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Cocaine and the Heart. Overview Epidemiology Pharmacology Cardiovascular effects of cocaine Treatment Conclusions. Epidemiology. In 1997: - 25 million Americans admitted using cocaine at least once -3.7 million had used it within the previousyear

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Presentation Transcript
slide2
Overview
  • Epidemiology
  • Pharmacology
  • Cardiovascular effects of cocaine
  • Treatment
  • Conclusions
epidemiology
Epidemiology
  • In 1997:

- 25 million Americans admitted using cocaine at least once

-3.7 million had used it within the previousyear

-1.5 million were current users

  • Cocaine was mentioned in 30% of all drug related ER visits the same year
  • Between 1994 and 1998, the number of new users per year increased 82%
pharmacology
Pharmacology
  • Cocaine is an alkaloid extracted from the leaf of Erythroxylon Coca bush
  • Available in the two forms:

-alkaloid dissolved in HCL to make hydrochloride salt:

-PO, IV, intranasal

-not heat stable so cannot be smoked

-“free base”, alkaloid dissolved in ammonia or sodium bicarb (baking soda) to make ‘crack’;

-heat stable so can be smoked

pharmacology5
Pharmacology
  • Cocaine hydrochloride is well absorbed through all mucous membranes
  • As compared to the intravenous route, mucosal administration results in slower onset of action, later peak effect and a longer duration of action
  • Euphoria is almost immediate after crack cocaine is smoked
  • Crack cocaine is considered the most addictive form of the drug
pharmacology7
Pharmacology
  • Principal metabolites (benzoylecgonine and ecgonine methyl ester) are excreted in urine
  • Serum half life of cocaine is 45-90 minutes
  • However, the metabolites are detectable in blood or urine for 24 to 36 hours post use
  • Cocaine acts as a powerful sympathomimetic agent: blocks the presynaptic reuptake of norepinephrine and dopamine; results in an excess of these neurotransmitters at the site of the postsynaptic receptor
slide8

Cocaine blocks the reuptake of norepinephrine by the neuron (red X), resulting in excess amounts of this neurotransmitter at receptor sites on the effector cell.

cv effects of cocaine ischemia
CV effects of cocaine: Ischemia
  • Risk of AMI increases 24 fold during the 60 minutes following cocaine use
  • There is NO dose-response relationship between cocaine use and AMI
  • Six percent of patients with cocaine-related chest pain have cardiac enzyme elevation
  • Most patients with cocaine-related AMI have no risk factors except concomitant use of tobacco
cocaine and atherosclerosis
Cocaine and atherosclerosis

Normal endothelium

Cocaine has been shown to cause disruption in platelet cytoskeleton, as well as structural injury to the endothelium

Cocaine-induced injury

cocaine and atheroclerosis
Cocaine and Atheroclerosis

In vitro studies have shown cocaine can cause damage to endothelial lining that enhances permeability to LDL

Also, promotes leukocyte migration to endothelium which may further accelerate premature atherosclerosis.

cocaine and atherosclerosis13
Cocaine and atherosclerosis

Experimental studies:

-rabbits fed a low-cholesterol diet and injected with cocaine or placebo

-cocaine fed rabbits with aortic atherosclerosis and increased aortic collagen

Langer et al. Fed Proc 1983; 42: 1360

cocaine and atherosclerosis14
Cocaine and atherosclerosis

Kollodgie et al, JACC 1991:

-Review of 5871 autopsies, 495 subjects with evidence of cocaine use

-studied degree of atherosclerosis and mean number of adventitial mast cells per coronary segment

-Results:

-significantly more mast cells in subjects with cocaine-associated thrombosis than in the other age matched groups

-subjects with cocaine-associated thrombosis also had significant coronary atherosclerosis without plaque hemorrhage despite a mean age of 29 +/- 2 years

cocaine and cardiomyopathy
Cocaine and Cardiomyopathy

Proposed mechanisms:

1) Myocardial ischemia or infarction

2) Microscopic changes of subendocardial contraction band necrosis possibly through profound repetitive sympathetic stimulation

3) Animal studies have shown that cocaine alters cytokine production in the endothelium, changes the composition of myocardial collagen and myosin, and induces myocyte apoptosis

cocaine and dysrhythmias18
Cocaine and Dysrhythmias
  • Cocaine has been shown to cause VT/VF in presence of ischemia
  • Also thought to:

-increase ventricular irritability and lower VF threshold

-increase QRS and QT through Na-channel blocking properties

-increase intracellular Ca++ leading to afterdepoloarizations

-reduces vagal activity thereby increasing sympathomimetic effects

cocaine and endocarditis
Cocaine and Endocarditis
  • IVDU is associated with endocarditis
  • Cocaine use is a greater independent risk factor for SBE than other IV drugs

-reasons unclear

-perhaps tachycardia and hypertensive effects induce valvular injury

-known immunosuppressive effects through inhibition of IL-8

  • Most often effects left-sided valves, unlike other IV drugs.
cocaine and aortic dissection
Cocaine and Aortic Dissection
  • Aortic dissection or rupture has been temporally related to cocaine use
  • Dissection probably results from the substantial increase in systemic arterial pressure induced by cocaine.
  • Also, the cocaine-related rupture of mycotic and intracerebral aneurysms has been reported
treatment
Treatment
  • Treatment of acute cocaine-induced ischemia and MI is directed towards inhibition of platelet aggregation and reversal of vasoconstriction/ spasm
  • Aspirin should be administered to all patients with suspected cocaine-induced ischemia
  • There is little experience with fibrinolytic therapy in this setting and it should be considered as a last resort
treatment22
Treatment
  • Cocaine-induced vasoconstriction is mediated through the α-adrenergic receptors
  • β-adrenergic blocking agents can exacerbate cocaine-induced vasoconstriction
  • Nitroglycerin and verapamil reverse cocaine-induced vasoconstriction and are first-line agents in this setting
  • Labetolol reverses cocaine-induced hypertension, but doesn’t reverse vasoconstriction
  • Benzodiazepines also help with reduction of blood pressure and pulse rate