Transcript Erickson-DrugsHandout

Street Drugs of Abuse
Timothy B. Erickson, MD
Professor: Department of Emergency Medicine
University of Illinois @ Chicago
Case #3 History
•17
y/o CF presents to the community
hospital emergency department at 2:00AM
with “fever and strange behavior” as per
her parents.
•While
waiting to be examined, the patient
has a witnessed tonic-clonic seizure lasting
1 minute in duration.
Earlier that night:
•Urine Tox Screen:
+ Amphetamines
+ Cannabis
- EtOH, ASA, APAP
AMPHETAMINES
Ecstasy: The drug of a new
generation.
Ecstasy = MDMA
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3,4 methylenedioxymethamphetamine
X, E, M, XTC, Rolls, Adam, Bean, Hug Drug
MDMA
Properties and Mechanism of Action
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Designer drug from the essential oil of the
sassafras tree
Ring substituted amphetamine
Pharmacological effects are a blend of
amphetamines and mescaline
Structure resembles natural
neurotransmitters of Epi, DA
Biological actions and effects resemble
those of Epi, DA, and serotonin
Pharmacodynamics
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Increases the net release of monoamine
neurotransmitters (5-HT, NE, DA) from their
axon terminals
MDMA binds to and blocks the serotonin
reuptake transporter – flooding the
terminals with 5-HT
Similar, weaker action on DA reuptake
Amphetamine like increase in NE
Increase in 5-HT and DA = mental effects
Increased NE=physical amphetamine effects
MDMA analogues
MDA (3,4-methylenedioxyamphetamine) –
“Love Drug” - similar in effect, more
stimulating, twice as neurotoxic
 MDE (N-ethyl-methylenedioxyamphetamine)
“Eve” – more introspective experience
 MMDA (3-methoxy-4,5methylenedioxyamphetamine) – closed eye
hallucinations, “brain movies”
 MBDB (N-methyl-1-(1,3-benzodioxol-5-yl)-2butanamine) – effects similar to MDA
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MDMA History
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1912 – first synthesized by Merck
1914 – patented by Merck –
manufactured as an appetite
suppressant, never marketed
1950’s- studied by US Army as potential
agent in psychological warfare
1970 – used in psychotherapy,
“penicillin for the soul”
1977 – class A illegal drug in UK
1985 – Schedule I illegal drug in U.S.
Trends in Ecstasy Use
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DEA seizures of
Ecstasy Tablets:
1996 – 13,342
tablets
2000 – 949,257
tablets
2001 - >4,000,000
tablets in 8 months
Ecstasy Use by Students,
2000 (NIDA Studies)
8thGraders
10thGraders
12thGraders
Ever Used 4.3%
7.3%
11.0%
Used in
Past Year
(1999)
5.4%
(4.4%)
8.2%
(5.6%)
2.6%
3.6%
3.1%
(1.7%)
Past
1.4%
month use
Perceived availability by 12th graders 51.4% (40.1%)
MDMA
Production and Sales
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Street value = $25 per pill
Wholesale price = $2-$8 per pill
Production cost = 2-5 cents per pill
Majority of production and distribution
linked to well organized crime
networks in Europe (Amsterdam,
Germany, UK) and Israel
Smaller labs all over US and Europe
Areas of Usage
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Highest at raves,
dance clubs (as
high as 91% of
clubbers in dance
scene in Scotland)
Dramatic increase
in college use,
suburban teens,
house parties
Millroy, CM, JRSM February 1999
Physical CLUES
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Glowsticks or lights
Lollipops
Pacifiers
Vick’s Vapor Rub
and Nasal Inhaler
Fuzzy Mittens
Most Predictive Factor of
Drug Use = CLUB MUSIC!
