No liver test predicts drug clearance well. In cirrhosis and acute liver failure prefer drugs with short half-lives or non-hepatic elimination, avoid long-acting sedatives, lower and titrate high-extraction and highly protein-bound drugs, and watch for encephalopathy and bleeding.
At the bedside
Timed steps- 1
Severity
AssessChild-Pugh class guides labels (B: reduce, C: avoid or major reduction); MELD does not predict PK.
- 2
Choose
SedationPropofol or low-dose dexmedetomidine titrated; avoid midazolam and lorazepam infusions; fentanyl in small boluses rather than morphine (M6G accumulates in hepatorenal syndrome).
- 3
Oral route
High-extraction drugsOral bioavailability rises with portosystemic shunting (e.g. propranolol, morphine, midazolam) – reduce oral doses.
- 4
Free fraction
Low albuminHighly protein-bound drugs (phenytoin, valproate, ceftriaxone) have higher free levels; interpret total levels cautiously (use free phenytoin).
- 5
Hepatotoxic and nephrotoxic
AvoidNSAIDs (renal failure, bleeding), aminoglycosides; paracetamol at 2-3 g/day is acceptable in cirrhosis.
Drug choice in liver disease
Step 1 of ~4
Decision: Child-Pugh C or acute liver failure?
Based on Verbeeck RK. Educational use; follow local protocol.
Pathophysiology
- Clearance of high-extraction drugs depends on hepatic blood flow; low-extraction drugs on enzyme capacity and protein binding. Glucuronidation is relatively preserved compared with CYP oxidation.
Evidence
- Verbeeck 2008: review of PK changes and dose-adjustment principles in hepatic dysfunction.
🇮🇳 India notes
- Alcohol, viral hepatitis and NASH-related cirrhosis are common; many patients also take unregulated herbal remedies with hepatotoxic potential.
References
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Educational reference for trained clinicians. Check doses against your hospital protocol and the patient in front of you.