Update on Drugs of Abuse (“some club-drug stuff”).

84
Update on Drugs of Update on Drugs of Abuse Abuse (“some club-drug (“some club-drug stuff”) stuff”)

Transcript of Update on Drugs of Abuse (“some club-drug stuff”).

Page 1: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 2: Update on Drugs of Abuse (“some club-drug stuff”).

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)

Page 3: Update on Drugs of Abuse (“some club-drug stuff”).

Overview of TopicsOverview of Topics

MethamphetamineMethamphetamine

Dextromethorphan (DM)Dextromethorphan (DM)

KetamineKetamine

FlunitrazepamFlunitrazepam

MescalineMescaline

InhalantsInhalants

AnticholinergicsAnticholinergics

Page 4: Update on Drugs of Abuse (“some club-drug stuff”).

GHBGHB((GGamma-amma-

hhydroxyydroxybbutyrate)utyrate)

Page 5: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 6: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 7: Update on Drugs of Abuse (“some club-drug stuff”).

Structure Activity Structure Activity RelationshipRelationship

COOH

CH2

CH2

CH2

OH

COOH

CH2

CH2

CH2

NH2

gamma hydroxybutyrate

gamma amino butyric acid

GHB GABA

Page 8: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 9: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 10: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 11: Update on Drugs of Abuse (“some club-drug stuff”).

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

O

=O

NaOH + H2O

Lactonasein vitro

In vivo

C OOHCH2

CH2

CH2 OH

GBL GHB

Page 12: Update on Drugs of Abuse (“some club-drug stuff”).

Gamma Butyrolactone Gamma Butyrolactone (GBL)(GBL)

Page 13: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 14: Update on Drugs of Abuse (“some club-drug stuff”).
Page 15: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 16: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 17: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 18: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 19: Update on Drugs of Abuse (“some club-drug stuff”).

EffectsEffects

““DESIRED”DESIRED”

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

UNDESIREDUNDESIRED

Decreased HR, Decreased HR, RRRR

ComaComa

Excessive Excessive salivationsalivation

Absence-like sz’sAbsence-like sz’s

Page 20: Update on Drugs of Abuse (“some club-drug stuff”).

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 %

Page 21: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 22: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 23: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 24: Update on Drugs of Abuse (“some club-drug stuff”).

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”

Page 25: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 26: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 27: Update on Drugs of Abuse (“some club-drug stuff”).

GHB Dependence : Case StudyGHB Dependence : Case Study

29 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 turkey

Arrived in ED 24 hr after his last dose Arrived in ED 24 hr after his last dose

Page 28: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 29: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 30: Update on Drugs of Abuse (“some club-drug stuff”).

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.

Page 31: Update on Drugs of Abuse (“some club-drug stuff”).

GHB Withdrawal : Clinical GHB Withdrawal : Clinical PresentationPresentation

Onset :Onset : 1 to 6 hours1 to 6 hours

Progression of sxs over 1 to 3 daysProgression of sxs over 1 to 3 days

Symptoms 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

Page 32: Update on Drugs of Abuse (“some club-drug stuff”).

GHB Withdrawal : GHB Withdrawal : ManagementManagement

AGGRESSIVE TREATMENT EARLYAGGRESSIVE TREATMENT EARLY

BenzodiazepinesBenzodiazepinesHigh doses may be requiredHigh doses may be required

BarbituratesBarbiturates

AntipsychoticsAntipsychotics

Unproven TherapyUnproven Therapy– Baclofen (GABA-B agonist)Baclofen (GABA-B agonist)

Page 33: Update on Drugs of Abuse (“some club-drug stuff”).

Stimulants of AbuseStimulants of AbuseMethamphetamineMethamphetamineMethylene dioxymethamphetamine : Methylene dioxymethamphetamine : MDMA (Ecstasy)MDMA (Ecstasy)

CocaineCocaine

Ketamine / PCP (phencyclidine)Ketamine / PCP (phencyclidine)

DextromethorphanDextromethorphan

Page 34: Update on Drugs of Abuse (“some club-drug stuff”).

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.

Page 35: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 36: Update on Drugs of Abuse (“some club-drug stuff”).

Ketamine : Clinical Ketamine : Clinical PresentationPresentation

Dissociative anestheticDissociative anesthetic

Clinical 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

Page 37: Update on Drugs of Abuse (“some club-drug stuff”).

