Adverse effects and the liver
As well as understanding how liver dysfunction can affect the way the body handles medicines, it is also important to consider how medicines can affect the liver. This depends on the type of liver disease, the degree of hepatic dysfunction, and the patient's signs and symptoms. So it needs to be considered for each individual patient.Some medicines have an adverse effect profile that can cause problems for patients with liver disease. Quite apart from this, there are also medicines that may damage the liver itself, and this is called hepatotoxicity.
Adverse effect profile
Consider the potential for medicines to cause adverse reactions such as those described below when choosing or monitoring a medicine in a patient with liver dysfunction. You can read more about this subject via the SPS website, but example side effects that may be of concern include:
✦ Changes to LFTs
Some drugs can cause mild, transient, insignificant rises in LFTs but this may not be an absolute contraindication in patients with liver dysfunction. The risks and benefits of using the medicine need to be considered, although be careful because interpretation of LFTs and monitoring of the course of a patient's liver disease may become more complicated.
✦ Pruritus
Patients with cholestatic liver disease often experience severe itch. Avoid drugs with a high incidence of urticaria or itching.
✦ Fatigue
Patients with cholestasis and cirrhosis often suffer from tiredness. Encephalopathy can be made worse by medicines that cause sedation. Avoid drugs which cause drowsiness.
✦ Clotting abnormalities
Patients with liver dysfunction may have impaired clotting. Drugs with a bleeding risk (e.g. anticoagulants, NSAIDs, antiplatelets) should only be used where the benefit outweighs the risk.
✦ Changes to electrolytes
Ascites is a build-up of fluid in the abdomen caused by significant liver disease. It can be made worse by increasing sodium levels. Avoid drugs which can increase sodium (e.g. NSAIDs inhibit sodium and water excretion) and consider the sodium content of drugs (e.g. effervescent tablets, IV preparations). Encephalopathy can be precipitated by electrolyte disturbances. Drugs which can cause electrolyte disturbances should only be used where the benefits outweigh the risks, and with appropriate monitoring.
✦ Constipation
Encephalopathy can be precipitated by constipation, so avoid drug-induced constipation.
✦ Gastrointestinal irritation
Patients with oesophageal varices due to liver disease may be at increased risk of bleeding from drugs that irritate the GI tract (e.g. NSAIDs, bisphosphonates).
✦ Nephrotoxicity
Certain types of liver disease increase the risk of developing renal impairment. Use potentially nephrotoxic drugs with caution, and avoid if possible – especially in patients with 'hepatorenal syndrome' (impaired kidney function in patients with severe liver disease in the absence of any other identifiable cause of renal pathology).
Some drugs can cause mild, transient, insignificant rises in LFTs but this may not be an absolute contraindication in patients with liver dysfunction. The risks and benefits of using the medicine need to be considered, although be careful because interpretation of LFTs and monitoring of the course of a patient's liver disease may become more complicated.
✦ Pruritus
Patients with cholestatic liver disease often experience severe itch. Avoid drugs with a high incidence of urticaria or itching.
✦ Fatigue
Patients with cholestasis and cirrhosis often suffer from tiredness. Encephalopathy can be made worse by medicines that cause sedation. Avoid drugs which cause drowsiness.
✦ Clotting abnormalities
Patients with liver dysfunction may have impaired clotting. Drugs with a bleeding risk (e.g. anticoagulants, NSAIDs, antiplatelets) should only be used where the benefit outweighs the risk.
✦ Changes to electrolytes
Ascites is a build-up of fluid in the abdomen caused by significant liver disease. It can be made worse by increasing sodium levels. Avoid drugs which can increase sodium (e.g. NSAIDs inhibit sodium and water excretion) and consider the sodium content of drugs (e.g. effervescent tablets, IV preparations). Encephalopathy can be precipitated by electrolyte disturbances. Drugs which can cause electrolyte disturbances should only be used where the benefits outweigh the risks, and with appropriate monitoring.
✦ Constipation
Encephalopathy can be precipitated by constipation, so avoid drug-induced constipation.
✦ Gastrointestinal irritation
Patients with oesophageal varices due to liver disease may be at increased risk of bleeding from drugs that irritate the GI tract (e.g. NSAIDs, bisphosphonates).
✦ Nephrotoxicity
Certain types of liver disease increase the risk of developing renal impairment. Use potentially nephrotoxic drugs with caution, and avoid if possible – especially in patients with 'hepatorenal syndrome' (impaired kidney function in patients with severe liver disease in the absence of any other identifiable cause of renal pathology).
Hepatotoxicity
There are two types of hepatotoxicity:
(1) Intrinsic is predictable, reproducible, and dose-dependent (e.g. when caused by paracetamol overdose or alcohol). It is the less common type.
(2) Idiosyncratic hepatotoxicity is unpredictable and independent of dose. It is more common and may involve signs of hypersensitivity such as fever, rash and eosinophilia.
The decision to use a drug with a hepatotoxicity risk depends on various factors, including:
- The reported frequency and severity of hepatotoxicity
- Clinical urgency of treating the condition concerned
- The other options available as treatment
- Reversibility of liver damage upon withdrawal of the drug
In general, patients with pre-existing liver disease are thought to be at no greater risk of drug-induced liver damage than the general population. There are a few exceptions to this rule (e.g. methotrexate, rifampicin). However, patients with pre-existing liver disease may have less hepatic reserve if hepatotoxicity occurs; therefore avoid drugs that have a high incidence of causing liver damage if at all possible.