Pharmacokinetics in Organ Failure — Renal, Hepatic and Polypharmacy Dosing

The answer first

Safe prescribing in organ failure rests on one discriminating question: how is this drug cleared? A water-soluble (hydrophilic) drug is cleared by the kidney and accumulates in renal failure — vancomycin, gentamicin, digoxin, lithium, metformin, atenolol, allopurinol, the direct oral anticoagulants and the gabapentinoids. A lipid-soluble (lipophilic) drug is cleared by the liver and is largely unaffected by renal function — diazepam, amiodarone, warfarin, phenytoin. Get that split right, then estimate renal function honestly, dose off the correct equation (Cockcroft-Gault for most drug labels, CKD-EPI 2021 for staging), and apply therapeutic drug monitoring where the therapeutic index is narrow. ^[1]

The registrar who can do four things will pass any pharmacology viva: estimate renal function correctly, identify the renally-cleared drugs, adjust the hepatically-metabolised drugs in cirrhosis, and defend a structured medication review in the elderly. The one who doses vancomycin off an uncorrected eGFR, interprets a phenytoin total level in renal failure, or co-prescribes lithium with a thiazide will cause harm and fail the station. ^[1]

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References34ShowHide

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