Uppers, Downers and Legal Highs STREET DRUGS. Ball

Transcription

1 Uppers, Downers and Legal Highs STREET DRUGS

2 Objectives Understand the pathophysiology of cocaine intoxication Appreciate differences between cocaine toxicity and MDMA, bath salts, and other synthetic stimulants Be aware of new contaminants of concern Develop a familiarity with new synthetic opioids

3 Cocaine Pharmacokinetics Rapidly absorbed in all routes of exposure 90% plasma protein bound V d 2.7L/kg t ½ of 1 hour Crack is lipid soluble

4 Mechanism of Toxicity Increases circulating biogenic amines, i.e.: Serotonin Epinephrine Norepinephrine Dopamine Also blocks sodium channels

5 Cocaine Metabolism

6 Toxidrome CNS excitation, mydriasis, lucidity maintained Hypertension, tachycardia, inotropy, spasm, Na / K channel blockade, hyperthermia Platelet activation, vasospasm, TPA inhibition Diaphoresis

7 What is the most important pharmacologic management of the sympathomimetic toxidrome? 1. Intravenous beta blockade 2. Oral beta blockade 3. Intravenous phenytoin 4. Intravenous midazolam

8 Management (sedation) Industrial doses of benzodiazepines Midazolam mg/kg boluses Q5-10 minutes Propofol for intubation +/- sedation Caution with succinylcholine (hyperkalemia)

9 Levamisole contamination Antihelminthic and immunomodulator Withdrawn from Canadian market in 2003 AGRANULOCYTOSIS!!! 69% of cocaine samples tested in 2009

10 Cocaine Management Avoid Dilantin Treat ACS (beware ICH, CVA) Dysrhythmia treatment Do not use β-blockers (beware amiodarone, labetolol) Body packers / stuffers

11 Bath Salts

12 Bath Salts / Synthetic Cathinones New group of psychoactive designer drugs Combination synthetic compound + vegetable matter Phenyalkylamine alkaloid present in the vegetable khat

13 What is Khat? Chata edulis Shrub native to Ethiopia Cultivated in East Africa / South West Arabian Peninsula / now Europe too 1 Leaves, stems and flower buds are used as stimulants Cathine and cathinone have amphetamine effects Kalix, P., The releasing effect of the alkaloid cathinone at centre and peripheral catecholamine storage sites. Neuropharmacology 25, Nencini, P., Amiconi, G., Befani, O., Abdullahi, M.A., Anania, M.C., Possible involvement of amine oxidase inhibition in the sympathetic activation by khat (Catha edulis) chewing in humans. J. Ethnopharmacol. 11, 78 86

14 Mechanism Increased norepinephrine, dopamine release from presynaptic storage sites AND monoamine oxidase inhibition Same effect on Serotonin Cozzi, N.V., Sievert, M.K., Shulgin, A.T., Jacob III, P., Ruoho, A.E., Inhibition plasma membrane monoamine transporters by beta-ketoamphetamines. Eur.J. Pharmacol. 381, Kalix, P., The releasing effect of the alkaloid cathinone at centre and peripheral catecholamine storage sites. Neuropharmacology 25,

15 Similar Clinical Presentation As: Cocaine Speed MDMA (Ecstasy) Less lipophilic and less able to cross the blood brain barrier Dargan, P.I., Sedefov, R., Gallegos, A., Wood, D.M., The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone). Drug Test. Anal. 3,

16 Epidemiology On recreational drug market since mid 2000s 2010 first Poison Centre calls received in US Many associated deaths since 2010 Widely available online as bath salt or fertilizer Very popular in teens Not detectable by routine drug screen James, D., Adams, R.D., Spears, R., Cooper, G., Lupton, D.J., Thompson, J.P., et al., Clinical characteristics of mephedrone toxicity reported to theuknational Poison Information Service. Emerg. Med. J. 28, Wood, D.M., Davies, S., Greene, S.L., Button, J., Holt, D.W., Ramsey, J., et al., Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin. Toxicol. 48,

17 Route Snorted, ingested, smoked, IM, per rectum Water solubility allows dilution for injection

18 Recreational Dose 3-5 mg for effects Average dose 5-20 mg Packages may contain as much as 500 mg Rapid absorption, but peak effect 1.5 hours Effects last 3-4 hours Total cost: approximately $30 HUGE POTENTIAL FOR OVERDOSE / TOXICITY

19 Which of the following is indicated in cases of suspected bath salt intoxication? 1. Urine drug screen 2. quantitative serum bath salt level 3. early electrocardiogram 4. Prophylaxis with 18 mg/kg phenytoin

20 Management Industrial doses of benzodiazepines Consider ICH, CVA Treat ACS (with notable exceptions) Dysrhythmia treatment Do not use β-blockers

21 MDMA (Ecstasy) Pill form Common in younger ages, students, club scene Similar sympathomimetic toxidrome Entactogen SIADH, hyponatremia from sweat loss No sodium channel blockade

22 Desomorphine Krokodil Reports from Russia in 2003 Easily synthesized from over-the-counter Codeine Large crackdown on Heroin Rapid onset Short duration (1.5 hrs)

23 Krokodil Red phosphorus from match tips Gasoline, other adulterants flesh eating narcotic

24 Treatment Pearls Industrial strength benzodiazepines Beware unopposed alpha / beta blockade Treat hyperthermia aggressively Beware end organ ischemia / thrombosis / ACS Manage sodium channel blockade Avoid phenytoin in cocaine, all toxicologic seizures Packers / stuffers

25 Questions?