title: Cocaine and cardiovascular toxicity.
abstract: Over the past 10 years a great deal has been learned about the cardiovascular effects of cocaine. In particular, the acute effects of cocaine have been studied extensively. Upon acute administration cocaine increases blood pressure and heart rate, primarily through an action on the sympathetic nervous system. Cocaine also suppresses the baroreflex response and vagal tone, further contributing to its effects on heart rate. At the same time cocaine is increasing the work-load on the heart it induces coronary artery vasoconstriction, potentially leading to cardiac ischemia. At higher doses cocaine can depress ventricular function and slow electrical conduction in the heart. Both these effects appear to be mediated by cocaine's local anesthetic action. The effects of cocaine mediated by the sympathetic nervous system are greatly reduced in anesthetized animals. Further, when cocaine is administered repeatedly over a short period of time, acute tolerance can develop to the sympathomimetic effects of cocaine. In contrast, the effects of cocaine mediated by its local anesthetic action do not appear blunted by anesthesia or susceptible to acute tolerance. With chronic administration, higher doses appear to induce tolerance while lower doses may induce sensitization to cocaine's sympathomimetic effects. Cocaine also induces a variety of pathological changes in the heart, including myocardial contraction band necrosis and ventricular hypertrophy. These effects of cocaine on the heart can all contribute to potentially lethal cardiovascular events. In addition to the effects of cocaine alone, the metabolites of cocaine may also contribute to cocaine's cardiovascular toxicity, and both licit and illicit drugs used in combination with cocaine might potentially alter its cardiovascular effects.
authors.affiliation: Preclinical Pharmacology Laboratory, National Institutes of Health/National Institute on Drug Abuse, Division of Intramural Research, Addiction Research Center, Baltimore 21224, USA. cschindl@helix.nih.gov
authors.forename: C W
authors.initials: CW
authors.lastname: Schindler