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Drugs of Abuse Part I

Drugs of Abuse Part I. Rebecca Burton-MacLeod R4, Emerg Med Preceptor: Dr. S. McPherson Core Rounds Mar 1 st , 2007. Drugs of abuse. Hallucinogens: LSD, mescaline, marijuana, mushrooms, PCP Stimulants: Amphetamines, caffeine, cocaine Depressants: Alcohol, benzos, opioids Inhalants:

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Drugs of Abuse Part I

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  1. Drugs of AbusePart I Rebecca Burton-MacLeod R4, Emerg Med Preceptor: Dr. S. McPherson Core Rounds Mar 1st, 2007

  2. Drugs of abuse • Hallucinogens: • LSD, mescaline, marijuana, mushrooms, PCP • Stimulants: • Amphetamines, caffeine, cocaine • Depressants: • Alcohol, benzos, opioids • Inhalants: • Volatile solvents, propellants, nitrites, nitrous oxide • OTC preparations: • Phenylpropanolamine, ephedrine, pseudoephedrine

  3. Almost any drug can be abused…!

  4. Case • 42F brought to ED after being found confused by roomate. C/o cough and chills x1wk. Last night out “partying” with friends, and this a.m. difficult to awaken. • O/e: 38.5 HR 124 BP 98/72 sats 91%r/a • Investigations? • Thoughts? • Immediate mgmt?

  5. Take-home • Always go through your differential…

  6. Cocaine

  7. Quiz • Which artist sings a song entitled “Cocaine cowgirl”…hint, they played at Mac Hall in mid-January 2007? • A) the Tragically Hip • B) Shania Twain • C) Matt Mays • D) Garth Brooks

  8. Cocaine • Natural alkaloid found in leaves of Erythroxylon coca • Grows abundantly in Mexico, South America, West Indies, Indonesia • Long hx of use…in 6th century Peruvians chewed leaves for social/religious reasons • First used as local anaesthetic in 1884

  9. Cocaine • In early 20th century, used briefly as ingredient in Coca-cola!!!

  10. Medical uses • Used as topical anesthetic for medical procedures (scopes, etc) • Max safe total dose is 1-3ml/kg body weight (4-10% soln) • Avoid if pt is: febrile, hepatic disease, known plasma cholinesterase defic, drugs that alter neurotransmitter metabolism (MAOI’s)

  11. Metabolism Cocaine N-demethylation Nonenzymatic hydrolysis Plasma cholinesterase Norocaine Benzoylecgonine Ecgonine methyl ester Minor metabolite About 40% Major metabolite: 30-50% Detected in urine tox screens as longest half-life (usually up to 48-72hrs)

  12. Modes of abuse • Intranasal • Smoked • IV • Ingested

  13. Pharmacokinetics

  14. Mechanisms of action • Blockade of fast Na channels • Local anesthetic effect • Type 1A and 1C antidysrhythmic properties • Interferes with re-uptake of neurotransmitters by nerve terminals • Vasoconstriction • Systemic effects due to alpha/beta adrenergic, DA, SE stimulation

  15. Na channel blockade

  16. Effects of Na channel blockade • Impaired conduction • Increased inotropy • Seen early before catecholamine response • Widened QRS • Terminal avR 40msec rightward axis deviation

  17. Clinical manifestations • Hyperthermia • Vasoconstriction dec heat dissipation, inc psychomotor activity, direct stimulatory effect on thermoregulatory centers, stimulates livers calorigenic activity • Neuro effects • Anxiety, agitation, seizures • Cerebrovascular events such as SAH, ICH, CVA, TIA, cerebral vasculitis, migraine-HA type s/o • Cardiac effects • Dysrhythmias, MI, cardiomyopathy, endocarditis, aortic dissection • Pulmonary/upper airway effects • Asthma exacerbations, pneumothorax, pneumomediastinum, acute lung injury, diffuse alveolar hemorrhage, pneumonia, BOOP, talc lung, upper airway burn and abscesses

