21st March 2024

Hepatic impairment

Metabolism is the main method of elimination for many drugs. In severe liver disease, the cytochrome P-450 system is reduced but can be complex and unpredictable. Dose adjustments may need to be made particularly if the drug is metabolised in the liver.

Hypoalbuminaemia

Severe hepatic disease can lead to reduced levels of albumin which is the most abundant plasma protein. In this state, there is a decrease in plasma protein binding. The unbound drug is able to pass through the cell membrane and exert its effects on cells. Highly protein bound drugs such as doxycycline, phenytoin and prednisolone exert larger effects than usual.

Coagulopathy

Patients with severe liver function may have impaired synthesis of clotting factors. This leads to increased sensitivity to drugs such as phenindione and warfarin.

Encephalopathy

Patients with hepatic encephalopathy may have symptoms exacerbated by sedatives, opioids, constipating agents and electrolyte disturbances which can also be precipitated by diuretics.