Methods of
Administration
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Mainly PO – stamped tablets, capsules
Intra-nasal – rapid absorption of
crushed tablets or opened capsules
Intra-rectal – faster absorption than PO
Recreational usage varies from ½ pill to
as much 15 pills in a 6 hour span
Content and Purity
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Numerous logos and names (Green Nike,
Mitsubishi, Buddha, Smiley Face)
Pills tested and results posted on Internet sites
such as dancesafe.org
Average MDMA content 90-100mg/pill
60% MDMA, 20% MDEA, 10% MBDB, 10% no
active ingredient or aspirin, 5% amphetamine,
ephedrine, or caffeine
Millroy, CM, JRSM February 1999
MDMA Adulterants
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MDEA
MBDB
MDA
PMA
Caffeine
Dextromorphan
Aspirin
Piracetam
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Methamphetamine
PCP
Ketamine
Heroin
Quinine
LSD
Marijuana
Ephedrine
MDMA
Onset
20-90
min
Rise up 5-20
min
Plateau 2-3
hours
Come
1-2
down
hours
After
3-24
Effects hrs
Pharmacokinetics
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Peak plasma concentration at ≈ 2 hrs
106ng/mL@50mg, 236ng/mL@125mg
Large tissue distribution
Metabolic breakdown by CYP2D6
Saturation kinetics
T1/2 ≈ 8 hours
Pharmacologically active first
metabolite (MDA)
Kalant, H; Canadian Medical Association Journal, October, 2001
Positive Effects
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Extreme euphoria
Increased energy
Feelings of
belonging and
closeness
Heightened
sensations (touch,
taste, smell,
hearing)
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Increased openness
Feelings of love and
empathy
Bright, intense
visual perceptions
Musical
appreciation
Fear dissolution
“Profound” thought
Other Effects
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Appetite loss
Vertical nystagmus
(rolling)
Moderate increases
in HR and BP
Mild visual
hallucinations
Mind racing
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Changes in
thermoregulation
Restlessness,
nervousness,
shivering
Strong desire to
take more drug
during come down
Mydriasis
Negative Side Effects
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Mild to extreme
trisma and bruxism
Short-memory loss
Confusion
HA, vertigo, ataxia
Muscle tension
Nausea & vomiting
Concentration
difficulties
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“Crash” come down
Hangover lasting
days to weeks
Depression and
fatigue for up to a
week
Psychological
addiction
Panic attacks
Major Toxic
Complications
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Hyperthermia/Heat Stroke
Dehydration
Hyponatremia
SIADH
Hepatitis/Liver Failure
Rhabdomyolysis/Renal Failure
Neurotoxic Effects
Acute Psychotic Break/Severe Depression
 Death!
Ecstasy Related Fatalities
87 cases reported in the literature
caused by:
 Hyperpyrexia – 30
 Hepatic – 4
 Cardiovascular/Cerebrovascular – 8
 Cerebral, including Hyponatremia – 9
 Drug Related Accidents or Suicide – 14
 Unknown – 22
Kalant, H; Canadian Medical Association Journal, October, 2001
Major Physical Toxicity Hepatic
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Mild viral hepatitis – jaundice, enlarged
tender liver, elevated LFT’s/Coags – self
limited, 2 wks-3 mo, related to glutathione
decrease and oxidative cell destruction
Prolonged hepatitis – slow recovery with
potential permanent fibrosis
Fulminant liver failure – fatal without liver
transplant
Kalant, H; Canadian Medical Association Journal, October, 2001
Major Physical Toxicity Cardiovascular
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NE responsible: HTN and tachycardia
Major intracranial hemorrhage
Petechial hemorrhages – brain and other
organs
Retinal hemorrhage at autopsy
Intravascular thrombosis and CVA
Serious cardiac dysrhythmias
Pulmonary edema/heart failure
Major Physical ToxicityCerebral
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Hyponatremia- result of vigorous physical
activity, profuse sweating, large Na+ loss,
excessive water consumption
SIADH – less common mechanism of water
retention, but can complicate picture
Cerebral edema w/hyponatremic seizures –
therapy includes BZD’s and cautious
replacement of Na with hypertonic saline
Brain stem and cerebellum compression
Hyperpyrexic Pattern of
Toxicity
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Most dangerous form of ecstasy induced
toxicity
Results from a combo of drug action,
intense physical activity, and hot
environment
Adulterants such as dextromorphan can
inhibit sweating leading to further heat
retention
Changes resemble those seen
in severe heatstroke
Features of Hyperpyrexia
