Paracetamole

Question 1

How is paracetamol metabolised normally?

Answer 1

Glucoronidation & sulfation in the liver

Question 2

What occurs to paracetamol in toxicity?

Answer 2

Glu and sulf pathways saturated leading to production of NAPQI which is toxic

NAPQI can be reduced by glutathione but in OD gluatathione stores are depleted

Glucoronidation is dependent on carbohydrate stores so malnourished patients are at higher risk e.g. anorexics

Question 3

Which drugs can increase cyto P450 and therefore increase risk of toxicity?

Answer 3

Anti-eplipleptics: carbamazepine.pheyntoin
Anti-tuberculosis : rifampicin
All steroids
Nicotine + alcohol

Population at increased risk

Question 4

How does NAC work?

Answer 4

Stimulate glutathione synthesis

Question 5

What are the four clinical stages of paracetamol toxicity?

Answer 5

1st 24 hours: asymptomatic =/- emesis
24-72 hours: Emesis, RUQ +/- hypotension
72-96 hours: HAGMA, renal failure, coagulopathies, encephalopathy
4 days - 3 weeks: recovery

Question 6

What estimated paracetamol OD dose triggers treatment with activated charcoal?

Answer 6

IR ≳10 gram
OR ≳200mg/kg
within the last 2 hours

OR

MR >10grams or 200mg/kg
IR >30g
within last 4 HOURS

Whichever is less

Question 7

What dose of activated charcoal should be given?

Answer 7

1gram/kg
E.g. 50-100 in adult

Question 8

When should NAC be given in IR paracetamol OD after a single ingestion and what dose?

Answer 8

If APAP level is > treatment nomogram on a sample at 4 hours: NAC

Bag 1: 200mg/kg in 500ml 5% dextrose over 4 hours
Bag 2: 100mg/kg in 1000ml 5% dextrose over next 16 hours

Question 9

What are the adverse effects of NAC?

Answer 9

Vomiting
Bronchospasm
Oesophageal varices/PUD (increased risk of bleeding)

Question 10

What paracetamol level or OD would trigger an increase in NAC dosing?

Answer 10

> 2x the nomogram level at 4 hours

MR prep doses ≳30g or ≳500mg/kg

Double the dose of the second bag of NAC so both are 200mg/kg

Question 11

What are the endpoints for ceasing NAC after 20 hours?

Answer 11

ALT falling or normal
INR <2
Clinically well
APA <10mg/L

ALL criteria must be met

Question 12

What are the indications for discussion with a liver transplantation service?

Answer 12

INR >3 @ 48 hrs
INR 4.5 anytime
Oliguria or Cr >200 umol/L
Persistent acidosis <7.3 or lacatate >3
Fluid resistant shock SBP <80
Hypoglycaemia
Severe thrombocytopaenia plts <50
Encephalopathy