Salmonella (eggs)              Salmonella
 Bacillus cereus             Salmonella                 Campy (chicken)                Shigella
 EtEC                        Campy                      Brucella (goat)                Campy
 Ciguatera                   EIEC                       Listeria (processed meats)     EIEC
 Cholera                     Yersinia                   tB                             Yersinia

244 | Color Atlas of Human Poisonings and enenoming
   Bacterial Diseases
Bacillus anthracis                                        Prevention (Vaccination)
                                                            • Primary     prevention (vaccination): Inactivated,
                                                                six-shot series vaccine; cook meat and lamb
  • Large,     spore-forming, Gram-positive bacilli
                                                                thoroughly before eating; wear gloves when
      that multiply and align in snakelike chains
                                                                handling livestock, especially potentially con-
      (“Medusa head”).
                                                                taminated livestock.
  •   Reservoir: Livestock (cattle > sheep), long-lived
                                                            •   Secondary prevention (diagnosis): Diagnosis by
      spores in soil.
                                                                Gram stain on blood-stool-sputum, C&S (BSL-
  •   Endospores: 2–5 microns, environment stable,
                                                                4), chest x-ray — widened mediastinum.
      BW-A list.
  •   Like B. cereus, non-hemolytic on blood agar
                                                            •   Tertiary prevention (treatment): Skin and GI —
                                                                penicillin; inhalation — doxycline, quinolones.
      (culture only in biosafety level 4 [BSL-4]
                                                          Bacillus cereus (d-toxin)
Epidemiology                                              Microbiology

  • Transmission:    Direct contact — broken skin           • Large,      spore-forming Gram-positive bacilli
      > contaminated meat > aerosolized inhaled                 multiplies and aligns in long chains.
      contact.                                              •   Reservoir: Like B. anthracis, stable spores long-
  •   Vehicle: Raw and undercooked meat.                        lived in the environment.
  •   Inoculum: 6, 60, 6000 spores (secondary to            •   Looks like B. anthracis in culture, but hemo-
      inoculum size and host susceptibility).                   lytic on blood agar.
  •   Incubation: 2–60 days.
  •   Warning: Ranchers, cutaneous > inhalationbw >
      GI transmission rare.                               Epidemiology

Clinical Manifestations
                                                            • Transmission: Fecal–oral > direct contact.
                                                            • Vehicle: Contaminated meats (subs, Po-boys),
                                                                gravies, vanilla sauces.
  • Cutaneous: Black eschar, dramatic local edema,          •   Inoculum: Low (toxin).
      regional lymphadenopathy.                             •   Incubation: 10–16 hours.
  •   Gastrointestinal (GI): Nausea and vomiting,           •   Warning: French dip, roast beef (Po-boys, subs),
      malaise, bloody diarrhea, abdominal pain, sep-            sweet sauces and gravies.
      sis, case fatality rate (CFR) 50+%
  •   Inhalation: Upper respiratory illness (URI)
      — prodrome, pneumonia, adult respiratory dis-       Clinical Manifestations
      tress syndrome (ARDS), sepsis, hemorrhagic
      mediastinitis; case fatality rate (CFR) was 70%,      • Acute gastroenteritis: 24–48 hours of nausea,
      now <50% with ICU.                                        no vomiting, abdominal cramps, watery diar-
                                                                rhea without blood or pus.
                                                            •   Wound infections: More common with
                                                            •   Subacute bacterial endocarditis: Possible, but

                                                                                         Food Poisonings | 245
Prevention                                               Brucella spp.
  • Primary     prevention: No vaccine, avoid high-
      risk foods.
  •   Secondary prevention: Food and stool culture,
                                                           • Small, Gram-negative coccobacilli.
      diarrheal toxin identification in stool.
                                                           • Reservoir: Infected livestock–cattle (B. abortus),
                                                               pigs (B. suis), sheep and goats (B. melitensis).
  •   Tertiary prevention: Self-limiting, no antibiot-
                                                           • Rose-Bengal test for screening for B. abortus
      ics, supportive care only.
                                                               antibodies in infected beef cattle and dairy
B. cereus (enterotoxin)                                    •   Dye inhibition tests to differentiate among Bru-
                                                               cella spp.

  • Large, spore-forming Gram-positive bacilli.          Epidemiology
  • Reservoir: Like anthrax, environmentally stable
      spores.                                              • Transmission:    Fecal–oral > direct contact >
  •   Indistinguishable from Bacillus cereus — diar-           aerosol (suspect bioterrorism).

      rhea toxin.                                          •   Vehicle: Unpasteurized milk and cheeses, under-
  •   Hemolytic on blood agar, like B. cereus                  cooked meats.
      (d-toxin).                                           •   Inoculum: Low.
                                                           •   Incubation: 7–21 days.
                                                           •   Warning: Unpasteurized cheeses, especially feta
Epidemiology                                                   (goat) cheese.

  • Transmission: Fecal–oral > direct contact.           Clinical Manifestations
  • Vehicle: Improperly refrigerated cooked       and
      fried meats and especially fried rice.
  • Inoculum: Low (toxin).                                 • Brucellosis:    Brucellosis is a systemic illness
  • Incubation: 1–6 hours.                                     with high fever, chills, sweats, weakness, myal-
  • Warning: Chinese food,      especially spoiled or          gias, joint pain, lymphadenopathy, and bloody
      unrefrigerated meat and fried rice dishes.               diarrhea during the acute phase. Chronic ill-
                                                               ness mimics chronic fatigue syndrome and
Clinical Manifestations                                    •   Complications: Osteomyelitis, subacute bacte-
                                                               rial endocarditis, neuropsychiatric manifesta-
  • Acute    gastroenteritis: Sudden onset of severe           tions, especially depression.
      nausea, projectile vomiting, watery diarrhea
      without blood, pus may rarely be present, self-
      limiting within 12–48 hours, severe dehydra-
      tion possible.
                                                           • Primary prevention: No vaccine; avoid unpas-
Prevention                                                     teurized milk and cheeses.
                                                           • Secondary prevention: Blood culture and anti-
  • Primary     prevention: No vaccine, avoid high-            biotic sensitivity testing (C&S), serology, Rose-
      risk foods.                                              Bengal screening of cattle, Brucella blue-ring
  •   Secondary prevention: Food and stool culture,            agglutination tests on raw milk.
      enterotoxin identification in stool.                 •   Tertiary prevention: Rifampin and doxycycline
  •   Tertiary prevention: Self-limiting, no antibiot-         every day for 6 weeks. For complications, add
      ics, supportive care only.                               an aminoglycoside.

246 | Color Atlas of Human Poisonings and enenoming
Campylobacter jejuni                                     raw, Grocery-Bought Chickens
Microbiology                                               • Campylobacter:      Currently the most common
                                                               cause of U.S. foodborne illnesses; found in 42%
                                                               of grocery chickens; 90% of cultures demon-
  • Gram negative, thin, spiral, “gull wing,” motile-          strated multiple antibiotic resistances.
      darting bacilli, 1 flagellum.
  • Reservoir: Wild and domestic birds (especially         •   Salmonella: Found in 12% of grocery chickens;
                                                               34% antibiotic resistant.
      chickens and turkeys) and mammals.
  • United States: No. 2 cause of foodborne bacte-         •   Campylobacter and Salmonella: Found in 5%
                                                               of grocery-bought chickens.
      rial diarrheas, alternating with Salmonella spp.
  •   World: No. 2 cause of traveler’s diarrhea (#1
                                                           •   Antibiotic resistance: Due to an increase in
                                                               the use of prophylactic antibiotics in domestic
                                                               chicken and turkeys (quinolones > tetracyclines
                                                               > penicillins).
                                                         Clostridium botulinum
  • Transmission: Fecal–oral.                            Microbiology
  • Vehicle: No. 1 undercooked      poultry (chicken
      > turkey) > No. 2 unpasteurized milk > No. 3
      contaminated water.                                  • Anaerobic,      spore-forming   Gram-positive
  •   Inoculum: 104 –106 organisms.                            bacilli.
  •   Incubation: 1–5 days.                                •   Reservoir: Ubiquitous environmentally stable
  •   Warning: Common, mimics Crohn’s Disease vs.              spores.
      chronic ulcerative colitis (CUC); serious com-       •   Hemolytic on blood agar.
      plications = post-infection Guillain-Barré syn-
      drome and arthritis.

Clinical Manifestations                                    • Transmission: Environment > fecal–oral > aero-
                                                               solbw (suspect bioterrorism).
  • Prodrome: Fever, headache, nausea and vomit-           •   Vehicle: Contaminated home-canned fruits,
      ing, malaise, myalgias.                                  vegetables (garlic), fish; herb-infused salad oils;
  •   Colitis: Cramps, 1–10 days diarrhea, mucus,              honey.
      blood (50%), pus (75%), chronic relapsing            •   Lethal dose: 1 pg/kg.
      colitis (differential diagnosis (DDx) includes:      •   Incubation: Adults, 12–72 hours; infants, 3–30
      Crohn’s and CUC).                                        days.
  •   Complications: Guillain-Barré syndrome (10–          •   Warning: Home-canning, home-preserving,
      20%), reactive arthritis (1–14%).                        dented tuna and whitefish cans; raw, decom-
                                                               posing marine mammal meat — whale (“muk-
                                                               tuk”), seal, walrus.

  • Primary prevention: No vaccine; avoid under-         Clinical Manifestations
      cooked poultry and raw, unpasteurized milk.
  • Secondary      prevention: Fecal polymorphonu-         • Adult    botulism: Nausea and vomiting, diar-
      clear cells (pmns), Gram stain, C&S, stool for           rhea, then blurred vision, diplopia, dyspha-
      radioimmunoassay detected antigens.                      gia, descending paralysis, respiratory failure,
  •   Tertiary prevention: Macrolides are best (eryth-         CFR 50+%, pathognomonic manifestations =
      romycin, azithromycin) > quinolones > tetra-             descending paralysis and normal mental status.
      cycline (TCN); resistant to penicillin (pcn),        •   Infant botulism: <12 months, lethargic — weak,
      vancomycin, trimethoprim-sulfamethoxazole                poor feeding, poor gag and suck, hypotonia =
      (TMP/SMX).                                               floppy baby/floppy head.
                                                           •   Warning: Honey in bottled milk.

                                                                                          Food Poisonings | 247
Prevention                                                  • Secondary    prevention: Quantitative stool cul-
                                                                ture to rule out normal flora, Gram stain on
                                                                stool and pus, identification of enterotoxin in
  • Primary prevention: Avoid high-risk foods.                  stool.
  • Secondary prevention: Food and stool cultures,          •   Tertiary prevention: Self-limiting; supportive
      identification of botulinum toxin in food, vomi-
                                                                care only.
      tus, and stool.
  •   Tertiary prevention: Trivalent botulinum anti-
      toxin (adults), botulinum immune globulin and
                                                          Escherichia coli
      pentavalent antitoxin (infants), life support;
      broad-spectrum antibiotics to decrease toxin        Microbiology
      production in gut is controversial.
                                                            • Aerobic, flagellated Gram-negative bacilli.
Clostridium perfringens                                     • Reservoir: GI flora of animals > humans.
                                                            • Three (3) antigen groups: Somatic (O), capsular
Microbiology                                                    (K), flagellar (H) antigens.
                                                            • Five    (5) clinical groups: Enterotoxic E. coli
                                                                (ETEC), enteropathogenic E. coli (EPEC),
  • Anaerobic,      spore-forming      Gram-positive
                                                                enteroinvasive E. coli (EIEC), enterohemor-
                                                                rhagic E. coli (EHEC, zoonosis), enteroadhesive
  •   Reservoir: Domestic livestock and poultry, envi-
                                                                E. coli (EAEC). Clinical groups may overlap.
      ronmentally stable spores.
  •   Unique double zone of hemolysis on blood
                                                            •   ETEC > EPEC > EAEC as causes of traveler’s

Epidemiology                                              Epidemiology

  • Transmission: Fecal–oral.                               • Transmission: Fecal–oral, person-to-person.
  • Vehicle: Contaminated poultry, meats, gravies,          • Vehicle: Food (ground beef, apple/orange juice)
                                                                > water.
      dried and precooked foods.
  •   Inoculum: Low (toxin).
                                                            • Inoculum: 10–100 organisms.
  •   Incubation: 8–16 hours.
                                                            • Incubation: 3–14 days.
  •   Warning: Dried meats, beef “jerky,” chitterlings
                                                            • Duration: 5–7 days (unless hemolytic    uremic
                                                                syndrome [HUS] or thrombotic thrombocyto-
      (“chitlins”), unrefrigerated meat gravies.
                                                                penic purpura [TTP] with EHEC).
                                                            •   Warning: Water parks, wading pools, day care,
Clinical Manifestations                                         petting zoos, undercooked hamburgers, unpas-
                                                                teurized fruit juices.

  • Acute     gastroenteritis: 24–48 hours of watery
      diarrhea without blood or pus, nausea, no vom-      Clinical Manifestations
      iting, fever rare.
  •   Wound infections: Gas gangrene potential.
                                                            • ETEC: Two Shiga-like toxins, 1–7 days watery
  •   Enteritis     necroticans:  Pseudomembranous
                                                                diarrhea without blood or pus.
      enterocolitis and pneumatosis intestinalis (“pig-
      bel” — Papua New Guinea).
                                                            • EPEC: Same as ETEC, 3–6 days, diarrhea with
                                                                blood/pus, high fever.
                                                            • EA(I)EC:     Rare, O124:B17, 3–7 days of low
Prevention                                                      fever, cramps, diarrhea with blood/pus.
                                                            •   EHEC: O157:H7, 3–10 days of low fever,
                                                                cramps, diarrhea with blood/pus, HUS 5–10%
  • Primary    prevention: No vaccine; avoid high-              primarily in children, TTP 5% primarily in
      risk foods.                                               adults.

