Paracetamol Overdose

Question 1

What enzyme is responsible for ‘mopping up’ reactive intermediates of paracetamol and so prevents toxicity and liver failure?

Answer 1

Glutathione transferase.

Question 2

What 4 features would you expect to see in the blood test results taken from someone who has overdosed on paracetamol.

Answer 2

1. Metabolic acidosis.
2. Prolonged pro-thrombin time (due to coagulability).
3. Raised creatinine (renal failure).
4. Raised ALT.

Question 3

What drug would you give to someone that has overdosed on paracetamol?

Answer 3

IV N-Acetyl-Cysteine.

Question 4

Describe the processing of paracetamol in the body on the normal therapeutic dose.

Answer 4

1. Predominantly metabolised via a Phase II reaction - conjugated with glucuronic acid & sulphate

• If stores of glucuronic acid and sulphate are running low:
  2. Paracetamol will undergo Phase I metabolism via oxidation

3. To produce a highly reactive toxic compound called NAPQI that is then IMMEDIATELY conjugated

4 Conjugated with glutathione and subsequently excreted

Question 5

Describe the processing of paracetamol in the body on an overdose.

Answer 5

1. Large amounts of paracetamol are metabolised by oxidation because of saturation of the sulphate conjugation pathway (Phase II reaction).
2. Liver GLUTATHIONE stores become depleted so that the liver is unable to conjugate and deactivate NAPQI.
3. This results in hepatotoxicity as well as paracetamol-induced kidney injury.

Question 6

Clinical presentation of a paracetamol overdose.

Answer 6

1. Nausea
2. Vomiting
3. Anorexia
4. RUQ pain

Question 7

When would liver damage reach its peak?

Answer 7

Liver damage reaches its peak with raised ALT and prothrombin time at 72-96 hours after ingestion.

Question 8

What can the patient develop after liver damage?

Answer 8

1. Jaundice
2. Encephalopathy

Question 9

What would the patient develop if no treatment is given?

Answer 9

Fulminant hepatic failure.

Question 10

Treatment of a paracetamol overdose.

Answer 10

1. Activated Charcoal (Gastric decontamination)
   - Within 1 hour of ingestion
2. Give IV N-Acetylcysteine
   - Which acts by replenishing cellular glutathione stores
   * Rash is common side effect and treat with CHLORPHENAMINE
   * Do not stop unless anaphylactoid reaction with shock, vomiting and wheeze