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Drugs of Abuse

Drugs of Abuse. Dawn R. Sollee, Pharm.D., DABAT Florida Poison Information Center-Jax. Cocaine. History. 6th Century - Peruvian Indians chewed for religious and social reasons 1880s - first used for medicinal purposes 1886 - birth of Coca-Cola, decocainized in 1906

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Drugs of Abuse

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  1. Drugs of Abuse Dawn R. Sollee, Pharm.D., DABAT Florida Poison Information Center-Jax

  2. Cocaine

  3. History • 6th Century - Peruvian Indians chewed for religious and social reasons • 1880s - first used for medicinal purposes • 1886 - birth of Coca-Cola, decocainized in 1906 • The Harrison Act of 1914 - narcotic labeling • 1970 - Drug Prevention and Abuse Act - Schedule II

  4. Epidemiology • US currently in last phase of the “third cocaine epidemic” • One of the most commonly abused substance, 4th to only alcohol, nicotine, and marijuana • 1992 - 22.6 million had tried once, 5 million abused regularly • Most abusers are male, < 40 yo, use multiple drugs

  5. Pharmacology • Cocaine HCl is the natural alkaloid contained in the leaves of Erythroxylon coca plant

  6. Pharmacology • Pharmacologic effects: • local anesthetic effect • central nervous system stimulation • inhibition of catecholamine re-uptake

  7. Dosage Forms • Cocaine HCl • highly water soluble, available as crystals, granules or white powder • high melting point so it can’t be smoked • snorted intranasally or dissolved in water and injected • vasocontrictive properties limits its own absorption • onset- 20 min, peak- 60 min, duration- 3 hr

  8. Dosage Forms • Free base • prepared by treating cocaine HCl with a basic solution • precipitated free alkaloid is filtered or dissolved in ether which is then removed by drying • smoked because it volatilizes at low temps • relatively pure and very expensive • onset- 1-2 mins, duration- 30min

  9. Dosage Forms • Crack • named for the sound it makes when heated • inexpensive, solid form of free base • prepared by mixing with baking soda and water • heating forms a “rock” and this is smoked • onset- secs, peak- 3- 5 min, duration-20 min

  10. Dosage Forms • Adulterants • street cocaine is usually < 15-20% pure cocaine • mannitol, sucrose, lactose, caffeine, talc, heroin, organophosphates, strychnine, amphetamine, lidocaine, acetaminophen

  11. Pharmacokinetics • Once absorbed, cocaine (t1/2 - 60 min) is metabolized by plasma and liver cholinesterases • Two inactive metabolites, benzoylecognine and ecgonine methyl ester • Metabolites excreted unchanged in urine • Urine drug screens qualitatively measure benzoylecognine • acute - detectable up to 72 hours • chronic - 7 to 21 days

  12. Clinical Presentation“Caine Reaction” • Acute Intoxication • early stimulative phase: excitement, HA, N/V, twitching, hypertension, tachypnea, hypernea • advanced stimulative phase: seizures, tachycardia, hypertension, cyanosis, dyspnea, rapid or irregular respirations • depressive phase: muscle paralysis, loss of reflexes, loss of vital functions, circulatory and respiratory failure, death

  13. Clinical Presentation • CV - chest pain, palpitations, arrhythmias, severe hypertension, coronary and peripheral vasoconstriction, myocardial infarction, cardiomyopathy • Neuro - AMS, seizures, status epilepticus, HA, syncope, ischemic stroke • Metabolic - hyperthermia, rhabdomyolysis, renal failure, hepatotoxicity, DIC

  14. Clinical Presentation • Chronic Intoxication • persistent rhinorrhea, epistaxis, septum perforation, paranoid psychosis, severe anxiety and panic states, depression, perceptual changes, extreme itching, hallucinations

  15. Clinical Presentation • Body Packers - swallowing containers, condoms, balloons or other packages to smuggle cocaine • Body Stuffers - street entrepreneurs who ingest cocaine to avoid arrest

  16. Treatment • Stabilization (ABCs, IV line, cardiac monitor, EKG) • GI decontamination • activated charcoal • whole bowel irrigation (packers, stuffers) • 500 cc/hr, inc. by 500cc/hr to 2L/hr • endpoint - clear rectal effluent

