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DR. Jekyll & Mr. Hyde

DR. Jekyll & Mr. Hyde. Rami Khouzam, MD. Which one of the following tests would be POSITIVE:. a- BNP b- Troponin I c- Urine Na+ d- UDS e- Urine Ca++ and Mg++. ?. INDEX CASE 1. 50 yo AA gentleman presents with: One month hx of  LEs edema 3 days hx of SOB &  DOE

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DR. Jekyll & Mr. Hyde

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  1. DR. Jekyll & Mr. Hyde Rami Khouzam, MD

  2. Which one of the following tests would be POSITIVE: • a- BNP • b- Troponin I • c- Urine Na+ • d- UDS • e- Urine Ca++ and Mg++ ?

  3. INDEX CASE 1 • 50 yo AA gentleman presents with: • One month hx of  LEs edema • 3 days hx of SOB &  DOE • Non-compliance with meds. (lately) • PMHx: • CHF • HTN

  4. Meds: • Aldactone • Lasix • Diltiazem • PE: • Remarkable for: RR; 28, P:101, BP: 196/110, O2 Sat: 93% on 4L • S1 S2 S4. PMI @ ant. axillary line • Bilat. diffuse lung crackles & wheezes • 2+ edema bilat. in LEs.

  5. CXR: •  Interstitial markings consistent with pulmonary edema • Cardiomegaly

  6. INDEX CASE 2 • 54 yo AA gentleman with 3-4 hrs. hx. of CP, SOB, diaphoresis & palpitations • Admits to not taking his meds x 3 days because he was more busy drinking whisky and smoking cocaine & marijuana • PHMX: • CHF • HTN • Gout

  7. Meds: • Lasix • KCl • Aldactone • PE: • Remarkable for P: 220, RR: 32, BP: 113/60, S1 S2. PMI laterally displaced

  8. Adenosine 6mg, 12mg, 12mg •  • HR: 160 then 220 SVT (called @ 2:00 AM from Med. ER) •  • Vagal maneuvers •  • Amiodarone 150mg IV over 10 minutes

  9. Cardizem 10mg IV

  10. HR: 105

  11. Hospital day # 4: • Left hospital AMA • Called @ 3:00 AM from VA • Patient found by EMT • HR: 180

  12. INDEX CASE 3 • 45 Yo AA lady presented with CP, substernal, 8/10, pressure-like, radiating to left arm, accompanied with SOB, nausea & diaphoresis • PMHx: • CAD.. MI x 2 in the past • Meds: • - ASA • - Metoprolol • - Zocor

  13. PE: • Remarkable for: • S1 S2, RR @ 110 • EKG: • Sinus tachycardia • ST in I, aVL, V5, V6 • Labs: • Trop: 1.8  2,4  8.0 • Cath. Lab: • Lt. Cx: 80% Stenosis  Stent

  14. Which one of the following tests was POSITIVE:(in the previous 3 cases) • a- BNP • b- Troponin I • c- Urine Na+ • d- UDS • e- Urine Ca++ and Mg++ ?

  15. Index case 1: Hypertensive emergency • Index case 2: Life-threatening dysrhythmia • Index case 3: NSTEMI • Correct answer: d • UDS + for COCAINE

  16. HISTORY OF COCAINE • In pre-Columbian times, the coca leaf was officially reserved for Inca royalty. The natives used coca for mystical, religious, social, nutritional and medicinal purposes • Coca was initially banned by the Spanish • 1551: the Bishop of Cuzco outlawed coca use on pain of death because it was "an evil agent of the Devil"

  17. The invaders discovered that without the Incan "gift of the gods", the natives could barely work the fields - or mine gold • So it came to be cultivated even by the Catholic Church • Coca leaves were distributed three or four times a day to the workers during brief rest breaks • Returning Spanish conquistadores introduced coca to Europe • It is told that even Shakespeare may have smoked it

