Drugs in Hepatic Failure

Introduction

• Definition — Hepatic failure / impairment = loss of the liver's drug-handling capacity sufficient to alter drug disposition (and sometimes drug action), requiring dose modification or avoidance to prevent toxicity. Prototype = cirrhosis; principles extend to acute liver failure, severe hepatitis and cholestatic disease.
• Why the liver matters — It is the dominant site of drug biotransformation (phase 1 oxidation/reduction/hydrolysis via CYPs; phase 2 conjugation), a major excretory organ (biliary/canalicular secretion ± enterohepatic recycling), and the seat of the first-pass effect that limits oral bioavailability.
• Compound insult — Hepatic dysfunction simultaneously degrades metabolic clearance, first-pass extraction, plasma-protein synthesis (albumin, clotting factors) and biliary excretion — a single failing organ perturbs nearly every PK parameter at once, making hepatic-failure prescribing more complex than renal.
• Key asymmetry vs renal failure — There is no simple test (like creatinine clearance for the kidney) to quantify the alteration in hepatic drug disposition, and different drugs are affected to different extents — the single most examinable concept of this topic.