Liver disease can alter the body’s response to drugs but due to the large hepatic reserve, hepatic impairment has to be severe before important changes in drug metabolism occur. Nevertheless, prescribing considerations include:^22,23

• Decreased blood levels of proteins (hypoalbuminaemia) can result in reduced binding of drugs such as phenytoin or prednisolone, increasing their drug toxicity.
• Bilirubin circulating in jaundice may displace protein-bound drugs increasing the proportion of free drug.
• A reduction in metabolising enzyme production can cause drug accumulation increasing the risk of adverse effects and requiring a reduction in maintenance dosing.
• Pro-drugs may not be converted as readily into their active form, but drug clearance enzymes may be unaffected making response highly unpredictable.
• Reduced blood clotting factor formation can increase sensitivity to anticoagulants such as warfarin or phenindione.
• In cholestasis, reduced bile salt secretion may inhibit lipid-soluble drug absorption or reduce elimination – reduced vitamin K uptake can also impair clotting.
• Hepatic encephalopathy symptoms can be exacerbated by sedatives, opioids, hypokalaemia-producing diuretics, and drugs with constipating effects.
• Ascites can delay (unpredictably) absorption of some drugs and water-soluble drugs may require higher dosing.
• Ascites can be worsened by drugs causing fluid retention such as NSAIDs and corticosteroids.
• Creatinine clearance may be affected with implications for drugs which are excreted via the kidneys.
• There can be increased sensitivity to drugs, especially those acting on the central nervous system and to the renal side-effects of NSAIDs, while response to diuretics may decrease.
• Varices and GI bleeding can be exacerbated by NSAIDs.