Paracetamol and Liver Toxicity

What is considered a GSL pack of paracetamol?

• 16 tablets in a pack

What is considered a P pack of paracetamol?

• 32 tablets in a pack

What kind of patient needs their dose of paracetamol to be reduced?

• patients with liver problems/ liver failure

What can increase the toxic effects of paracetamol?

• malnutrition and dehydration

What are the metabolic pathways that paracetamol can undergo and what is the percentage for each one?

• 60% undergoes glucuronidation

• 35% undergoes sulphonation

• 5% converts to NAPQI (TOXIC)

Why is NAPQI normally fine in normal doses of paracetamol?

• because the liver can detoxify the NAPQI by making it undergo glutathione conjugation (phase 2 metabolic pathway)

What happens with NAPQI when a paractemal overdose occurs?

• accumulation of NAPQI occurs and liver cannot get rid of all of it

• NAPQI starts attaching to hepatocytes, damaging them

What are the 2 treatments for paracetamol overdose?

• activated charcoal

• N-acetylcysteine

Why is activated charcoal not that great of a treatment for a paracetamol overdose?

• only works during first couple of hours and doesn’t work on the stomach or metabolites

What does N-acetylcysteine do?

• makes NAPQI more hydrophilic and polar allowing body to get rid of it

• Is nucleophilic due to suphydryl groups and these attack electron deficient carbon atoms on NAPQI

What is N-acetylcysteine a precursor to?

• glutathione