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Drugs Of Abuse

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					 Drugs Of Abuse

Core Rounds, Feb 6, 2003
 A.F. Chad, MD, CCFP
 M. Yarema, MD, FRCP
                        Case #1
• 24 yo M
• Car chase -> Pulled over
    by Crockett & Tubbs
•   “I’m F__kin’ High!!”
•   “I took a bunch of
    blow!!!”
•   Agitated, sweating,,
    aggressive, h/a & cp
•   Cuffed -> collapse -> no
    pulse
•   EMS -> CPR, tubed,
    pulse, Tx to Hospital
•   Now What?
                       Case #2
• 19 yo M
• Out “dancing and
    Partying”
•   Glow sticks & Soother &
    bottled water
•   Euphoric, sl agitation
•   Tachy, mydriatic,
    hyperthermic, brown urine
•   What now?
                        Case # 3
• 21 yo “Hot Chick”
• “Girls Night Out”
• Dude with earrings,
    sideburns, soul patch &
    silver sequined cowboy
    hat buys her a drink
•   She feels “off”
•   Sluggish -> LOC
•   Friends freak-> Sonny &
    Rico (who happened to be
    there undercover) escort to
    FHH
•   What now?
                         Case # 4
• Same creepy dude looking
    for love (after getting shut
    down by “Hot Chick”)
•   Buys drink for previous
    21 yo “Hot Chick’s”
    “Sweet looking friend”
•   Drink tastes fine
•   She becomes sleepy, “out
    of it”, separated from
    friends
•   Wakes up in strange apt.
•   No memories of night out
•   What’s up?
                       Case # 5
• 32 yo Cletus from
    Spokane
•   EMS called re explosion
    inside trailer
•   He comes out agitated,
    aggressive, wielding axe
•   “detained” by our Miami
    Vice heroes and escorted
    to FHH
•   Tachy, HTN, psychotic
•   What’s up?
                       Case # 6
• 18 yo F
• Dancing all night
• Ate some powder given by
  a Kellogg’s rep
• Feels like she’s floating
• Nystagmus, “out of it”
• What’s up?
                         Outline
• Cocaine
  • History, pharmacology, presentation, complications, treatment
• MDMA
  • History, pharmacology, presentation, complications, treatment
• GHB
  • History, pharmacology, presentation, complications, treatment
• Methamphetamine
  • History, pharmacology, presentation, complications, treatment
• Ketamine
  • History, pharmacology, presentation, complications, treatment
• Flunitrazepam
  • History, pharmacology, presentation, complications, treatment
USA Controlled Substances Act
            1984
A couple general approach slides
COCAINE

