Project: Ghana Emergency Medicine Collaborative

Document Title: Drugs of Abuse

Author(s): Tim Albertson, M.D., Ph.D. (University of California- Davis); Jim Holliman, M.D., F.A.E.C.P. (Pennsylvania State University) 2012

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22

Update on Drugs of Update on Drugs of AbuseAbuse ((““some club-drug stuffsome club-drug stuff””))

Tim Albertson, M.D.,Ph.D. Tim Albertson, M.D.,Ph.D.

Professor of Medicine, Pharmacology Professor of Medicine, Pharmacology and Toxicologyand Toxicology

UC Davis School of MedicineUC Davis School of Medicine

CPCS, Sacramento DivisionCPCS, Sacramento Division

Jim Holliman, M.D.Jim Holliman, M.D.Penn State UniversityPenn State University

Bearstache, Flickr

Overview of TopicsOverview of Topics

Gamma hydroxybutyrate (GHB)Gamma hydroxybutyrate (GHB)– GHBGHB– GHB AnalogsGHB Analogs– GHB / Analog WithdrawalGHB / Analog Withdrawal

Ecstasy : MDMA (Methylene Ecstasy : MDMA (Methylene dioxymethamphetamine)dioxymethamphetamine)

Overview of TopicsOverview of Topics

MethamphetamineMethamphetamine

Dextromethorphan (DM)Dextromethorphan (DM)

KetamineKetamine

FlunitrazepamFlunitrazepam

MescalineMescaline

InhalantsInhalants

AnticholinergicsAnticholinergics

GHBGHB((GGamma-amma-

hhydroxyydroxybbutyrate)utyrate)

United States Department of Justice, Wikimedia Commons

What is GHB?What is GHB?Gamma hydroxybutyrateGamma hydroxybutyrateNaturally occurring in brain tissueNaturally occurring in brain tissue– neurotransmitter-like substanceneurotransmitter-like substance– dopamine release in substantia nigradopamine release in substantia nigra

Similar structure to GABASimilar structure to GABAGABA-B agonist effectsGABA-B agonist effectsApproved for narcolepsy 2002Approved for narcolepsy 2002– Sodium oxybate (Xyrem) Orphan MedicalSodium oxybate (Xyrem) Orphan Medical– 4.5 gms a night AWP $739 / month limited 4.5 gms a night AWP $739 / month limited

to certain pharmacies and physiciansto certain pharmacies and physicians

GHBGHBInvestigated as an anesthetic agent : Investigated as an anesthetic agent : caused myoclonus and delirium ; current caused myoclonus and delirium ; current IND for sleep apneaIND for sleep apneaCrystalline saltCrystalline saltSoluble in water and methanolSoluble in water and methanolTastelessTastelessGBL-gamma-butyrolactone & BD-1,4 GBL-gamma-butyrolactone & BD-1,4 butanediol precursor molecules convert to butanediol precursor molecules convert to GHB in-vivoGHB in-vivo

Structure Activity Structure Activity RelationshipRelationship

COOH

CH2

CH2

CH2

OH

COOH

CH2

CH2

CH2

NH2

gamma hydroxybutyrate

gamma amino butyric acid

GHB GABA

History of GHBHistory of GHB

1960’s1960’s France - Synthesized as an AnestheticFrance - Synthesized as an Anesthetic19871987 Orphan Drug (IND-narcolepsy) ; USFDAOrphan Drug (IND-narcolepsy) ; USFDA1990-11990-1 Body Builders “Undetectable steroid”Body Builders “Undetectable steroid”

Growth hormone stimulatorGrowth hormone stimulator 1992-51992-5 Sleep aid, Rave party, Popularity risesSleep aid, Rave party, Popularity rises19961996 Sexual enhancer, “Date-Rape” DrugSexual enhancer, “Date-Rape” Drug19971997 Emergence of GHB AnalogsEmergence of GHB Analogs