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Rhabdomyolysis – heat production
and muscle necrosis
Myoglobinuria and renal failure –
secondary to rhabdomyolysis
Hepatic necrosis
DIC
Treatment of Hyperpyrexic
Pattern of Toxicity
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Mainly symptomatic – rehydration, monitor
electrolytes, treat possible co-ingestions
Early rapid cooling measures: ice-water
sponging, IV infusion of chilled saline,
gastric and bladder lavage with cooled
fluids, general supportive care
Dantrolene - 1mg/kg – good evidence for
use as a potential life-saving measure
Kalant, H; Canadian Medical Association Journal, October, 2001
Toxic Blood Levels
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Poor correlation overall – shows
importance of environmental factors
“Recreational” use: 100-250ng/mL
Most cases of serious toxicity or
fatality w/ levels from 500ng/mL–
10μg/mL – 40x higher than usual
recreational range
Some cases of serious toxicity w/
levels as low as 111-255ng/mL
PMA
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Paramethoxyamphetamine
Pills contain 50mg of PMA, look like MDMA
tablets
Longer duration to onset – toxic in doses of
60-80mg
Rapid rise in BP and temp leading to
convulsions, coma, and death
Responsible for 10 deaths (3 in suburbs of
Chicago)
Case Revisited
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Supportive care and rapid cooling
measures
Volume replacement and Na+
correction with 3% NS
Labs corrected (Na=137 @ 30 hrs
after admission
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VSS, no further seizures, mental status
improved throughout the day
Stable after 3 days in ICU
CASE #4 HISTORY
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The patient is a 23 yr old who suffered
a witnessed seizure and is brought to
the ED by concerned friends.
He has no prior seizure disorder and
the friends deny history of drug use.
Gamma Hydroxybutyrate Acid
(GHB)
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Liquid ecstacy
Liquid G
Gamma Oh
Grievous bodily harm
Scoop
Samatomax
Bioski
Cow Growth Hormone
Georgia Home Boy
GHB
Analogue
of inhibitory neurotransmitter
gamma-aminobutyirc acid- CNS depressant
Synthesized
in 1960 and used in 1970’s for
sleep disorders because it induces REM sleep
Used
in Europe as anesthetic agent until found
that it caused seizures
1977,
study claimed it stimulated effects of
Growth Hormone
GHB
Unapproved
drug in US, but
legally obtainable under FDA
investigational New Drug
exemption for treatment of
narcolepsy
–20 states have controlled its
use with penalties similar to
marijuana possession
Gamma Hydroxybutyrate Acid
(GHB)
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Readily available in drug market and
inexpensive and relatively easy to make
– recipes are obtainable on the internet
Obtainable as clear and odorless liquid,
gel, or powder which have a salty taste
– however, taste is masked by ETOH
which increases its clinical effects
GHB
Used
in date rape because:
–quick onset of effect
– easily obtainable
– small quantities are needed
–causes hallucinations and amnesia
making the patient an unreliable
witness
GHB
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GHB - Toxicity
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Acts as neurotransmitter affecting GHB and
GABA- B receptors causing CNS depression
– takes effects in 15-30 minutes causing
drowsiness, dizziness, and disorientation
– duration of action up to 3 hours
– half life of 20 min to 1 hour
– hallmark is marked agitation upon
stimulation despite apnea and hypoxia
10mg/kg
causes vomiting, rapid
onset of coma and amnesia
20-30mg/kg
cause rapid cycles of
REM and non-REM sleep
50mg/kg
can cause resp
depression, bradycardia, clonic
muscle contractions, and decreased
cardiac output
GHB - Other forms
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Gamma butyrolactone (GBL) - can be
purchased from chemical supply stores or
catalogues and converted to GHB with
NaOH
– GBL is rapidly converted to GHB by
peripheral lactonases within minutes
1,4-Butanediol
- can be purchased in
similar manner as GBL
–converted to gamma
hydroxybutyaldehyde by alcohol
dehydrogenase
–then, converted to GHB by aldehyde
dehydrogenase
GHB - Diagnosis
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High clinical suspicion based on history and
clinical presentation
– abrupt on set of coma with recovery within
a few hours
Lab tests for GHB not readily available
– few national reference labs
Duration of detection of GHB in blood and
urine are 6 and 12 hours, respectively
GHB - Treatment
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Mainly supportive
Antidotes for GHB: Physostigmine?