  Blow
                  Cocaine
• From Coca Leaves
• Use noted from 2000 B.C.
• 1859 Spanish MD’s use as Rx
• 1863 French wine with 6mg cocaine sold
• 1884 William Stewart Halsted does 1st Cocaine
  nerve block
• Halsted: 1st cocaine impaired MD on record
• 1893 cocaine related deaths noted
• 1914 Harrison Narcotics Act bans non-Rx cocaine
         Cocaine in the USA
        (New Springsteen hit?)
• 2000: 926,000 new users
• average age of 1st time users: 20 years
• 27.8 million (12.%) Americans ages 12 or older
  tried cocaine at least once
• 4.2 million (1.9%) used cocaine in the past year
• 1.7 million (0.7%) used cocaine w/i the month
• peak use in 1985: 5.7 million Americans ( 3% of
  the population)
          Rock, Blow, Snow
• benzoylmethylecgonine
• leaves of Erythroxylon coca: shrub
  indigenous to Peru, Bolivia, Mexico, West
  Indies and Indonesia
• crystalline alkaloid: C17H21NO4
• Commonly in cocaine HCl form
• Ester-type local anaesthetic
 Jimmy Crack Pipe & He Don’t
            Care
• Remove HCl via ether extraction = crack
• Frees the basic cocaine molecule = “free
  basing”
• Crack -> cracking sound when smoked
• Vaporizes @ 98 degs C -> no ruining
• Allows for smoking a bowl
       Cocaine Pharmacology
• 1st - blocks norepinephrine uptake
• 2nd - causes norepinephrine release
• 3rd - moderate release and reuptake
  blockade of dopamine & serotonin
• Has Na+ & K+ channel blockade effects
      Cocaine Pharmacology
• Fat soluble -> easily crosses BBB
• Stimulates CNS esp in Limbic area with
  dopamine -> “high as a frikkin’ kite”
• metabolized by hepatic esterases and
  plasma pseudocholinesterase
• benzoylecgonine & ecgonine methylester
  are active metabolites
    Cocaine: How Can You do it?
• ALL mucous membranes
• IV (100% bioavailability)
• Eaten (20-30% bioavailability)
    • poor absorption in stomach, good in duodenum
•   Smoked (crack) (20-30% bioavailability)
•   1 inch line = 25-100mg coke
•   Spoon = 5-25mg coke
•   LD50 = 1 gm (po)
   When am I gonna Get High?
• Inhalation
  • 7 s onset, 1-5 min peak, 20 min duration, 40-60 min
       half-life
• IV
  • 15 s onset, 3-5 min peak, 20-30 min duration, 40-60
       min half-life
• Nasal
  • 3 min onset, 15 min peak, 45-90 min duration, 60-90
       min half-life
• Oral
  • 10 min onset, 60 min peak, 60 min duration, 60-90 min
       half- life
When Coke Alone Ain’t Enough
• EtOH: Metabolite
   • Ethylbenzoylecgonine (cocaethylene) Increases
    T1/2 and Lowers LD50
• Nicotine
  • increases sympathetic response
• Heroin
  • speedball = IV/smoke heroin, then smoke
    crack, moderates withdrawal -> higher doses
            3 Phases of Toxicity
• Phase I - Early stimulation
• CNS: Mydriasis, headache, bruxism, nausea,
    vomiting, vertigo, nonintentional tremor ,tics,
    preconvulsive movements, pseudohallucinations
•   CVS - HTN / HypoTN, tachy / brady, pallor
•   Respiratory - Increased rate & Vt
•   Temperature - Elevated
•   Behavioral - Euphoria, elation garrulous talk,
    agitation, apprehension, excitation, restlessness,
    verbalization of impending doom, emotional
    instability
          3 Phases of Toxicity
• Phase II - Advanced stimulation
• CNS: Malignant encephalopathy, seizures and
  status, decreased responsiveness, increased DTR,
  incontinence
• CVS: HTN, tachy; ventricular dysrhythmias,
  weak, rapid, irregular pulse and hypotension;
  peripheral cyanosis
• Respiratory: Tachypnea, dyspnea, gasping,
  irregular breathing
• Temperature: Severe hyperthermia
          3 Phases of Toxicity
• Phase III - Depression and premorbid
  state
• CNS: Coma, areflexia, pupils fixed and dilated,
  flaccid paralysis, and loss of vital support
  functions
• CVS: Circulatory failure, cardiac arrest
  (ventricular fibrillation or asystole)
• Respiratory: Respiratory failure, gross pulmonary
  edema, cyanosis, agonal respirations,
           Cocaine: Not so safe
•   CVS
•   CNS
•   Respiratory
•   Packers / Stuffers
•   Other
         Cocaine Dysrhythmias
• ST, SVT, A.Flutter, A.Fib, VT, V.Fib,
    AVB, Asystole, long QT ->TdP
•   Like a type 1A Na+ blocker (procainamide,
    quinidine)
•   Direct SNS overload?
•   Cardiotoxic -> arrythmogenic foci
•   Accelerated atherosclerosis
      Rx Cocaine Dysrhythmias
• Depends on Rhythm
• NO B-blocker, procainamide, quinidine
• NaHCO3 may be of help
   • Beckman KJ, Parker RB, Hariman RJ, et al.
     Hemodynamic and electrophysiological actions of
     cocaine: Effects of sodium bicarbonate as an
     antidote in dogs. Circulation 1993;83:1799-1807.
• Benzos if 2nd to increased catacholamines
• Lidocaine is safe if indicated
   • Shih RD, Hollander JE, Burstein JL, et al. Clinical
     safety of lidocaine in patients with cocaine-