  18. 1814: an editorial in Gentleman's Magazine urged researchers to begin experimentation so that coca could be used as "a substitute for food so that people could live a month, now and then, without eating..." • Around 1860: the active ingredient of the coca plant was first isolated in the West by Albert Niemann • To Sherlock Holmes, cocaine was "so transcendentally stimulating and clarifying to the mind that its secondary action is a matter of small moment” • Robert Louis Stephenson wrote The Strange Case of Dr Jekyll and Mr Hyde during a six-day cocaine-binge

  19. Cocaine was soon sold over-the-counter. Until 1916, one could buy it at Harrods • Cocaine was widely used in tonics, toothache cure and patent medicines; in coca cigarettes "guaranteed to lift depression”; and in chocolate cocaine tablets • When combined with alcohol, the cocaine alkaloid yields a further potently reinforcing compound, now known to be cocaethylene

  20. Cocaine was a popular ingredient in wines, notably Vin Mariani • Coca wine received endorsement from prime-ministers, royalty and even the Pope • Architect Frédérick-Auguste Bartholdi remarked that if only he had used Vin Mariani earlier in his life, then he would have engineered the Statue of Liberty a few hundred meters higher

  21. Cocaine & The Heart • 1911: the earliest report of cocaine damaging the heart • Price & Leaky reported that cocaine use for local dental anesthesia could induce severe myocardial damage leading to death • (Braunwald)

  22. Cocaine Pharmacology by Route of Administration (Braunwald)

  23. Exploited by humans for at least 5000 years • Except for medicinal purposes, the drug is illegal in North America

  24. Cocaine • 2nd. most commonly used illicit drug in the US (after Marijuana) • ~ 30 million (~ 11%) persons in the US have used cocaine at some time • 5-6 million on regular basis

  25. Adulterants • Sugars • Stimulants (ephedrine, caffeine, amphetamines) • Quinine, strychnine • Local anesthetics

  26. Review of Simple Physiology • Caliber of the coronary arteries is controlled by a complex interplay between: • Local metabolic factors AND • Neural input • Oxygen delivery to the myocardium is achieved through changes in coronary artery caliber

  27. A) Sympathetic • Norepinephrine from presynaptic vesicles onto alpha-and B2- receptors •  coronary v.c. • 2  coronary v.d. (mild) • B) Parasympathetic: • Acetylcholine on M3 Cholinergic receptors  v.d. • (Gutterman DG. The heart and cardiovascular system. 2nd ed. 1991)

  28. Cocaine, more than just an illicit drug • Pharmacological effects: • Blocking reuptake of cathecholamines in the presynaptic neurons:  Norepinephrine •  Dopamine and Serotonin • Cholinergic stimulation • Blocking sodium channels : • Local anesthetic • Class I antiarrhythmic

  29. Effects of cocaine on Hemodynamics •  HR, •  BP •  myocardial contractility  cardiac output •  Cardiac function (Direct myocardial toxicity)

  30. CVS toxicity: • Hypertensive emergency/ Pulmonary edema • Arrhythmias • Myocardial ischemia and infarction • Acute aortic dissection or rupture to stroke • Sudden death • Acute reversible myocarditis • Dilated cardiomyopathy • (Pasternack, PF Am J Cardiol 1985)

  31. Hypertensive Emergencies • Phentolamine or direct -adrenergic antagonist: the antihypertensive of choice • Should -B be avoided with cocaine because of paradoxical hypertension ? • (class IIa for SBP > 150 or HR > 100) • IV NTG or nitroprusside can be used • (Braunwald)

  32. Dysrhythmias • Atrial or ventricular • Sinus tachycardia: most common • A. fib, SVT (sympathetic stimulation) • Respond to sedation with benzodiadepines • Other standard therapies to slow rate

  33. Cardiac Dysrhythmia Cocaine (lidocaine-like effect) Rhabdomyolysis & ischemia   Blockade of fast Na+ channels Hyperkalemia  slowing depolarization Wide complex tachycardia (Braunwald)

  34. Wide complex tachycardia from cocaine of unknown etiology  iv bolus of sodium bicarbonate, 1-2 mEq/kg will empirically treat sodium channel blockade as well as cardiotoxicity from hyperkalemia • (Braunwald)

