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.

Source Information

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.
References

  _{1. Office of Applied Studies. Year-end 1999 emergency department data from the Drug Abuse Warning Network. Rockville, Md.: Substance Abuse and Mental Health Services Administration, August 2000. (DHHS publication no. (SMA) 00-3462.)
  2. Office of Applied Studies. Summary of findings from the 1999 National Household Survey on Drug Abuse. Rockville, Md.: Substance Abuse and Mental Health Services Administration, August 2000. (DHHS publication no. (SMA) 00-3466.)
  3. Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE. Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking. Drug Metab Dispos 1989;17:153-159.
  4. Ness RB, Grisso JA, Hirschinger N, et al. Cocaine and tobacco use and the risk of spontaneous abortion. N Engl J Med 1999;340:333-339.
  5. Kidwell DA, Blanco MA, Smith FP. Cocaine detection in a university population by hair analysis and skin swab testing. Forensic Sci Int 1997;84:75-86.
  6. Fendrich M, Johnson TP, Sudman S, Wislar JS, Spiehler V. Validity of drug use reporting in a high-risk community sample: a comparison of cocaine and heroin survey reports with hair tests. Am J Epidemiol 1999;149:955-962.
  7. Coleman DL, Ross TF, Naughton JL. Myocardial ischemia and infarction related to recreational cocaine use. West J Med 1982;136:444-446.
  8. Minor RL Jr, Scott BD, Brown DD, Winniford MD. Cocaine-induced myocardial infarction in patients with normal coronary arteries. Ann Intern Med 1991;115:797-806.
  9. Hollander JE, Hoffman RS. Cocaine-induced myocardial infarction: an analysis and review of the literature. J Emerg Med 1992;10:169-177.
  10. Pitts WR, Lange RA, Cigarroa JE, Hillis LD. Cocaine-induced myocardial ischemia and infarction: pathophysiology, recognition, and management. Prog Cardiovasc Dis 1997;40:65-76.
  11. Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation 1999;99:2737-2741.
  12. Brody SL, Slovis CM, Wrenn KD. Cocaine-related medical problems: consecutive series of 233 patients. Am J Med 1990;88:325-331.}

Richard A. Lange, M.D., and L. David Hillis, M.D.