     associated myocardial infarction. Ann Emerg Med
       Coke: close to the Heart
• Vasoconstriction, plt clumping, thrombi
• Higher O2 demand
• Direct myocardial toxicity
   • Goldfrank LR, Hoffman RS. The cardiovascular
     effects of cocaine. Ann Emerg Med 1991;20:165-175.
• Accelerated atherogenesis
   • Minor RL Jr, Scott BD, Brown DD, et al. Cocaine-
     induced MI in patients with normal coronary
     arteries. Ann Intern Med 1991; 115:797-806.
           Coke Chest Pain
• Most common complaint post coke use
• 6% will have MI (rookies or crack heads)
• Often classic sounding cp
• ECG non-diagnostic in 60%
• CK-MB and TNT NOT increased by coke
  alone (cardiac event)
• CK increased (rhabdo)
               Coke & CP
• Need observation x 12 hours (consensus)
   • 33% develop bad stuff
• Serial ECG & enzymes
• 0.2% problems post 12 hours
   • Hollander JE. The management of cocaine-
    associated myocardial infarction. N Engl J
    Med 1995;333:1267-1272.
                   Coke & CP
•   Is 6 hours good enough?
•   197 pts
•   Check enzymes 0, 3, 6 hrs
•   If all N + no ECG changes -> OK
    • Kushman SO, Storrow AB, Liu T et al. Cocaine-
      associated chest pain in a chest pain center. Am J
      Cardiol 2000;85:394-396.
         MI with your Coke?
• Same Rx as normal but NO B-blockers!!!!
• phentolamine or verapamil?
  • Hollander JE, Carter WA, Hoffman RS. Use of
    phentolamine for cocaine-induced myocardial
    ischemia. N Engl J Med 1992;327:361.
• Benzos as good as NTG as good as both
  • Weber JE, Chudnofsky CR, Boczar M, et al. Cocaine-
    associated chest pain: How common is MI? Acad
    Emerg Med 2000;7:873-885.
       Thrombolysis & Coke?
• Crap?
  • Hollander JE, Burstein JL, Hoffman RS, et al. Cocaine-
    associated MI: Clinical safety of thrombolytic
    therapy. Cocaine Associated Myocardial Infarction
    (CAMI) Study Group. Chest 1995;107: 1237-1241.
• Good?
  • Mueller PD, Benowitz NL, Olson KR. Cocaine. Emerg
    Med Clin North Am 1990;8:481-493.
• Be REALLY Careful?
  • Hollander JE, Wilson LD, Leo PJ, et al. Complications
    from the use of thrombolytic agents in patients with
    cocaine associated chest pain. J Emerg Med
    1996;14:731-736.
 Well, we have Angio in Calgary
• Case reports suggest ok
  • Shah DM, Dy TC, Szto GY, et al. PTCA and
    stenting for cocaine-induced AMI: A case
    report and review. Catheter Cardiovasc Interv
    2000;49:447-451.
              Coke Shake
•   Seizures in 2-10%
•   Stoke not uncommon
•   Need CT
•   BENZOS!!!!
•   Phenobarb
•   GA
              Strokey Cokey
•   Most common cause of stroke in young
•   60% users get h/a post use
•   Stroked pts usually h/a 3-6 hours post
•   Can cause SAH, ischemia, ICH, vasculitis
•   NEED CT +/- LP if concerned
                  Crack Lung
• Distinct entity 1-12 hours post smoking
• fever, dyspnea, hemoptysis, hypoxia, chest pain,
  infiltrates, respiratory failure
• Rx steroids (eosinophils on Bx)
• Other Resp Problems
   • Upper airway burn, epiglotitis, asthma, pneumothorax,
     pneumomediastinum, noncardiogenic pulmonary
     edema, pulmonary hemorrhage/infarction
              Snow Stuffers
•   Hiding it from Crockett & Tubbs
•   Quickly ingested, not prepared
•   Toxicity!!!
•   AC + whole bowel irrigation
         Put it in my Crack Pack
•   Packers = well prepared packets of drug
•   Large amounts
•   Bowel obst, sudden death (bag bursts)
•   + tox screen (95% sensitive)
•   Xray, contrast, CT
•   NO SCOPE!!!
•   AC -> polyethylene glycol -> clear fluid
•   Admit until all packets out
•   Surgery if concerns
                   Other
• Rhabdo
  • Normal Rx
• Excited Delirium
• Loss of pregnancy
• Hyperthermia
  • Dopaminergic regulated
               Pepsi vs Coke
• ABCD!!!
• Need monitors, IV’s, Tubes, O2
• Remove any residual cocaine from nasal use.
• Protect the patient from hypoglycemia,
• Rely on clinical findings re toxidrome
• Reassurance if the patient is oriented.
• Avoid physical or pharmacological restraints if
  possible.
• Symptoms usually abate by 6 hours unless
  complications arise or coingested with longer
  acting agent (amphetamines)
                Pepsi vs Coke
• CBC, lytes, coags, glucose, U/A, CK, TNT, Bhcg,
    ABG, creatinine, tox screen
•   CXR
•   ECG
•   CT +/- LP
•   Fancy tests
•   NB: Urine screen for cocaine metabolites detects
    use within past 3-4 days, sometimes as long as 3
    weeks
                   Pepsi Drugs
• BENZOS!!!!
  • As much as needed!!!!
• Epi?
  • Still use in arrest
• Lido?
  • Theoretically can worsen
• B-Blockers?
  • BAD -> uncontrolled A stim
  • Even labetalol has 7:1 beta:alpha effect ratio
  Crank the Techno,
   Grab a Dasani,
Soother & Glow Sticks
    Rave it Up!!!
           MDMA