  17. Treatment • CNS - benzodiazepines • Seizures - benzodiazepines • refractory: barbiturates, no role for phenytoin • Tachyarrhythmias and Hypertension - benzodiazepines • refractory: combination nitroprusside and esmolol • Dysrhythmias - lidocaine, magnesium • Hypotension - fluids, norepinephine or dopamine

  18. ECSTASY • MDMA-methylenedioxymethamphetamine • Ecstasy, XTC, Adam, E • MDEA-methylenedioxyethamphetamine • Eve • MDA-methylenedioxyamphetamine • Eve

  19. ECSTASY • 1914 - Originally patented as an appetite suppressant, but never actually marketed • 1970s - adjunct psychotherapy • 1972 - recreational use first reported • 1980s - gained popularity and increased use • 1985 - Schedule I substance • 1986 - Controlled Substances Analogue Enforcement Act

  20. Epidemiology • Stanford University • 1987: 149/369 (39%) used MDMA at least once • mean usage 5.4 times/person • Tulane University • 1990: 307/1264 (24%) used MDMA at least once • up from 15.5% in 1986 • more likely than any other drug to have been used first during college

  21. Pharmacology o NH o CH3 CH3 MDMA

  22. Pharmacology • Chemically related to both hallucinogens and stimulants • Entactogens - don’t cause classic hallucinogens, but reduce negative feelings, breakdown communication barriers, allow psychotherapeutic breakthroughs • Available forms: white powder, capsules, tablets, Red Bull

  23. Pharmacokinetics • Readily absorbed across most biologic membranes, highly lipid solubility • Onset of action: ~ 30 min • Duration of effect: 4 - 6 hours • Elimination: demethylation to MDA, 65% unchanged urine Dosing: 50-150mg hallucinogenic effect

  24. Mechanism of Toxicity • Sympathetic receptor stimulation (peripheral and central nervous system) • Indirect receptor stimulation causing NT release (primarily serotonin) • Inhibition of monoamine oxidase • Inhibition of catecholamine reuptake • Biotransformation of agents to indolamines related to serotonin

  25. Common effects tachycardia tremor tight jaw muscles bruxism nausea headache Less common effects numbness tingling of extremities hallucinations ataxia blurry vision nystagmus mydriasis hyperreflexia Clinical Presentation Acute reactions at therapeutic doses

  26. Clinical Presentation • Overdose reactions • tachycardia/dysrhythmias • hypertension or hypotension • hyperthermia • muscular rigidity • seizures • ARDS • disseminated intravascular coagulation • rhabdomyolysis • renal failure

  27. Clinical Presentation • Mild residual reactions ( 2 hrs - 2 wks) • exhaustion • fatigue • depression • nausea • numbness • flashbacks • anxiety attacks • Long term - 5HT neuron damage

  28. Treatment • ABCs • GI decontamination - activated charcoal • Symptomatic/supportive • agitation - benzos, butyrophenones • hyperthermia - benzos, cooling with mist and fans, dantrolene • seizures - benzos, barbs • sinus tach/HTN - nitroprusside and esmolol

  29. LSD • Ingestion results hallucinations, paranoia, fluctuations in mood • Can be in the form of powder, tablet, capsule, sugar cube, drop on blotting paper, in gelatin

  30. LSD

  31. LSD • Other names: blotter, blue caps, brain buster, CA sunshine, cubes, face melter, ghost, heavenly blue, hawk, microdot, pearly gates, royal blue, wedding bells, white lightning, window pane

  32. LSD • Mechanism of action • agonist at presynaptic receptors for 5-HT in the midbrain • etiology of flashbacks is unknown • tolerance develops after 3-4 daily doses

  33. PCP • Dissociative anesthetic with sympathomimetic and hallucinogenic properties • Thought to stimulate alpha-adrenergic receptors (potentiating NE, Epi, 5-HT) • Closely related to ketamine

  34. PCP • S/Sx: • common: nystagmus, htn (57%), violent/agitated behaviour, tachy (30%), delusions/hallucinations • uncommon: coma, lethargy, hyperthermia, mydriasis, seizures, miosis

  35. Gamma Hydroxybutyrate

  36. GHB • “Grievous Bodily Harm”, “Georgia Home Boy”, “Liquid Ecstasy”, “Liquid X”, “Soap”, “Easy Lay”, “Scoop”, “Salty Water”, “Organic Quaalude”, “Somatomax”, “G-riffick” • “Max”: GHB + ETOH + amphetamine • Falsely promoted for strength training, muscle building, weight loss and insomnia • Primarily used by party and nightclub attendees and bodybuilders • It is also sold and used as a hallucinogen and a “date rape” drug