Emergence of Withdrawal CasesEmergence of Withdrawal Cases20002000 Federal Schedule I statusFederal Schedule I status2002 2002 FDA approval for Narcolepsy : XyremFDA approval for Narcolepsy : Xyrem

Slang Names : Slang Names : Gamma HydroxybutyrateGamma Hydroxybutyrate

Cherry methCherry meth

Easy layEasy lay

G, G capsG, G caps

Gamma hydrateGamma hydrate

Georgia home boyGeorgia home boy

GHBGHB

GH BeersGH Beers

Liquid ELiquid E

Liquid XLiquid X

Liquid ecstasyLiquid ecstasy

Natural sleep 500Natural sleep 500

Organic QuaaludeOrganic Quaalude

Oxy sleepOxy sleep

ScoopScoop

What are GHB Analogs?What are GHB Analogs?

Organic solvents Organic solvents – √√-Butyrolactone, 2(3) Dihydrofuranone,-Butyrolactone, 2(3) Dihydrofuranone,– 1,4-Butanediol, Tetramethylene Glycol1,4-Butanediol, Tetramethylene Glycol

Converted to GHB Converted to GHB in vitroin vitro or or in vivoin vivo– In vitro using NaOH, heatIn vitro using NaOH, heat– In vivo (Lactonase enzymes) : GBLIn vivo (Lactonase enzymes) : GBL– In vivo (alcohol / aldehyde In vivo (alcohol / aldehyde

dehydrogenase)dehydrogenase)

Identical clinical effects to GHBIdentical clinical effects to GHB

Conversion : Conversion : Gamma Butyrolactone (GBL)Gamma Butyrolactone (GBL)

O

=O

NaOH + H2O

Lactonasein vitro

In vivo

C OOHCH2

CH2

CH2 OH

GBL GHB

Gamma Butyrolactone Gamma Butyrolactone (GBL)(GBL)

United States Department of Justice, Wikimedia Commons

Slang Names :Slang Names : Gamma Butyrolactone or Dihydro Gamma Butyrolactone or Dihydro

FuranoneFuranone

Blue NitroBlue Nitro

FirewaterFirewater

Furanone ExtremeFuranone Extreme

Gamma GGamma G

GBLGBL

GH ReleaseGH Release

Insom-XInsom-X

InvigorateInvigorate

JoltJolt

Liquid LibidoLiquid Libido

RegenerizeRegenerize

ReneTrientReneTrient

RevivarantRevivarant

Revivarant-GRevivarant-G

Renewtrient and Blue Nitro, GHB precursors, have been removed from the market.

Source Undetermined

Slang Terms : Slang Terms : 1,4 Butanediol or Tetramethylene 1,4 Butanediol or Tetramethylene

glycolglycol

Biocopia PMBiocopia PM

BorametzBorametz

BVMBVM

EnlivenEnliven

FXFX

NRG3NRG3

Inner GInner G

Thunder NectarThunder Nectar

Pro GPro G

PromusolPromusol

Rest-ezeRest-eze

Revitalize PlusRevitalize Plus

SerenitySerenity

SomatoProSomatoPro

Incidence : GHB and Incidence : GHB and PrecursorsPrecursors

18 10 934

1937

89105

199

232

356

0

50

100

150

200

250

300

350

400

CASES

1990 1991 1992 1993 1994 1995 1996 1997 1997 1998 1999

SF POISON CONTROL CA POISON CONTROL

Source Undetermined

PathologyPathology

Structurally similar to GABAStructurally similar to GABA

Stimulates GABAStimulates GABABB receptors receptors

Influences dopamine release from Influences dopamine release from substantia nigrasubstantia nigra

Readily crosses the BB barrierReadily crosses the BB barrier

GHB / Analogs : GHB / Analogs : Clinical PresentationClinical Presentation

Vomiting, Coma, BradycardiaVomiting, Coma, Bradycardia

Myoclonic jerkingMyoclonic jerking

Loss of protective airway reflexesLoss of protective airway reflexes– Aspiration riskAspiration risk