3,4Methylenedioxymethamphetamine
             Ecstasy
                E
                       E! Now
• 1914 German Appetite Suppressant
    • “Who needs bratwurst when you are High?”
•   1970’s adjunct to psychotherapy
•   1980’s big hit on the street
•   1985 DEA schedule 1 controlled substance
•   1990’s Rave culture’s drug of choice
    • Gross SR, Barrett SP, Shestowsky JS, Pihl RO. Ecstasy
      and drug consumption patterns: a Canadian rave
      population study. Can J Psychiatry 2002
      Aug;47(6):546-51
               E Pharmacology
•   3,4-methylenedioxy-methamphetamine
•   Derivative of methamphetamine
•   Has similarities to hallucinogen mescaline
•   Similar to epinephrine and dopamine
•   Not naturally occurring
•   Amines (free bases or salts)
•   Increased Norepinephrine release
•   Blocks serotonin & dopamine reuptake
•   Hepatic Metabolism
    • Cytochrome P450 (CYP2D6)
         How can I score some E?
•   Check out a Rave
•   Very high boiling point -> hard to inhale
•   IV
•   Snorting
•   Orally most common
    •   Onset 30-60 mins
    •   Peak levels = 2 hrs, T1/2 = 8-9 hrs
    •   Tabs anywhere from 50-150mg
    •   Birds, dolphins, pop culture
           But I’m so Happy
• Deaths not related to dose, rookies / chronic
  • Patel, Manish M, Bruemmer, Susan, Parramore,
    Constance S, Miller, Michael A. Pathology,
    Toxicology, Cause, and Manner of Death in
    MDMA-related Fatalities. Acad Emerg Med
    2002 9: 533
       Soothers & Glow Sticks
•   General
•   CVS
•   Hyponatremia
•   CNS
•   Psych
•   Hepatic
•   Renal
           I Love You Man!
• Early (30-60mins):
  • anxiety, tachycardia, and elevated BP
    diaphoresis, bruxism, jaw clenching,
    paresthesias, dry mouth, increased psychomotor
    activity, blurred vision.
• Peak (60-90mins): feelings of relaxation,
  euphoria, increased empathy and
  communication
     I love you with all my Heart
           (what’s left of it)
•   Catacholamine & serotonin mediated
•   Dysrhythmias
•   HTN
•   Hyperthermia
•   Cardiotoxic
E is great, but I need to score me
            some 5-HT
•   Serotonin syndrome
•   Massive 5-HT release
•   “vigorous” dancing, not enough H20
•   hyperthermia, mental status changes,
    autonomic instability, altered muscle tone
    and/or rigidity, DIC, renal / hepatic failure
    No Salt for me, the dancin’ fool
•   Hyponatremia
•   Excess H20 intake
•   Excess sweating
•   ADH release
•   LOC, SZ, confusion
          It’s all in your Head
•   SZ
•   Stroke
•   ICH
•   SAH
•   Retinal Hemorrhage
         It’s all in your Mind
• Long term psychiatric effects 2nd to 5-HT
  toxicity
• Impairment of: Memory, executive fnc,
  anxiety / panic attacks, paranoia, severe
  depression
   • Harold Kalant .The pharmacology and
    toxicology of “ecstasy” (MDMA) and related
    drugs. CMAJ: Volume 165 • Number 7 •
    October 2, 2001
           I’ll be Liver-ing it up
•   Overwhelm enzymes?
•   allergy?
•   hyperpyrexia?
•   Cytochrome P450
     • Metabolites interact with glutathione
     • ?Role for NAC?
        I’ll be Liver-ing it up
• Mild Hepatitis
  • Like viral hepatitis picture
  • jaundice, enlarged tender liver, increased
    bleeding tendency, raised liver enzyme levels,
    biopsy picture of acute hepatitis
  • Recovery over several wks to mos
  • Can have chronic attacks in chronic users
         I’ll be Liver-ing it up
• Severe Hepatitis
  • fulminant hepatic failure needing Transplant
• Moderate severity
  • chronic fibrosis
          I’m just kidney-ing
• Rhabdomyalysis +/- ARF
  • direct toxicity, intense physical activity
                     E History
• Central nervous system
   • Change in mental status, seizures,Anxiety, paranoia,
     Increased psychomotor activity, restlessness,
     Hyperthermia, hot flashes, Headache, Ataxia , Blurred
     vision, halos, Syncope
• Cardiovascular
   • Palpitations, Chest pain
• Gastrointestinal
   • Dry mouth, N&V,Abdo cramping, Anorexia
• Skin
   • Diaphoresis, Piloerection
• Urinary retention, Sexual dysfunction
                   E Physical