Ketamine TreatmentKetamine Treatment

SupportiveSupportive

SedationSedation

Page 38: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 39: Update on Drugs of Abuse (“some club-drug stuff”).

MethamphetamineMethamphetamine

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

Page 40: Update on Drugs of Abuse (“some club-drug stuff”).

StructuresStructures

PhenethylaminePhenethylamine

AmphetamineAmphetamine

MethamphetamineMethamphetamine

Page 41: Update on Drugs of Abuse (“some club-drug stuff”).

ProductionProduction

EphedrineEphedrine

MethamphetamineMethamphetamine

Page 42: Update on Drugs of Abuse (“some club-drug stuff”).
Page 43: Update on Drugs of Abuse (“some club-drug stuff”).
Page 44: Update on Drugs of Abuse (“some club-drug stuff”).
Page 45: Update on Drugs of Abuse (“some club-drug stuff”).

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.

Page 46: Update on Drugs of Abuse (“some club-drug stuff”).
Page 47: Update on Drugs of Abuse (“some club-drug stuff”).
Page 48: Update on Drugs of Abuse (“some club-drug stuff”).

Signs and SymptomsSigns and Symptoms

Action phaseAction phase

Skin pickingSkin picking

Head bangingHead banging

PacingPacing

Paranoid psychosisParanoid psychosis

Extreme Extreme suspiciousnesssuspiciousness

Resolution phaseResolution phase

ExhaustionExhaustion

FatigueFatigue

SleepSleep

DepressionDepression

Page 49: Update on Drugs of Abuse (“some club-drug stuff”).

Other Signs and SymptomsOther Signs and Symptoms

Pulmonary hypertensionPulmonary hypertension

DyspneaDyspnea

Pleuritic chest painPleuritic chest pain

Anorexia/weight lossAnorexia/weight loss

UlcersUlcers

RhabdomyolysisRhabdomyolysis

Page 50: Update on Drugs of Abuse (“some club-drug stuff”).

TESS DATATESS DATAMethamphetamine Exposures Without Concomitants, 2001

(Cardiovascular Effects)

0

50

100

150

200

250

300

350

400

Fig 3 American Association of Poison Control Centers Toxic Exposure Surveillance System, 2001

Page 51: Update on Drugs of Abuse (“some club-drug stuff”).

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 insuranceIncrease 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

Page 52: Update on Drugs of Abuse (“some club-drug stuff”).

Methamphetamine and Methamphetamine and TraumaTrauma

UCDMC Level 1 Trauma CenterUCDMC Level 1 Trauma Center

Retrospective Study 1989 to 1994Retrospective Study 1989 to 1994

Results :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 %

Page 53: Update on Drugs of Abuse (“some club-drug stuff”).

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 MCA’sMeth (+) in MVA or MCA’sCocaine (+) in assaults, GSW’s or stab Cocaine (+) in assaults, GSW’s or stab woundswounds

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

Page 54: Update on Drugs of Abuse (“some club-drug stuff”).

TreatmentTreatment Don’t forget to r/o other causes :Don’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.

Page 55: Update on Drugs of Abuse (“some club-drug stuff”).

Treatment (cont.)Treatment (cont.)

Control stimulant effectsControl stimulant effects

DecontaminationDecontamination

Control 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.

Page 56: Update on Drugs of Abuse (“some club-drug stuff”).

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

3,4-Methylenedioxymethamphetamine3,4-Methylenedioxymethamphetamine

Sympathetic 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

Page 57: Update on Drugs of Abuse (“some club-drug stuff”).

MDMAMDMA

Page 58: Update on Drugs of Abuse (“some club-drug stuff”).

History of EcstasyHistory of Ecstasy

19141914 Patented as Appetite suppressantPatented as Appetite suppressant

Never MarketedNever Marketed

1970’s1970’s Use by psychiatristsUse by psychiatrists

1980’s1980’s “LSD of the 60’s” “LSD of the 60’s”

1990’s1990’s Increasing abuse, Rave party useIncreasing abuse, Rave party use

20002000 Continuing abuseContinuing abuse

Illicit adulterants commonIllicit adulterants common

Page 59: Update on Drugs of Abuse (“some club-drug stuff”).

Illicit Ecstasy TabletsIllicit Ecstasy Tablets

Page 60: Update on Drugs of Abuse (“some club-drug stuff”).
Page 61: Update on Drugs of Abuse (“some club-drug stuff”).
Page 62: Update on Drugs of Abuse (“some club-drug stuff”).

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.