248 | Color Atlas of Human Poisonings and enenoming
Prevention                                                    • Secondary     prevention: Blood and CSF C&S,
                                                                  serology-Listerolysin O antibodies.
  • Primary prevention: No vaccine; “boil it, cook            •   Tertiary prevention: GI, supportive; systemic-
                                                                  IV penicillin or ampicillin > TMP/SMX.
      it, peel it, or forget it,” bottled drinks, prophy-
      lactic antibiotics, Pepto-Bismol®.
  •   Secondary prevention: Fecal pmns, Gram stain,
                                                            Salmonella spp.
      C&S, ELISAs for ETEC and EHEC.
  •   Tertiary prevention: Quinolones, resistant to         Microbiology
      doxycycline and TMP/SMX, avoid anti-motil-
      ity agents.
                                                              • Flagellated, Gram-negative bacilli.
                                                              • Reservoir: Humans (typhoidal), birds/reptiles
                                                                  (commensal non-typhoidal strains).
Listeria monocytogenes
                                                              •   Three (3) antigens: Somatic (O), flagellar (H),
Microbiology                                                      and capsular (Vi).
                                                              •   Environmentally stable — fresh water/sewage.
  • Small, aerobic Gram-positive bacilli, non-spore-          •   Non-typhoidal (S. choleraesuis) vs. typhoid —
                                                                  S. typhi and paratyphi — strains.
  • Reservoir:       Humans,       livestock    (cattle),
                                                              •   CFR: S. typhi > S. paratyphi > non-typhoidal
                                                                  Salmonella spp.
  • Pale colonies on blood agar.
                                                              • Transmission:    Typhoidal — fecal–oral; non-
                                                                  typhoidal — direct contact.
  • Transmission: Fecal–oral > direct contact.                •   Vehicle: Contaminated food/water, raw eggs,
  • Vehicle: Unpasteurized milk and soft cheeses,                 poultry, reptiles/amphibians (turtles/lizards
      ready-to-eat deli/luncheon meats, hot dogs,
  •   Inoculum: Low.
                                                              •   Inoculum: 105 –107 organisms.
  •   Incubation: GI, 8–28 hours; systemic listerosis,
                                                              •   Incubation: Non-typhoidal, 12–48 hours;
                                                                  typhoidal, 7–21 days.
      2–6 weeks.
  •   Warning: Hot dogs and “cold cuts” (processed
                                                              •   Warning: Chronic female carriers >40+-year-
                                                                  old females with cholelethiasis = “Typhoid

Clinical Manifestations
                                                            Clinical Manifestations

  • Acute gastroenteritis: Fever, myalgias, nausea,           • Non-typhoidal:      3–10 days of diarrhea with
      no vomiting, diarrhea.
                                                                  blood and pus, fever, cramps, chronic biliary
  •   Perinatal listerosis: Spontaneous abortion
                                                                  carriage possible.
      (SAB), preterm delivery, stillbirth, puerperal
      fever — chorioamnionitis and maternal sepsis,
                                                              •   Typhoidal: 5-day prodrome, fever, chills, sore
                                                                  throat, joint pain, rose spots (30%); cramps,
      neonatal sepsis.
                                                                  hepatosplenomegaly (H/S) (50%), neuropsychi-
  •   Geriatric listerosis: Meningitis, sepsis.
                                                                  atric symptoms, lymphadenopathy, constipa-
                                                                  tion, no diarrhea, bradycardia, CFR ≤ 30%.
Prevention                                                    •   Complications: Bowel perforations from perfo-
                                                                  rated Peyer’s patch, osteomyelitis.
                                                              •   Warning: Infants and elderly in homes with pet
  • Primary    prevention: No vaccine, avoid high-                amphibians and reptiles; turtles > lizards (igua-
      risk foods.                                                 nas) > snakes.

                                                                                           Food Poisonings | 249
Prevention                                                 Prevention

  • Primary prevention: Three typhoidal vaccines:            • Primary prevention: No vaccine; handwashing,
      (1) oral live vaccine, (2) IM, vaccines = approxi-         hygienic food preparation, avoid contaminated
      mately 70% efficacy; “boil-it, bottle-it, peel-it,         drinking water and recreational water.
      or forget-it”; no amphibian/reptile pets (espe-        •   Secondary prevention: Fecal pmns, fecal Gram
      cially with children and elderly in household).            stain, stool C&S, Shiga toxin ELISA, flexible
  •   Secondary prevention: Blood (50%)/urine/rose               sigmoidoscopy with colon biopsy.
      spot (70%)/bone marrow (90%) C&S; Widal                •   Tertiary prevention: Quinolones preferred;
      H/O antibodies.                                            resistant to ampicillin, TMP/SMX, and TCN.
  •   Tertiary prevention: Non-typhoidal — quino-
      lones, TMP/SMX; typhoidal — quinolones >
      ampicillin.                                          Staphylococcus aureus
Shigella sonnei
                                                             • Aerobic Gram-positive cocci in chains.
Microbiology                                                 • Reservoir: Ubiquitous, man, animals, environ-
  • Aerobic Gram-negative bacilli.                           • Yellow-gold colonies on blood agar.
  • Reservoir: Humans only.                                  • Catalase and coagulase positive.
  • Environmentally stable and GI acid-resistant.
  • Four (4) serotypes: A — Shigella dysenteriae, B
      — S. flexneri, C — S. boydii, D — S. sonnei.         Epidemiology
  •   World: S. dysenteriae most pathogenic.
  •   United States: S. sonnei > S. flexneri.                • Transmission: Direct > food > fecal–oral > aero-
                                                                 solbw (suspect bioterrorism).
                                                             •   Vehicle: Contaminated egg/ potato/chicken/sea-
                                                                 food salads with mayonnaise > cream pastries
                                                                 > meats.
  • Transmission: Fecal–oral, food > water.                  •   Inoculation: Low (toxin).
  • Vehicle: Food, water, anal–oral sex, flies       =       •   Incubation: 1–6 hours.
      mechanical vectors.                                    •   Warning: Cream-filled pastries: éclairs, cream
  •   Inoculum: 10–100 organisms.                                puffs, and doberge cakes > salads.
  •   Incubation: 6–72 hours.
  •   Warning: Salad barsbw, day care, mental institu-
      tions, wading pools, male homosexuals — men          Clinical Manifestations
      having sexual intercourse with men (MSM).
                                                             • Acute gastroenteritis: Sudden onset nausea, pro-
                                                                 jectile vomiting, low-grade fever, diarrhea may
Clinical Manifestations                                          be present, lasts 24–48 hours.
                                                             •   Skin infections: Boils, abscesses, impetigo.
  • S.     sonnei, flexneri, boydii: Fever, cramps,          •   Complications: Osteomyelitis, sepsis.
      watery-then-bloody, mucoid diarrhea with pus;
      seizures (children).
  •   S. flexneri: Reiter’s syndrome possible in HLA-      Prevention
      B27 genotypes.
  •   S. dysenteriae: Shiga toxin, severe dysentery,         • Primary prevention: No vaccine; avoid high-risk
      tenesmus, rectal prolapse, hemolytic uremic                foods, personal hygiene.
      syndrome (HUS) in children, thrombotic throm-          • Secondary    prevention: Identification of Staph
      bocytopenic purpura (TTP) in adults.                       enterotoxins in food, vomitus, and stool.
                                                             •   Tertiary prevention: Self-limiting, supportive
                                                                 care only.

250 | Color Atlas of Human Poisonings and enenoming
Vibrio cholerae                                            • Transmission: Raw shellfish (especially raw oys-
                                                               ters) > water.
Microbiology                                               • Clinical   manifestations: 1 week fever, nausea
                                                               and vomiting, watery diarrhea without blood
  • Aerobic, Gram-negative, flagellated, “comma”               or pus.
      bacilli.                                             •   Warning: Avoid raw/undercooked shellfish,
  • Reservoir: Humans.                                         especially in warm months, do not count on
  • Chlorine-resistant, acid-sensitive,   thrives in           cold months with “Rs” and Tabasco® to pre-
      brackish estuaries.                                      vent Vibrio infections.
  •   O1 and O139 strains — cholera toxin blocks
      Cl pump; O1 strains = classical cholera, El Tor
      strain = current epidemic strain.                  Vibrio vulnificus
  •   Non-O strains: Mild diarrhea, wound
      infections.                                          • Marine,       non-cholera Vibrios, salt- and
                                                           •   Transmission: Raw shellfish-oysters, direct
                                                               inoculums — seawater.
                                                           •   Clinical manifestations: Ulcerating cellulitis,
  • Transmission:        Fecal–oral, especially during         ecthyma gangrenosa, sepsis has high CFRs.
      warm periods.                                        •   Prevention: No raw shellfish; treat all penetrat-
  • Vehicle: Contaminated water > shellfish > non-             ing injuries in seawater with quinolones.
      acidic fish.                                         •   Warning: Alcoholism, liver disease, especially
  • Inoculum: 10 –10 organisms.
                     5    8
  • Incubation: 1–5 days.
  • Warning: Raw/under-boiled shellfish, low gas-
      tric pH (B12 deficiency, pernicious anemia),       Prevention
      blood type O, safest consumption during “R”
      months (September–April) = folklore, hemosid-        • Primary     prevention: Vaccine <50% effective,
      erosis or iron therapy (Vibrio organisms seek            adequate sewage treatment, breast-feeding pro-
      iron sources).                                           tects infants with maternal IgA, avoid raw and
                                                               undercooked shellfish.
Clinical Manifestations
                                                           •   Secondary prevention: Dark-field microscopy,
                                                               stool C&S will show blue-green colonies on
                                                               TCBS agar, rapid stool cholera screens.
  • Classical and El Tor strain (90%): Early nausea        •   Tertiary prevention: Oral rehydration solutions
      and vomiting, no fever, painless watery diar-            (ORS), antibiotics may decrease diarrhea and
      rhea, without blood or pus, dehydration, chol-           Vibrio shedding — doxycycline 300 or cipro-
      era — excreters for days.                                floxacin 1 gm orally every day.
  •   Cholera gravis (10%): Abdominal cramps, ful-
      minant rice — watery diarrhea, metabolic aci-
      dosis, hypovolemic shock, cholera — excreters      Yersinia enterocolitica
      for weeks; CFR 40%.

Non-cholera Vibrios                                        • Gram-negative “safety pin” bacilli, resembling
                                                               other Yersinia spp.
Vibrio parahemolyticus
                                                           • Reservoir:    Humans and many domestic ani-
                                                               mals, especially pigs.
                                                           •   Acid and cold stable (Canada, North Europe >
  • Marine, non-cholera Vibrio.                                United States), heat sensitive.
  • Salt-tolerant, acid-sensitive (use    Tabasco® to      •   Three species: Y. enterocolitica, Y. pseudotuber-
      prevent infection = folklore).                           culosis (rare in United States), Y. pestis plague

                                                                                        Food Poisonings | 251
      (four-corner area of United States = Colorado,     Clinical Manifestations
      Utah, Arizona, and New Mexico).
  •   Requires special media for C/S (CIN).
                                                           • Enterocolitis: Canada, Northern Europe, Russia
                                                               > rare in United States; fever, cramps, diarrhea.
                                                           • Acute mesenteric lymphadenitis: Mimics acute
                                                               appendicitis in adolescents.
                                                           • Complications: Erythema nodosum (30%): 2:1
  • Transmission:     Fecal–oral, food > drinking              female:male; polyarthritis (<30%), especially
      water > recreational water > blood > nosoco-             HLA-B27 genotypes; purulent pharyngitis
      mial (households).                                       (<10%).
  •   Vehicle: Contaminated pork, tofu, milk, well
  •   Inoculum: High, 109 organisms.                     Prevention
  •   Incubation: 1–3 days.
  •   Warning: Raw, undercooked pork and pork
                                                           • Primary      prevention: No vaccine; cook pork
      products (chitterlings = fried pork small intes-
                                                               well, especially frozen pork; deep-freeze pork <
      tines), tofu; mimics acute appendicitis, espe-
                                                               4° C.
      cially during winter (Canada and Northern
                                                           •   Secondary prevention: Stool and blood C&S
                                                               with special media, HAI and ELISA rarely
                                                           •   Tertiary prevention: Susceptible to most antibi-
                                                               otics; quinolones > macrolides.

252 | Color Atlas of Human Poisonings and enenoming
   Viral Diseases
Hepatitis A Virus (HAV)                                   Hepatitis e Virus (HeV)
Microbiology                                              Microbiology

  • Small, ssRNA picornavirus, like polio.                  • Small, round ssRNA calicivirus.
  • Reservoir: Humans only.                                 • Reservoir: Humans only.
  • Environmentally stable: Heat (to 60°C)    and           • Environmentally stable: Acid, salt,       cold-resis-
      acid (to pH 1.0)-resistant.                               tant; probably chlorine-sensitive.
  •   Replicates in duodenal epithelial cells and           •   Never successfully cultured in vitro.
      spreads hematogenously to hepatocytes.

                                                            • Transmission: Fecal–oral, water > food (espe-
  • Transmission: Fecal–oral, direct person–person              cially shellfish).
      > food (shellfish–oysters) > water.                   • Vehicle: Human waste-contaminated drinking
  •   Vehicle: Human sewage-contaminated water                  water.
      and food, especially berries and greens (lettuce,     •   Inoculum: High.
      spring mix, green onions).                            •   Incubation: 2–8 weeks.
  •   Inoculum: 104 –108 virions.                           •   Warning: Pregnant women traveling in develop-
  •   Incubation: 2–6 weeks.                                    ing countries (high CFR).
  •   Warning: Day care/mental facilities, male
      homosexuals; occupational exposures — sewer
      workers, primate handlers.                          Clinical Manifestations

Clinical Manifestations
                                                            • Hepatitis: Occurs predominantly in developing
                                                                areas in 15- to 40-year-olds, especially pregnant
                                                                women; high bilirubin levels, deeper jaundice
  • Prodrome: Anorexia, fever, nausea and vomit-                than HAV, otherwise same as HAV; no chronic
      ing, malaise, lethargy.                                   carriers. CFR 0.5–3%; CFR in pregnancy 10–
  • Hepatitis: Right upper quadrant (RUQ) pain,                 20% (mechanism unknown).
      hepatomegaly, dark urine, pale feces, jaundice
      for up to 6 weeks (adults 66%), infants/toddlers    Prevention
      often asymptomatic (80%); lifelong immunity,
      CFR 0.5%.                                             • Primary prevention: No vaccine; use boiled or
                                                                bottled drinking water in developing countries.
                                                            • Secondary prevention: Immunofluorescent elec-
                                                                tron microscope (IFEM), viral RNA ampli-
                                                                fication by PCR; ELISA and Western blot for
  • Primary    prevention: Two formalin-inactivated             antibodies not widely available.
      vaccines, two (2) doses, 90% efficacy.                •   Tertiary prevention: Supportive therapy only.
  •   Secondary prevention: IgM RIA or ELISA,
      IEM, PCR for RNA amplification.
  •   Tertiary prevention: Supportive therapy.