• HEENT
  • Mydriasis, Nystagmus ,Decreased VA,Bruxism,
• CNS
  • Hyperthermia, psychomotor agitation, Hypervigilance,
    Agitation, anxiety, Ataxia, Hallucinations,
• Cardiovascular
  • Tachycardia, Dysrhythmias, Hypertensive crisis
• Respiratory
  • Resp distress /failure, noncardiogenic pulmonary
    edema
• Diaphoresis, Abdo cramping, Muscle spasm,
  Sexual dysfunction, Urinary retention
                     E Tests
•   CBC,
•   lytes (Na)
•   glucose
•   coags
•   LFT’s
•   U/A, CK, creatinine, Bhcg
•   tox screen
•   ABG
•   Fancy tests as indicated
            Down from Ecstasy
•   ABCD!!!
•   Need monitors, IV’s, Tubes, O2
•   Protect the patient from hypoglycemia,
•   Rely on clinical findings re toxidrome
•   Reassurance if the patient is oriented.
•   Avoid physical or pharmacological restraints if
    possible.
              Down from Ecstasy
•   Charcoal
•   Urine output / Foley
•   Benzos!!!
•   Hyperthermia
    •   Undress the patient.
    •   Apply evaporative cooling with water and a fan.
    •   ice packs to the groin and axilla.
    •   Iced gastric lavage may be considered.
    •   Control shivering with benzos
    •   Antipyretics are not useful.
    •   Dantrolene?
   GHB (GAMMA-
HYDROXYBUTYRATE)
          • Easy Lay
          • fantasy
                     HISTORY
• 1963-73: studied as a potential anesthetic but abandoned
  when it was found to have no analgesic effects and cause
  seizures
• 1980’s: sold as a dietary supplement that enhanced body-
  building and hastened weight loss (unproven)
• 1990’s: popular for its intoxicating, euphoric and sexually-
  enhancing effects, and therefore as a date-rape drug
                 HISTORY
• 1990: FDA declares that GHB is unsafe and illicit
  unless consumed under FDA-approved, MD-
  supervised protocols. OTC sales banned.
• 1995: CNS GHB receptors discovered, solidifying
  GHB’s status as a neurotransmitter
• 1997: FDA issues second warning against GHB
                    HISTORY
• 1999: listed as schedule III under Controlled
  Drugs and Substances Act in Canada
   • prohibits possession, possession from trafficking,
     trafficking, importation, exportation, possession for
     purposes of exportation and production of this drug and
     related products
   • legitimate distribution and possession under controlled
     conditions for medical or scientific purposes is allowed
                    HISTORY
• March 13, 2000: classified as a Schedule 1
  substance in the U.S.
  • definition of Schedule I:
     • the drug has a high potential for abuse
     • the drug has no currently accepted medical use in
       treatment in the United States
     • there is a lack of accepted safety for use of the drug
       under medical supervision
                      HISTORY
• Schedule 1 (con’t)
   • illicit manufacture or trafficking of GHB can result in a
     sentence of up to 20 years in prison
   • if death occurs, a life sentence can be imposed
• currently being studied for treatment of:
   • narcolepsy (GHB increases REM sleep efficiency)
   • opioid withdrawal
   • ethanol withdrawal
             WHAT IS GHB?
• naturally-occurring 4 carbon molecule
    (short chain fatty acid) formed from
    metabolism of GABA and GBL
•   found in basal ganglia, kidney, heart,
    skeletal muscle, and brown fat
•   rapidly absorbed by oral and IV routes
•   small volume of distribution
•   not bound to plasma proteins
           WHAT IS GHB?
• exhibits clinical effect within 15 minutes
• elimination t1/2 = 27-35 minutes
• crosses BBB and placenta
• binding sites in cortex, midbrain, substantia
  nigra, basal ganglia, and hippocampus
• mostly eliminated in expired air as CO2, 2-
  5% eliminated in urine
   MECHANISM OF ACTION
• functions:
   • binds to GHB and GABA-B receptors
   • inhibits norepinephrine release in hypothalamus
   • mediates release of opiate-like substance
   • biphasic effect on dopamine release
   • may increase serotonin
• predominant clinical effect is CNS depression
STRUCTURE OF GHB AND
       GABA
               O



