Cardiovascular Complications of Cocaine Use

The deaths of several celebrities in recent years in association with the nontherapeutic use of cocaine have focused widespread attention on the problem of cocaine abuse. In 1999, an estimated 25 million Americans admitted that they had used cocaine at least once; 3.7 million had used it within the previous year; and 1.5 million were current users. During the same year, cocaine was mentioned in 30 percent of all drug-related visits to emergency departments. Cocaine is the most commonly used illicit drug among subjects seeking care in hospital emergency departments or drug-treatment centers. In addition, it is the most frequent cause of drug-related deaths reported by medical examiners.

Cocaine use rose to epidemic levels in the early and mid-1980s, after which it declined in prevalence. However, between 1994 and 1998, the number of new cocaine users per year increased 82 percent, from 514,000 to 934,000. Several factors account for this recent increase in cocaine use, including the ease of its administration, the increased availability and purity of the drug, reduced cost, and the misperception that the recreational use of cocaine is safe. In a recent survey conducted by the Department of Health and Human Services, only 50 percent of young people expressed the belief that monthly cocaine ingestion carries a great risk of harm. In fact, as cocaine abuse has become widespread, the number of cocaine-related cardiovascular events, including angina pectoris, myocardial infarction, cardiomyopathy, and sudden death from cardiac causes, has increased dramatically.

Pharmacology and Mechanisms of Action
Cocaine (benzoylmethylecgonine) is an alkaloid extracted from the leaf of the Erythroxylon coca bush, which grows primarily in South America. It is available in two forms: the hydrochloride salt and the “free base.” Cocaine hydrochloride is prepared by dissolving the alkaloid in hydrochloric acid to form a water-soluble powder or granule that decomposes when heated. It can be taken orally, intravenously, or intranasally, the slang terms for which are “chewing,” “mainlining,” and “snorting,” respectively. The free-base form is manufactured by processing the cocaine with ammonia or sodium bicarbonate (baking soda) to remove the hydrochloride. This form is heat-stable and melts at 98°C, which allows it to be smoked. It is known as “crack” because of the popping sound it makes when heated.

Since cocaine hydrochloride is well absorbed through all mucous membranes, abusers may achieve a high blood concentration by means of intranasal, sublingual, intravaginal, or rectal administration. As compared with the intravenous injection of cocaine, the mucosal administration of the drug results in a slower onset of action, a later peak effect, and a longer duration of action. Euphoria occurs within seconds after crack cocaine is smoked and is short-lived. Crack cocaine is considered to be the most potent and addictive form of the drug.

Cocaine is metabolized by plasma and liver cholinesterases to water-soluble metabolites (primarily benzoylecgonine and ecgonine methyl ester), which are excreted in the urine. The serum half-life of cocaine is 45 to 90 minutes; only 1 percent of the parent drug can be recovered in the urine after it is ingested. Thus, cocaine can be detected in blood or urine for only several hours after its use. However, its metabolites are detectable in blood or urine for 24 to 36 hours after ingestion, thereby providing a useful indicator of recent drug ingestion. Hair analysis provides an extremely sensitive marker of cocaine use in the preceding weeks or months, depending on the length of the hair analyzed. Interestingly, the results of studies that have used hair analysis suggest that the prevalence of cocaine use may be three to five times as high as that estimated by standard surveys and interviews with patients.

When applied locally, cocaine acts as an anesthetic because of its ability to inhibit membrane permeability to sodium during depolarization, thereby blocking the initiation and transmission of electrical signals. When given systemically, its effects are mediated through alterations in synaptic transmission. Cocaine blocks the presynaptic reuptake of norepinephrine and dopamine, producing an excess of these neurotransmitters at the site of the postsynaptic receptor. In short, cocaine acts as a powerful sympathomimetic agent.

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.

  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.

Provided by ArmMed Media