Hypothermia, Mild respiratory acidosisHypothermia, Mild respiratory acidosis

HOTN when combined with ethanolHOTN when combined with ethanol

EffectsEffects

““DESIREDDESIRED””

EuphoriaEuphoriaMood elevationMood elevationHallucinationsHallucinationsGH-Muscle GH-Muscle growth?growth?AmnesiaAmnesia

UNDESIREDUNDESIRED

Decreased HR, Decreased HR, RRRR

ComaComa

Excessive Excessive salivationsalivation

Absence-like szAbsence-like sz’’ss

Emergency Department (ED) Course of Emergency Department (ED) Course of Gamma Hydroxybutyric Acid (GHB) Gamma Hydroxybutyric Acid (GHB)

Intoxication Study Intoxication Study Acad Emerg MedAcad Emerg Med 2002 Jul;9(7):730-9 Mason 2002 Jul;9(7):730-9 Mason

StudyStudy IntubatedIntubated Duration Duration of of

IntubationIntubation

Time in Time in ED if Not ED if Not AdmittedAdmitted

Number Number AdmittedAdmitted

Chin et al. Chin et al.

( n = 88)( n = 88)13 %13 % 179 min179 min NRNR 11 %11 %

Mahon et Mahon et al. ( n = 8)al. ( n = 8)

50 %50 % 80 min80 min NRNR 0 %0 %

Li et al.Li et al.

( n = 7)( n = 7)57 %57 % 210 min210 min 360 min360 min 43 %43 %

Garrison & Garrison & Mueller ( n Mueller ( n = 78)= 78)

10 %10 % NRNR 180 min180 min 4 %4 %

Case Study …..Case Study …..

26 y/o F with chronic insomnia doubled 26 y/o F with chronic insomnia doubled her dose of Blue Nitro (GBL) : 3 oz.her dose of Blue Nitro (GBL) : 3 oz.

– Vomiting within 15 minutesVomiting within 15 minutes

– Pt was unresponsive within 30 minutesPt was unresponsive within 30 minutes

– Myoclonic jerkingMyoclonic jerking

– EMS was calledEMS was called

– VS: BP 120 / 70, HR 50, RR 22, T 35VS: BP 120 / 70, HR 50, RR 22, T 35

Case Study continued ….Case Study continued ….

Unresponsive to pain, GCS 3.Unresponsive to pain, GCS 3.

CT scan normal, glucose 125CT scan normal, glucose 125

No response to naloxone or flumazenilNo response to naloxone or flumazenil

Woke up within 4 hoursWoke up within 4 hours

Discharged Discharged

Urine Toxicology screen negativeUrine Toxicology screen negative

GHB / Analogs : KineticsGHB / Analogs : Kinetics

OnsetOnset 15 minutes15 minutes– Immediate conversion of analogs to GHBImmediate conversion of analogs to GHB

ComaComa within 30 minuteswithin 30 minutes

PeakPeak 1 hour1 hour

T 1/2T 1/2 ShortShort

DurationDuration 1 to 6 hours (1 to 6 hours (Average 2.5 hr)Average 2.5 hr)

Most patients require < 5 hr observationMost patients require < 5 hr observation

Emergence DeliriumEmergence Delirium

Myoclonic jerking motionsMyoclonic jerking motions

Confusion, agitation, combativenessConfusion, agitation, combativeness– Transient symptoms (< 30 minutes)Transient symptoms (< 30 minutes)– Symptoms worsen with stimulationSymptoms worsen with stimulation

TreatmentTreatment– Supportive CareSupportive Care– Minimize stimulation. “Back off”Minimize stimulation. “Back off”

GHB / Analogs : DiagnosisGHB / Analogs : Diagnosis

History of use and circumstancesHistory of use and circumstances

Clinical PresentationClinical Presentation

Short Duration Short Duration

Role of LaboratoryRole of Laboratory– Suspected assaultSuspected assault– Obtain sample within 12 hoursObtain sample within 12 hours– National Medical LaboratoriesNational Medical Laboratories

