Many patients with cocaine-associated angina pectoris or myocardial infarction are cigarette smokers who admit to smoking while using cocaine. Cigarette smoking induces vasoconstriction of the coronary arteries through an α-adrenergic mechanism similar to that of cocaine. In fact, recent studies have demonstrated that the deleterious effects of cocaine on myocardial oxygen supply and demand are exacerbated substantially by concomitant cigarette smoking. This combination markedly increased the product of the heart rate and systemic arterial pressure, a value that determines myocardial oxygen demand, while simultaneously decreasing the diameter of diseased segments of the coronary arteries.
The results of a recent survey suggest that 9 million people in the United States abuse cocaine and ethanol simultaneously. Among those with abuse of multiple substances who are seen in emergency departments, the combination of cocaine and ethanol is the most common. It is the second most common combination in patients who die of substance abuse, accounting for more than 1000 deaths per year. The concomitant use of cocaine and ethanol appears to be associated with higher rates of disability and death than either agent alone.
Randall reported that the simultaneous use of these substances increased the risk of sudden death by more than a factor of 20 in patients with postmortem evidence of coronary artery disease. Others reported that patients who died of a combined overdose of cocaine and ethanol had much lower blood cocaine concentrations than those who died of an overdose of cocaine alone (900 and 2800 mg per liter, respectively), suggesting an additive or synergistic effect of ethanol on catastrophic cardiovascular events induced by cocaine.
Persons who abuse cocaine in temporal proximity to the ingestion of ethanol produce cocaethylene, a metabolite synthesized by hepatic-transesterification. Like cocaine, it blocks the reuptake of dopamine at the synaptic cleft, thereby possibly potentiating the systemic toxic effects of cocaine. At postmortem examination, cocaethylene is often detected in patients who died of cocaine and ethanol toxicity. In animals, cocaethylene is more lethal than cocaine. In humans, the combination of cocaine and ethanol has been shown to cause increases in myocardial oxygen demand.
From the Cardiovascular Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Address reprint requests to Dr. Hillis at the Department of Internal Medicine, Room CS7.102, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9047.
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Richard A. Lange, M.D., and L. David Hillis, M.D.