  35. Mechanism of Myocarditis 1) Direct effect on lymphocyte activity 2)  natural killer cell activity in blood  cytotoxic to myocardial cells 3) Cocaine-related eosinophilic infiltrate  hypersensitivity reaction 4) Focal myocarditis also direct, negative inotropic effect on cardiac muscle

  36. Cathecolamine excess  Contraction band necrosis  anatomic substrate for ventricular dysrhythmias • Autopsy support scattered foci of necrosis, myocarditis independent of CAD • (Braunwald)

  37. THE ORIGIN OF COCAINE • Erythroxylon coca is a densely-leafed plant native to the eastern slopes of the Andes • Coca is widely cultivated in Bolivia, Peru and Ecuador, but the lead producer is Colombia, currently the source of 80% of the world's cocaine • There are around 250 species of erythroxylon plants. At least 20 produce cocaine. Only 2 of them typically yield enough cocaine to justify commercial cultivation

  38. Typically, coca thrives in warm, moist, frost-free valleys between 1500 and 6000 metres above sea level • The plant grows to a height of up to 8 feet and can be harvested 4 times a year • The leaves are rich in vitamins, protein, calcium, iron and fiber • The cocaine content of the leaves ranges from O.1% to 0.9%

  39. CRACK-COCAINE • To obtain crack-cocaine, ordinary cocaine hydrochloride is concentrated by heating the drug in a solution of baking soda until the water evaporates. • This type of base-cocaine makes a cracking sound when heated; hence the name “Crack” • Base-cocaine vaporizes at a low temperature, so it can be easily inhaled via a heated pipe

  40. CHEMISTRY OF COCAINE • C17H21NO4 • Cocaine can be manufactured by converting tropinone into 2-carbomethoxytropinone, reducing this to ecgonine,and then converting the ecgonine to cocaine • This isn't as easy as it sounds

  41. Cocaine Body Packers • Cocaine is smuggled by a variety of techniques • Body packers ingest cocaine wrapped tightly into condoms or other latex products before crossing international borders • Each packet can contain up to 10g of cocaine and packers may swallow as many as 150 packets

  42. On arrival at their destination: cathartic • Unfortunately rupture of cocaine packet can result in death, as each packet contains close to 10 times the lethal dose • (Braunwald)

  43. Mechanisms of AMI 1)  HR +  BP   myocardial oxygen demand 2)  coronary artery flow, coronary vasospasm or thrombosis 3) Active myocarditis (hypersensitivity or toxicity)

  44. A recreational dose of cocaine: • HR ~ 30 beats/min. • Also BP by 20/10 mm Hg.(equivalent to mild exercise) • Not sufficient to result in myocardial ischemia

  45. [I] VASOCONSTRICTIONA- Animal Studies • Hale et al: anesthetized dogs: IV bolus cocaine 10 mg/kg  15%  in circumflex artery diameter • (This dose ~ 5 times the dose used recreationally by humans) • (Hale SL, Am Heart J 1989)

  46. Kuhn et al: cocaine 2mg/kg in a dog model  LAD diameter by 19% &  coronary blood flow of 55% • Attenuation of the effects of cocaine: pretreating with phentolamine:  VC • Potentiation of the effects of cocaine: • pretreating with propanolol:  VC • (Kuhn FE, J Am Coll Cardiol 1990)

  47. Egashira et al: a swine model • Significant  in v.c. associated with denuded coronaries compared with native ones (59% cross-sectional area reduction vs 48%) • Vasoreactivity to cocaine may be greater in diseased coronaries • Egashira K, J Clin Invest 1991

  48. B- Human Studies • Human coronary arteries differ from animal arteries in a number of ways • Difference in the density and distribution of alpha-and beta-receptors • Most human studies have documented a  in coronary artery diameter ranging from 4% to 29% associated with cocaine use

  49. Lange et al: phentolamine  abolishment of cocaine-induced V.C. • Flores et al: 13% reduction in coronary caliber was observed in disease-free coronary arteries, a 29% reduction in caliber in coronary arteries with significant stenoses (>50%)

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