GHB / Analogs : TreatmentGHB / Analogs : Treatment

Supportive CareSupportive Care– Approximately 35 % patients require Approximately 35 % patients require

airway protectionairway protection

Gastrointestinal DecontaminationGastrointestinal Decontamination– Limited ValueLimited Value– Consider Charcoal in massive ingestionsConsider Charcoal in massive ingestions

Education regarding DependenceEducation regarding Dependence

GHB Dependence : Case StudyGHB Dependence : Case Study29 year old male started taking GHB for 29 year old male started taking GHB for

the “anabolic effects” 2 yrs agothe “anabolic effects” 2 yrs ago Gradually increased dose to 4 to 6 Gradually increased dose to 4 to 6

“capfuls” every 4 hours “capfuls” every 4 hours Discontinued the GHB cold turkeyDiscontinued the GHB cold turkeyArrived in ED 24 hr after his last dose Arrived in ED 24 hr after his last dose

Case Study continued ….Case Study continued ….

– Patient was highly agitatedPatient was highly agitated

– Visual and auditory hallucinationsVisual and auditory hallucinations

– Delusional, paranoid Delusional, paranoid

– Tremulous, diaphoreticTremulous, diaphoretic

– VS: HR 110, BP 160 / 112, T 99.1VS: HR 110, BP 160 / 112, T 99.1

Case Study continued ...Case Study continued ...

Patient received :Patient received :– Ativan : 90 mg in the first 24 hoursAtivan : 90 mg in the first 24 hours– Phenobarbital, HaloperidolPhenobarbital, Haloperidol

10 day withdrawal course 10 day withdrawal course Discharged symptom and drug freeDischarged symptom and drug free

GHB WithdrawalGHB Withdrawal

Similar to ETOH and sedative-hypnotic Similar to ETOH and sedative-hypnotic withdrawal.withdrawal.

Symptoms start within a few hours of Symptoms start within a few hours of discontinuation. discontinuation.

Seen with long-term use or daily use.Seen with long-term use or daily use.

GHB Withdrawal : Clinical GHB Withdrawal : Clinical PresentationPresentation

Onset :Onset : 1 to 6 hours1 to 6 hoursProgression of sxs over 1 to 3 daysProgression of sxs over 1 to 3 daysSymptoms Symptoms

– Agitation, hallucinations, paranoiaAgitation, hallucinations, paranoia– Tremulous, diaphoreticTremulous, diaphoretic– Tachycardic, hypertensiveTachycardic, hypertensive– Hyperthermia, Rhabdomyolysis possibleHyperthermia, Rhabdomyolysis possible

Duration :Duration : 5 to 15 days5 to 15 days

GHB Withdrawal : GHB Withdrawal : ManagementManagement

AGGRESSIVE TREATMENT EARLYAGGRESSIVE TREATMENT EARLY BenzodiazepinesBenzodiazepines

High doses may be requiredHigh doses may be required

BarbituratesBarbituratesAntipsychoticsAntipsychoticsUnproven TherapyUnproven Therapy

– Baclofen (GABA-B agonist)Baclofen (GABA-B agonist)

Stimulants of AbuseStimulants of AbuseMethamphetamineMethamphetamineMethylene dioxymethamphetamine : Methylene dioxymethamphetamine :

MDMA (Ecstasy)MDMA (Ecstasy)CocaineCocaineKetamine / PCP (phencyclidine)Ketamine / PCP (phencyclidine)DextromethorphanDextromethorphan

Rave Party : Case Study ...Rave Party : Case Study ...

