title: Cocaine, HIV, and their cardiovascular effects: is there a role for ACE-inhibitor therapy?
abstract: Cocaine abuse and HIV disease each have potentially adverse effects upon the heart and cardiovascular system which may be exacerbated when these risk factors are combined. The development of a safe and effective agent to treat both cocaine addiction and its cardiovascular sequelae, that is well-tolerated by HIV patients, would thus be of considerable clinical utility. In this article we discuss the rationale for the investigation of angiotensin converting enzyme (ACE) inhibitors, commonly used to treat hypertension, for treatment in cocaine-abusing populations, based on their potential to reduce cocaine use by modulating levels of dopamine and corticotropin releasing factor in the brain, and on their ability to reverse cardiovascular and platelet abnormalities. We present preliminary findings from echocardiographic and platelet activation studies in 16 HIV-positive, cocaine abusing patients, as well as tolerability and efficacy studies of the ACE-inhibitor, fosinopril, for the treatment of cocaine abuse in both HIV-positive (n=6) and HIV-negative (n=5) methadone-maintained cocaine abusers. Findings suggest that HIV-positive cocaine-abusing patients possess abnormalities of diastolic heart function and platelet activation that are potentially reversible with ACE-inhibitor therapy. Findings also suggest that fosinopril is well-tolerated regardless of HIV serostatus, does not appear to cause hypotension, and may possess effectiveness for reducing cocaine use. We conclude that ACE-inhibitor therapy may offer a new pharmacologic approach to the treatment of cocaine abuse and its complications, and that controlled research of this class of agents may be promising.
authors.affiliation: Department of Psychiatry, Substance Abuse Center, Yale University School of Medicine, 34 Park St., New Haven, CT, 06519, USA. arthur.margolin@yale.edu
authors.forename: A
authors.initials: A
authors.lastname: Margolin
authors.forename: S K
authors.initials: SK
authors.lastname: Avants
authors.forename: J F
authors.initials: JF
authors.lastname: Setaro
authors.forename: H M
authors.initials: HM
authors.lastname: Rinder
authors.forename: L
authors.initials: L
authors.lastname: Grupp
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D019970:Cocaine-Related Disorders / Q000150:complications* / Q000188:drug therapy*; D004361:Drug Tolerance; D004562:Electrocardiography; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017328:Fosinopril