The liver is the primary site of drug metabolism, and hepatic impairment fundamentally alters pharmacokinetics through multiple mechanisms. Phase I metabolism (oxidation, reduction, hydrolysis) via cytochrome P450 enzymes (CYP3A4, CYP2D6, CYP2C9, CYP1A2) is reduced in proportion to functional hepatocyte loss. Phase II metabolism (conjugation — glucuronidation, sulfation, acetylation) is generally preserved until advanced cirrhosis. First-pass metabolism is reduced by both hepatocyte dysfunction and portosystemic shunting, dramatically increasing oral bioavailability of high-extraction drugs (propranolol, morphine, midazolam — oral doses may produce IV-equivalent drug levels). Hypoalbuminemia in cirrhosis increases the free fraction of highly protein-bound drugs (phenytoin, warfarin, diazepam), potentiating their effects despite normal total drug levels. The Child-Pugh score (albumin, bilirubin, INR, ascites, encephalopathy) classifies hepatic impairment severity (A = mild, B = moderate, C = severe) and guides dose adjustment. MELD score (bilirubin, INR, creatinine) predicts 90-day mortality and transplant priority. Key prescribing principles: avoid hepatotoxic drugs (acetaminophen limit to 2g/day, avoid NSAIDs which reduce renal blood flow and cause GI bleeding, avoid statins in decompensated cirrhosis); reduce doses of hepatically metabolized drugs by 50% in Child-Pugh B and 75%...