Use of medicines in liver dysfunction (part 1)

Last updated: Tuesday, July 16, 2019

General principles
Be aware of liver involvement in clearance: use a renal one (if function is ok), or a non-systemic medicine.
Start low, go slow
Monitor LFTs
Limit number of drugs

Things that determine dose and choice because of effects of liver impairment on ADME/clearance

✦  Is the drug water soluble? Larger doses of water soluble drugs may be needed in patients with ascites as the drug distributes into the ascitic fluid resulting in lower blood concentrations.

✦  Does the drug undergo high first pass metabolism? In portal hypertension, varices can form between the portal and venous system, bypassing the liver. This can mean more un-metabolised drug passing into the venous system.

✦  Is the drug metabolised (or activated) by the liver? In liver dysfunction CYP450 and other enzyme levels may be reduced. This means that some drugs might accumulate as they are not metabolised readily, or inactive pro-drugs are not changed into their active forms.

✦  Does the drug undergo enterohepatic recirculation? If the patient has cholestasis then reabsorption via this route may be reduced, resulting in lower levels.