Non-opioids - Paracetamol

Question 1

What is paracetamol used for?

Answer 1

1st line analgesic for acute/chronic pain.

Can also reduce fever and symptoms e.g. shivering

Question 2

How does paracetamol work?

Answer 2

weak inhibitor of COX-2 enzyme. so less prostaglandins that cause pain. (it is a weak anti-inflammatory

Question 3

What are the side effects of paracetamol?

Answer 3

• very safe BUT:

- in overdose causes liver failure

Question 4

how does paracetamol overdose cause hepatocellular necrosis?

Answer 4

Paracetamol is metabolised by cytochrome P450 enzymes to a toxic metabolite which is then conjugated with glutathione so it can be eliminated.

In overdose this conjucation pathway gets saturated so the toxic metabolite remains in the liver .

Question 5

How can hepatotoxicity be prevented in paracetamol overdose?

Answer 5

glutathione precursor acetylcysteine.

glutathione conjugated the toxic metabolite of paracetamol so it can be eliminated

Question 6

What are the contraindications of paracetamol?

Answer 6

• dose should be reduced in liver impairement.
• dose should be reduced in people with lower glutathione stores e.g. malnourished, low weight, severe hepatic impairment.

Question 7

What are the drug interactions of paracetamol?

Answer 7

Paracetamol interacts with cytochrome P450 inducers as they increase the rate of NAPQI (toxic metabolite) production and therefor the risk of liver toxicity after paracetamol overdose.

• Phenytoin
• Carbamazepine

Question 8

What is the dose and route of paracetamol?

Answer 8

0.5 to 1g every 4-6hours

PO, IV, Rectal

Question 9

After overdose of paracetamol what blood tests help to establish the efficacy f acetycysteine (glutathione precursor

Answer 9

1) INR
2) Serum alanine transferase (ALT)
3) creatinine conc