GHB
        HO         OH


               O



GABA
       H2N         OH
         A RECIPE FOR GHB
• GHB’s ease of preparation has led to its easy
  accessibility
• formed by ester hydrolysis of GBL in the presence of
  sodium or potassium hydroxide (e.g. add wood
  cleaner or paint remover to lye)
• improper preparation can lead to caustic burns due to
  undissolved sodium hydroxide and citric acid
• multiple internet sites provided simple instructions on
  how to make GHB in the kitchen (now outlawed)
      A RECIPE FOR GHB


 O                                O
      O
          hydrolysis

           NaOH        HO             OH

GBL                         GHB
     STREET NAMES FOR GHB
•   cherry meth                  liquid ecstasy  G
•   easy lay                     liquid E
•   everclear                    liquid X
•   fantasy                      organic quaalude
•   Georgia home boy             oxy-sleep
•   goops                        poor man’s heroin
•   great hormones at bedtime    salty water
•   grievous body harm           scoop
•   G-riffick                    soap
•   growth hormone booster       somatomax PM
•   liquid E                     water
•   wolfies                      zonked
          COST FOR A “HIT”
• GHB sold as a either a colorless, odorless liquid or
  a grainy, white or sandy-colored powder
• dispensed in water-bottle cap doses (equivalent to
  hotel shampoo bottle or vial of Liquid Paper)
• cost per capful ranges from $5-10 U.S. and has the
  approximate equivalent intoxication of 26 oz. of
  hard liquor
      DOSE EQUIVALENTS
• usually 1-2 capfuls taken or poured into a
  drink
• 1 vial or capful can contain 3-10 doses with
  anywhere from 3-20g per dose
• 1 tsp. ~ 2.5 g
• 4 tbsp. ~ 30 g
                  USES
• as a CNS depressant, thereby inducing an
  intoxicated state
• as a sedative to reduce the effects of
  stimulants (cocaine, amphetamine, and
  ephedrine) or hallucinogens
• for prevention of withdrawal symptoms
      CLINICAL FEATURES
• H + N:
  • nystagmus
• Resp:
  • bradypnea
  • apnea
• CVS:
  • bradycardia
  • orthostatic hypotension
  • hypertension
       CLINICAL FEATURES
• GI:
   • nausea
   • vomiting
   • increased salivation
   • esophageal burns
• GU:
   • incontinence
   • hematuria
     CLINICAL FEATURES
• MSK:
  • hypotonia
  • extrapyramidal symptoms
• DERM:
  • profuse sweating
         CLINICAL FEATURES
• CNS:
   • altered LOC (confusion --> coma)
   • euphoria
   • delusions and hallucinations
   • headache
   • ataxia
   • seizures or seizure-like activity
   • agitation when stimulated
   • emergence phenomena
  KEY CLINICAL FEATURES
• extreme combativeness in the face of near
  or total respiratory failure (esp. when trying
  to intubate)
• brief duration of coma (1-2 hours) with
  rapid awakening
• effects enhanced by co-ingestion of other
  CNS depressants
DOSE/EFFECT RELATIONSHIP
DOSE (mg/kg)   CLINICAL EFFECTS
10             Short term amnesia,
               hypotonia

20-30          Drowsiness, sleep,
               euphoria

50-70          Hypnosis, bradycardia,
               bradypnea, nausea,
               vomiting, coma

