Outline the normal metabolism of paracetamol and outline the use of n-acetylcysteine (NAC) in treating paracetamol overdose

- Orally, IV or rectally.

How is paracetamol ingested?

- Metabolised by hepatocytes in the liver (achieved through glucuronidation and sulfation).

- Small amount is metabolised by cytochrome P450 enzymes.

- Metabolised portion forms NAPQI which is highly toxic and can only be inactivated by glutathione.

Process of metabolisation of paracetamol

- In therapeutic doses the liver is able to break it all down, but in overdoses the hepatocytes cannot break it all down.

- More paracetemol therefore undergoes metabolism by cytochrome P450, creating NAPQI.

- There is a limited supply of glutathione, so not all of the NAPQI can be inactivated.

- Oversupply of NAPQI causes cell death and acute hepatic necrosis.

What happens to metabolism of paracetamol in overdose?

- Readily absorbed from the GI tract and peaks in plasma around 10-60 mins after oral administration.

- Elimination half life of 1-3 hours.

Pharmacokinetics of paracetamol

- Analgesic by central inhibition of prostaglandin synthesis.

- Antipyretic activity.

Pharmacodynamics of paracetamol

- Safe to wait for paracetamol concentration and decide on need for NAC within 8 hours of ingestion.

- Patients who present more than 8 hours after overdose/have symptoms of toxicity should be commenced on NAC.

- If NAC is not given then patients are at risk of liver injury.

Acute management of someone presenting with paracetamol overdose

- Increases glutathione so that NAPQI can be inactivated.

Role of N-acetylcysteine in treating paracetamol overdose