title: Cocaine-induced heart disease: mechanisms and pathology.
abstract: Cocaine use has increased in recent years, in part as a result of the increased availability of "crack," the inexpensive freebase form. Although it is used medicinally and initially was considered a relatively safe street drug, cocaine clearly has addictive potential as well as adverse health consequences even in low doses. Some of its most serious adverse effects involve the cardiovascular system. Understanding the cellular mechanisms of the action of cocaine on the heart allows insight into the pathophysiology of its adverse effects. Blockade of sodium channels accounts for cocaine's anesthetic effects and acts directly on myocytes to impair action potential generation and conduction, predisposing to dysrhythmias. Blockade of neurotransmitter reuptake has many deleterious effects, including dysrhythmogenesis via increased intracellular calcium, myocardial ischemia via vasospasm and increased myocardial oxygen demand, and contraction band necrosis also via increased intracellular calcium. In addition, alterations in platelet-endothelial cell function predispose to coronary artery thrombosis and ischemia. Alterations in immune function of natural killer cells may, among other effects, predispose to the development of myocarditis, the etiology of which is probably multifactoral. Finally, a direct toxic effect of cocaine on myocytes may, in some cases, produce heart muscle dysfunction. These multiple mechanisms of action combined with the deleterious effects of often-present adulterants give rise to an unpredictable, variable, and potentially life-threatening cardiovascular response to cocaine administration.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
authors.forename: E A
authors.initials: EA
authors.lastname: Laposata
mesh_terms: D000772:Anesthesia, Local; D001792:Blood Platelets / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D003042:Cocaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D009205:Myocarditis / Q000139:chemically induced; D018377:Neurotransmitter Agents / Q000502:physiology; D019966:Substance-Related Disorders / Q000150:complications*
chemical_list: D018377:Neurotransmitter Agents; D003042:Cocaine