The Disposition and Effects of Sedatives and Analgesics in Liver Disease

The aim of drug therapy is to deliver a drug concentration sufficient to affect the site of action. Whether the desired intensity and duration of action are attained or exceeded depends largely on the efficiency of drug disposition and on the sensitivity of the receptor site(s). The pharmacologic effects of sedatives and analgesics have been shown to be exaggerated in some patients with significant liver disease or portasystemic shunts, with coma as a potential outcome (1). In recent years a number of studies revealed impaired disposition and altered response to such widely used drugs as tranquilizers, sedatives, and analgesics in the presence of significant hepatic dysfunction (2). The purpose of the present discussion is to review the disposition and effects of drugs in hepatic dys­ function, and thus provide a rational approach to the management of liver disease.