Download Drugs Of Abuse - Calgary Emergency Medicine

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 cocaineassociated 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. Cocaineinduced 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 cocaineassociated 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. Cocaineassociated 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. Cocaineassociated chest pain: How common is MI? Acad
Emerg Med 2000;7:873-885.
Thrombolysis & Coke?
• Crap?
• Hollander JE, Burstein JL, Hoffman RS, et al. Cocaineassociated 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 (GAMMAHYDROXYBUTYRATE)
• 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 bodybuilding and hastened weight loss (unproven)
• 1990’s: popular for its intoxicating, euphoric and sexuallyenhancing effects, and therefore as a date-rape drug
HISTORY
• 1990: FDA declares that GHB is unsafe and illicit
unless consumed under FDA-approved, MDsupervised 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, 25% 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
OH
HO
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
GBL
HO
OH
GHB
STREET NAMES FOR GHB
•
•
•
•
•
•
cherry meth
easy lay
everclear
fantasy
Georgia home boy
goops
•
great hormones at bedtime
•
•
•
•
•
grievous body harm
G-riffick
growth hormone booster
liquid E
wolfies
 liquid ecstasy  G
 liquid E
 liquid X
 organic quaalude
 oxy-sleep
 poor man’s heroin
 salty water
 scoop
 soap
 somatomax PM
 water
 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 postingestion 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
Chalk
Crank
Crystal
Glass
Go-Fast
Ice
LA Glass
Meth
•
•
•
•
•
•
•
•
•
Methlies Quick
Mexican Crack
Quartz
Shabu
Sketch
Speed
Stove Top
West Coast
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
• Similar presentation
• ++++ longer T1/2
• ?faster onset?
• Easy to make
vs
Coke
• Similar routes
• Short acting
• Quick onset
• “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!