  18. Cont’d • Skeletal muscle effects • rhabdo • Ophthalmic effects • Corneal abrasions/ulcerations, CRAO, bilateral blindness from diffuse vasospasm • Uteroplacental/perinatal effects • IUGR, inc SA, abruptio placentae, fetal prematurity, neonatal withdrawal symptoms • GI effects • Hepatotoxic, mesenteric ischemia • Psych effects • Tolerance, addiction, tactile hallucinations common (Magnan’s sign), withdrawal

  19. Cocaine

  20. Hyperthermia

  21. Cardiac effects • How does cocaine contribute to MI? • Vasospasm • Inc platelet aggregation • Inc atherosclerosis • Tachycardia/hypertension • Inc myocardial oxygen demand • Thrombus formation **risk of MI is increased 24x in first hour following use**

  22. Cocaine and MI’s • First case of cocaine related MI in 1982 Coleman DL. West J Med. 1982. 136:444. • 91 MI’s reviewed from previous reports: • 81 males, avg age 32.8yrs • Time to onset: mean 30min, max 24hrs • Tobacco used in 87%, other risk factors rare • Atherosclerotic HD in 31%, thrombosis without atherosclerotic HD in 24% Hollander and Hoffman. J Emerg Med. 1992; 10:169.

  23. Cocaine and MI • Unrelated to dose or route administered or frequency of use • Reported in 200-2000mg • Found after taking by any route • Occurs in habitual or first-time users • All CP pts should be asked about cocaine use…found in urine tox screen of 14-25% of urban ED non-traumatic CP pts Hollander JE et al. Ann Emerg Med. 1995. 26:671.

  24. Cocaine and MI

  25. Increased oxygen demand • Increased catecholamines with cocaine: • Norepi 345-622mg/L (normal 0-90mg/L) • Epi 135-202mg/L (normal 0.55mg/L) • Resultant hypertension and tachycardia Karch. Ann Emerg Med. 1987; 16:481.

  26. Vasospasm • Human volunteer study of pts given IN cocaine while undergoing cardiac cath • Coronary sinus blood flow decreases • Left coronary art diameter decreases • Coronary vascular resistance increases • Effects reversed by phentolamine • Effects exacerbated by propanolol Lange RA. NEJM. 1989. 321;1557. Lange RA. Ann Intern Med. 1990. 112;897.

  27. Thrombus formation • Cocaine use results in increased tissue plasminogen activator inhibitor activity • Impaired thrombolysis Moliterno DJ. Am J Med. 1994. 96;492.

  28. Increased platelet aggregation • Effects on endothelium: • Loss of NO • Impaired relaxation • Impaired inhibition of platelet aggregation • Effects on platelets: • Inc responsiveness to thromboxane and prostacycline • Increased aggregation Tonga G. Hemostasis. 1985; 15:100.

  29. Increased atherosclerosis • Animal studies: • Rabbits fed high-cholesterol diet did not develop atherosclerotic HD, but rabbits with cocaine added to diet all developed AHD Langner RO. FASEB. 1989. 3;297. • Human studies: • Higher (than expected for age) rate of atherosclerosis on cocaine abusing pts undergoing cath • Up to 77% of pts undergoing cath following MI due to cocaine will have some abnormality of their CA Kontos MC. J Emerg Med. 2003. 24:9.

  30. Investigations • EKG • CXR • TNT • CK • Echo • Must be relied on more heavily as hx is usually not useful!!!

  31. EKG • Abnormalities occur in 90% of pts using cocaine who develop an MI • Up to 43% of cocaine abusers without MI will meet show STE>0.1mV • Sensitivity 36% • Specificity 90% Lange RN et al. NEJM. 2001. 345(5):351.

  32. Cardiac enzymes • CK often unreliable as frequently elevated due to rhabo • TNT more specific for cardiac issues • Study comparing elevation of CK and CK-MB with TNI/T: • N=19 pts with cocaine abuse and CP • Elevated CK in 14pts, but no pts had elevated troponins • No pts diagnosed with MI McLaurin et al. Ann Clin Biochem. 1996. 33;183.

