can someone please explain the toxicity process here? including the NAPQI stuff and acetaminophen's adduction to something on the hepatocyte. i can't find a good explanation of this in first aid
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Step I acetaminophen toxicity
Started by Chaoticsheath
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This is very brief because I don't remember all of it....Acetaminophen is metabolized by the P450 system in the Liver and one of the products is the toxic metabolite NAPQI. Glutathione (GSH) is normally present to convert NAPQI to a non-toxic compound, however, if there is an overdose NAPQI accumulates because there isn't enough of GSH around and results in liver damage. The antidote is n-acetylcysteine which helps bind to toxic compounds like NAPQI BUT also helps in regenerating and gathering the body's stores of GSH.....hope it helps some.
I've also encountered in a practice question that N-acetylcysteine can be used instead of Mesna to prevent haemorrhagic cystitis associated with cyclophosphamide/ifosfamide.
Here's what I found in my notes...
90% acetaminophen is metabolized in liver by sulfation and glucuronide conjugation, 10% by P450 system and urinary excretion of un-metabolized drug. The P450 system produces the metabolite N-acetyle-p-benzoquinoneimine (NAPQI), which is toxic and highly reactive.
In low doses of acetaminophen, NAPQI is still produced but sulfated and eliminated easily. At high doses, the sulfation system is saturated, so the NAPQI is left to cause hepatocellular injury and centrilobular necrosis.
N-acetyl-cysteine provides sulfhydryl groups in the acetaminophen metabolism, and it also acts as a glutathione substitute and binds the toxic metabolite NAPQI.
I hope that helps!
