Cardiovascular Drug Therapy in Patients with Hepatic Diseases and Patients with Congestive Heart Failure.
Sokol, Seth I. MD; Cheng, Angela PharmD; Frishman, William H. MD; Kaza, Chatargy S. MD
Journal of Clinical Pharmacology.
40(1):11-30, January 2000.
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Hepatic impairment can alter the pharmacokinetic profiles of cardiovascular drugs, which can lead to unwanted toxicity. In the presence of cirrhosis, portosystemic shunting occurs and cytochrome P450 activity is reduced. Impaired oxygen uptake caused by changes in the liver's sinusoids, as proposed by the oxygen limitation theory, may also explain the alteration of drug metabolism seen in cirrhosis. With congestive heart failure, sinusoidal congestion and hypoperfusion of the liver are seen. Similar to cirrhosis, the common pathway for hepatic damage in congestive heart failure seems to be liver hypoxia, which may explain the disease's effect on drug metabolism. Since routine hepatic function tests do not always relate to the liver's ability to eliminate drugs, existing guidelines for dosing cardiovascular drugs in patients with hepatic impairment are limited. This article provides guidance for dosing cardiovascular drugs in cirrhotic and heart failure patients based on available research data. Altered drug metabolism, especially in congestive heart failure, tends to be overlooked or not realized in clinical practice. Therefore, further research is needed in congestive heart failure to better elucidate safe prescribing patterns.
(C)2000 SAGE Publications