Pharmacological considerations in acute and chronic liver disease

Abstract

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have profound effects on human physiology that extend well beyond hepatic considerations. Virtually every organ system is affected to some degree, as are the medications used to treat both chronic and acute conditions for these organ systems. Even a small therapeutic misadventure can precipitate an acute decompensation in liver failure patients, further emphasizing the importance of appropriate drug dosing. Liver disease results in significant alteration in the pharmacokinetic and pharmacodynamic characteristics of medications. While the magnitude of these alterations is dependent upon the extent of liver disease and the physiochemical characteristics of a given medication, the effect of most medications will be amplified as a result of liver disease. This chapter provides a practical overview of drug dosing considerations, with a focus on basic pharmacokinetic and pharmacodynamics principles, in the context of ALF and ACLF. This is followed by medication considerations organized by organ system, with a focus on neurology, pulmonary, cardiovascular, renal, hematologic, gastrointestinal, and endocrine. Infectious disease considerations are also reviewed. The use of objective monitoring tools and the establishment of therapeutic goals will help facilitate the optimal use of drug therapy for each organ system. In many cases, treatment guidelines are lacking for the management of acute and chronic disease observed concurrently in patients with liver failure. Avoiding medications that have unpredictable pharmacokinetic profiles, or that are prone to drug-drug interactions, will reduce sequela. Employing evidence-based pharmacotherapy should yield improved outcomes. Practical considerations for the aforementioned are provided.