Decontamination
– charcoal has doubtful benefits since small
amounts used are absorbed rapidly and
may increase risk of pulmonary aspiration
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Enhanced Elimination
– no role
CASE #5 HISTORY
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The patient is an 18 yr old transferred
from the H.S. health center to the ED
after he was caught wondering the
hallways by the art department
demonstrating “bizzare behavior”
The patient is normally healthy
PHYSICAL EXAM
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Gen: Sleepy, blank catatonic stare when
awakened, good airway
Vs: P=90 BP=110/70 RR=16 T=99
HEENT: NC/AT Eyes: Pupils 3mm Rotary
nystagmus noted; moist mm’s (+)drooling
Lungs: CTA CV: RRR S1S2
Abd: Benign Ext: Good pulses
Neuro: Motor sensory grossly intact
no focal defs
Ketamine
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Ketamine
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AKA: Special K, Super Acid, Super C
used as an anesthetic in EM and veterinary
medicine
Ketamine is a controlled substance in 18
states as schedule III drug
Used in date rape because:
– rapid onset
– dissociative hallucinogenic
Ketamine - Toxicity
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Chemically related to PCP
takes effect 15-20 minutes, producing
analgesia
Higher doses produces dissociative
hallucinations, delirium, resp depresion,
Sz, arrythmias and cardiac arrest
Effects last 20-45min
Ketamine - Diagnosis
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High index of suspicion based on
history and presentation
Urine tox screens may mistakenly
ID as PCP since structurally
related to PCP
Specific test for ketamine not
widely available
Ketamine - Treatment
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Mainly supportive
No antidote
Pt should be placed in quiet room with
minimal stimulation
References
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1991; 9: Holden R, Jackson MA. Near-fatal
hyponatremic coma due to vasopressin over-secretion
after “ecstasy” (3,4-MDMA). The Lancet
1996;347:1052.
Kalant H. The pharmacology and toxicity of “ecstasy”
(MDMA) and related drugs. CMAJ 2001;165(7):917-928.
Milroy CM. Ten years of ecstasy. JRSM 1999;92(2):6872.
Schwartz RH, Miller NS. MDMA (Ecstasy) and the rave:
A review. Pediatrics 1997;100(4): 705-708.
www.erowid.org www.dancesafe.org
Centers for Disease Control and Prevention: GHB use
1995-1996 JAMA 1997; 277;1511.
Dyer JE: GHB: A health-food product producing coma
and seizures. Am J Emerg Med 321-324.
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Gussow, Leon “Inhalants of Abuse” in Clinical Toxicology, ed.
Ford, Delaney, Ling, Erickson (Philadelphia, PA: WB
Saunders, 2001) pp. 651-656.
Bass, Millard, “Sudden Sniffing Death.” JAMA 1970 June 22;
212(12): 2075-79.
Committee on Substance Abuse and Committee on Native
American Child Health, “Inhalant abuse.” Pediatrics 1996
Mar;97(3):420-3.
Henretig, Fred. “Inhalant abuse in children and adolescents.”
Pediatric Annals 1996 Jan;25(1):47-52.
2001 Research Report "Inhalant Abuse.”
Steffee CH, Davis GJ, Nicol KK. “A whiff of death: fatal
volatile solvent inhalation abuse.” South Med J 1996
Sep;89(9):879-84.
(www.drugabuse.gov/ResearchReports/Inhalants/RRInhalant
s.pdf)
MICROMEDEX, Inc., Greenwood Village, Colorado (Edition expires 12/2001).
2001
NIDA Infofax: “Inhalants”
(www.drugabuse.gov/Infofax/inhalants.html)
Brecher,
Edward M., et al “The Consumers Union Report on Licit
and Illicit Drugs.”
www.druglibrary.org/schaffer/Library/studies/cu/CU43.htm
ONDCP
Drug Policy Information Clearinghouse Fact Sheet,
June, 2001.
(www.whitehousedrugpolicy.gov/publications/pdf/inhalants_facts
heet.pdf)
Broussard
LA, “The role of the laboratory in detecting inhalant
abuse.” Clin Lab Sci 2000 Fall;13(4):205-9
Spiller
HA, Krenzelok EP. “Epidemiology of inhalant abuse
reported to two regional poison centers.” J Toxicol Clin Toxicol
1997;35(2):167-73.
Litovitz
TL, “2000 Annual report of the American Association of
Poison Control Centers Toxic Exposure Surveillance System.” Am
J Emerg Med - 01-Sep-2001; 19(5): 337-95.
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