Decompensated Liver Disease

Question 1

Describe the considerations for drug absorption that are required in selecting drugs for patients with liver disease

Answer 1

• check if drug is lipid soluble (may be reliant on action of bile salts for absorption = as liver synthetic function is decreased in disease, absorption may be decreased)
  ^ leads to decreased plasma concentrations and efficacy of drug
• be aware that absorption of some drugs are delayed (cirrhosis/ascites), however this cannot be predicted

Question 2

Describe the considerations for drug distribution that are required in selecting drugs for patients with liver disease

Answer 2

• check if drug is water soluble (may distribute to ascitic fluid = lower concentrations of drug in areas of the body where it is needed)
• check if drug is highly protein bound (liver disease = low albumin levels = larger quantities of unbound drug = drug toxicity)

Question 3

Describe the considerations for drug metabolism that are required in selecting drugs for patients with liver disease

Answer 3

• check if drug is metabolised by liver (reduced liver mass in cirrhosis = reduction in metabolising enzymes = drug accumulation = toxicity)
• check if drug undergoes high first pass metabolism (esp in advanced cirrhosis) = portal hypertension (from reorganisation of cells = variceal formation = increased amount of drug in systemic system = increase in bioavailability = toxicity
• does drug require activation in liver (decreased metabolism due to disease can limit activation and therapeutic effect of drug)

Question 4

What marker can be used to monitor metabolism of drug in liver?

Answer 4

• INR (elevated if reduced capacity eg. In cirrhosis)
• reduced initial/maintenance doses required (amount cannot be predicted)

Question 5

Describe the considerations for drug excretion that are required in selecting drugs for patients with liver disease

Answer 5

• check if drug needs biliary excretion (if cholestatic this can be reduced = drug accumulation)
• check if drug needs renal excretion (dose reduction may be required)

Question 6

Describe the pharmacodynamic effects of liver disease

Answer 6

• cirrhosis/liver = increased sensitivity to therapeutic/adverse effects of drugs
• eg. Increased sensitivity to CNS drugs
• some drugs can have a reduced response eg. Diuretics

Question 7

Why must careful consideration be needed in paracetamol prescribing for patients with chronic liver disease/cirrhosis?

Answer 7

• liver disease reduced the body’s glutathione stores which are required to block the formation of the toxic metabolite NAPQI which is formed by paracetamol (results in a prolonged half-life)
• avoid use in advanced disease/cirrhosis with alcohol consumption/anorexia/malnourishment/receiving medication which is either being cleared by the liver/induces liver enzymes
  ^ use opioid instead