18 year old F was at a Rave party with a 18 year old F was at a Rave party with a friend. She was drinking ethanol and friend. She was drinking ethanol and using the following:using the following:– MidnightMidnight 1 tablet of Ecstasy1 tablet of Ecstasy– 3 am3 am Snorted 1 line of KetamineSnorted 1 line of Ketamine– 5 am5 am Drank a “capful” of GHBDrank a “capful” of GHB

At 6:30 am patient found slumped in At 6:30 am patient found slumped in bathroom, cyanotic. EMS called.bathroom, cyanotic. EMS called.

Case Study continued ….Case Study continued ….

In ED, comatose but not cyanotic. In ED, comatose but not cyanotic. Intubated for airway protection. Intubated for airway protection. No response to flumazenil or narcanNo response to flumazenil or narcanVS: HR 58, BP 110 / 60, RR 16, p VS: HR 58, BP 110 / 60, RR 16, p

5mm, T 375mm, T 37

ICU admission. Woke up at 12 hoursICU admission. Woke up at 12 hoursExtubated, dischargedExtubated, discharged

Ketamine : Clinical Ketamine : Clinical PresentationPresentation

Dissociative anestheticDissociative anestheticClinical PresentationClinical Presentation

– Separation of perception and sensationSeparation of perception and sensation– Nystagmus, hallucinations, lethargy, szNystagmus, hallucinations, lethargy, sz– tachycardia, HTN, RR depressiontachycardia, HTN, RR depression– hyperthermiahyperthermia

DurationDuration– 2 to 4 hours2 to 4 hours

Ketamine TreatmentKetamine Treatment

SupportiveSupportiveSedationSedation

Phencyclidine EffectsPhencyclidine Effects

Tremors, agitation, hallucinations : Tremors, agitation, hallucinations : visual and auditory.visual and auditory.

Tachycardia, HTN.Tachycardia, HTN.

Wernicke-Korsakoff syndrome.Wernicke-Korsakoff syndrome.

Treatment is same as for ketamine

MethamphetamineMethamphetamine

First synthesized by a Japanese First synthesized by a Japanese pharmacologist in 1893pharmacologist in 1893

Ephedrine most common precursorEphedrine most common precursorRed phosphorus-hydriotic acid most Red phosphorus-hydriotic acid most

common reduction method.common reduction method.D-isomer : CNS stimulant effects.D-isomer : CNS stimulant effects.L-isomer : peripheral sympathomimetic L-isomer : peripheral sympathomimetic

activity.activity.

StructuresStructures

PhenethylaminePhenethylamine

AmphetamineAmphetamine

MethamphetamineMethamphetamine

Source Undetermined

Source Undetermined

Source Undetermined

ProductionProduction

EphedrineEphedrine

MethamphetamineMethamphetamineSource Undetermined

Source Undetermined

PathologyPathologyIncrease release of Increase release of

neurotransmitters from nerve neurotransmitters from nerve terminals.terminals.

Serotinergic and dopaminergic ATP Serotinergic and dopaminergic ATP decrease.decrease.

5HT and D2 depletion.5HT and D2 depletion.ApoptosisApoptosisEndothelial injury.Endothelial injury. Reactive oxygen species.Reactive oxygen species.

Model of Methamphetamine Neurotoxicity

O2, H2O2, OH, NO

DNA Damage

P53

ROS

Terminal Degeneration Apoptosis

P53 Regulated GenesBax

Bcl-2

Bax/Bcl-2

Cytochrome Release

Caspase Activation

Lena Carleton, University of Michigan

Source Undetermined

Signs and SymptomsSigns and Symptoms

Action phaseAction phase

Skin pickingSkin pickingHead bangingHead bangingPacingPacingParanoid psychosisParanoid psychosisExtreme Extreme

suspiciousnesssuspiciousness

Resolution phaseResolution phase

ExhaustionExhaustionFatigueFatigueSleepSleepDepressionDepression

Other Signs and SymptomsOther Signs and Symptoms

Pulmonary hypertensionPulmonary hypertensionDyspneaDyspneaPleuritic chest painPleuritic chest painAnorexia/weight lossAnorexia/weight lossUlcersUlcersRhabdomyolysisRhabdomyolysis

