Paracetamol overdose (195/1700)

A 16yo girl is admitted after taking a paracetamol OD 4 h ago. She has consumed lare amounts
of alcohol. Her plasma paracetamol conc is just below the conc that would suggest tx. What
should be the tx option for her?
a. Refer to psychiatry ward
b. Refer to medical ward
c. N-acetylcystine
d. Serum plasma paracetamol
e. No further investigation
























answer C, though under the treatment line slightly, the fact she consumed a lot of alcohol means her p450 sytem is going to be overloaded causing her toxicity at lower serum paractemol levels than used in the chart!



Some pathophysiology!
After taken orally, paracetamol is well absorbed from the stomach and small intestine. It reaches a peak plasma concentration in one hour, but this may be 30 minutes if taken in liquid or rapidly absorbed form. It is inactivated by the liver by conjugation leading to two metabolites; glucuronide or sulfate. It is then renally excreted through urine.

• When taken in overdose the liver conjugation becomes inundated, causing paracetamol to be metabolised by an alternative pathway.
• This results in a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is itself inactivated by glutathione, rapidly preventing any harm.
• When glutathione stores are depleted to less than approximately 30%, NAPQI reacts with nucleophilic aspects of the cell, leading to necrosis. Necrosis occurs in the liver and in the kidney tubules.

Toxicity is increased in patients with induction of the P450 system through drugs such as rifampicin, phenobarbital, phenytoin, carbamazepine and alcohol. This also occurs in patients with low glutathione reserves, as a product of:

• Genetic variation.
• HIV-positive.
• Malnutrition.
• Alcohol-related or other liver disease.