                                                                                         Food Poisonings | 253
Norwalk-like Viruses                                       Rotairuses
Microbiology                                               Microbiology

  • Small, round caliciviruses (virions resemble six-        • Virions   resemble small round wheels (rotors),
      pointed stars) and astroviruses (virions resemble          two concentric icosohedral shells, surface pro-
      snowflakes).                                               tein bumps.
  •   Reservoir: Humans and shellfish.                       •   Reservoir: Humans, domestic animals, mam-
  •   Linear, ssRNA genome.                                      mals and birds.
  •   Intracellular replication within jejunal villi.        •   Environmentally stable: Acid, salt, cold, and
  •   Heat (to 60 ° C), acid (to pH 3.0), and                    chlorine resistant.
      chlorine-resistant.                                    •   Six (6) serotypes: A–F (A is most common
                                                                 causative agent); infection confers limited

  • Transmission:     Fecal–oral, shellfish > salad >
      person to person > water.
  •   Vehicle:      Human         sewage-contaminated        • Transmission: Fecal–oral.
      shellfish.                                             • Vehicle: Contaminated         water > food >
  •   Inoculum: Low, < 102 virions.                              person-to-person.
  •   Incubation: Short, 24–48 hours.                        •   Inoculum: 105 –1010 virions.
  •   Warning: Raw/inadequately cooked shellfish,            •   Incubation: 1–3 days.
      seafood salads, food handlers, travel cruises,         •   Warning: Nurseries, day care, diaper-change
      naval vessels, sea cruises.                                stations (diaper-changers acquire 106 virions on
                                                                 their surfaces per change).

Clinical Manifestations
                                                           Clinical Manifestations
  • Acute     gastroenteritis: 12–60 hours of watery
      diarrhea (80%) with no mucus, blood, or pus;           • Acute     gastroenteritis: Nausea and vomiting
      abdominal cramps (80%), nausea and vomiting                precede 4–5 days of watery diarrhea without
      (50%), fever (50%), headache (50%), and myal-              mucus, blood, or pus; low K+/Cl--metabolic
      gias (< 50%).                                              alkalosis mixed with hypoperfusion metabolic
  •   Always self-limited.                                       acidosis possible; most common in infants 6–
                                                                 24 months old. Mimics pyloric stenosis during
  • Primary      prevention: No vaccine; well-cooked
      shellfish; proper human waste disposal on shell-       • Primary     prevention: RotaShield® live vaccine,
      fish harvesting (especially oyster-fishing) boats.         80% efficacy, withdrawn due to infant small
  •   Secondary prevention: EM, IEM; EIA-RIA-                    bowel intussusception; breast-feeding confers
      PCR are not widely available.                              IgA protection.
  •   Tertiary prevention: Rehydration, supportive           •   Secondary prevention: Stool EM, ELISA, latex
      therapy.                                                   particle agglutination; serum ELISA.
                                                             •   Tertiary prevention: Oral rehydration, support-
                                                                 ive treatment, no anti-motility agents.

254 | Color Atlas of Human Poisonings and enenoming
   Protozoal Diseases
Entamoeba histolytica                                            bodies (antibody detection, acute-convalescent
                                                                 sera-fluorescent antibodies), liver ultrasound >
Microbiology                                                     CT-guided — fluid aspirate.
                                                             •   Tertiary prevention: Cyst passers/colitis: metro-
  • Parasitic, not free-living.                                  nidazole 750 mg three time daily for 10 days;
  • Reservoir: Humans, domestic pets.                            extraintestinal: same and paromomycin 25–35
  • Cysts infective, prefer warm climates,  iodine/              mg/kg/d in three daily doses for 10 days.
      chlorine resistant; excyst in small intestine
      to allow trophozoites to invade colorectal
      mucosa.                                              Giardia lamblia
  •   Pathogenic and nonpathogenic strains (E. dis-
      par) infect 10% of world population.

                                                             • Flagellated, upper GI (duodenal) protozoan.
Epidemiology                                                 • Reservoir: Humans and wild mammals, espe-
                                                                 cially beavers and raccoons.
  • Transmission: Fecal–oral, person-to-person.              • Infective stage: Fecal cysts; acid, heat, cold, and
                                                                 chlorine resistant.
  • Vehicle: Contaminated drinking water, fruits/            • Sexual stage: Trophozoites, detected by Entero-
      vegetables irrigated with human wastes.
                                                                 test®, or passed during severe diarrhea.
  • Inoculum: Low.
  • Incubation: 1–14 weeks.
  • Warning: Susceptibles include male homosexu-           Epidemiology
      als (MSM), infants, pregnant, malnourished.

                                                             • Transmission: Fecal–oral, waterborne > person-
Clinical Manifestations                                          to-person > foodborne.
                                                             •   Vehicle: Cyst-contaminated drinking water, or
                                                                 direct contact.
  • Asymptomatic cyst passers (80%): Usually due             •   Inoculum: Low, few cysts.
      to E. dispar.
  •   Amebiasis (10%): Watery diarrhea without
                                                             •   Incubation: 1–2 weeks.
      blood and pus, fever.
                                                             •   Warning: Inadequate water treatment in moun-
                                                                 tain communities, campers in beaver habitats,
  •   Amebic dysenteric colitis (10%): Diarrhea with
                                                                 wading pools, day-care facilities, food handlers,
      blood, pus and mucus, fever, weight loss, peri-
                                                                 male homosexuals.
      anal ulcers, perforated megacolon.
  •   Extraintestinal amebiasis (1%): 3–10% colitis,
      liver abscess, right > left (rupture into adjacent
                                                           Clinical Manifestations
      body cavities).

                                                             • Cyst passers: No symptoms.
Prevention                                                   • Acute diarrhea (90%): 1–5        days, and mal-
                                                                 aise (80%), nausea, cramps/bloating, anorexia
                                                                 (70%), fever and vomiting rare.
  • Primary prevention: No vaccine, no chemopro-             •   Chronic diarrhea: Greasy foul-smelling stools,
      phylaxis, boil water, adequate sanitation.
                                                                 high fecal fat (75%), no blood or pus, malab-
  •   Secondary prevention: Stool trophozites, flexible
                                                                 sorption (30%), lactose intolerance (30%), >10-
      sigmoidoscopy with colon biopsy, stool/serum
                                                                 lb. wt loss (65%).
      antigen detection (ELISA), stool/serum anti-

                                                                                          Food Poisonings | 255
Prevention                                                Prevention

  • Primary      prevention: Proper water treatment,        • Primary prevention: No vaccine; drinking water
      especially filtration; treat all cyst passers.            filtration <3 microns, bottled drinking water for
  •   Secondary prevention: Fecal cysts and trophozo-           susceptibles (AIDS).
      ites, stool antigen detection by ELISA, Entero-       •   Secondary prevention: Fecal acid-fast stain and
      test® or duodenal aspirate for trophozoites.              autofluoresces under ultraviolet light, jejunal
  •   Tertiary prevention: Metronidazole (250 mg) 3             biopsy.
      times daily for 7 days.                               •   Tertiary prevention: Supportive; consider paro-
                                                                momycin, 750 four times daily for 4 days and
                                                                somatostatin, 500 mcg four times daily for 4
Coccidial Protozoan:                                            days to control diarrhea.

Cryptosporidium parvum
Microbiology                                              Coccidial Protozoan:
                                                          Cyclospora cayatenesis
  • Intracellular coccidian, like malaria.                Microbiology
  • Reservoir: Juvenile domestic animals and pets,
  • Heat, cold, iodine, and chlorine-resistant; infec-      • Coccidian with large, iodine/chlorine-sensitive
      tive sporocysts (4–6 m); asexual and sexual rep-          sporocysts (8–10 m) that require maturation to
      lication cycle in jejunum.                                be infective for man.
  •   Sporocysts take acid-fast stain and immuno-           •   Reservoir: Humans, no animals.
      fluoresce.                                            •   Asexual/sexual      replication   in   jejunal
                                                            •   Takes acid-fast stain, autofluoresces under
Epidemiology                                                    ultraviolet light.

  • Transmission:      Drinking water contaminated
      with feces of juvenile livestock (especially
      calves), pets, infected humans.
  •   Vehicle: Sporocysts.                                  • Transmission:     Fecal–oral, food > water, not
  •   Inoculum: Very low, few cysts.                            person-to-person.
  •   Incubation: 3–10 days.                                •   Vehicle: Contaminated foods (raspberries,
  •   Warning: HIV, male homosexuals, day care,                 strawberries, lettuce) or drinking water.
      child travelers, petting zoos, occupational expo-     •   Inoculum: Low.
      sures — wild animal handlers.                         •   Incubation: 1 week.
                                                            •   Warning: Travel to South Africa or Nepal,
                                                                high-risk foods, susceptibles include children,
Clinical Manifestations                                         HIV/AIDS patients.

  • Immunocompetent: Low fever, malaise, 3 days           Clinical Manifestations
      to 3 weeks of watery diarrhea without blood or
  •   Immunocompromised (HIV): Severe, prolonged,           • Immunocompetent: 5 days of watery diarrhea
      voluminous diarrhea, 25 bowel movements/day,              without blood or pus; anorexia, cramps, nausea
      3 L/day, weight loss, malabsorption.                      without vomiting, no weight loss.
  •   Complications: Ascending cholangitis, acalcu-         •   Immunocompromised: More severe, prolonged
      lous cholecystitis.                                       diarrhea with weight loss.

256 | Color Atlas of Human Poisonings and enenoming
Prevention                                                Prevention

  • Primary prevention: No vaccine; filtered, bot-          • Primary prevention: No vaccine; adequate water
      tled, or chlorine/iodine treated drinking water           and sewage treatment; avoid human waste-fer-
      for susceptibles and in Nepal; avoid unwashed             tilized or irrigated fruits and vegetables.
      South African berries such as raspberries, straw-     •   Secondary prevention: Acid-fast, UV-fluoresc-
      berries, blueberries.                                     ing football-shaped cysts in stool.
  •   Secondary prevention: Fecal acid-fast, UV-fluo-       •   Tertiary prevention: TMP/SMX doses 2 times
      rescent microscopy, jejunal biopsy.                       daily for 10 days.
  •   Tertiary prevention: TMP/SMX ds, twice daily
      for 7 days; 14–30 days in immunocompromised
      susceptibles.                                       Coccidial Protozoan:
                                                          Toxoplasma gondii
Coccidial Protozoan:                                      Microbiology
Isospora belli
                                                            • Coccidian parasite.
                                                            • Reservoir: Rodents     and wild cats > domestic
                                                                cats > sheep > pigs > deer.
  • Coccidian     protozoan with infective, football-       •   Oocysts excreted in cat feces, mature and
      shaped sporocysts.                                        become infective.
  •   Reservoirs: Humans, no animals.                       •   Two trophozoite forms: Tachyzoites (replica-
  •   Sporocysts excyst in jejunum and invade epithe-           tive) and bradyzoites (encysting).
      lium for asexual and sexual replication.
  •   Cysts take acid-fast stains and autofluoresce
      under UV light microscopy.                          Epidemiology

                                                            • Transmission: Fecal–oral > food (pork, lamb,
                                                            • Vehicle: Cat feces; raw and undercooked pork,
  • Transmission:     Fecal–oral, drinking water >              lamb, venison.
      food; person-to-person transmission unlikely.         • Inoculum: High.
  •   Vehicle: Human feces-contaminated water,              • Incubation: 6–10 days.
      food.                                                 • Warning: Pregnancy, outside       cat litter boxes,
  •   Inoculum: Low.                                            wild (feral) cats.
  •   Incubation: 1 week.
  •   Warning: Travel to tropical, developing areas,
      especially by immunocompromised susceptibles        Clinical Manifestations
                                                            • Asymptomatic: 50+%.
Clinical Manifestations
                                                            • Immunocompetent: 2%,          URI-like, low fever,
                                                                cervical lymphadenopathy.
                                                            •   Immunocompromised: Encephalomyelitis, myo-
  • Immunocompetent: 2–3 weeks of watery diar-                  carditis, pneumonia.
      rhea without blood or pus; mimics ETEC and            •   Congenital: Slow onset mental retardation,
      EPEC — traveler’s diarrhea.                               cerebral palsy, seizures, intracranial calcifica-
  •   Immunocompromised: Prolonged (6 months)                   tions, chorioretinitis, microcephaly.
      watery diarrhea, abdominal cramps and pain,
      nausea without vomiting, weight loss.

                                                                                         Food Poisonings | 257

  • Primary prevention: No vaccine; avoid high-risk
      foods and practices.
  • Secondary prevention: Parasites in blood, CSF,
      lymph, sputum, placenta, cord, amniotic fluid;
      IgM > IgA antibodies, PCR on white blood cells
      and CSF.
  •   Tertiary prevention: Asymptomatic — no treat-
      ment; others — spiramycin or pyrimethamine
      and sulfadiazine.

258 | Color Atlas of Human Poisonings and enenoming
   Parasitic Diseases
Trichinella spiralis                                     Clinical Manifestations
                                                           • Trichinosis: Months of nausea, vomiting, diar-
                                                               rhea without blood or mucus, then high fever,
  • Nematodes       with characteristic sexual organs
                                                               periorbital edema, myalgias, muscle masses,
      (stichosomes) on posterior ends.
                                                               CN palsies.
  •   Reservoir: Encysted larvae in muscles of domes-
      tic (pigs) and wild (bear, moose) animals.         Prevention
  •   Sexual mating in small intestine produces larvae
      that encyst in muscles, especially cranial nerve
      (CN)–subserved muscles (particularly extraoc-        • Primary prevention: No vaccine; avoid raw and
      ular muscles) and diaphragm.                             undercooked high-risk meats, especially pork.
                                                           • Secondary     prevention: Eosinophilia, encysted
                                                               larvae in muscle biopsies, serology, rarely adult
Epidemiology                                                   worms in stool.
                                                           •   Tertiary prevention: Supportive, mebendazole.
  • Transmission: Foodborne, pork > wild game.
  • Vehicle: Raw and undercooked pork > moose
      and bear.
  • Inoculum: Low, few cysts.
  • Incubation: 2 days to 8 weeks.
  • Warning: Pork sausage, boudin.

