16th May 2025

Impairment of drug distribution

One of the synthetic functions of the liver is the production of plasma proteins, many drugs are bound to these proteins to allow for transport of drug molecules around the body. The proportion of a drug bound to plasma proteins is not free to bind to receptors and exert a pharmacological effect.

In liver disease this synthetic function can become impaired resulting in reduced circulating plasma proteins (hypoalbuminaemia). This can lead to an increase in the unbound fraction of drugs leading to more drugs to be available. In medications that are highly protein bound (e.g. phenytoin and prednisolone) this can result in increased adverse effects and a reduction in dose may be indicated.

Complications of oedema and ascites are driven by low levels of circulating plasma proteins. Medications which cause fluid retention may exacerbate this e.g. NSAIDs and corticosteroids.