Effects of Liver Disease on Patient Response

The relationship between drug concentration and response also can be altered in patients with advanced liver disease. Of greatest concern is the fact that customary doses of sedatives may precipitate the disorientation and coma that are characteristic of portal-systemic or hepatic encephalopathy. Experimental hepatic encephalopathy is associated with increased y-aminobutyric acid-mediated inhibitory neurotransmission, and there has been some success in using the benzodiazepine antagonist flumazenil to reverse this syndrome (50). This provides a theoretical basis for the finding that brain hypersensitivity, as well as impaired drug elimination, is responsible for the exaggerated sedative response to diazepam that is exhibited by some patients with chronic liver disease (51). Bakti et al. (52) conducted a particularly well-controlled 

It is advisable to avoid using certain drugs in patients with advanced liver disease. For example, angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs should be avoided because of their potential to cause acute renal failure. Paradoxically, administration of captopril 

TABLE 7.6 Some Drugs Requiring at Least a 50% Dose Reduction in Patients with Moderate Cirrhosis 

Rowland M, Benet LZ, Graham GG. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1973 1 123-36. 

Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975 18 377-90. 

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