> 70           Cardiorespiratory
               collapse/arrest
            INVESTIGATIONS
• mild hyperglycemia
• hypernatremia if the sodium salt of GHB is used
• ECG
   • U waves (with normal potassium)
   • 1st degree AV block
   • A fib
   • RBBB
   • ventricular ectopy
   • wide QRS (inconsistently found)
          INVESTIGATIONS
• GHB detection
  • multiple assays described for detection (GC, MS)
  • qualitative spot urine test described but not commonly
    in use
  • undetectable in blood or urine after 8 hours post-
    ingestion in doses up to 4.5 g
  • assays not available locally
           MANAGEMENT
• ABC’s and good supportive care
  (ventilation and oxygenation, fluids,
  sedation PRN)
• GI decontamination if co-ingestants
  suspected
   • not expected to be of benefit in GHB,
         REVERSAL AGENTS
• naloxone
   • not useful
• flumazenil
   • not useful
   • may interfere with use of benzos for sedation
• physostigmine
   • limited effect
   • 2 case reports demonstrating improved LOC after
     physostigmine
• neostigmine
   • limited effect
       REVERSAL AGENTS
• overall, these agents have limited use in
  management of GHB toxicity as most
  patients improve with good supportive care
                 SEQUELAE
• symptoms last from 3-6 hours if not intubated and
  ~ 6 hours if intubated
   • longer if mixed with other CNS depressants
• emergence phenomena may occur once
  consciousness returns
   • myoclonus, altered mental status, combativeness,
     insomnia
   • can last for 3-12 days
• dizziness may last for up to 2 weeks
Flunitrazepam
Flunitrazepam: Rohypnol
          History of Roofies
• 1975 Used as anaesthetic & sleeping pill
  Latin America, Europe, Asia
• 1995 changed to Sched 3 drug
• 1996 Drug-Induced Rape Prevention and
  Punishment Act
              Pharm Roof
• Benzodiazepine
• Benzo receptors in CNS enhance affinity of
  GABA receptors for GABA
• Influx Cl -> hyperpolarization of cell
  membranes -> inhibits action potentials
• Hepatic CP450 metabolism
• T1/2 = 16-35 hrs
                Pharm Roof
• Tablet form, can be crushed to powder
• Tasteless, odourless, colourless
  • Hoffman-LaRoche now added a green colour
    to aid detection
• PO, snorted, parenteral, crushed and slipped
  into drinks
• Onset 30 mins, peak 2 hrs, lasts 8hrs
• 10 X more potent than Diazepam
             On the Roof again
•   Amnesia
•   Anxiolysis
•   Sedation
•   Hypnosis
•   Anticonvulsant
•   Muscle relaxation
•   H/A
•   HypoTN
•   Resp depression
   You won’t go on a date with
    me!?!? We’ll see about
      that…Wanna Drink?
• Original date rape drug
• Amnesia induced while under influence
• "Some patients may have no recollection of
  any awakenings occurring in the 6 to 8
  hours during which the drug exerts its
  action."
           What’s on the Roof?
•   Decreased LOC
•   Resp depression
•   Amnesia
•   Hypotonia
•   HypoTN
•   Effects potentiated by EtOH, other seds, hyps
               Get off the roof
• ABC’s
• Supportive care
• Consider sexual assault
   • rape kit, CPS, social work
• Flumazenil
• May not show up on benzo drug screen
• May show up on specific urinalysis test up to 72
  hrs post ingestion
   • Important in forensic cases
Methamphetamine

   Crystal Meth
              Methamphetamine
•   Blue Mollies      •   Methlies Quick
•   Chalk             •   Mexican Crack
•   Crank             •   Quartz
•   Crystal           •   Shabu
•   Glass             •   Sketch
•   Go-Fast           •   Speed
•   Ice               •   Stove Top
•   LA Glass          •   West Coast
•   Meth              •   Yellow Bam
            History of Meth
• 1919 made by Japanese pharmacologist
• 1930 structure confirmed
• 1930’s Rx asthma & rhinitis
• 1937 reported meth = smarter, more alert
• WW2 military kept “up”
• 1970 Comprehensive Drug Abuse Prevention and
  Control Act: Sched 2 drug
• 1991 Desert Storm troops felt “up”
• 2000’s “War on Meth” all over USA (Midwest)
          Meth for Dummies
• Easy to make, lots of fun on web
• Derivative of phenylethylamine
• Ephedrine, chloroephedrine, or
  methylephedrine reduced by hydriodic acid
  & red phosphorus -> Meth
  • Lipid soluble pure base, volatile @ Room T
  • H2O soluble as HCl salt
         Meth for Dummies
• Blocks pre-synaptic uptake of
  norepinephrine & dopamine
• Prevents catacholamine storage
• Prevents cytoplasmic catacholamine
  destruction
• T1/2 = 10-20 hrs
     Meth for Dummies 2: ICE
• Smoked form
• Purify meth HCl via adding to H2O and
  heating to 80-100 degs
• Supersaturated sol’n -> cools -> ppt to ICE
• Put on foil -> heat -> inhale -> high
     I gonna get me my Meth fix!
• ALL mucous membranes, oral, inhaled,
    snorted, smoked, IV, IM
•   Peak 30 mins post IM / IV
•   Peak 2-3 hrs po
•   CSF levels @ 80% of plasma
•   Hepatic metabolism, urinary excretion
     • glucuronide and glycine addition
                Meth Lab
• From Rolling stone,paraphrased from a
  Midwest Detective:
• “2 things you find at a meth lab: tonnes of
  porn and more guns than you can imagine...
  More often than not, the labs are full of
  booby traps”
                Meth Lab
• Can make Meth ANYWHERE
• Contaminated “home brew” from impure
  ingredients
• Lead, mercury, solvents, volatile meth often
  present
• Need big-time WHIMS action + HAZMAT
  suits if going in
       Meth              vs            Coke
• Similar presentation    • Similar routes
• ++++ longer T1/2        • Short acting
• ?faster onset?          • Quick onset

