Liver dysfunction and drug handling

Last updated: Thursday, June 13, 2019

Liver dysfunction can affect how the body handles medicines in several different ways. An understanding of a particular drug’s pharmacokinetic and pharmacodynamic properties can help guide us when making decisions.

Absorption

✦  Is the drug lipophilic? Lipophilic drugs often need bile salts for absorption, so patients with cholestasis may experience a reduction in drug absorption.

Distribution

✦  Is the drug highly plasma protein bound? For drugs that are highly protein bound (>80%) the risk of side effects might be increased in patients with low albumin levels. This is because there is less protein for the drug to bind to, leading to higher levels of free drug. Sometimes, highly protein bound drugs can be displaced from albumin in patients with high bilirubin levels which also gives higher levels of free drug.

✦  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.

Metabolism

✦  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.

Elimination

✦  Is the drug excreted in bile? If the patient has cholestasis, biliary excretion may be impaired. This may particularly become an issue if the drug is excreted in an active form.

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