nadiabarati wrote:
I think more drug causes more toxic metabolite by MORE stimulation of CYTp450. because there are more toxic metabolite, glutathione is not enough to detoxify it. In fact there isn't any decrease in glutathione but more toxic metabolite overcome it.
Please correct me if I'm wrong somewhere...
I think it doesn't stimulate cytochrome p450 but this oxidation pathway just become more significant (or more used) when the other alternative pathways (normal conjugation) for metabolism become saturated with the high conc. of acetamenophen(so I don't see it as stimulate the enzyme), causing more formation of the metabolite which then consumes the glutathione to become detoxified, and once glutathione is depleted the accumulating metabolite(N-acetyl-benzoquinineimine) causes the liver toxicity.
Feel free to correct me 
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| nadiabarati
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asherif, if it's not stimulation! why did you choose 2 which says stimulation?!
Anyway I think we are saying the same thing.
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| asherif
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nadiabarati wrote:asherif, if it's not stimulation! why did you choose 2 which says stimulation?! Anyway I think we are saying the same thing.
cytochrome oxidase looked more logic as an answer for me so I assumed it as "stimulation of cytochrome oxidase pathway" 
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| DrVirgo
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This is how the acetaminophen toxicity happens:
OD of acetaminophen.... Acetaminophen is converted by the hepatocyte cytochrome system to free radicals (I don't know if this is considered "stimulation" of cytochrome system or not, but if anyone knows, please say)... This is the MCC of fulminant hepatic necrosis due to drugs (according to Goljan).
Then GSH which is made up of NAC breaks down acetamophen free radicals and gets used up. Thats why we give NAC to replenish GSH so it can neutralize the remaining FR's.
Nadia, where is this question from? Or were you just asking?
I guess 2 happens first and then 1.
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| mjl1717
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i like answer #1
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| robin082006
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The question asks: "what is the primary mechanism for hepatotoxicity in acetaminophen overdose?"--> so choice 1 is the best.
If the question asks: what can increase the toxic metabolite in acetaminophen overdose?"--> choice 2 is best.
In qbank there is about the mechanism for hepatotoxicity in acetaminophen overdose and answer is choice 1.
In Rapid review CD there is a question about the drug that increases the severity for hepatotoxicity in acetaminophen overdose--> answer is any drug that induces P450.
Hope this helps.
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