• Easy to make
                          • “Trip down South to
                              warmer climes to visit
                              gents in silk suits”

• Haldol Rx of Choice,
  (benzos still good)     • Benzos Rx of Choice
    Haldol better than Benzos?
• Better sedation and return of VSs in RCT
• N=146
  • Richards JR, Derlet RW, Duncan DR:
    Methamphetamine toxicity: treatment with a
    benzodiazepine versus a butyrophenone. Eur
    J Emerg Med 1997 Sep; 4(3): 130-5
                  Ketamine
• Special K, vitamin K,
  K, Super K, Ketaset,
  Jet, Super Acid,
  Green, Purple, Mauve,
  and Special LA Coke
        Special K pharmacology
•   1960 - dissociative anaesthetic Parke-Davis
•   1970’s abuse begins
•   1980’s New Age Spiritualists adopt
•   2000 -> techno is king
                    K Pharm
• Binds to PCP receptor in N-methyl-D-aspartate
  (NMDA) channel
• Non-competitive inhibitor of glutamate
• Effects on other receptors
   • non-NMDA-glutamate, nicotinic & muscarinic, sigma,
     monoaminergic, opioid, Ca & Na channels
• Stimulates NO release
• Inhibits reuptake Norepinephrine, dopamine, 5-HT
                       K Pharm
• Hepatic CP450 metabolism
• Oral undergoes +++ 1st pass
• Norketamine is active metabolite
   • Urinary excretion
• T1/2 = 2 hrs
• Dosing: 15-300mg
• High therapeutic index
   • Difficult to OD
       Is this Special K in a box?
• IV
  • onset 1 min, lasts 30 mins
• IM
  • Onset variable, lasts 30 mins
• PO
  • Onset 30 mins, lasts 3 hrs
• Snorted & Smoked
  • Onset 15 mins, lasts 1 hr
  • Liquid form heated and dried to powdered form
      What’s so special about it?
•   Out of body, floating sensation
•   Derealization
•   Positive & Negative Sx of Schizophrenia
•   Emotional w/d, psychomotor slowing
•   Flashbacks & hallucinations
•   Short & Long lasting memory lapses
    • Curran HV, Monaghan L.In and out of the K-hole: a
      comparison of the acute and residual effects of
      ketamine in frequent and infrequent ketamine
      users. Addiction. 2001 May;96(5):749-60.
    What’s so special about it?
• CNS:
  • nystagmus, mydriasis, agitation, slurred speech,
    delirium, floating sensations, hypertonus, rigidity,
    anxiety, vivid dreams, hallucinations, seizures, bizarre
    facial expressions, loss of coordination, bizarre limb
    movements, dystonic reactions, persistent repetition of
    acts or words, shouting,
• Rhabdomyalysis
• CVS
  • palpitations, tachycardia, HTN, increased CO
• Resp
  • respiratory depression, apnea, pulmonary edema,
                     K in the ED
• Tests:
   • As indicated, CK
   • Can do ketamine level, but hard to get & why?
• Rx:
   • Benzos, supportive, Rx rhabdo
   • ?Haldol
        • Giannini AJ, Underwood NA, Condon M. Acute ketamine
         intoxication treated by haloperidol: a preliminary study.
         Am J Ther. 2000 Nov;7(6):389-91.
          Although safe . . .
• Breitmeier D, Passie T, Mansouri F,
  Albrecht K, Kleemann WJ.Autoerotic
  accident associated with self-applied
  ketamine. Int J Legal Med. 2002
  Apr;116(2):113-6
              Shout Outs
• Dr.Mark Yarema
   • Info, “borrowed slides”
• Don “Sonny Crockett” Johnson &
  Philip Michael “Rico Tubbs” Thomas
   • For keepin’ it real
   • Need I say more?
Don’t Do Drugs!

				
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