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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 3,4 methylenedioxymethamphetamine X, E, M, XTC, Rolls, Adam, Bean, Hug Drug MDMA Properties and Mechanism of Action 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 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 MDMA History 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 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 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 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 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 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 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 MDEA MBDB MDA PMA Caffeine Dextromorphan Aspirin Piracetam 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 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 Extreme euphoria Increased energy Feelings of belonging and closeness Heightened sensations (touch, taste, smell, hearing) Increased openness Feelings of love and empathy Bright, intense visual perceptions Musical appreciation Fear dissolution “Profound” thought Other Effects Appetite loss Vertical nystagmus (rolling) Moderate increases in HR and BP Mild visual hallucinations Mind racing Changes in thermoregulation Restlessness, nervousness, shivering Strong desire to take more drug during come down Mydriasis Negative Side Effects Mild to extreme trisma and bruxism Short-memory loss Confusion HA, vertigo, ataxia Muscle tension Nausea & vomiting Concentration difficulties “Crash” come down Hangover lasting days to weeks Depression and fatigue for up to a week Psychological addiction Panic attacks Major Toxic Complications 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 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 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 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 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 Rhabdomyolysis – heat production and muscle necrosis Myoglobinuria and renal failure – secondary to rhabdomyolysis Hepatic necrosis DIC Treatment of Hyperpyrexic Pattern of Toxicity 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 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 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 Supportive care and rapid cooling measures Volume replacement and Na+ correction with 3% NS Labs corrected (Na=137 @ 30 hrs after admission VSS, no further seizures, mental status improved throughout the day Stable after 3 days in ICU CASE #4 HISTORY 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) 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) 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 GHB - Toxicity 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 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 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 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 Enhanced Elimination – no role CASE #5 HISTORY 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 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 Ketamine 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 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 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 Mainly supportive No antidote Pt should be placed in quiet room with minimal stimulation References 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. 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. http://www.google.com/url?sa=t&rct= j&q=&esrc=s&source=web&cd=1&ved =0CCAQFjAA&url=http%3A%2F%2Fw ww.uic.edu%2Fdepts%2Fmcpt%2Fcur riculum%2Fcpp%2Fppt%2FEricksonDrugsHandout.ppt&ei=WlFYVJztD4uGi gLd14GYAQ&usg=AFQjCNGsK-ZHSCeSoYtGnhC2Knwtg7XIg&sig2=GnpLCm MWlkRJYEpsnfgSbw&bvm=bv.786774 74,d.cGE