                                                                                        Food Poisonings | 259
   Cruise Ship Diarrhea
   - Bon Voyage

                tABLe 12.2 Diarrhea Outbreaks (31): 1986–1993
                                             No. Outbreaks
                        Agents                      (%)                     People Sick
                Bacteria                         12 (39)                       2150
                EtEC                                 5                         1155
                Shigella                             4                          450
                Salmonella                           2                          380
                Staph aureus                         1                          165
                Norwalk/NLV                       9 (29)                       3028
                Unknown                          10 (32)                       3049
                total                           31 (100)                      10,377

         tABLe 12.3 Diarrhea Outbreaks (5): 2002
         Lines and Ships                             People Sick                People Aboard
         Carnival Fascination                            203                          3348
         Carnival Conquest (#1)                          230                          4320
         Disney Magic                                    160                          3488
         Holland am. Amsterdam                           181                          1878
         radisson 7-Seas Mariner                          21                          1035
         totals (Source: CDC-VSP)             795 (Incid. rate = 5.99%)   14,069 (Attack rate = 5.65%)

  tABLe 12.4 Diarrhea Outbreaks (4): 2003
  Lines and Ships                                 People Sick                        People Aboard
  Sun Princess                                        296                                2906
  Sun Cruises Sundream                                107                                1488
  royal Olympic Olympia Voyager                        40                                 1112
  Carnival Spirit                                      112                               3045
  totals (Source: VSP to 3/1/03)            555 (Incid rate = 6.94%)           8551 (Attack rate = 6.49%)

  tABLe 12.5 Food Items (31 Outbreaks): 1986–1993
  Food Items Implicated                    No. Outbreaks/Agent id.                     Organisms
  Scallops (undercooked)                              3                                   EtEC
  Eggs (unpasteurized)                                2                                Salmonella
  Potato salad (onshore)                              2                               Shigella spp.
  Fresh sliced fruits                                 1                              Norovirus-NLV
  Calamari (marinated)                                1                                 Unknown
  Chicken or lobster salad                            1                              Norovirus-NLV
  Smoked fish salad                                   1                                 Unknown
  Flan (Sp., custard)                                 1                              Staph aureus
  Ice cream                                           1                              Norwalk virus

260 | Color Atlas of Human Poisonings and enenoming
Preention and Control

 • Wash hands frequently with soap and water.
 • Cook all seafood thoroughly.
 • Drink bottled water.
 • Serve pasteurized eggs.
 • Prevent food handlers from working while ill.
 • Avoid onshore caterers for offship excursions.
 • Avoid salads and all raw fruits that you do not
 • Report outbreaks promptly to the Vessel Sanita-
   tion Program (VSP) of the CDC.

                                                     Food Poisonings | 261
Final Recommendations

  • Wash      hands frequently after using restroom,
      shaking hands, and before eating.
  •   Eat only pasteurized dairy products and eggs.
  •   Avoid tapwater and ice if uncertain about
  •   Recognize high-risk foods: creams, custards,
      eggs, berries, lettuce (salads), undercooked fish
      and shellfish.
  •   When traveling “Boil it, bottle it, peel it, or for-
      get it.”

262 | Color Atlas of Human Poisonings and enenoming
            Chapter 13

Seafood Poisoning

         Seafood Poisoning | 263
Chapter Outline
                  Ancient history
                  Modern history

                  Burden of disease
                  Determinants of seafood-borne disease

                  Marine toxins
                  Feeding habitats and feeding habits

              Shellfish poisoning
                  Paralytic shellfish poisoning
                  Neurotoxic shellfish poisoning
                  Diarrhetic shellfish poisoning
                  Amnesic shellfish poisoning

              Pfiesteria-complex organisms (PCOs)

              Crustacean poisoning

              Finfish poisoning
                  Ciguatera fish poisoning
                  Scombroid fish poisoning
                  Tetrodotoxic fish poisoning
                  Miscellaneous saltwater fish poisoning
                  Freshwater fish poisoning
                  Marine botulism

              General management strategies

              Preention strategies


                                             Seafood Poisoning | 265
Ancient History                                             Modern History

  • Ancient Israel: Mosaic law forbade consump-              • London, 1774: William Anderson, M.D., Royal
      tion of all fish without scales (Example: all puff-        Navy, ship’s surgeon, described an outbreak of
      erfish [most are tetrodotoxic] and eels [many are          ciguatera poisoning on Capt. James Cook’s sec-
      ciguatoxic]).                                              ond voyage to the South Pacific after the crew
  •   Old Testament: The Red Sea, normally bright                consumed a red snapper caught in the New
      blue, was probably so named after a red tide               Hebrides.
      harmful algal bloom (HAB).                             •   Berlin, 1885: Rudolph Virchow, M.D., per-
  •   Old Testament: Moses probably “parted” the                 formed forensic autopsies on the 6 of the 26
      Red Sea in a known tidal zone, where shell-                severely poisoned patients who died after
      fish and crustaceans were routinely harvested              consuming toxic blue mussels in a Berlin
      between tides.                                             restaurant.
                                                             •   Maryland, 1997: Massive Pfiesteria-associated
                                                                 dinoflagellate fish kills (sea bass, speckled trout,
                                                                 and mullet) reported in Chesapeake Bay.

                                                                                          Seafood Poisoning | 267
Burden of Disease                                         Determinants of Seafood-Borne Disease

  • Most     shellfish and 300+ finfish species: Can       • More frequent harmful algal blooms (HABs):
      cause poisonings with potentially lethal (case           HABs are a result of global warming; irrigation
      fatality rate [CFR] 1–62%) toxins not inactivated        and wastewater runoff = agricultural runoff
      by cooking, freezing, smoking, or salting.               (nitrogen-loading) + sewage runoff (sulfur-load-
  •   70% of the world’s population: Lives near                ing) + household detergent runoff (phospho-
      seacoasts; seafood provides 40% of world’s               rous-loading) + soil sediment (pesticides); more
      protein.                                                 natural disasters = hurricanes/typhoons, earth-
  •   25,000–50,000 cases of ciguatera occur annu-             quakes; and increased trade and industrializa-
      ally: 2300 cases/year in the United States and           tion = port docks/seawalls; ship ballast/sewage.
      Canada, and 5 cases/10,000 in Florida.               •   Coral reef destruction: Filtering reefs are often
  •   Scombroid fish poisoning: Causes 5% of all               damaged or destroyed by atmospheric and
      CDC-reported foodborne diseases and 37% of               deep-sea nuclear warhead testing; drag-net fish-
      all reported seafood-borne disease.                      ing methods; and the pacific crown-of-thorns
                                                               starfish, Acanthaster planci (see Figure 13.2).
                                                           •   Long-line commercial fishing: High levels of
                                                               scombrotoxins are produced in deep sea finfish
                                                               (tuna, cobia, mahi mahi, wahoo) hooked and
                                                               dying in warm water over 20+ hours.

            Figure 13.1 A world map depicting the global ranges of the most common types
            of toxic seafood poisonings.

268 | Color Atlas of Human Poisonings and enenoming
  • Plankton: Phytoplankton vs. zooplankton                • Okadaic        acid: Dinophysis species dino-
  • Marine toxins: Exotoxins vs. endotoxins                    flagellates.
  • Marine habitats: Reef vs. deep sea                     •   Domoic acid: Pseudonitzschia pungens
  • Feeding habits: Filtering vs. reef-grazing                 diatoms.
                                                           •   Palytoxin: Zoanthid coral-feeding parrotfish
                                                               (rarely triggerfish) and all tidal xanthid crabs.
Plankton                                                   •   Ciguatoxins: Gambierdiscus toxicus.
                                                           •   Shark carchatoxins: Bull and tiger sharks; pri-
                                                               mary source of bioaccumulated exotoxin is
  • Chlorophyta: Green algae.                              •   Buffalo fish myotoxin: Primary source of bioac-
  • Chrysophyta: Yellow-brown            algae    and          cumulated freshwater exotoxin unknown.
  •   Cyanophyta: Freshwater blue-green algae (see
      Figure 13.4).                                      Endogenous Endotoxins: Primary Sources
  •   Euglenophyta: Freshwater euglenoids — non-
      toxic pond dwellers.                                 • Scombrotoxins: Produced by gut bacteria-cata-
  •   Pyrrophyta: Red tide dinoflagellates — larg-             lyzed l-histidine decarboxylation to histamine
      est number of toxic plankton species (10%),              and its primary metabolite, saurine, in decom-
      includes Pfiesteria piscicida (see Figure 13.5).         posing deep-sea finfish, especially scombroid
                                                               species (tuna, mackerel, albacore, skipjack, and
                                                               bonito), and even non-scombroid species (mahi
                                                               mahi, wahoo, cobia, and amberjack).
                                                           •   Tetrodotoxin: Produced by endosymbiotic bac-
  • Larval crustaceans: Xanthid (Xanthidae) crabs              teria in all pufferfish (porcupine fish, globefish,
      — bioaccumulate palytoxin.                               balloon fish, blowfish, toadfish), marine sun-
  •   Larval coelenterates: Zoanthid corals — pri-             fish, and many other marine animals (stored in
      mary palytoxin producers in reef habitats (see           fish skin, gonads, liver, roe) and invertebrates
      Figure 13.6).                                            (blue-ringed octopus — saliva), and amphibians
  •   Larval marine round and flatworms: Tetrodo-              (newts and toads — skin secretions).
      toxin (TTX) producers.
  •   Larval copepods, krill and shrimp: Nontoxic;
      preferred food source by marine mammals,           Feeding Habitats and Feeding Habits
      especially whales.
                                                         reef: Filter Feeders

Marine toxins                                              • Bivalved mollusks: Clams (Saxidomus species),
                                                               cockles, blue mussels (Mytilus species), oysters,
Bioaccumulated Exotoxins:
                                                               and scallops can all bioaccumulate and concen-
       Primary Sources
                                                               trate both dinoflagellate and diatom exotoxins.
                                                           •   Coelenterates: Some anemones and all zoanthid
  • Saxitoxin: Alexandrium species dinoflagellates.            corals produce palytoxin (parrotfish and, occa-
  • Gonyautoxins: Alexandrium species dino-                    sionally, triggerfish feed on these and bioaccu-
      flagellates.                                             mulate palytoxin).
  • Brevetoxins:     Gymnodinium       breve     dino-

                                                                                       Seafood Poisoning | 269
                   tABLe 13.1 Biotoxin Potency
                           Biotoxins: in Potency Order        (mcg/kg IV in mice)
                   #1 = Botulinum toxin (marine mammals)            0.0026
                   #2 = Palytoxin (parrotfish)                       0.15
                   #3 = Frog batrachotoxin                            2.0
                   #4 = taipan (snake) venom                          2.0
                   #5 = tetrodotoxin (puffers)                        9.0
                   #5 = Saxitoxin (shellfish)                         9.0
                   #6 = tiger snake venom                            25.0
                   #7 = Cobra (snake) venom                          75.0

Deep-Sea/reef: Baitfish Feeders                        • Predatory    reef fish: All can bioaccumulate
  • Predatory deep-sea finfish: Mackerel and tuna          − Carnivorous: Barracuda > grouper, jacks,
                                                              and all snappers (especially red snappers).
     (Scombridae), and non-scombroid amberjack,
                                                              Miscellaneous potentially ciguatoxic reef-
     bonito, cobia, wahoo, and mahi mahi can pro-
                                                              dwelling fish: amberjack, sea bass.
     duce endogenous scombrotoxins on slow, high-
     temperature decomposition of muscle protein
                                                           − Herbivorous: Triggerfish > surgeonfish and
                                                              parrotfish (palytoxic).

270 | Color Atlas of Human Poisonings and enenoming
   Shellfish Poisoning
Paralytic Shellfish Poisoning                                   larization (opposite of saxitoxin and tetrodo-
                                                                toxin [TTX]).
  • Agents:       Alexandrium species dinoflagel-
                                                            •   Vectors: Clams > oysters.
      lates, Gymnodinium catenatum, Pyrodinium
                                                            •   Incubation: 15 minutes to 3 hours.
                                                            •   Symptoms: Mild ciguatera-like symptoms with
                                                                perioral paresthesias and temperature reversal;
  •   Toxins: Saxitoxin, neosaxitoxin, gonyautoxins
                                                                rarely nausea and diarrhea; unique conjuncti-
      #1–#8, epigonyautoxin.
                                                                vitis, rhinitis, and/or asthmatic bronchitis from
  •   LD50 (IV in mice): 9 mcg/kg.
                                                                aerosolized brevetoxins in breaking surf.
  •   Mechanism: Reversible binding to the outer
                                                            •   Diagnosis: By history, TLC or HPLC.
      pore of the sodium (Na) channel, blocking Na
      influx, preventing depolarization and nerve
                                                            •   Treatment: Supportive only.
      action potential (NAP) propagation.
                                                            •   Prognosis: Full recovery in 48 hours.
  •   Vectors: Mussels and clams > oysters, scallops,
                                                            •   Prevention: Monitor shellfish bed dinoflagel-
                                                                late counts; adhere to shellfish consumption
      and Southern pufferfish (most puffers are tet-
      radotoxic; Gulf Stream puffers may also be
  •   Incubation: 30 minutes to 2 hours.
                                                          Diarrhetic Shellfish Poisoning
  •   Symptoms: Perioral burning and tingling, then
      paresthesias that spread from lips, to tongue,
      to throat; generalized weakness and numbness;         • Agents: Dinophysis acuminata (Atlantic Ocean)
      nausea and vomiting; descending paralysis with            and Dinophysis fortii (Pacific Ocean).
      dysphagia and dysphonia; respiratory failure;         • Toxins: Okadaic acid > dinophysotoxins, pec-
      cardiovascular instability.                               tenotoxins, and yessotoxin.
  •   Diagnosis: Mouse bioassay, thin layer chroma-         •   LD50: Unknown; no human fatalities reported.
      tography (TLC), high-pressure liquid chroma-          •   Mechanism: Inhibits protein phosphatases, dis-
      tography (HPLC), RIA, ELISA.                              rupting cell metabolism; deregulates mitosis
  •   Treatment: Protect airway, gastric lavage                 promoting neoplasia, specifically benign gastric
      then AC, IV fluids, mechanical ventilation,               tumors.
      vasopressors.                                         •   Vectors: Blue mussels — Mytilus edulis (Atlan-
  •   Prognosis: Symptoms peak in 12–24 hours and               tic) and Mytilus californianus (Pacific) > clams
      resolve in 3–4 days, CFR 8.5–14%; rare com-               (Saxidomus spp.) > cockles, oysters, and
      plications and/or sequelae with appropriate ICU           scallops.
      care.                                                 •   Incubation: 30 minutes to 15 hours (mean 5–6
  •   Prevention: Close beds when toxin levels exceed           hours).
      80 mcg/kg; avoid eating all pufferfish; adhere to     •   Symptoms: Exclusively gastrointestinal with
      shellfish consumption advisories.                         nausea, vomiting, cramping abdominal pain,
                                                                severe diarrhea (>20 stools/day), no CNS
Neurotoxic Shellfish Poisoning                              •   Diagnosis: Mouse bioassay, HPLC.
                                                            •   Treatment: Supportive, IV fluid and electrolyte
  • Agent:    Gymnodinium (Karenia) breve, for-
                                                            •   Prognosis: Self-limited, symptoms resolve
      merly Phytodiscus brevis.
                                                                within 3 days; no fatalities.
  •   Toxins: Brevetoxins (polycyclic ethers).
                                                            •   Prevention: Monitor shellfish bed dinoflagellate
  •   LD50: Unknown; no human fatalities.
                                                                counts; adhere to local shellfish consumption
  •   Mechanism: Forced opening of Na channels
      with increased Na influx and prolonged depo-

                                                                                       Seafood Poisoning | 271
Amnesic Shellfish Poisoning                             • Incubation: <24 hours.
                                                        • Symptoms: Initial nausea, vomiting, diarrhea,
                                                            and cramping abdominal pain; then ataxia,
  • Agents: The diatom, Pseudonitzschia (Nitzschia)         confusion, dizziness, headache, seizures, poten-
      pungens, and, rarely, some red algae (Chondria
                                                            tially chronic antegrade and short-term memory
                                                            loss, especially in the elderly. Mimics Alzheim-
  •   Toxin: Domoic acid (from the Japanese “domoi”
                                                            er’s disease.
      for seaweed); used in Japan as a very effective
      antihelminthic agent.
                                                        •   Diagnosis: Mouse bioassay, HPLC.
  •   LD50: Unknown; 4 deaths reported in elderly
                                                        •   Treatment: Supportive only.
      patients over the age of 70.
                                                        •   Prognosis: Full recovery within 48 hours; per-
                                                            sistent short-term memory loss possible (mimics
  •   Mechanism: CNS glutamate receptor stimu-
                                                            Alzheimer’s), especially in the elderly.
      lation causing Na channel up-regulation and
      unopposed, prolonged depolarization with
                                                        •   Prevention: Closure of shellfish beds when
                                                            domoic acid levels exceed 20 mcg/g shellfish;
      increased Na and Ca influx and neuronal cell
                                                            always adhere to local shellfish consumption
                                                            advisory advisories (particularly in Canada).
  •   Vectors: Blue mussels (Mytilus species) > razor
      clams (Seliqua patula).

