Associate editor: G.E. BillmanCardiovascular disorders associated with cocaine use: myths and truths
Section snippets
Overview
The widespread use of cocaine has stimulated some interest in the research community to improve our understanding of the actions of this drug. Cocaine is responsible for considerably more hospital admissions than any other illicit drug [Drug Abuse Warning Network (DAWN) Report, NIDA, 2001: www.samhsa.gov/oas/dawn.htm], emphasizing the importance of understanding the mechanism by which cocaine produces toxicity. The incidence of cocaine toxicity is likely to be substantially under-reported,
History of cocaine use
Cocaine has been used as a pharmacological tool for centuries, if not millennia. Several excellent reviews describing the early history of cocaine use are available Das, 1993, Karch, 1989, Johanson & Fischman, 1989, Petersen, 1977, Rappolt et al., 1979, Van Dyke & Byck, 1982. The earliest use of cocaine is believed to be in South America, where the native population discovered that the leaves of the coca plant (Erythroxolon coca), when chewed, appeared to help overcome weariness and altitude
Pharmacological actions of cocaine
Cocaine has two well-defined pharmacologic actions: it is a local anesthetic and a monoamine reuptake blocker. In addition, there are several other purported actions of cocaine that may be responsible for its unusual euphoric, addictive, and toxic effects. These effects will be discussed briefly, although other reviews have dealt with these properties in greater detail Johanson & Fischman, 1989, Kuhar et al., 1991, Ritchie & Greene, 1990, Sherer, 1988. In this review, the pharmacologic
Cardiac responses to cocaine and hypotheses
Numerous reviews have described the occurrence of serious, and sometimes fatal, heart disease in individuals using cocaine Benowitz, 1993, Benzaquen et al., 2001, Billman, 1995, Cregler & Mark, 1986, Karch & Billingham, 1988, Kloner et al., 1992, Lange & Willard, 1993, Minor et al., 1991, Om et al., 1992, Rezkalla et al., 1990, Rowbotham & Lowenstein, 1990, Pellegrino & Bayer, 1998, Virmani, 1991. The most common symptom is chest pain, occasionally associated with ventricular fibrillation,
Variable responsivity to cocaine
Considering the extent of the clinical problem that cocaine use presents and the considerable resources of the National Institute of Drug Abuse and health care organizations devoted to resolving the problem, it is unusual that we seem no closer to understanding or preventing adverse responses to cocaine now than we were three decades ago when the problem became obvious. The single greatest difficulty in understanding the actions of cocaine lies in determining the causes of varying sensitivity
Arterial pressure and heart rate responses
Cocaine produces cardiovascular responses that reflect its sympathomimetic actions (Table 4). Cocaine administration produces an increase in arterial pressure and little change or an increase in heart rate in humans Cascella et al., 1989, Fischman & Schuster, 1982, Fischman et al., 1976, Fischman et al., 1983, Fischman et al., 1985, Foltin et al., 1995, Resnick et al., 1977, Rowbotham et al., 1987, Walsh et al., 1996. The pressor response and tachycardia are attenuated by labetalol or
Does cocaine produce its cardiotoxic effects by eliciting coronary vasospasm?
Coronary vasospasm is the most commonly ascribed cause of myocardial dysfunction caused by cocaine Amin et al., 1990, Ayala & Altieri, 1993, Brody et al., 1990, Cregler & Mark, 1985, Howard et al., 1985, Isner et al., 1986, Kossowsky & Lyon, 1984, Kossowsky et al., 1989, Nademanee et al., 1989, Pasternack et al., 1985, Rollingher et al., 1986, Schachne et al., 1984, Zimmerman et al., 1987, yet in only a few cases, vasospasm has been documented using coronary angiography Ascher et al., 1988,
Special considerations for experimental studies
This review has attempted to identify not only our advances in understanding the effects of cocaine, but, more importantly, a number of areas in which further study is necessary to verify the causes of toxicity and appropriate treatments. It is apparent from the data obtained to date that some of the confusion regarding the pharmacologic and cardiotoxic effects of cocaine result from limitations of specific experimental protocols. These have been referred to throughout this review, but it is
Remaining challenges and summary
In conclusion, research efforts designed to improve our understanding of the cardiovascular effects of cocaine are, on one hand, promising and, at the same time, daunting. The efforts of many investigators have clarified a number of mechanisms by which cocaine acts on the body, and a number of anomalies that have yet to be understood. Some of the salient findings are summarized here:
(1) Despite the considerable research efforts in the past two decades, the causes of cardiovascular responses to
Acknowledgements
The editorial assistance of Drs. Steven Karch and Vernon Fischer and of Tracy Bloodgood, Ruth Rauls, and Erin Winkeler is gratefully acknowledged. This work was supported by USPHS grants DA 05180 and DA 13256.
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