Drug and Toxin Induced Liver Disease

Question 1

How is paracetamol metabolised?

Answer 1

Hepatic cytochrome p450 system

Question 2

Dose paracetamol for FHF?

Answer 2

• 10-15g in healthy adults

- 4-6g in alcohlics / anticonvulsant users

Question 3

Mechanisms of paracetamol hepatoxicity?

Answer 3

• High acetaminophen dose
• Saturates glucuronidation and sulfation elimination pathways (glutathione depleted)
• Reactive metabolite formed
• Covalently binds hepatocyte membrane

Question 4

Presentation of paracetamol hepatotoxicity?

Answer 4

• 1st 24h: N/V
• 24-48: asymptomatic. Ongoing hepatic necrosis w/ elevation of transaminases
• > 48: continued hepatic necrosis +/- FHF or resolution

Question 5

What is the purpose of testing blood paracetamol levels?

Answer 5

Blood levels of paracetamol correlate with the severity of hepatic injury, esp if time of injury known

Question 6

Rx paracetamol overdose?

Answer 6

-Gastric lavage (

Question 7

AEx of chlorpromazine?

Answer 7

Cholestasis in 1% after 4/52; +/- fever, rash, jaundice, pruritus, eosinophilia

Question 8

AEx of isoniazid?

Answer 8

20% develop transaminase elevation;

Question 9

AEx methotrexate?

Answer 9

• Causes cirrhosis
• Inc risk w/ obesity, DM, EtOH (i.e. w/ underlying risk for pre existing fatty liver)
• Scarring develops w/o Sx or LFT change
• Bx may be needed in long term Rx

Question 10

Amiodarone effect on liver?

Answer 10

Can cause same histology and clinical outcome as alcoholic hepatitis