272 | Color Atlas of Human Poisonings and enenoming
 Pfiesteria-Complex Organisms
• Agents: Pfiesteria piscicida and 10–12 related        • Symptoms: Confusion and/or memory loss and
    dinoflagellates, all collectively known as Pfies-       more than three (3) of the following symptoms:
    teria-Complex Organisms (PCOs).                         headache, skin rash, conjunctivitis, upper respi-
•   Toxins: (1) Water-soluble, ichthyotoxic neu-            ratory tract (URT) irritation and sensitivity,
    rotoxin; (2) lipid-soluble necrotoxin causing           muscle cramps, and any type of gastrointestinal
    “punched out” necrotic fish lesions.                    symptoms (abdominal cramps, nausea, vomit-
•   LD50: No human fatalities, but neurotoxin is            ing, usually no diarrhea).
    always lethal in fish.                              •   Diagnosis: By history of aerosol exposure only.
•   Mechanism: Like brevetoxins, aerosolized neu-       •   Treatment: Supportive only.
    rotoxins force open Na channels, prolonging         •   Prognosis: Symptoms resolve in 1–2 weeks.
    depolarization, especially in brain.                •   Prevention: Avoid swimming, skiing, fish-
•   Vectors: No seafood vectors; does not enter             ing, and all other recreational exposures in all
    human seafood chain.                                    waters with extensive fish kills; citizens should
•   Incubation: 2 weeks after aerosol exposures to          immediately report large fish kills to state envi-
    PCO toxins.                                             ronmental and public health agencies and to the

                                                                                    Seafood Poisoning | 273
   Crustacean Poisoning
  • Agents     and toxins: Bioaccumulated red algal           seizures with rhabdomyolysis, myoglobinuria,
      gonyautoxins and zoanthid coral palytoxin;              acute tubular necrosis (ATN); cardiovascular
      endogenous tetrodotoxin.                                collapse. TTX — respiratory paralysis.
  •   LD50 (IV in mice): Gonyautoxins and tetrodo-        •   Diagnosis: Mouse bioassay, TLC, HPLC, high
      toxin (TTX) — 9 mcg/kg; palytoxin — 0.15                levels of serum creatine phosphokinase (CPK)
      mcg/kg.                                                 from rhabdomyolysis.
  •   Mechanism: Gonyautoxins and TTX reversibly          •   Treatment: Protect airway; gastric emptying,
      bind to outer pore of Na channels, decreasing           orogastric lavage with NaHCO3, then activated
      Na influx and depolarization; palytoxin inhibits        charcoal (AC), 1 g/kg; mechanical ventilation;
      Na-K ATPase, Na and K can enter but cannot              consider multi-dose AC, alkalinize urine, forced
      leave axon, Ca cannot enter, causing hypocalce-         osmotic diuresis with mannitol.
      mic tetanic contractions.                           •   Prognosis: CFR-TTX: 62%, CFR-palytoxin:
  •   Vectors: Most Indo-Pacific xanthid crabs, ter-          >60%; most recover in ICU by 48 hours to 5
      restrial coconut crab, and Asian horseshoe              days.
      crabs; rarely herbivorous reef triggerfish and      •   Prevention: Avoid unusual crab species and local
      parrotfish (palytoxin).                                 crab “miso” — soups made from tidal xanthid
  •   Incubation: 10–15 minutes to 3–4 hours.                 crabs; always adhere to local seafood consump-
  •   Symptoms: Palytoxic — initial nausea, vomiting,         tion advisories.
      diarrhea, facial-to-limb paresthesias; tonoclonic

274 | Color Atlas of Human Poisonings and enenoming
   Finfish Poisoning
Ciguatera Fish Poisoning                                   • Prevention: Avoid ciguatoxic species, especially
                                                               barracuda and fish organs (especially liver, ova-
                                                               ries, and roe); adhere to all advisories; promote
  • Agents: Dinoflagellates — Gambierdiscus toxi-              healthy coral reefs, limit drag-line fishing, ban
      cus (worldwide), Ostreopsis lenticularis (Carib-
                                                               atmospheric and deep-sea nuclear weapons
      bean only).
                                                               testing, and support increased crown-of-thorns
  •   Toxins: Three neurotoxins = ciguatoxin,
                                                               starfish (Acanthaster planci) control.
      gambierol, and scaritoxin; one myotoxin =
  •   LD50 (IV in mice): Ciguatoxin — 0.45 mcg/kg;       Potentially Ciguatoxic Fish
      maitotoxin — 0.05 mcg/kg.
  •   Mechanism: Ciguatoxic-forced opening of
      Na channels with increased Na influx, pro-           • Schooling Jack Crevalle carnivorous: not tasty
      longed depolarization, and myospastic con-           • Solitary triggerfish herbivorous: very tasty
      tractures. Maitotoxic-forced opening of Ca           • Surgeonfish
      channels with increased Ca influx and pro-
      longed myospasticity.                              Scombroid Fish Poisoning
  •   Vectors: >100 reef fish species; predatory reef
      fish — barracuda, grouper, snapper, all jacks,       • Agents:    Toxic decomposition metabolites col-
      wrasse, moray eel; herbivorous reef fish — file-         lectively called scombrotoxins; the scombro-
      fish, parrotfish, surgeonfish, triggerfish.              toxins are not bioaccumulated dinoglagellate or
  •   Incubation: Within 24 hours.                             diatom exotoxins.
  •   Symptoms: Cramps, nausea, vomiting, diarrhea         •   Toxins: Scombrotoxins = histamine and its pri-
      (75%); metallic oral taste, perioral and distal          mary N-methylhistamine metabolite, saurine.
      paresthesias, glove and stocking numbness,           •   LD50: No known human fatalities.
      palmar pruritus, hot–cold sensation reversal,        •   Mechanism: Scombrotoxins form during gut
      tremor, ataxia, vertigo, decreased DTRs then             bacteria-catalyzed, normothermic decarbox-
      seizures, myopathy, arthralgias, weakness,               ylation (Proteus, Klebsiella, Lactobacillus, E.
      stupor-coma.                                             coli, Enterobacter species) of muscle l-histidine
  •   Diagnosis: Mouse bioassay, RIA, stick-enzyme             in decomposing finfish dangling on commercial
      immunoassay (IA) (Cigua-Check®) on sus-                  long lines or in underrefrigerated ship holes.
      pected seafood, gas chromatography and mass          •   Vectors: Paradoxically, non-scombroid fish are
      spectrometry (GC/MS).                                    the most common food vectors of scombroid
  •   Treatment: Supportive; anticonvulsants (ben-             poisoning (amberjack, bonito, bluefish, mahi
      zodiazepines [BZs]); IV mannitol 1 g over 45             mahi, anchovies, sardines, herrings) > scom-
      minutes two times within 24–48 hours and                 broid fish (albacore, cobia, tuna, mackerel,
      gabapentin 1200–2400 mg/d orally for chronic             wahoo).
      symptoms (untested); avoid fish, alcohol, nuts       •   Incubation: Minutes to 3–4 hours.
      for 3–6 months, which may precipitate recur-         •   Symptoms: Sudden warm facial flushing and
      rent pruritus (mechanism unknown).                       “sunburn-like” rash, metallic-peppery taste,
  •   Prognosis: Symptoms resolve in 10–58 hours;              perioral burning and blistering sensations; then
      persistent distal numbness, pruritus and tem-            urticaria, pruritus, bronchospasm, palpitations,
      perature reversal possible.                              tachycardia, hypotension; fewer gastrointestinal
                                                               symptoms of abdominal cramps, nausea, vom-
                                                               iting, and diarrhea.
                                                           •   Diagnosis: Histidine-to-histamine spot indica-
                                                               tor tests, thin-layer chromatography (TLC),

                                                                                      Seafood Poisoning | 275
      gas chromatography/mass spectrometry, high            • Prevention: Avoid eating all pufferfish; travelers
      serum and urine histamine and saurine levels.             may consume fugu only in Japan, prepared by
  •   Treatment: Severe poisoning — gastric emptying,           commercially licensed fugu chefs. Ban importa-
      then AC gut decontamination; otherwise, H1-               tion of all fugu fish and other pufferfish.
      and H 2-blockers, β -agonists for bronchospasm
      with wheezing, and consider corticosteroids for
      allergic bronchospasm and urticaria/pruritus.        Miscellaneous Saltwater Fish Poisoning
  •   Prognosis: Symptoms resolve in 12–24 hours

      even without treatment.                               • Shark poisoning: Consumption of cooked shark
      Prevention: Patients on isoniazid (INH), a                meat from large bull and tiger sharks has caused
      gastrointestinal histaminase inhibitor, are at            an initial ciguatera-like illness with perioral par-
      increased risk; avoid nonrefrigerated and spoil-          esthesias, ataxia, and pruritus, then coma and
      ing (pale gills) deep-sea fish; avoid seafood with        death (increased CFR = 30%). Structure of two
      histamine levels >50 mg/100 mg fish (FDA);                toxins (carchatoxins A and B) is unknown.
      regulate long-line fishing; require mandatory         •   Mackerel poisoning: Mild, self-limited diarrhea
      cold-chain (0 °C) for all seafood from harvest            after consumption of cooked mackerel species
      until cooking/consumption.                                due to a castor oil-like toxin. Mackerel liver
                                                                consumption has also caused a hypervitamin-
                                                                osis-A-like syndrome with headache, nausea,
tetrodotoxic Fish Poisoning                                     vomiting, diarrhea, and a macular rash that
                                                                later desquamates. A similar hypervitamin-
  • Agent: Endogenous toxin.                                    osis-A-like syndrome occurs after polar bear
  • Toxin: Endogenous toxin production by endo-                 liver consumption and may cause pseudotumor
      symbiotic gut bacteria (Bacillus, Micrococcus,            cerebri.
      Acinetobacter, Altermonas, Vibrio, and other          •   Mullet poisoning: Mild, self-limited intoxica-
      enterobacterial species).                                 tion with delusions, hallucinations, ataxia,
  •   LD50 (IV in mice): 9 mcg/kg.                              and nightmares within minutes to hours after
  •   Mechanism: Reversible binding to the outer pore           consumption of reef-schooling mullet. Toxin
      of the Na channel, with decreased Na influx,              unidentified.
      preventing depolarization and subsequent nerve
      action potentials (NAPs).
  •   Vectors: All pufferfish (balloonfish, blowfish,      Freshwater Fish Poisoning
      fugu fish, globefish, swellfish, toadfish), porcu-
      pine fish, marine sunfish; xanthid crabs, marine      • Fish egg (fish roe) poisoning: Headache, nausea,
      worms; blue-ringed octopus bites; skin secre-             vomiting, diarrhea, cold sweats, metallic taste,
      tions of some newts, frogs, and toads.                    tinnitus, and syncope after the consumption
  •   Incubation: 10–20 minutes.                                of raw or cooked roe during the spawning sea-
  •   Symptoms: Initial paresthesias, perioral burn-            son of several freshwater fish species including
      ing, then salivation, headache, nausea and                barbel, bream, carp, catfish, pike, salmon, and
      vomiting (diarrhea rare), sweating, glove and             sturgeon. The uncharacterized toxin is probably
      stocking paresthesias then numbness, tremor,              a phospholipid egg-white nutrient. Prevention:
      ataxia, dysarthria, dysphagia, respiratory                avoid eating fish roe of high-risk species.
      depression then paralysis, cardiovascular insta-      •   Haff (Haff-Iuksov-Sartlen) disease: Paroxys-
      bility, stupor, and coma.                                 mal myalgias and myospastic contractures with
  •   Diagnosis: Mouse bioassay, TLC, HPLC, gas                 rhabdomyolysis and myoglobinuria (high levels
      chromatography/mass spectrometry.                         of CPK) within 6–21 hours (mean 8 hours) of
  •   Treatment: Supportive = protect airway, gastric           consuming cooked buffalo fish (Ictiobus cypri-
      lavage then AC-MDAC, IV fluids, vasopressors,             nellus), or rarely (two cases) crayfish, from the
      and mechanical ventilation.                               Mississippi-Missouri River basin and similar
  •   Prognosis: CFR = 62%; survivors will recover              basins (Volga-Caspian) worldwide. Primary
      within 1 week of ICU care (not universally                source of endotoxin is unknown, with a CFR =
      available, especially in developing world).               1%. Prevention: no buffalo fish consumption.

