Gastro - Paracetamol OD

Question 1

describe the metabolism of paracetamol at therapeutic doses

Answer 1

1. Mostly metabolised by conjugation to glucuronide or sulphate to form non-toxic metabolites which are renally excreted.
2. <15% metabolised into NAPQI (hepatotoxic) by CYP450s which is then conjugated with glutathione.

Question 2

what are the effects of paracetamol OD on the liver?

Answer 2

When taken in OD, liver conjugation system is overwhelmed… increased NAPQI production… depletion of glutathione to <30%… oxidative stress and NAPQI reacts with nucleophilic aspects of cells… necrosis of liver and kidney tubules.
Can result in acute liver failure within several days.

Question 3

how do pts who have taken paracetamol OD usually present?

Answer 3

1st 24 hrs: asymptomatic or nausea and vomiting.

Hepatic necrosis begins after 24 hrs: RUQ pain and jaundice. Can progress to acute liver failure. May also develop:

• encephalopathy
• oliguria or renal failure
• hypoglycaemia
• lactic acidosis

Question 4

how would you investigate a pt with suspected paracetamol OD?

Answer 4

Bloods:

• paracetamol level: measure 4 hrs post-ingestion or as soon as pt arrives if >4 hrs
• LFTs: may be normal if pt presents early, but may rise to ALT >1000 iU/L
• UandE and creatinine: for baseline and to assess for renal failure
• glucose: hypoglycaemia common in hepatic necrosis, CBG should be checked hourly
• clotting screen: PT is best indicator of severity of liver failure and INR should be checked every 12 hrs
• ABG: acidosis can occur at a very early stage, even when pt is asymptomatic

Question 5

how would you manage a pt with paracetamol OD?

Answer 5

1. Consider 50g activated charcoal PO if ingestion of >150mg/kg Pctml <1 hr.
2. Acetylcysteine infusion: for all pts with timed plasma paracetamol level on or above line on nomogram. Give without delay if any doubt about timing of ingestion, inc. staggered OD >1 hr.
3. Refer to ICU if fulminant liver failure.
4. List for transplantation if required.

Question 6

explain the MOA of acetylcysteine

Answer 6

Acts as precursor for glutathione, promoting conjugation of excess NAPQI, and contains thiols that act as antioxidants.

Virtually 100% effective in preventing liver damage when given <8 hrs of ingestion.