TESS DATATESS DATAMethamphetamine Exposures Without Concomitants, 2001

(Cardiovascular Effects)

0

50

100

150

200

250

300

350

400

Source: American Association of Poison Control Centers Toxic Exposure Surveillance System, 2001

Methamphetamine and the EDMethamphetamine and the ED

6 months UCDMC ED ending February 19976 months UCDMC ED ending February 1997461 methamphetamine (+) patients461 methamphetamine (+) patientsCaucasian males without health insuranceCaucasian males without health insurance Increase use of ambulances and acute Increase use of ambulances and acute

hospitalizationhospitalizationSignificant association with trauma : blunt Significant association with trauma : blunt

33 % and penetrating 4 %33 % and penetrating 4 %Altered LOC (23 %), Abd pain (13 %), suicide Altered LOC (23 %), Abd pain (13 %), suicide

(8 %), chest pain (8 %), skin infections (6 %)(8 %), chest pain (8 %), skin infections (6 %)Richards, et al., Richards, et al., West J MedWest J Med 1999 ; 170:198- 1999 ; 170:198-

202202

Methamphetamine and Methamphetamine and TraumaTrauma

UCDMC Level 1 Trauma CenterUCDMC Level 1 Trauma CenterRetrospective Study 1989 to 1994Retrospective Study 1989 to 1994Results :Results :

– 18,004 pts ; 3.1 / 1000 population per year18,004 pts ; 3.1 / 1000 population per year– + methamphetamine defined as urine > + methamphetamine defined as urine >

1000 ng / ml1000 ng / ml– Rates increased from 7.4 to 13.4 %Rates increased from 7.4 to 13.4 %– Cocaine rates 5.8 to 6.2 %Cocaine rates 5.8 to 6.2 %

Methamphetamine and Methamphetamine and TraumaTrauma

Decrease in ethanol from 43 % to 35 %Decrease in ethanol from 43 % to 35 %Meth (+) most common in Caucasian or Meth (+) most common in Caucasian or

HispanicHispanicCocaine (+) most common African AmericanCocaine (+) most common African AmericanMeth (+) in MVA or MCAMeth (+) in MVA or MCA’’ssCocaine (+) in assaults, GSWCocaine (+) in assaults, GSW’’s or stab s or stab

woundswounds

Schermer and Wisner, Schermer and Wisner, J Am Coll SurgJ Am Coll Surg 1999; 189: 1999; 189: 442-449442-449

TreatmentTreatment DonDon’’t forget to r/o other causes :t forget to r/o other causes :

– Look-alike diseases : e.g. Pheo, scorpion Look-alike diseases : e.g. Pheo, scorpion bites.bites.

– Drugs : e.g. LSD, psilocybin-hallucinations, Drugs : e.g. LSD, psilocybin-hallucinations, etc.etc.

– Elevated temperature : e.g. malignant Elevated temperature : e.g. malignant hyperthermia, NMS, anticholinergic hyperthermia, NMS, anticholinergic syndrome.syndrome.

– Seizures : e.g. cocaine, ETOH withdrawal.Seizures : e.g. cocaine, ETOH withdrawal.– CVS : e.g. GHB withdrawal.CVS : e.g. GHB withdrawal.

Treatment (cont.)Treatment (cont.)

Control stimulant effectsControl stimulant effectsDecontaminationDecontaminationControl hyperthermia : how ?Control hyperthermia : how ?Control seizures : how ?Control seizures : how ?Be careful of physical restraints.Be careful of physical restraints.Treat psychiatric conditions.Treat psychiatric conditions.

What is Ecstasy (MDMA) ?What is Ecstasy (MDMA) ?