276 | Color Atlas of Human Poisonings and enenoming
Marine Botulism                                           respiratory failure, cranial nerve (CN) palsies
                                                          (blurred vision, diplopia, dysphagia, dysar-
                                                          thria), autonomic dysfunction (bradycardia,
 • Agent: Clostridium botulinum (marine).                 hypotension, nausea, vomiting, constipation >
 • Toxin: Botulinum toxin, exclusively Type E, in         diarrhea).
     decomposing marine mammals and seafood.
     Botulinum toxins include Types A–G, but Types
                                                      •   Diagnosis: Normal CSF, positive EMG, positive
                                                          stool botulinum E toxin on mouse bioassay.
     A, B, and E (saltwater toxin) cause most human
     botulism cases.
                                                      •   Treatment: Polyvalent equine antitoxin, ICU
                                                          support, mechanical ventilation.
 •   LD50 (IV in mice): 0.0026 mcg/kg.
                                                      •   Prognosis: High CFR without ICU care.
 •   Mechanism: Clostridial contamination of raw
                                                      •   Prevention: Boil all raw or fermented Alaskan
     or improperly preserved seafood with exclusive
                                                          native dishes and home-canned seafoods ≥10
     production of botulinum toxin Type E on skin,
                                                          minutes before eating; notify state public health
     in tissues, and muscle, particularly near gut.
                                                          authority and CDC (for release provision of
 •   Vectors: All home-canned salt- or freshwater
                                                          human botulinum antitoxin).
     seafood, raw seafood, raw marine mammals,
     especially dolphin, seal, whale-muktuk (raw
     whale skin and underlying pink blubber).
 •   Incubation: ≤36 hours.
 •   Symptoms: Afebrile, weakness, oriented × 3,
     descending flaccid paralysis progressing to

                                                                                 Seafood Poisoning | 277
   General Management Strategies
  • Seek     pathognomonic symptoms: Temperature         • Provide supportive ICU care: IV fluids and vaso-
      reversal = ciguatera and sunburn-like rash =           pressors, mechanical ventilation.
      scombroid; submit fish samples to toxicology       • Consider     specific pharmacotherapy: H1- and
      labs for TLC, HPLC, GC/MS.                             H 2-blockers for scombroid; initial IV manni-
  •   Protect airway and empty the stomach: Induce           tol, then gabapentin po for neuropathic pain in
      vomiting in witnessed ingestions only; orogas-         ciguatera (untested).
      tric lavage, then activated charcoal (AC). Avoid   •   Notify public health authorities: In order to
      all cathartics.                                        conduct epidemiologic outbreak analysis.

278 | Color Atlas of Human Poisonings and enenoming
    Preention Strategies
• Monitor      all harmful algal blooms (HABs):        • Avoid consumption of well-known highly toxic
    Use satellite and weather reports to predict red       species and any unrefrigerated or spoiled fish:
    tides and issue timely seafood consumption             Pufferfish = TTX; parrotfish and xanthid crabs
    advisories.                                            = palytoxin; barracuda = ciguatoxin.
•   Protect marine environments: Regulate drag-        •   Adhere to all regional seafood consumption
    net and long-line commercial fishing; decrease         advisories: If unavailable, seek advice from local
    atmospheric and deep-sea nuclear weapons               health providers, hotel and tour operators.
    testing; control crown-of-thorns starfish.

                                                                                   Seafood Poisoning | 279
  • All shellfish, >300 finfish species, and marine     • Seafood     poisonings affect the autonomic and
      mammals can cause poisoning with potent bio-          central nervous systems and/or the gastroin-
      logical toxins and increased CFRs ranging from        testinal tract, causing symptoms ranging from
      1–62%. Example: botulinum toxin (botox) is            mild gastrointestinal distress to fatal respira-
      #1, palytoxin is #2, TTX and saxitoxin are #5         tory paralysis.
      among the living world’s most potent biological   •   Although the Food and Drug Administration
      toxins.                                               monitors interstate sales, seafood is not feder-
  •   Seafood toxins are not inactivated by cooking,        ally inspected, and there are few available tests
      smoking, salting, marinating, or freezing, and        to assess seafood quality (e.g., Cigua-Check®),
      cannot be detected by human sight (pale gill          and few specific therapies to manage toxicity.
      color is very nonspecific), smell, or taste.          Prevention is key!

280 | Color Atlas of Human Poisonings and enenoming
                 Chapter 14

Mushroom Poisonings

           Mushroom Poisonings | 281
Chapter Outline
              Descriptie epidemiology

              toxicological classification
                  Cyclopeptide toxicity
                  Gyromitrin toxicity
                  Muscarine toxicity
                  Coprine toxicity
                  Ibotenic acid—muscimol
                  Psilocybin toxicity
                  Orellanine nephrotoxicity
                  Miscellaneous gastrointestinal toxicity

              “Carefully” edible mushrooms: conclusions

                                          Mushroom Poisonings | 283
 Descriptie epidemiology
• Incidence rate (United States): 5 mushroom poi-                           Scales
                                                                   (remains of universal veil)
    sonings per 100,000 persons per year.
•   95% of toxic mushrooms ingested cannot be                                                              Cap or pileus
•   50% of patients are asymptomatic, 25% require
    treatment, 15% of these have minor toxicity, 5%
    moderate toxicity, and 0.2% major toxicity.
•   1–2 patients die of mushroom poisoning each          Ring or annulus
                                                      (remains of partial veil)
    year (United States).
•   95% of deaths are due to Amanita species inges-
                                                                                                 Gills or lamellae
                                                                                                  (with spores)
    tions; case fatality rates (CFRs) for Amanita
    ingestions are 25–50%.                                             Stem                         Universal
                                                                      or stipe                        veil

                                                               of universal

                                                                   or bulb
                                                                                                 Roots or

                                                      Figure 14.1 Anatomy of a mushroom. The anatomy
                                                      of a poisonous mushroom, Amanita muscaria or fly
                                                      amanita, with the juvenile mushroom button (right)
                                                      and the mature adult mushroom or toadstool (left).

                                                                                        Mushroom Poisonings | 285
 tABLe 14.1 An Onset Time and Target System Classification of Mushroom Poisoning by Common Mushroom Species
 early Onset toxicity                  Late Onset toxicity                      Delayed Onset toxicity
 (<6 hours)                            (within 6–24 hours)                      (1 or more days)
 Neurotoxic                            Hepatotoxic                           Nephrotoxic
 Cholinergic:                          amatotoxic:                           Orellanine:
 Clitocybe spp. (Funnel caps)          Amanita spp.                          Cortinarius spp. (Corts)
 Inocybe spp.                          Galerina spp.
                                       Lepiota spp.
 Glutaminergic:                        Nephrotoxic                           Rhabdomyolytic
 Amanita muscaria (Fly amanita)
 Amanita pantherina (Pantheramanita)   Amanita proxima                       Tricholoma equestre (Yellow
                                       Amanita smithiana (toxic Lepidella)    trich)
                                                                             Russula subnigricans
                                                                              (Blackening russula)
 Epileptogenic:                        Erythromelalgia                       Neurotoxic
 Gyromitra spp. (False morels)         Clitocybe acromelalga                 Hapalopilus rustilans (Purple-
                                       Clitocybe amoenolens (Poison dwarf     dye polypore)
                                        bamboo mushroom)
  Psilocybe spp. (Mellow mushrooms)
  Paxillus involutus (Poison Pax)
  Lycoperdon spp. (Puffballs)
 Gastrointestinal (GI)
 Disulfiran reaction:
  Coprinus atramentarius
  (alcohol inky caps)
 Miscellaneous GI:
  Boletus spp.
  Chlorophyllum spp.
  Entoloma spp.

286 | Color Atlas of Human Poisonings and enenoming
   toxicological Classification
  • Cyclopeptide-containing        mushrooms (poten-        • Diagnosis: Onset 6–10 hours; initial gastroin-
      tially lethal hepatotoxicity)                             testinal symptoms, then seizures and hepatore-
  •   Monomethylhydrazine-containing mushrooms                  nal failure, mimics INH toxicity.
      (B6 -inhibitors, mimic isoniazid [INH] toxicity)      •   Treatment: Supportive, anticonvulsants.
  •   Muscarine-containing mushrooms (muscarinic,
      cholinergic toxidrome)
  •   Coprine-containing mushrooms (“disulfiram           Muscarine toxicity
      reaction” following ethanol intake)
  •   Ibotenic acid–muscimol-containing mushrooms           • Representative    genera: All Inocybe and some
      (GABA-nergic)                                             Clitocybe species.
  •   Psilocybin-containing mushrooms (hallucino-           •   Toxin: Muscarine.
      genic, “mellow mushrooms”)                            •   Antidote: Atropine, 1–2 mg/kg IV titrated to
  •   Orellanine-containing mushrooms (nephro-                  anticholinergic effects.
      toxic, oliguric renal failure)                        •   Diagnosis: Onset 0.5–2 hours; symptoms
  •   Miscellaneous gastrointestinal toxin-contain-             — muscarinic cholinergic, SLUDE*, no CNS
      ing mushrooms (nonlethal nausea, vomiting,                effects.
      and diarrhea)                                         •   Treatment: Supportive.
  •   Puffball poisoning or Lycoperdonosis (not a
      true poisoning, but extrinsic allergic asthma       [*Salivation,   lacrimation,   urination,   defecation,
      following spore inhalation)                         emesis.]

                                                          Coprine toxicity
Cyclopeptide toxicity
                                                            • Representative genus: Coprinus species.
  • Representative      genera: Amanita, Galerina,          • Toxin: Coprine.
      Lepiota species.                                      • Antidote: None specific.
  •   Toxins: cyclopeptides = amatoxin > phallotoxin        • Diagnosis: Onset 0.5–2 hours; disulfiram      —
      > virotoxin (nontoxic).                                   reaction following ingestion of alcohol with
  •   Antidote: none specific, silibinin, penicillin G,         facial flushing, nausea and vomiting, tachycar-
      thioctic acid, cimetidine — inhibits CYP-450              dia, hypertension.
  •   Diagnosis: Onset 6–10 hours; phase 1 — gas-           •   Treatment: Supportive, IV fluids.
      trointestinal toxicity — nausea, vomiting, diar-
      rhea; phase 2 — liver function deteriorates;
      phase 3 — jaundice, liver failure, hepatorenal      Ibotenic Acid — Muscimol
  •   Treatment: Supportive, liver transplant.              • Representative     genus: Amanita muscaria, A.
                                                                pantherina, A. gemmata.
                                                            •   Toxins: Ibotenic acid and its primary metabo-
Gyromitrin (MMH) toxicity                                       lite, muscimol, a GABA-nergic glutamic acid
  • Representative genus: Gyromitra species.                •   Antidote: None specific; benzodiazepines for
  • Toxin: Gyromitrin, a monomethylhydrazine B /                convulsions.
      GABA inhibitor.
                                                            •   Diagnosis: Onset 0.5–2 hours; vertigo, somno-
  •   Antidote: B6 or pyridoxine, 25 mg/kg IV.                  lence, delirium, hallucinations; myoclonus and
                                                                seizures in children.
                                                            •   Treatment: Anticonvulsants (BZs).

                                                                                   Mushroom Poisonings | 287
            Intense yellow-orange cap;
                     no odor                                 Cap surface wipes
                                                            off easily onto fingers;
                                                                   no odor

             & folded cap
             (not pitted)

Gyromitra Esculenta                                       Amanita Smithiana
(Conifer False Morel)                                      (Smith’s Amanita)
                            Omphalotus Olearius
                             (Jack O’Lantern)

Figure 14.2a Study of three poisonous mushrooms.
Study of three poisonous mushrooms and their unique
identifying features. Left: Gyromitra esculenta (coni-
fer false morel). Center: Omphalotus clearius (Jack
                                                                Figure 14.3 Amanita muscaria (fly amanita)-pink
O’Lantern). Right: Amanita smithiana (Smith’s Amanita).
                                                                cap. A mature adult Amanita muscaria (fly amanita)
          Edible mushrooms           Poisonous mushrooms
          (common names)               (Common names)           characterized by its distinctive pinkish-red cap dot-
                                                                ted with white scales, the remnants of the juvenile
                           fragrant                             button’s universal veil. (Courtesy of Charles P. Sea,
                                                 Cap surface
Brown fibers
                                                wipes off easily
                                                                M.D., Department of Emergency Medicine, Ochsner
near margin                                       on fingers     Clinic Foundation Hospital, New Orleans, LA. Origi-
   of cap                                        no odor        nal Source: U.S. Government Document, U.S. For-
                                                                est Service Document, 1979, “Wild Mushrooms of
                                                                North America.”)
        Tricholoma Magnivalere              Amanita Smithiana
           (White Matsutake)                 (Smith’s Amanita)

                        Irregularly         Wrinkled & folded cap
                        pitted cap              (not pitted)

          Morchella Esculenta               Gyromitra Esculenta
        (Common Edible More)                (Conifer False Morel)
                                                                                     Figure 14.4        Amanita muscaria (fly amanita)-
                                                                                     orange cap. Mature adult Amanita muscaria (fly ama-
        Pale yellow                                                 Intense          nita) characterized by orange caps rather than the
       to orange cap                                                yellow-orange
                                                                    cap              more common pinkish-red caps. The caps are dot-
                        Apricot                                                      ted with white scales, the remnants of the universal
                                                                                     veils of juvenile buttons. (Courtesy of Charles P. Sea,
                                                                                     M.D., Department of Emergency Medicine, Ochsner
                                                                                     Clinic Foundation Hospital, New Orleans, LA. Origi-
                                                                                     nal Source: U.S. Government Document, U.S. For-
        Cantharellus Cibarius                 Omphalotus Olearius                    est Service Document, 1979, “Wild Mushrooms of
       (Common Chanterelle)                    (Jack O’ Lantern)                     North America.”)
Figure 14.2b Study of edible and poisonous look-
alike mushrooms. Some commonly confused look-
alike mushrooms.
288 | Color Atlas of Human Poisonings and enenoming
Psilocybin toxicity                                       Miscellaneous Gastrointestinal toxicity

  • Representative genus: Psilocybe species.                • Representative      genera: Many miscellaneous
  • Toxins: Psilocybin (serotonin agonist/antago-               species = Boletes, Lactarius, Tricholoma, Chlo-
      nist) and psilocin indoles, both analogs of               rophyllum species.
      LSD.                                                  •   Toxins: Ill-defined gastrointestinal toxins.
  •   Antidote: None specific; benzodiazepines for          •   Antidote: None specific.
      convulsions.                                          •   Diagnosis: Onset 0.5–3 hours; severe epigastric
  •   Diagnosis: Onset rapid 0.5–1 hour; hyperkine-             pain, nausea, vomiting, diarrhea, hypovolemic
      sis, ataxia, hallucinations.                              shock.
  •   Treatment: Anticonvulsants.                           •   Treatment: Supportive, fluids and electrolytes.