  37. GHB • FDA banned its use in 1991 after reports of seizures and coma in individuals using nutritional and weight loss supplements • Illegal to possess in California, Massachusetts, Hawaii, and Florida • Schedule I drug in Georgia, Rhode Island, Michigan, Illinois, Texas, Nevada and Hawaii

  38. Pharmacology • Four-carbon molecule found naturally in the central nervous system (CNS) with higher concentrations in the peripheral tissues • GABA metabolite with possible role as a central neurotransmitter • inhibition of dopamine at low doses • promotes dopamine release at high doses • Inhibits release of norepinephrine in the hypothalamus

  39. Pharmacology • CNS depressant that facilitates slow-wave sleep • In animals, produces abnormal EEG activity similar to absence seizures • Can be synthesized from G-butyrolactone and sodium hydroxide

  40. Pharmacokinetics • Readily crosses the BBB • Rapidly absorbed after ingestion • Elimination t1/2 is 27 minutes • Primary route of elimination is expired breath as carbon dioxide

  41. Clinical Use • First use was as a general anesthetic (50 mg/kg), but no longer used • Only FDA approved for investigational uses • narcolepsy • Outside US • opiate and alcohol addiction tx • shock

  42. Clinical Presentation • 10 mg/kg • amnesia, hypotonia • 20-30 mg/kg • euphoria, somnolence, drowsiness, dizziness • 50-70 mg/kg • coma, hypotonia, bradycardia, hypotension, bradypnea, N/V • Hallucinations, delirium, diaphoresis, hypothermia, seizures

  43. Clinical Presentation • Abrupt LOC leading to coma, a strong persistent gag reflex, and rapid awakening without apparent adverse aftereffects • Effects potentiated by alcohol and benzos • Chronic withdrawal symptoms - insomnia, anxiety, tremor, paranoia, agitation, confusion, delirium, irritability- resolves in 3-12 days without long-term effects

  44. Clinical Presentation • Onset • IV: 2-15 min • PO: 15-30 min • Duration • coma typically lasts 1-2 hours, with full recovery by 8 hours • dizziness may linger for up to 2 weeks

  45. Treatment • Supportive • Stabilization and Observation • cardiac monitoring, pulse oximetry, airway maintenance and ventilatory support if needed • temperature regulation if hypothermia present • Standard treatment for polysubstance OD • GI decontamination • (activated charcoal) • naloxone can be considered

  46. Treatment • No clinically effective GHB antagonists have been identified in the literature • Undetectable by routine drug screens and doesn’t appear to alter lab studies • Because of the lack of distinctive diagnostic markers, R/O all other causes of acute unresponsiveness even if h/o GHB ingestion is known

  47. Labs • MedTox Laboratories • 402 W. County Rd. D, St. Paul, Minn, 55112 • (612) 636-7466 • Urine GHB ($97), flunitrazepam ($74) • National Medical Services • 3701 Welsh Rd, Willow Grove, Penn, 19090 • (215) 657-4900 • Urine GHB ($111), flunitrazepam ($169), chain of custody ($29)

  48. Similar Agents • Gammabutyrolactone • RenewTrient, Blue Nitro, Revivarant, Gamm-G, Pro-G, FireWater, Remforce, GH Revitalizer, Rest Eze • 4-butyrolactone, dihydro-2(3H) furanone, 4-butanolide, Borametz, False Borametz • 1, 4-butanediol, 1, 4-butylene glycol, tetramethylene glycol, tetrahydrofuran • GHRE, OrangeFX Rush, Lemon FX Drop, Pine Needle Extract, Promusol, BVM, Cherry FX Bomb, Enliven, Serenity

  49. Similar Agents • On January 21, 1999 the FDA asked manufacturers to recall their GBL containing products • Issued an alert to consumers not to purchase or consume products containing GBL • Considering all potential regulatory actions at its disposal if products are not recalled

  50. GBL • Used as an industrial solvent and dietary supplement • Better absorption and bioavailability than GHB • Seizures more common than GHB • Metabolized to GHB endogenously, converts exogenously in alkaline environment

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