Page 63: Update on Drugs of Abuse (“some club-drug stuff”).

EffectsEffects

DESIREDDESIRED

Increased energyIncreased energy

EuphoriaEuphoria

EmpathyEmpathy

Visual Visual hallucinationshallucinations

UNDESIREDUNDESIRED

Jaw clenchingJaw clenching

ParanoiaParanoia

Hot / cold flashesHot / cold flashes

HyperpyrexiaHyperpyrexia

SeizuresSeizures

Page 64: Update on Drugs of Abuse (“some club-drug stuff”).

Clinical Signs and SymptomsClinical Signs and Symptoms

RhabdomyolysisRhabdomyolysis

HyponatremiaHyponatremia

DICDIC

Renal failureRenal failure

HepatotoxicityHepatotoxicity

Aplastic anemia : rareAplastic anemia : rare

Page 65: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 66: Update on Drugs of Abuse (“some club-drug stuff”).

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 issue

Controlling hyperthermia predicts Controlling hyperthermia predicts survival in several studiessurvival in several studies

Page 67: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 68: Update on Drugs of Abuse (“some club-drug stuff”).

Dextromethorphan (DXMF) Dextromethorphan (DXMF) AbuseAbuse

Many DXMF containing OTC productsMany DXMF containing OTC products

Coricidin : 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

Page 69: Update on Drugs of Abuse (“some club-drug stuff”).

DextromethorphanDextromethorphan

Therapeutic doses : mild CNS effectsTherapeutic doses : mild CNS effects

High doses : significant CNS effectsHigh doses : significant CNS effectsSpecific DXMF receptors (opiate - sigma)Specific DXMF receptors (opiate - sigma)

Anticholinergic-like symptomsAnticholinergic-like symptoms

Hallucinations, delusion, dysphoriaHallucinations, delusion, dysphoria

Opiate kappa and mu receptorsOpiate kappa and mu receptorsOpiate effectsOpiate effects

Page 70: Update on Drugs of Abuse (“some club-drug stuff”).

Dextromethorphan : Dextromethorphan : TreatmentTreatment

Gastrointestinal decontaminationGastrointestinal decontamination

Narcan may be usefulNarcan may be useful

Supportive CareSupportive Care

LaboratoryLaboratory– Rule out aspirin and acetaminophenRule out aspirin and acetaminophen

Page 71: Update on Drugs of Abuse (“some club-drug stuff”).

MescalineMescaline

Page 72: Update on Drugs of Abuse (“some club-drug stuff”).

CharacteristicsCharacteristics

Derived from peyote cactus.Derived from peyote cactus.

Hallucinogen.Hallucinogen.

Can mimic an acute gastroenteritisCan mimic an acute gastroenteritis

Page 73: Update on Drugs of Abuse (“some club-drug stuff”).

Mescaline TreatmentMescaline Treatment

SupportiveSupportive

Page 74: Update on Drugs of Abuse (“some club-drug stuff”).

FlunitrazepamFlunitrazepam

Used throughout Europe.Used throughout Europe.

Not approved in the US.Not approved in the US.

One of the “date-rape” drugs.One of the “date-rape” 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.

Page 75: Update on Drugs of Abuse (“some club-drug stuff”).

Flunitrazepam tabletsFlunitrazepam tablets

Page 76: Update on Drugs of Abuse (“some club-drug stuff”).

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.

Page 77: Update on Drugs of Abuse (“some club-drug stuff”).

EffectsEffects

““DESIRED”DESIRED”

EuphoriaEuphoriaHallucinationsHallucinationsDisinhibitionDisinhibitionSM relaxationSM relaxationSedationSedationMemory impairmentMemory impairment

UNDESIREDUNDESIRED

HypotensionHypotension

DrowsinessDrowsiness

ApneaApnea

Urinary retentionUrinary retention

TremorsTremors

Page 78: Update on Drugs of Abuse (“some club-drug stuff”).

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).

Page 79: Update on Drugs of Abuse (“some club-drug stuff”).

Inhalant AbuseInhalant Abuse

Freon PropellantsFreon Propellants

Xylene, TolueneXylene, Toluene

Gasoline FumesGasoline Fumes

Page 80: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 81: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 82: Update on Drugs of Abuse (“some club-drug stuff”).

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

Page 83: Update on Drugs of Abuse (“some club-drug stuff”).

Questions?

Page 84: Update on Drugs of Abuse (“some club-drug stuff”).