Liver Failure

Question 1

What factors would be considered in the assessment of liver disease? (9)

Answer 1

• Plasma enzymes are generally not specific indicators of hepatic dysfunction (ALP isoenzyme is an exception)
• ALT is more specific than AST
• GGT usually indicates hepatocellular damage and is an indicator of alcohol damage
• LFT are a measure of liver damage rather than liver function
• Liver disease can effect drug kinetics in different ways so it’s hard to give general advice
• Critical to obtain good background about the liver disease and overall medical condition
• Not all pts with liver disease have liver disfunction
• INR is a good indicator of metabolic capacity

Question 2

How do drugs effect absorption in liver disease? (3)

Answer 2

• Lipid soluble drugs may be reliant on bile salts to aid absorption
• These drugs may be less well absorbed in a pt with cholestasis, potentially leading to reduced plasma concentration and reduced efficiency
• The absorption of drugs (eg furosemide) is delayed in pt with cirrhosis and ascites - this is unpredictable

Question 3

How do drugs effect distribution in liver disease? (3)

Answer 3

• If a drug is water soluble it may distribute into ascitic fluid
• Chronic liver disease may result in low albumin levels, which will effect drugs that are protein bound
• Some drugs with high protein binding can be displaced from their binding site by bilirubin in presence of hyperbilirubinaemia, leading to a high concentration of free drug

Question 4

How do drugs effect metabolism in liver disease? (3)

Answer 4

• Reduction in drug metabolising enzymes may lead to an accumulation of active drug and the potential for enhanced response and increased side effects
• CYP450 mediated phase 1 reactions are more likely to be effected than conjugation reactions such as glucuronidation (phase 2 reactions are preserved)
• If the drug undergoes substantial first pass metabolism (portal hypertension) then greater proportion of oral drug can enter the systemic system causing a large rise in bioavailability

Question 5

How do drugs effect excretion in liver disease? What are the two considerations?

Answer 5

• Does the drug undergo biliary excretion?
• Does the drug undergo enterohepatic re circulation?