Hepatotoxicity Associated with Angiotensin-Converting Enzyme Inhibitors

Author:

Hagley Michael T.1,Hulisz Darrell T.2,Burns Colleen M.3,Hartshorn Edward A.4

Affiliation:

1. Akron City Hospital, Akron, OH; Cardiology Research Division, Jewish Hospital of St. Louis, Washington University Medical Center, St. Louis, MO

2. Akron City Hospital; Department of Pharmacy, Akron General Medical Center, Akron, OH, and College of Pharmacy, Department of Pharmacy Practice, Ohio Northern University, Ada, OH

3. College of Pharmacy, University of Toledo, Toledo, OH; Department of Pharmacology, College of Medicine, Vanderbilt University, Nashville, TN.

4. University of Texas, and University of Texas Health Sciences Center, San Antonio, TX 78284.

Abstract

Objective To review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury. Data Sources Published reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury. Data Synthesis Nineteen cases of ACE-inhibitor–associated hepatotoxicity are presented. Early theories regarding mechanisms are reviewed. Laboratory investigations of hepatic effects of eicosanoids on hepatic function are reviewed and a novel mechanism by which ACE inhibitors may cause hepatic injury is postulated. Conclusions Hepatotoxicity, usually cholestatic in nature, has been reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity has been reported twice. Potential mechanisms of injury include idiopathic hypersensitivity and modulation of eicosanoid metabolism by inhibition of kininase II and subsequent increased hepatic bradykinin activity. Mediation via altered eicosanoid metabolism provides a plausible explanation for cross-reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are stopped but may progress to liver failure if treatment is continued.

Publisher

SAGE Publications

Subject

Pharmacology (medical)

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