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Toxicology

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					                                   TOXICOLOGY
Introduction

      In general, adverse effects of poisoning result in an imbalance between the
       sympathetic and parasympathetic nervous systems




      ANS: both arms use Ach nicotinic receptors at their preganglionic synapse sites
      Sympathetic NS:
          o Fight or flight
          o Neurotransmitters: norepinephrine or epinephrine
          o 3 major branches that have separate mechanisms: sweat glands, adrenergic
              neurotransmission, paracrine via adrenal medulla
                   Sweat glands utilize Ach muscarinic receptors
                   Noradrenergic neurotransmission utilize either alpha or beta
                     receptors
                   Adrenal medulla releases both epinephrine and norepinephrine
      Parasympathetic NS:
             o Rest and digest
             o Neurotransmitters: acetylcholine
             o A single branch
             o Utilizes Ach muscarinic receptors at the effector site
         Neurotransmitters
             o Acetylcholine: binds to nicotinic (N) and muscarinic (M) cholinergic
                 receptors
                      Broken down by acetylcholinesterase
             o Norepinephrine (NE): binds to alpha and beta noradrenergic receptors
                      Broken down by COMT

                     ANS Branch                                                   Clinical Effect
Sympathetic (adrenergic)                                    Diaphoresis
                                                            Mydriasis
                                                            Positive chronotropy + inotropy (tachycardia, HTN)
                                                            Vasoconstriciton (alpha)
                                                            Vasodilation (beta)
                                                            Bronchodilation
                                                            Increase urethral sphincter tone (retention)
                                                            Metabolic effects:
                                                                     Increase: WBC, glucose, ketones
                                                                      Decrease: pH, K+, PO4-
Parasympathetic (cholinergic)                               Miosis
                                                            Lacrimation
                                                            Salivation
                                                            Bronchospasm
                                                            Bronchorrhea
                                                            Bradycardia
                                                            Increase detrusor muscle tone (urination)
                                                            Increase GI motility

             Receptor                                  Agonism                             Antagonism
Alpha 1                                  Vasoconstriction                       Vasodilation
         Post-synaptic                  Positive inotropy
                                         Increased HR
         Vascular smooth mm,
          heart tissue
Alpha 2                                  Vasoconstriction (peripheral)          Vasodilation (peripheral)
         Pre + extrasynaptic            Vasodilation (central)                 Hypertension
                                         Sedation (central)                     Tachycardia
         Vasculature only               Bradycardia                            Agitation
                                                                                Mydriasis
                                                                                Diaphoresis
Beta 1                                   Increased HR (one, heart)              Decreased HR
         Post-synaptic                  Positive inotropy
         Heart only
Beta 2                                   Vasodilation                           Bronchoconstriction
         Pre + extrasynaptic            Bronchodilation (two, lungs)
         Vascular + bronchiolar
          smooth mm

Opioid        Mu:
receptors                Miosis, euphoria, respiratory depression, decreased GI motility, pruritis
              Kappa:
                      Miosis, sedation, dysphoria, analgesia
              Delta:
                   Supraspinal/spinal analgesia, antidepressant, physical dependence
              Nociceptin:
                      Anxiety, depression




Toxidromes

      Toxidrome              Pathophysiology              Clinical Manifestations          Common culprits
Anticholinergic            Inhibition of all        CNS: delirium, agitation, seizures,   Antihistamines
                           muscarinic receptors     mumbling speech, “picking             Antidepressants
                            sympathetic            movements” with fingers (mad as a     Antipsychotics
                           system uninhibited,      hatter)                               (typical > atypical)
                           this includes                                                  Antispasmodics
                           decreased                HEENT: mydriasis (blind as a bat),    Antiparkinsonians
                           diaphoresis              decreased salivation, decreased
                                                    lacrimation

                                                    CV: tachycardia, HTN, hyperthermia,
                                                    hyperemia (hot as a hare)

                                                    Skin: dry and flushed (dry as a
                                                    bone, red as a beet)

                                                    GI/GU: urinary retention, decreased
                                                    bowel sounds

                                                    Can’t see, can’t pee, can’t spit,
                                                    can’t shit
Cholinergic                Stimulation of           DUMBELS:                              Organophosphates
                           muscarinic receptors     Defection, Urination, Miosis/Muscle   (fertilizers)
                            widespread             weakness,                             Pesticides
                           activation of the ANS    Bronchorrhea/Bronchoconstriction/     (carbamate)
                           with variable clinical   Bradyarrhthmias, Emesis,              Physostigmine
                           responses depending      Lacrimation, Seizures/Salivation      Edrophonium
                           on the agent                                                   Mushrooms
                                                    CNS: confused, CNS depression,
                                                    muscle fasciculations

                                                    HEENT: miosis, lacrimation,
                                                    salivation

                                                    CV: variable BP/HR, normothermic

                                                    RESP: wheeze, cough
                                                  Skin: diaphoresis

                                                  GI: N/V/D

                                                  GU: urination/incontinence
Sympathomimetic           Stimulation of NE       CNS: agitated, tremor, seizures,      Cocaine
                          adrenergic system       hyperreflexia, paranoia               Amphetamines
                          and adrenal medulla                                           Methamphetamines
                                                  HEENT: mydriasis                      (MDMA)
                                                                                        Decongestants
                                                  CV: tachycardic, HTN, hyperpyrexia.   (pseudoephedrine,
                                                  dysrhythmias                          phenylephrine)
                                                                                        Caffeine
                                                  Skin: diaphoretic

                                                  GI/GU: urinary retention, decreased
                                                  bowel sounds
Opioid/Sedative/Ethanol   Stimulation of either   Classic opioid triad: decreased       Narcotics
                          opioid system, GABA     LOC, respiratory depression, miosis   Benzodiazepines
                          system                                                        Barbituates
                                                  CNS: coma, decreased LOC,             Ethanol
                                                  hyporeflexia, seizures                Clonidine

                                                  HEENT: miosis

                                                  CV: hypotension, bradycardia,
                                                  hypothermia

                                                  RESP: respiratory depression,
                                                  pulmonary edema

                                                  GI/GU: decreased bowl sounds

                                                  Skin: needle marks

				
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posted:8/30/2011
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