Cocaine and the Heart

1. Cocaine and the Heart John L. Tan, MD, PhD Presbyterian Hospital of Dallas

2. Clinical Case • IB is a 44 y/o painter who recently presented with a prolonged episode of chest discomfort • His history was pertinent for smoking cocaine within the past 72 hours • Physical examination was unremarkable

3. Clinical Case • ECG revealed only non-specific ST/T- wave abnormalities • Initial cardiac enzymes were within normal limits

4. Epidemiology of Cocaine Use • ~25 million Americans admit to using cocaine at least once (1999) • ~1.5 million are active users 1999 National Household Survey on Drug Abuse

5. Epidemiology of Cocaine Use • Cocaine is the most commonly used illicit drug among patients seen in the ER and drug-treatment centers • Cocaine is the most frequent cause of drug-related deaths 1999 National Household Survey on Drug Abuse

6. Erythoxylon coca • Native to eastern slopes of Andes • Cocaine alkaloid serves as natural pesticide • Leaves contain 0.1-0.9% cocaine www.cocaine.org

7. Cocaine Inc. www.cocaine.org

8. Cocaine Inc. www.cocaine.org

9. Cocaine Hydrochloride www.cocaine.org

10. Free-base cocaine: Crack www.cocaine.org

11. Pharmacokinetics of Cocaine NEJM, 345:351, 2001

12. Metabolism of Cocaine • Serum half life of 45-90 minutes • Only 1% of the drug is recovered in urine after ingestion • Cocaine can be detected in blood or urine only for several hours after its use

13. Metabolism of Cocaine • Cocaine metabolites are detectable for 2-5 days • Hair analysis provides a very sensitive marker for cocaine use within the preceding weeks to months

14. Cocaine: A Short History • In pre-Columbian times, the coca leaf was officially reserved for Inca royalty • Later used by natives but initially banned by the Spanish • Labeled “an evil agent of the Devil”

15. Cocaine: A Short History • Without it, natives could barely work the fields or gold mines, . . .So, Distributed to workers 3-4 times a day Cultivated even by the Catholic Church

16. Cocaine: A Short History • Active ingredient isolated by Albert Niemann in 1860 • Widely used recreationally and medicinally in late 1800’s • The first cocaine cartel, the Cocaine Manufacturers’ Syndicate, founded in 1910

17. The First Cocaine Cartel www.cocaine.org Merck, along with Sandoz, and Hoffman-LaRoche

18. A Panacea for Your Ills www.cocaine.org

19. A Panacea for Your Ills www.cocaine.org

20. A Panacea for Your Ills “ sustains and refreshes both the body and brain. . .It may be taken at any time with perfect safety. . . It has been effectually proven that in the same space of time more than double the amount of work could be undergone when Peruvian Wine of Coca was used, and positively no fatigue experienced. . .” Sears, Roebuck and Co. Consumers’ Guide (1900)

21. Anatole France Henrik Ibsen Jules Verne Alexander Dumas Robert L. Stephenson Sir Arthur C. Doyle Massenet Gounod Faure Queen Victoria King George I (Greece) King Alphonse XIII Shah of Persia William McKinley Grand Rabbi of France Pope Pius X Pope Leo XIII A Panacea for Your Ills: Coca Wine Lovers

22. The Pope on Coke www.cocaine.org

23. American Ingenuity • John Pemberton (1832-1888) Pemberton’s French wine coca “an intellectual beverage” “a most wonderful invigorator of the sexual organs”

24. American Ingenuity • Introduction of Prohibition in 1886 Pemberton’s French wine coca Coca-Cola The temperance drink

25. American Ingenuity • Coca-Cola • “Offering the virtues of coca without the vices of alcohol” • “a valuable brain-tonic and cure for all nervous afflictions” • TheReal Thing: 60 mg cocaine per serving (until 1903)

26. Mechanism of Action Cocaine blocks the presynaptic reuptake of NE and dopamine, producing an excess of these neurotransmitters at the postsynaptic receptor site, thereby acting as a powerful sympathomimetic agent NEJM, 345:351, 2001

27. Cocaine-induced Baroreflex Activation Circulation 105:1054, 2002

28. Myocardial ischemia/infarction Hypertensive Crisis Aortic Dissection Cardiac arrhythmias (VT/VF) Myocarditis Dilated cardiomyopathies Stroke Limb Ischemia Endocarditis Acceleration of atherosclerosis Cardiovascular Consequences of Cocaine Use

29. Mechanisms of Cocaine-related Ischemia NEJM, 345:351, 2001

30. Medical Epidemiology of Cocaine • Estimated 175,000 cocaine-related ER visits annually • Approximately 40% (>70,000) are due to chest pain • Of these, ~57% are admitted to the hospital, at an annual cost of $ 83 million in hospitalization expenses alone

31. Risk of Myocardial Ischemia and Infarction in Cocaine Users • Cocaine use increases risk of acute MI by 24-fold during the first hour after its use • Cocaine users have a 7-fold increase in their lifetime risk of MI than non-users

32. Risk of Myocardial Ischemia and Infarction in Cocaine Users • Cocaine use accounts for up to 25% of AMI in patients 18-45 years of age • The risk of MI is unrelated to amount of drug used, route of administration, or the frequency of use

33. Possibly a Once in a Life-time Experience www.cocaine.org

34. Challenges in Diagnosing Cocaine-related Acute MI • ECGs are abnormal in 56-84% of cocaine users with chest pain • Up to 43% of cocaine users with chest pain, but no MI, may present with >0.1mV ST-segment elevation

35. Challenges in Diagnosing Cocaine-related Acute MI • Serum CK enzymes are elevated in 50% of cocaine users who do not have MI, presumably from rhabdomyolysis • Serum troponins may be more specific in diagnosing MI in this population • About half the patients with cocaine- related MI’s have normal coronary arteries on cardiac cath

36. Complications of Cocaine-related Acute MI • Most complications occur within 12 hours after presentation to the ER • Incidence of arrhythmias and heart failure is relatively low, compared to general pool of patients with MIs

37. Observational Unit Care for Cocaine-induced Chest Pain NEJM 348:510, 2003

38. Clinical Recommendations NEJM, 345:351, 2001