Transcript Cocaine and the Heart

Cocaine and the Heart
Overview
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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
-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
• 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
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
Pharmacokinetics
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
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
• 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
Pathogenesis of cocaine related ischemia
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
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 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 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
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 Dysrhythmias
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
• 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
• 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 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
Treatment
• Cocaine-induced vasoconstriction is mediated
through the α-adrenergic receptors
• β-adrenergic blocking agents can exacerbate
cocaine-induced vasoconstriction
• Nitroglycerin and verapamil reverse cocaineinduced 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
Treatment