3,4-Methylenedioxymethamphetamine3,4-MethylenedioxymethamphetamineSympathetic effects mild in low dosesSympathetic effects mild in low doses Potent releaser of serotoninPotent releaser of serotonin OverdoseOverdose

– Symptoms similar to amphetaminesSymptoms similar to amphetamines– Risk of serotonin syndromeRisk of serotonin syndrome– Risk of hyponatremia Risk of hyponatremia

SIADH and / or increased water intakeSIADH and / or increased water intake

MDMAMDMA

Source Undetermined

Drug Enforcement Agency, Wikimedia Commons

History of EcstasyHistory of Ecstasy

19141914 Patented as Appetite suppressantPatented as Appetite suppressant Never MarketedNever Marketed

1970’s1970’s Use by psychiatristsUse by psychiatrists1980’s1980’s “LSD of the 60’s” “LSD of the 60’s” 1990’s1990’s Increasing abuse, Rave party useIncreasing abuse, Rave party use20002000 Continuing abuseContinuing abuse Illicit adulterants commonIllicit adulterants common

Illicit Ecstasy TabletsIllicit Ecstasy Tablets

Drug Enforcement Agency, Wikimedia Commons

PathologyPathology

Similar to other amphetamines in Similar to other amphetamines in causing release of catecholamines.causing release of catecholamines.

Alpha and beta-adrenergic agonist.Alpha and beta-adrenergic agonist.Can cause SIADH by an unclear Can cause SIADH by an unclear

mechanism.mechanism.

EffectsEffects

DESIREDDESIRED

Increased energyIncreased energyEuphoriaEuphoriaEmpathyEmpathyVisual Visual

hallucinationshallucinations

UNDESIREDUNDESIRED

Jaw clenchingJaw clenchingParanoiaParanoiaHot / cold flashesHot / cold flashesHyperpyrexiaHyperpyrexiaSeizuresSeizures

Clinical Signs and SymptomsClinical Signs and Symptoms

RhabdomyolysisRhabdomyolysisHyponatremiaHyponatremiaDICDICRenal failureRenal failureHepatotoxicityHepatotoxicityAplastic anemia : rareAplastic anemia : rare

Illicit MDMA AdulterantsIllicit MDMA Adulterants

Assayed tablets have contained :Assayed tablets have contained :– MDMAMDMA– MDMA with CaffeineMDMA with Caffeine– Dextromethorphan 122 to 143 mg / tabletDextromethorphan 122 to 143 mg / tablet– CaffeineCaffeine– Ephedrine, Pseudoephedrine, PPAEphedrine, Pseudoephedrine, PPA– PlaceboPlacebo

TreatmentTreatment

Similar to amphetamines and Similar to amphetamines and derivativesderivatives

Controlling cerebral edema from Controlling cerebral edema from hyponatremia important.hyponatremia important.

Pneumomediastinum also an issuePneumomediastinum also an issueControlling hyperthermia predicts Controlling hyperthermia predicts

survival in several studiessurvival in several studies

Dextromethorphan : Case Dextromethorphan : Case Study …..Study …..

14 year old M ingested 30 Coricidin 14 year old M ingested 30 Coricidin tablets to get high. At 2.5 hours : tablets to get high. At 2.5 hours : – Lethargic, slurred speechLethargic, slurred speech, , hallucinatinghallucinating

– Flushed , tremulousFlushed , tremulous

– Nystagmus presentNystagmus present

– VS : HR 114, BP 170 / 100, T 97.8, p 7mmVS : HR 114, BP 170 / 100, T 97.8, p 7mm

Dextromethorphan (DXMF) Dextromethorphan (DXMF) AbuseAbuse

Many DXMF containing OTC productsMany DXMF containing OTC productsCoricidin : many combinationsCoricidin : many combinations

– DXMF 30 mg, CTM, APAP, PPA, etc.DXMF 30 mg, CTM, APAP, PPA, etc.

