Prescribing for patients with liver disease can be challenging. Unlike in renal disease there is no direct measure that allows you to quantify liver function in terms of ability to metabolise drugs. Variation in the type (e.g. acute vs. chronic, cholestatic vs. hepatitis vs. cirrhotic) and severity of liver disease will both affect how drug metabolism is altered. This makes it difficult to make definitive dosage recommendations.

How would you adjust doses in liver disease?

The most important indicators of a reduced metabolic function are a raised INR and a reduced albumin. If this is the case you may need to reduce the dose of liver metabolised drugs. Sometimes medicines may have been studied in patients with liver disease and there are specific recommendations in the BNF or SPCs (available at www.medicines.org.uk). These are most commonly based on the Child Pugh category of liver disease, which were developed to predict mortality rather than as an indicator of metabolic function. Where the drug has not been studied in liver disease, it possible to make a number of recommendations based on the pharmacokinetic s of the drug and likely changes that will occur in liver disease, though this is often difficult to predict. Your local medicines information centre will be able to help with advice as interpreting information is often not straightforward.

Drug choice with regards to complications of liver disease

If you have a patient with liver failure under your care, you are likely to encounter some of the complications of liver disease such as encephalopathy, ascites and variceal bleeding. You may need to adjust drug therapy if these are present. Encephalopathy Generation of ammonia by bacteria in the large bowel is thought to contribute to encephalopathy, hence agents that cause constipation should be used with caution or given with laxatives. Examples include opiates, tricyclic antidepressants, 5HT3 antagonists, antidiarrhoeals and antimuscarinic drugs (e.g. procyclidine, oxybutynin, antispasmodics) Drugs that affect the central nervous system should also be used with caution or avoided, as their sedating effects may increase the risk of or worsen encephalopathy. Examples include opiates, tricyclic antidepressants, benzodiazepines, sedating antihistamines, antipsychotics.

Bleeding

Coagulopathy is a complication of liver disease, and hypersplenism secondary to portal hypertension may also result in thrombocytopenia. Variceal bleeding may also occur. Therefore any drug that increases the risk of bleeding should be used with caution or avoided in patients with these complications. Examples include NSAIDs, anti-platelets, anticoagulants, and SSRIs (e.g. fluoxetine)

Ascites

A high sodium intake may worsen ascites. You should avoid using sodium chloride 0.9% as a diluent for intravenous drugs if compatibility allows, and avoid soluble/effervescent preparations as they are often high in sodium content.

Can you use potentially hepatotoxic drugs in liver disease?

With the exception of sodium valproate and methotrexate, hepatotoxicity is no more likely to occur in someone with pre-existing liver disease, however the consequences are likely to be more serious. You may need to make a clinical judgement as to whether to prescribe. You should consider whether a less hepatotoxic drug can be used to treat the same problem, or whether treatment can be delayed until liver function improves. If neither is possible you will need to balance the risks of liver toxicity (based on the reported probability and severity) versus the benefits of the drug therapy you wish to use. You may wish to discuss this with a more senior member of your team.

Choice of antiemetic in liver disease

Choice of anti-emetic in liver disease A patient with a history of alcoholic liver disease presents with encephalopathy. His liver function tests are as follows -

ALP 183 (70-300iu/l)

Bilirubin 133 (3-15 micromol/l)

ALT 25 (0-35iu/l)

Albumin 24 (37-49g/l)

INR 2.9

The patient complains of nausea. Which of the following anti-emetics is the most appropriate choice? cyclizine, metoclopramide, prochlorperazine, ondansetron, domperidone