  33. Observation and CP • N=344 pts with cocaine and CP • 12% admitted directly to hospital • Remainder were observed x12h • 30day f/u • None of 302 pts died from CV causes (mortality – 2 died from GSW/heroin OD) • 1.6% had non-fatal MI during this period (all pts continued to use cocaine after d/c) Weber JE et al. NEJM. 2003. 348:510.

  34. Management ?

  35. Management • Oxygen • ASA • Nitro • Benzos • CaCB • Phentolamine • Beta-blockers? • Thrombolytics?

  36. Benzos • N=40 pts with cocaine and CP • NTG-12 • Diazepam-13 • Both-15 • Received q5min until symptoms resolved • CP improved similarly for both agents Bauman BM. Acad Emerg Med. 2000. 7:878.

  37. Benzos

  38. Beta-blockers • Teaching is that AVOID • Unopposed alpha effects may actually worsen outcomes • ++ studies

  39. Beta-blockers • N=30 human volunteers for cardiac cath and randomized IN saline or cocaine • Arterial pressure increased • Coronary sinus blood flow decreased • Coronary vascular resistance increased • Coronary arterial diameters decreased • Intra-coronary propanolol given after initial measurements • No change in arterial pressure • Further decreased coronary sinus blood flow (p<0.05) • Further increased coronary vascular resistance (p<0.05) Lange RA et al. Ann Intern Med. 1990. 112(12):897.

  40. Beta-blockers cont’d • N=15 volunteers • Similar procedure as before, except labetolol vs. N/S given post-cocaine • Labetolol reduced MAP • No significant change in coronary artery area • Labetolol does not alleviate coronary vasoconstriction Boehrer JD et al. Am J Med. 1993. 94(6):608.

  41. Beta-blockers cont’d

  42. Thrombolytics ? • + case reports of catastrophes following lytic administration in cocaine pts • Hypertensive • Inc risk of neuro complications • Lower rate of thrombosis (relative to other MI pts) • Much preferable to undergo angio • Trial NTG, ASA, benzos first and if unable to get to cath lab, may consider lytics • Bottomline: try to avoid!!! Lange RA et al. NEJM. 2001. 345(5):351.

  43. Dysrhythmias

  44. Dysrhythmias • Increases ventricular irritability and lowers threshold for fibrillation • Prolongs QRS/QT as a result of Na-channel blocking properties • Increases intracellular Ca concentrations which causes afterdepolarizations and triggers ventricular arrhythmias • Reduces vagal activity which increases cocaine’s sympathomimetic activities

  45. Mgmt • If wide-complex tachy: • Bicarb • Lidocaine • AVOID class 1a antiarrhythmic drugs (procainamide, quinidine) as may worsen QRS / QT widening and slow metabolism of cocaine • Correct lytes • Overdrive pacing as indicated

  46. Case • 19F from Mexico; arrived in Calgary today. En route, c/o palpitations, diaphoretic, slightly agitated. EMS brought pt from YYC to ED. • Denies any drug use, previously healthy • While in ED, becomes ++hypertensive, tachycardic. Seizes x1. • Any thoughts…mgmt?

  47. Body packers • In 7mo period during ’01-’02, 193 arrests were made at New York Kennedy Int’l airport for body packing • Most commonly cocaine/heroin, but may also swallow packets with amphetamines, ecstasy, marijuana • For clarification…body stuffers are people who ingest small amounts of drug for fear of arrest

  48. Body packers • Carry about 1kg of drug on average • From 50-100 packets each containing up to 10gm of drug • Each packet contains life-threatening dose

  49. Diagnosis • Hx—often unreliable • o/e—worsening symptoms despite treatment • Investigations: • XR • CT • Urine tox screen

  50. XR • Multiple radio-dense FB • “rosette like finding” • “Double-condom” sign • Sensitivity 85-90%

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