Teenage DXMF abuse is rising Teenage DXMF abuse is rising Easy OTC availability Easy OTC availability

DextromethorphanDextromethorphan

Therapeutic doses : mild CNS effectsTherapeutic doses : mild CNS effectsHigh doses : significant CNS effectsHigh doses : significant CNS effectsSpecific DXMF receptors (opiate - sigma)Specific DXMF receptors (opiate - sigma)

Anticholinergic-like symptomsAnticholinergic-like symptomsHallucinations, delusion, dysphoriaHallucinations, delusion, dysphoria

Opiate kappa and mu receptorsOpiate kappa and mu receptorsOpiate effectsOpiate effects

Dextromethorphan : Dextromethorphan : TreatmentTreatment

Gastrointestinal decontaminationGastrointestinal decontaminationNarcan may be usefulNarcan may be usefulSupportive CareSupportive CareLaboratoryLaboratory

– Rule out aspirin and acetaminophenRule out aspirin and acetaminophen

MescalineMescaline

Source Undetermined

CharacteristicsCharacteristics

Derived from peyote cactus.Derived from peyote cactus.

Hallucinogen.Hallucinogen.

Can mimic an acute gastroenteritisCan mimic an acute gastroenteritis

Mescaline TreatmentMescaline Treatment

SupportiveSupportive

FlunitrazepamFlunitrazepam

Used throughout Europe.Used throughout Europe.Not approved in the US.Not approved in the US.One of the One of the ““date-rapedate-rape”” drugs. drugs.By weight 10x more potent than By weight 10x more potent than

diazepam.diazepam.Produces effects within 15 mins.Produces effects within 15 mins.

Flunitrazepam tabletsFlunitrazepam tablets

New Rohypnol tablets include a dye that make the drug visible if slipped into a drink

Drug Enforcement Agency, Wikimedia Commons

PathologyPathology

A benzodiazapine working on the A benzodiazapine working on the GABAGABAAA receptor. receptor.

Lipid soluble rapidly crossing the BB Lipid soluble rapidly crossing the BB barrier.barrier.

EffectsEffects

““DESIREDDESIRED””

EuphoriaEuphoriaHallucinationsHallucinationsDisinhibitionDisinhibitionSM relaxationSM relaxationSedationSedationMemory impairmentMemory impairment

UNDESIREDUNDESIRED

HypotensionHypotensionDrowsinessDrowsinessApneaApneaUrinary retentionUrinary retentionTremorsTremors

TreatmentTreatment

Supportive care.Supportive care.

AC, lavage (use with caution, may be AC, lavage (use with caution, may be contraindicated)contraindicated)

Benzodiazepine antagonists Benzodiazepine antagonists (flumazenil) :(flumazenil) :

NONO!!!! (very few indications). (very few indications).

Inhalant AbuseInhalant Abuse

Freon PropellantsFreon PropellantsXylene, TolueneXylene, TolueneGasoline FumesGasoline Fumes

United States Department of Defense, Wikimedia Commons

Anticholinergic AbuseAnticholinergic Abuse

AntihistaminesAntihistaminesJimson WeedJimson WeedAnticholinergic Syndrome:Anticholinergic Syndrome:

– Mad as a hatterMad as a hatter– Blind as a batBlind as a bat– Hot as HadesHot as Hades– Dry as a boneDry as a bone– Red as a beetRed as a beet

SummarySummary

GHB / GHB AnalogsGHB / GHB Analogs– Classic Symptoms in OverdoseClassic Symptoms in Overdose– Withdrawal SymptomsWithdrawal Symptoms

Rave PartiesRave Parties– Multiple drugs commonly usedMultiple drugs commonly used

Rising OTC Dextromethorphan UseRising OTC Dextromethorphan Use– Rule out aspirin and acetaminophenRule out aspirin and acetaminophen

SummarySummary

Methamphetamine is a major problemMethamphetamine is a major problemOlder drugs of abuse have not gone Older drugs of abuse have not gone

awayaway– PCPPCP– LSDLSD– HeroinHeroin– CocaineCocaine– EthanolEthanol– MarijuanaMarijuana