Expansion
Reduced metabolism, reduced protein binding and increased sensitivity
Expansion
Why drug handling changes
- Reduced metabolic capacity and reduced first pass metabolism, so oral bioavailability of drugs such as propranolol and morphine rises sharply
- Portosystemic shunting bypasses the liver entirely
- Hypoalbuminaemia increases the free fraction of highly bound drugs such as phenytoin and warfarin
- Reduced clotting factor synthesis exaggerates the effect of anticoagulants
- Increased cerebral sensitivity, so sedatives precipitate encephalopathy
- Fluid retention worsened by sodium-containing and fluid-retaining drugs
Drugs to avoid or use cautiously
- Sedatives and opioids: precipitate encephalopathy; use lorazepam if a benzodiazepine is unavoidable
- NSAIDs: cause fluid retention, renal failure and variceal bleeding
- Warfarin: unpredictable, with a baseline prolonged prothrombin time
- Paracetamol: still usable but at reduced dose in severe disease
- Prodrugs requiring hepatic activation, such as clopidogrel and codeine, may be ineffective
Practical approach: use the lowest effective dose, prefer drugs eliminated renally, avoid hepatotoxins, monitor for encephalopathy and fluid retention, and remember that the prothrombin time reflects synthetic function rather than bleeding risk in isolation.