14. Illness as a factor modifying drug action: Impact of chronic renal failure and chronic hepatic failure · Clinical Pharmacology · MU Sofia

14. Illness as a factor modifying drug action: Impact of chronic renal failure and chronic hepatic failure.

Explains how chronic kidney disease and chronic liver disease alter drug handling and drug response, covering changes in drug elimination, protein binding and first-pass metabolism alongside pharmacodynamic risks such as bleeding, hyperkalaemia and encephalopathy. It sets out prescribing rules for each organ failure, including dose adjustment by creatinine clearance or eGFR, grading severity with the Child-Pugh score, and specific drugs to avoid or use with caution.

Inside: 3 sections · 16 flashcards · 2 min

Topic 14 of 30 in the MU Sofia syllabus for Clinical Pharmacology (Medicine, Year 5). The free AceMed note covers it in 3 sections, about 346 words (2 min of reading), with 16 flashcards.

Introduction

Disease changes how the body handles drugs (pharmacokinetics) and how it responds to them (pharmacodynamics). The two most important organs are the kidney and the liver, which eliminate most drugs.

Chronic kidney disease (CKD)

Pharmacokinetic changes

Reduced renal excretion of the drug and its active metabolites → accumulation, longer half-life (e.g. aminoglycosides, vancomycin, digoxin, lithium, metformin, LMWH, gabapentin, morphine's metabolite M6G).
Lower protein binding of acidic drugs (phenytoin) in uraemia; changes in Vd (oedema).

Pharmacodynamic changes

Greater sensitivity to sedatives and opioids; higher risk of bleeding (uraemic platelets), hyperkalaemia (ACE inhibitors, ARBs, spironolactone), fluid retention (NSAIDs).
Some drugs stop working: thiazides lose effect at GFR < 30 ml/min (use loop diuretics); nitrofurantoin is ineffective and toxic.

Prescribing rules

Estimate kidney function: creatinine clearance (Cockcroft–Gault) or eGFR.
Keep the loading dose; reduce the maintenance dose or extend the interval (e.g. once-daily gentamicin given less often).
Monitor levels (TDM) where possible.
Avoid nephrotoxic drugs: NSAIDs, aminoglycosides, contrast media; avoid the "triple whammy" (ACE inhibitor/ARB + diuretic + NSAID).
Stop metformin at eGFR < 30 ml/min (lactic acidosis).