Concurrent alcohol intake lowers these thresholds significantly. The lethal dose is usually between 10 g and 15 g. The minimum dosage at which paracetamol causes toxicity usually is 7.5 to 10g in the average person. The amount of NAPQI produced differs in certain populations. In an average adult, only a small amount (approximately 10% of a therapeutic paracetamol dose) of NAPQI is produced, which is inactivated by conjugation with glutathione (GSH). A small amount of the drug is metabolized via the cytochrome P-450 pathway (to be specific, CYP3A4 and CYP2E1) into NAPQI, which is extremely toxic to liver tissue, as well as being a strong biochemical oxidizer. This yields a relatively non-toxic metabolite, which is excreted into bile and passed out of the body. In adults, the primary metabolic pathway for paracetamol is glucuronidation. Pathways shown in blue and purple lead to non-toxic metabolites the pathway in red leads to NAPQI, which is toxic if not conjugated to glutathione. Acetaminophen (paracetamol) metabolism (click to enlarge).
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