Analgesics and Anti-inflammatories - Paracetamol (1) Flashcards Preview

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Flashcards in Analgesics and Anti-inflammatories - Paracetamol (1) Deck (10):
1

Paracetamol overdose - give an overview of the pharmacology.

At toxic doses, the three different Phase II reactions in the metabolism of paracetamol are saturated. This results in accumulation of a toxic Phase I metabolite, which leads to hepatotoxicity and death. (See Chapter 4 of Katzung)

2

Name the two dominant phase II reactions in the metabolism of paracetamol. These two make up 95% of the total excreted metabolites - producing non-toxic metabolites.

Glucuronidation and Sulfation.

3

Name the third phase II reaction in the metabolism of paracetamol - the one that detoxifies the toxic phase I metabolite.

Conjugation with glutathione.

4

As hepatic _______ decreases, in paracetamol overdose, the toxic phase I metabolite may bind to hepatocyte proteins, leading to liver cell damage and necrosis.

Glutathione.

5

Paracetamol can be toxic after doses as low as _____ are ingested.

10g

6

Paracetamol can be fatal after doses as low as _____ are ingested.

25g

7

What is the basic guideline for management of paracetamol overdose?

If it has been less than 4hrs since ingestion of unknown dose: wait until 4hrs, take a serum level.
If it has been 4-8hrs since ingestion of unknown dose: take a serum level, and treat as per nomogram.
If the dose is known to be >15g, give NAC.

8

Describe what you know about the mechanism of action of the antidote to paracetamol overdose.

N-acetylcysteine is a sulfhydryl group donor. It may restore depleted hepatic glutathione levels.

9

NAC is most effective when administered ____ hours after paracetamol ingestion.

Within 8 hours.

10

What is the dose of NAC to give?

Initial dose of 150mg/kg over 15 minutes. Then 50mg/kg infusion over 4 hours. Then 100mg/kg infusion over 16 hours.

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