PAracetamol overdose
see ingestion, liver disease
paracetamol = N-acetyl-p-aminophenol
Normally
90 % metabolized in the liver to sulfate and glucuronide conjugates, which are then excreted in the urine
2% is excreted in the urine unchanged
8% metabolized via the hepatic cytochrome P450 (CYP2E1, CYP1A2, CYP3A4 subfamilies) into a toxic, highly reactive, electrophilic intermediate, N-acetyl-p-benzoquinoneimine (NAPQI)
these small amounts of NAPQI rapidly conjugated with hepatic glutathione and excreted in the urine
Overdose
Sulfate and glucuronide pathways overwhelmed
NAPQI depletes glutathione stores
NAPQI causes hepatocellular centrilobular necrosis
Synthetic function best predictor of need for transplant
Rx
N-acetylcysteine (NAC) within 8 hours if required