Medicines and the liver

Last updated: Sunday, July 12, 2015

The effects of liver disease on drug handling are determined by the nature and severity of the impairment. However, these are examples of what may occur:

  • Hepatocellular damage can reduce the metabolising capacity of the liver. When metabolism is slowed, drugs may accumulate.
  • If the levels of plasma proteins fall, due to reduced synthesis by the liver, drugs that are normally highly protein bound will have a greater proportion of free drug in circulation. This may result in increased potency and the half-life may be affected.
  • If there is cholestasis, excretion via the bile is impaired.
  • Cirrhosis may result in blood from the gastrointestinal tract bypassing the liver, so that first-pass metabolism is reduced. For drugs that are normally subject to a high rate of first-pass metabolism, this increases bioavailability and therefore the potency of a given dose.
  • Hepatic encephalopathy may occur when nitrogenous compounds absorbed from the gut accumulate and render the brain more susceptible to the CNS depressant effects of drugs.

Cirrhosis of the liver 
Courtesy of St Bartholomew's Hospital Archives and Wellcome images

Prescribing in liver disease

The following tips may be helpful:

  • Avoid hepatotoxic drugs where possible. Patients with existing hepatic disease are not more prone to hepatotoxicity (unless it is dose-related), but they do have diminished reserve hepatic function and may suffer disproportionately if hepatotoxicity does occur. The advent of drug hepatotoxicity on top of existing liver disease will also confuse the diagnostic picture.
  • Continue to monitor LFTs regularly while liver dysfunction persists.
  • For drugs cleared or metabolised by the liver, be alert to signs of drug side effects: know what they are and monitor for them. Monitor drug levels where appropriate.
  • Non-systemic treatments should be chosen where possible. Renally-excreted drugs are also preferred as long as renal function is normal. Monitor for any changes in renal function regularly.
  • Drugs that increase the risk of bleeding should be avoided or used with extreme caution, depending on the severity of liver disease.

  • Drugs that are highly dependent on the liver for deactivation or clearance are likely to need dose reduction in moderate to severe liver disease.
  • Avoid sedating drugs in patients at risk of developing encephalopathy. Many of these drugs have long half-lives and are liver metabolised, so their duration and intensity of action may be prolonged in liver disease. The brain also becomes more sensitive to sedating effects in liver disease. A sedative drug may precipitate or mask encephalopathy.
  • The doses of highly protein bound drugs may need reducing in patients with low albumin levels due to chronic liver disease.
  • Keep drug prescribing to a minimum – use the smallest effective doses at greatest interval, and titrate according to clinical response.