Orellanine Nephrotoxicity                                 Lycoperdonosis

  • Representative genera: Cortinarius spp.                 • Definition:   Acute extrinsic allergic alveolitis
  • Toxins: Orellanine, a nephrotoxic bipyridyl.                following the inhalation of aerosolized puffball
  • Antidote: None specific.                                    spores.
  • Diagnosis: Initial gastrointestinal symptoms            •   Representative genus: Lycoperdon species
      with headache and chills in 24–36 hours; then             puffballs.
      oliguric renal failure may develop days to weeks      •   Toxins: Myco-allergens.
      later.                                                •   Diagnosis: Onset rapid, in hours, acute naso-
  •   Treatment: Hemodialysis, renal transplant.                pharyngitis, nausea, vomiting, inflammatory
                                                            •   Treatment: IV steroids, amphotericin B,
                                                                mechanical ventilation.

                                                          “Carefully” edible Mushrooms:

                                                            • “There     are old mushroom hunters, and bold
                                                                mushroom hunters, but no old, bold mushroom
                                                            •   Avoid pure white mushrooms, little (and
                                                                large) brown mushrooms, red- or pink-pored
                                                                boletes (Boletus species), and all decomposing
Figure 14.5 Cortinarius collinitus (deadly cort). Neph-     •   Cook all wild mushrooms. Cooking does not
rotoxic Cortinarius species. (Courtesy of Charles P.            inactivate all mushroom toxins, and even edible
Sea, M.D., Department of Emergency Medicine, Och-               mushrooms, if allowed to age or deteriorate,
sner Clinic Foundation Hospital, New Orleans, LA.               may become toxic.
Original Source: U.S. Government Document, U.S.             •   Select mushrooms at the grocery, not in the
Forest Service Document, 1979, “Wild Mushrooms of               woods.
North America.”)

                                                                                   Mushroom Poisonings | 289
Figure 14.6 Lepiota subclypeolaria (amatoxic lepiota).
An amatoxin-containing poisonous Lepiota species
mushroom. (Courtesy of Charles P. Sea, M.D., Depart-
ment of Emergency Medicine, Ochsner Clinic Founda-
tion Hospital, New Orleans, LA. Original Source: U.S.
Government Document, U.S. Forest Service Docu-
ment, 1979, “Wild Mushrooms of North America.”)

                                                         Figure 14.8 Lycoperdon candidum (white puffballs).
                                                         Common white puffballs (Lycoperdon candidum),
                                                         release spores when crushed, which can cause acute
                                                         bronchospasm or lycoperdonosis when inhaled. (Cour-
                                                         tesy of Charles P. Sea, M.D., Department of Emer-
                                                         gency Medicine, Ochsner Clinic Foundation Hospital,
                                                         New Orleans, LA. Original Source: U.S. Government
                                                         Document, U.S. Forest Service Document, 1979,
                                                         “Wild Mushrooms of North America.”)

Figure 14.7 Morchella esculenta (edible morel).
The prized edible morel, Morchella esculenta, often
confused with the poisonous false morel look-alike,
Gyromitra esculenta (conifer false morel). (Courtesy
of Charles P. Sea, M.D., Department of Emergency
Medicine, Ochsner Clinic Foundation Hospital, New
Orleans, LA. Original Source: U.S. Government Docu-
ment, U.S. Forest Service Document, 1979, “Wild
Mushrooms of North America.”) Also see Figure 14.2:
Color diagram. Study of three poisonous mushrooms.

290 | Color Atlas of Human Poisonings and enenoming
           Chapter 15

Poisonous Plants

         Poisonous Plants | 291
Chapter Outline
              epidemiology of plant poisonings

              Plant toxicology
                  Cardiovascular toxicity
                  Neurotoxicity group
                  Hepatotoxicity group
                  Cyanogenic group
                  Gastrointestinal toxicity
                  Dermatotoxicity group

                                              Poisonous Plants | 293
 epidemiology of Plant
• 10% of all calls to Poison Control Centers con-          • Outdoor   plant ingestions are now increasing
    cern plant ingestion and toxicity.                       among adolescents and adults seeking halluci-
•   80% of these calls involve children younger              nogenic effects, and have greater toxicity than
    than age 6.                                              indoor plant ingestions.
•   Household plant poisonings are most common:
    80% asymptomatic, <20% symptomatic, <7%
    hospital admits, Case Fatality Rate (CFR) =

tABLe 15.1 Common Plant Poisonings: United States
Botanical Name                    Common Name                           Primary toxin
Schefflera species                Umbrella tree                         Calcium oxalate
Capsaicin species                 Chili pepper                          Capsaicin
Crassula species                  Jade plant                            Calcium oxalate
Diffenbachia                      Dumbcane                              Calcium oxalate
Euphoria species                  Poinsettia                            Diterpenes
Ilex species                      Holly                                 triterpenes
Philodendron                      Parlor ivy                            Calcium oxalate
Phytolacca                        Pokeweed                              Phytolaccine
Spathiphyllyum                    Peace lily                            Calcium oxalate
toxicodendron                     Poison ivy                            Urushiol

tABLe 15.2 Lethal Plant Poisonings: United States
Botanical Name                       Common Name                        Primary toxin
Ricinus communis                     Castor bean                        ricin
Abrus precatorius                    Jequirty pea                       abrin
Conium maculatum                     Poison hemlock                     Coniine
Cicuta maculata                      Water hemlock                      Cicutoxin
Blighia sapida                       ackee tree                         Hypoglycin a
Nerium oleander                      Oleander                           Oleandrin (“digitalis”)
Convallaria majalis                  Lilly-of-the-Valley                Digitalis glycoside
Urginea species                      red squill                         Scilliroside (cardiac glycoside)
Digitalis species                    Foxglove                           Digitalis glycoside
Prunus species                       almond, apricot                    amygdalin (cyanide)

                                                                                     Poisonous Plants | 295
    Plant toxicology
Cardioascular toxicity

  • Cardiac     glycoside group: Foxglove, common
      oleander, yellow oleander, lily-of-the valley, red
  •   Aconitine group: Monkshood (wolfsbane).
  •   Grayanotoxin group: Rhododendron, azalea,
      mountain laurel.
  •   Nicotine group: Poison hemlock, tobacco.
  •   Belladonna alkaloids: Jimson weed, nightshade,
      Angel’s trumpet, henbane, mandrake.                  Figure 15.2 Convallaria majalis (Lily-of-the-Valley).
                                                           Like foxglove and oleander, Convallaria majalis (lily-of-
                                                           the-valley), a common household plant, also contains
                                                           cardiac glycosides that will heighten vagal tone and
                                                           cardiac automaticity following ingestion. (Courtesy
                                                           of Charles P. Sea, M.D., Department of Emergency
                                                           Medicine, Ochsner Clinic Foundation Hospital, New
                                                           Orleans, LA. Original Source: U.S. Government Docu-
                                                           ment, U.S. Department of Health and Human Services,
                                                           1981, “Common Poisonous and Injurious Plants.”)

                                                           Cardiac Glycosides

                                                             • Representative plants: Oleander, foxglove, red
                                                                 squill, lily-of-the-valley.
                                                             • Toxins: Digitalis, oleandrin, digitoxigenin: all
                                                                 inhibit the membrane-bound Na/K-ATPase
                                                                 pump increasing intracellular Na and Ca con-
                                                                 centrations and extracellular (serum) K increas-
                                                                 ing automaticity, contractility, and vagal tone.
                                                             •   Antidote: DigiBind® (digoxin-specific Fab).
                                                             •   Diagnosis: Nausea, vomiting, dysrhythmias
                                                                 (bradydysrythmias, heart blocks).
                                                             •   Treatment: Gastrointestinal decontamination
                                                                 (lavage and AC), monitor ECG and digitalis
                                                                 (digoxin) levels.
Figure 15.1 Digitalis purpurea (Foxglove). The car-
diotoxic Digitalis purpurea (Foxglove) plant, a common
garden flower, contains high concentrations of digitalis   aconitine Group
glycosides (digitalis, digitoxigenin), especially in its
leaves. (Courtesy of Charles P. Sea, M.D., Department
of Emergency Medicine, Ochsner Clinic Foundation
                                                             • Representative      plants: Monkshood (wolfs-
Hospital, New Orleans, LA. Original Source: U.S. Gov-
ernment Document, U.S. Department of Health and
                                                             •   Toxin: Parasympathomimetic terpene and acon-
                                                                 itine alkaloids cause prolonged opening of car-
Human Services, 1981, “Common Poisonous and Inju-
rious Plants.”)
                                                                 diac Na channels with increased vagomimesis

296 | Color Atlas of Human Poisonings and enenoming
                                                             • Treatment:    Gastrointestinal decontamination
                                                                 (lavage and activated charcoal [AC]); grayano-
                                                                 toxins do not bind to digoxin Fabs.

                                                           Nicotine Group

                                                             • Representative plants: Poison hemlock (Socrates)
                                                                 — resembles Queen Anne’s lace (wild carrot)
                                                                 and wild tobacco.
Figure 15.3 Aconitum napellus (Monkshood). Aco-              •   Toxin: Coniine, a nicotine alkaloid, blocks
nitum napellus (monkshood), so named for its purple              coniine nicotinic cholinergic receptors.
flower that resembles a helmet or monk’s hood, con-          •   Antidote: None.
tains the cardiotoxin, aconitine, which prolongs the         •   Diagnosis: Initial salivation, nausea, vomiting
opening of cardiac sodium channels inducing ven-                 and diarrhea; then diaphoresis, tachycardia,
tricular dysrhythmias. (Courtesy of Charles P. Sea,              tremors, seiwzures, ascending paralysis, respi-
M.D., Department of Emergency Medicine, Ochsner                  ratory failure, coma.
Clinic Foundation Hospital, New Orleans, LA. Original        •   Treatment: Gastrointestinal decontamination
Source: U.S. Government Document, U.S. Depart-                   (lavage and AC).
ment of Health and Human Services, 1981, “Common
Poisonous and Injurious Plants”.)
                                                           Belladonna alkaloids
      and ventricular automaticity, similar to digitalis
      effects.                                               • Representative   plants: Nightshade, jessamine,
  •   Antidote: None.                                            jimson weed (thornapple), Brugmansia and
  •   Diagnosis: Nausea, vomiting, diarrhea, par-                Solandra species (Angel’s trumpet).
      esthesias, atrioventricular block, ventricular         •   Toxins: Atropine = its plant isomer is hyo-
      tachycardia, ventricular fibrillation, respiratory         scyamine; scopolamine = its plant isomer is
      failure.                                                   hyoscine.
  •   Treatment: Gastrointestinal decontamination            •   Antidote: Physostigmine for CNS effects.
      (lavage and AC), temporary pacemaker, aconi-
      tine is not bound by digoxin Fab.


  • Representative     plants: Azalea, rhododendron,
      mountain laurel, and local honey containing
      plant nectar.
  •   Toxins: Parasympathomimetic oily diterpene —
      grayanotoxins force open cardiac Na channels
      increasing cardiac automaticity and enhancing
      vagal tone, similar to digitalis effects.
                                                           Figure 15.4 Conium maculatum (Poison hemock).
  •   Antidote: None.
                                                           Conium Maculatum (poison hemlock) resembles com-
  •   Diagnosis: Gastrointestinal symptoms, SLUDE
                                                           mon herbs, such as wild carrot and Queen Anne’s
      syndrome (salvation, lacrimation, urination,         lace, and contains the nicotinic receptor blocker, coni-
      defecation, emesis) or DUMBBELS syndrome             ine, which induces seizures and paralysis on inges-
      (diarrhea, urination, miosis, bronchospasm,          tion. (Courtesy of Charles P. Sea, M.D., Department
      bronchorrhea, emesis, lacrimation, salivation),      of Emergency Medicine, Ochsner Clinic Foundation
      weakness, bradydysrhythmias, ataxia, pares-          Hospital, New Orleans, LA. Original Source: U.S. Gov-
      thesias, seizures.                                   ernment Document, U.S. Department of Health and
                                                           Human Services, 1981, “Common Poisonous and Inju-
                                                           rious Plants.”)

                                                                                          Poisonous Plants | 297
Figure 15.5 Nicotiana glauca (Wild Tree Tobacco).
Like poison hemlock, Nicotiana glauca or wild tobacco
contains epileptogenic nicotine-like alkaloids. (Cour-
tesy of Charles P. Sea, M.D., Department of Emer-
gency Medicine, Ochsner Clinic Foundation Hospital,        Figure 15.7 Nerium oleander (dogbane). All parts of
New Orleans, LA. Original Source: U.S. Government          the oleander shrub are highly toxic and contain digitalis
Document, U.S. Department of Health and Human              glycosides that can cause nausea, vomiting, tacha-
Services, 1981, “Common Poisonous and Injurious            rryhythmias, and cardiac conduction disturbances,
Plants.”)                                                  including complete heart block, on ingestion. Olean-
                                                           der grows up to 9 meters tall in warm beachfront loca-
                                                           tions and produces abundant white, yellow, pink, or
                                                           red flowers. Oleander has poisoned beach-goers who
                                                           have selected oleander branches to use as skewers to
                                                           roast their hot dogs over beachside bonfires. Source:
                                                           Department of the Army, The Illustrated Field Guide to
                                                           Edible Wild Plants, 2003.

Figure 15.6 Laburnum anagyroides (Goldenchain) 1.          Figure 15.8 Datura stramonium (Jimson Weed or
Laburnum anagyroides or golden chain also contains         Thornapple). The belladonna alkaloid-containing jimson
nicotine-like alkaloids, which can induce headache,        weed or thornapple plant (Datura stramonium). Legend
ataxia, and seizures with respiratory arrest on inges-     holds that early American colonists encouraged occu-
tion. (Courtesy of Charles P. Sea, M.D., Department        pying British troops to consume salads of local “jim-
of Emergency Medicine, Ochsner Clinic Foundation           son” (for Jamestown, Virginia) weed and to suffer the
Hospital, New Orleans, LA. Original Source: U.S. Gov-      central and peripheral anticholinergic consequences
ernment Document, U.S. Department of Health and            (Courtesy of Charles P. Sea, M.D., Department of
Human Services, 1981, “Common Poisonous and Inju-          Emergency Medicine, Ochsner Clinic Foundation Hos-
rious Plants.”)                                            pital, New Orleans, LA. Original Source: U.S. Gov-
                                                           ernment Document, U.S. Department of Health and
                                                           Human Services, 1981, “Common Poisonous and Inju-
  • Diagnosis: Atropine toxicity = fever, dry mouth,       rious Plants.”)
      tachycardia, ileus, urinary retention, hallucina-
      tions, seizures, “red as a beet, hot as Hades, dry
      as a bone, mad as a hatter.”
  •   Treatment: Gastrointestinal decontamination.

298 | Color Atlas of Human Poisonings and enenoming
                                                          Figure 15.10 Commercial Landscaping with Angel’s
Figure 15.9 Angel’s Trumpet (Brugmasia spp. as            Trumpet (Brugmasia sauveolens), San Diego, CA.: The
shown and Solandra spp.). The angel’s trumpet plants,     angel’s trumpet plant was introduced into the temper-
Brugmasia spp. (shown) and Solandra spp. (not shown)      ate and tropical areas of the U.S. from southeastern
are very common perennials in the Southern US, and        Brazil for landscaping purposes. All parts of the plants
contain a scopolamine-like belladonna alkaloid that can   are toxic and contain a combination of several anticho-
cause a central anticholinergic syndrome on inges-        linergic tropine alkaloids, including atropine, hyoscya-
tion. (Courtesy of Charles P. Sea, M.D., Department       mine, and scopolamine. Since the 1990s, there have
of Emergency Medicine, Ochsner Clinic Foundation          been increasing U.S. reports of central anticholinergic
Hospital, New Orleans, LA. Original Source: U.S. Gov-     syndromes following the ingestion of teas and potions
ernment Document, U.S. Department of Health and           made from angel’s trumpet in adolescents seeking
Human Services, 1981, “Common Poisonous and Inju-         legal hallucinogens.
rious Plants.”)

Neurotoxicity Group                                       Hallucinogens

                                                            • Representative plants: Morning glory (“LSD,”
                                                                contains “LSD-like” substance), peyote cactus,
  • Representative    plants: Water hemlock, also               nutmeg and mace (powdered spice made by
      resembles the edible herb Queen Anne’s lace               grinding nutmeg kernels).
      (wild carrot).                                        •   Nutmeg and mace: (Myristica fragrans,
  •   Toxin: Cicutoxin.                                         resembles methylene dioxymethamphetamine
  •   Antidote: None.                                           (MDMA) = Ecstasy toxicity).
  •   Diagnosis: Diaphoresis, nausea, vomiting, and         •   Toxins: Morning glory: lysergamide (LSD-
      abdominal cramps within 1 hour; then severe               like); peyote: mescaline; and nutmeg and mace:
      convulsions = status epilepticus, case fatality           myristicin (MDMA-like).
      rate (CFR) 30%.                                       •   Antidote: None.
  •   Treatment: Gastrointestinal decontamination           •   Diagnosis: Initial nausea and vomiting, diapho-
      (lavage and AC), anticonvulsants (barbiturates,           resis, mental status change, deep sleep (nutmeg),
      benzodiazepines).                                         hallucinations.
                                                            •   Treatment: Gastrointestinal decontamination,

                                                                                         Poisonous Plants | 299
Hepatotoxicity Group

  • Representative    plant: Ackee tree and its fruit
      (Blighia sapida) common in South Florida and
      the Caribbean.
  •   Toxins: Hypoglycins A and B-inhibit gluclose-
      6-phosphate dehydrogenase (G-6-PD) blocking
      hydrolysis of fatty acids and cause Jamaican
      vomiting sickness.                                     Figure 15.11 Cicuta maculata (Water Hemlock).
  •   Antidote: 50% dextrose.                                Cicuta maculata or water hemlock grows ubiquitously
  •   Diagnosis: Severe nausea and vomiting, hypo-           on riverbanks, resembles edible herbs, and contains
      glycemia, hyperammonemia, mental status                cicutoxin, which can induce seizures and rhabdomy-
      changes, hypothermia, metabolic acidosis, sei-         olysis following ingestion. (Courtesy of Charles P. Sea,
      zures, deteriorating liver function-centrilobular      M.D., Department of Emergency Medicine, Ochsner
      hepatic necrosis.                                      Clinic Foundation Hospital, New Orleans, LA. Original
  •   Treatment: Gastrointestinal decontamination            Source: U.S. Government Document, U.S. Depart-
      (lavage and AC).                                       ment of Health and Human Services, 1981, “Common
                                                             Poisonous and Injurious Plants.”)
Comfrey, Sassafras
  • Representative      plants: Comfrey, sassafras
      (gumbo file powder).                                   Gastrointestinal toxicity
  •   Toxins: Hepatotoxic pyrrolizidine alkaloids and        Calcium Oxalate
      safrole respectively.
  •   Antidote: None.
  •   Diagnosis: Hepatotoxicity, specifically hepatic          • Representative plants: Species of Diffenbachia,
      veno-occlusive disease (comfrey), and, possibly,             Philodendron, Brassaia, Schefflera, Pothos,
      hepatocellular carcinoma (sassafras).                        Caladium, Spathiphyllum.
  •   Treatment: Gastrointestinal decontamination              •   Toxin: Calcium oxalate crystals bundled in
      (lavage and AC).                                             raphides and loaded into idioblasts to be fired
                                                                   with additional proteolytic enzymes. Example:
Cyanogenic Group                                               •   Antidote: None.
                                                               •   Diagnosis: Salivation, dysphagia, dysarthria,
                                                                   mucosal edema and oral bullae, contact derma-
  • Representative plants: Prunus species, especially              titis and conjunctivitis.
      seeds of almond, apple, apricot, plum, peach,            •   Treatment: Cold milk/ice, ice cream; consider
      and cherry; also elderberry, hydrangea.                      corticosteroids.
  •   Toxin: Amygdalin, which is hydrolyzed to
      hydrocyanic acid (HCN) = Laetrile®, an illicit
      cancer chemotherapeutic made from apricot              Probably Calcium Oxalate
      pits and containing amygdalin.
  •   Antidote: Lilly cyanide kit ®: inhaled amyl nitrite,   The jade plant (Crassula argentea) is a very popular
                                                             houseplant from which no toxin has been isolated,
      IV sodium nitrite, and IV sodium thiosulfate.
  •   Diagnosis: headache, dizziness, vertigo, sei-          yet there is a case report of a 1-year-old who ingested
                                                             several leaves and had persistent diarrhea and peri-
      zures, hyperthermia, stupor, coma.
  •   Treatment: Gastrointestinal decontamination.           anal dermatitis (Schilling et al., Vet. Hum. Toxicity,

300 | Color Atlas of Human Poisonings and enenoming
Figure 15.12 Dumbcane (Diffenbachia spp.). Diffen-
bachia or dumbcane is a popular household decorative     Figure 15.14 Ricinus communis (Castor Bean Plant).
plant whose leaves contain idioblasts that discharge     The castor bean plant, Ricinus communis, is the source
irritant calcium oxalate crystals when damaged. (Cour-   of the ricin-containing castor bean seed. (Courtesy
tesy of Charles P. Sea, M.D., Department of Emer-        of Charles P. Sea, M.D., Department of Emergency
gency Medicine, Ochsner Clinic Foundation Hospital,      Medicine, Ochsner Clinic Foundation Hospital, New
New Orleans, LA. Original Source: U.S. Government        Orleans, LA. Original Source: U.S. Government Docu-
Document, U.S. Department of Health and Human            ment, U.S. Department of Health and Human Services,
Services, 1981, “Common Poisonous and Injurious          1981, “Common Poisonous and Injurious Plants.”)

Figure 15.13 Philodendron spp. Caption: Like Dif-        Figure 15.15 Abrus precatorius (Rosary or Jequirty
fenbachia or dumbcane, philodendrons, caladiums,         Pea): Seeds in Pods. Abrus precatorius (the rosary or
and pothos are all also very popular indoor decorative   jequirty pea) is a tropical shrub, whose seeds contain
plants whose leaves contain idioblasts that discharge    the toxalbumin, abrin, which can induce hemorrhagic
irritant calcium oxalate crystals when damaged, caus-    gastroenteritis following chewing and ingestion of
ing salivation and oropharyngeal edema. (Courtesy        seeds. (Courtesy of Charles P. Sea, M.D., Department
of Charles P. Sea, M.D., Department of Emergency         of Emergency Medicine, Ochsner Clinic Foundation
Medicine, Ochsner Clinic Foundation Hospital, New        Hospital, New Orleans, LA. Original Source: U.S. Gov-
Orleans, LA. Original Source: U.S. Government Docu-      ernment Document, U.S. Department of Health and
ment, U.S. Department of Health and Human Services,      Human Services, 1981, “Common Poisonous and Inju-
1981, “Common Poisonous and Injurious Plants.”)          rious Plants.”)


  • Representative     plants: Castor bean, jequirty       • Diagnosis: Severe hemorrhagic gastroenteritis,
      (rosary) pea, black locust.                              hematochezia, seizures, CNS depression, cere-
  •   Toxins: Ricin (castor bean), abrin (rosary pea)          bral edema, hepatorenal failure.
      — protein synthesis inhibitors, rapid cell death     •   Treatment: Gastrointestinal decontamination,
      (especially in gastrointestinal tract).                  whole-bowel irrigation.
  •   Antidote: None.

                                                                                       Poisonous Plants | 301
Solanine Group

  • Representative plants: Leaves of green potatoes
      (especially potato “eyes” and vines) and toma-
      toes (leaves and stems).
  •   Toxins: Solanine, solanidine.
  •   Antidote: None.
  •   Diagnosis: Within 2–24 hours, nausea, vomit-
      ing, diarrhea, abdominal cramps; later delir-
      ium, hallucinations, coma, death, no deaths
      since 1960s.                                       Figure 15.16 Abrus (Rosary Pea): Seeds. Rosary pea
  •   Treatment: Gastrointestinal decontamination        seeds are still used in the Caribbean tropics to make
      (lavage and AC).                                   colorful jewelry and rosaries, and may be swallowed
                                                         whole without serious gastrointestinal toxicity. On the
                                                         other hand, chewing the seeds can release the protein
Colchicine Group                                         synthesis inhibitor, abrin, which, like ricin, can cause
                                                         delayed hemorrhagic gastroenteritis with hypovolemic
                                                         dehydration and high case fatality. (Courtesy of Charles
  • Representative plants: Autumn crocus, glory lily.    P. Sea, M.D., Department of Emergency Medicine,
  • Toxin: Colchicine.                                   Ochsner Clinic Foundation Hospital, New Orleans, LA.
  • Antidote: Colchicine Fabs.                           Original Source: U.S. Government Document, U.S.
  • Diagnosis: Nausea, vomiting, bloody diar-            Department of Health and Human Services, 1981,
      rhea, agranulocytosis due to mitosis inhibition,   “Common Poisonous and Injurious Plants.”)
  •   Treatment: Gastrointestinal decontamination
      (lavage and AC).

Christmas Group

  • Representative       plants: Mistletoe,   holly,
  •   Toxins: Miscellaneous diterpene esters.
  •   Antidote: None.
  •   Diagnosis: Nausea, vomiting, abdominal
      cramps, oral mucosal burns; last death due to
      poinsettia ingestion — Hawaii, 1919.
  •   Treatment: Gastrointestinal decontamination
      (lavage and AC).

Miscellaneous                                            Figure 15.17 Euphorbia marginata (Snow-on-the-
                                                         Mountain). The Euphorbia species plants include a
                                                         wide variety of popularly cultivated indoor and outdoor
  • Representative   plants: Pokeweed, English ivy,
                                                         plants, specifically poinsettias, candelabra and pencil
      yew, horse chestnut.
                                                         cactus, creeping spurge, and snow-on-the-mountain.
  •   Toxin:     Phytolaccine     (phytolaccatoxin),     The Euphorbia species plants can induce a chemical
      phytolaccagenin.                                   dermatitis on contact with their milky sap or cause
  •   Antidote: None.                                    mild gastroenteritis on ingestion. (Courtesy of Charles
  •   Diagnosis: Nausea, vomiting, diarrhea,             P. Sea, M.D., Department of Emergency Medicine,
      abdominal cramps — colic, lymphocytosis            Ochsner Clinic Foundation Hospital, New Orleans, LA.
      (pokeweed).                                        Original Source: U.S. Government Document, U.S.
                                                         Department of Health and Human Services, 1981,
                                                         “Common Poisonous and Injurious Plants.”)

302 | Color Atlas of Human Poisonings and enenoming
Dermatotoxicity Group

  • Representative plants: Rhus family = poison ivy,
      poison oak, poison sumac. “Leaves of three, let
      them be.”
  •   Toxin: The active toxin, urushiol, is suspended
      in the oily and sticky resin, toxicodendrol, of all
      Rhus family plants.
  •   Antidote: None.                                       Figure 15.19 Toxicodendron radicans (Poison Ivy):
  •   Diagnosis: Pruritic linear vesiculobullous            Leaves. The Toxicodendron group of vines and shrubs
      dermatitis.                                           can induce severe chemical contact dermatitis on
  •   Treatment: Antihistamines, topical-systemic           exposure to their oily resin, toxicodendrol, which con-
      steroids.                                             tains the suspended active toxin, urushiol. The Toxico-
                                                            dendron group of plants includes poison ivy as shown
                                                            (Toxicodendron radicans), poison oak (Toxicodendron
                                                            toxicarium), and poison sumac (Toxicodendron ver-
                                                            nix). Note poison ivy’s cluster of three leaves on red
                                                            stems. (Courtesy of Charles P. Sea, M.D., Department
                                                            of Emergency Medicine, Ochsner Clinic Foundation
                                                            Hospital, New Orleans, LA. Original Source: U.S. Gov-
                                                            ernment Document, U.S. Department of Health and
                                                            Human Services, 1981, “Common Poisonous and Inju-
                                                            rious Plants.”)

Figure 15.18 Taxus spp. (Yew spp.). Shrub. One of
the many varieties of yew shrub or tree that contains
taxine, a cardiac sodium-potassium channel blocker          Figure 15.20 Toxicodendron radicans (Poison Ivy):
that can cause cardiac arrest on ingestion. The antican-    Vine. The Toxicodendron plants may resemble peren-
cer drug, tamoxifen, is derived from a Taxus spp. Shrub     nial ivy vines, low growing shrubs (poison oak), or small
or tree, the Pacific yew. (Courtesy of Charles P. Sea,      trees (poison sumac). (Courtesy of Charles P. Sea,
M.D., Department of Emergency Medicine, Ochsner             M.D., Department of Emergency Medicine, Ochsner
Clinic Foundation Hospital, New Orleans, LA. Original       Clinic Foundation Hospital, New Orleans, LA. Original
Source: U.S. Government Document, U.S. Depart-              Source: U.S. Government Document, U.S. Depart-
ment of Health and Human Services, 1981, “Common            ment of Health and Human Services, 1981, “Common
Poisonous and Injurious Plants.”)                           Poisonous and Injurious Plants.”)

 tABLe 15.3 Dermatotoxicity Group
 Allergic Contact Dermatitis           Allergic Contact Urticaria            (Due to Sunlight-Actiated Psoralens)
 Poison ivy                            Stinging nettle                       Celery
 Poison oak                            Wood nettle                           Figs
 Poison sumac                          Bull nettle                           Limes
 Gingko                                agavé (Century cactus)                C