PSA on acetaminophen (Tylenol)

[conuly]

I believe that in the UK you call it paracetamol, right?

The dangerous dose is apparently much lower than many of us think:

http://siderea.livejournal.com/1072745.html

http://www.propublica.org/article/tylenol-mcneil-fda-use-only-as-directed

Comments

[andrewducker]

Yup, paracetomol in the UK.

And we're _very_ aware of the dangers over here - you can't buy more than a packet at a time, or both paracetomol and cold medication that contains it.

[janewilliams20]

This is news?
It doesn't have the risks for asthmatics that aspirin does, and it doesn't cause the digestive problems of codeine, but yeah, overdoses kill, and the "recommended dose" is there for a reason.

[conuly]

It most definitely is in the US.

[ksol1460.livejournal.com]

This was covered on This American Life, here. (http://www.thisamericanlife.org/radio-archives/episode/505/use-only-as-directed)

[conuly]

Yes, but I couldn't find a transcript. (Admittedly, I didn't look all that hard.)

[ksol1460.livejournal.com]

woops! transcript here

http://www.thisamericanlife.org/radio-archives/episode/505/transcript

[dandelion.livejournal.com]

I think a decent proportion of this is incorrect.

Short version: paracetamol overdose is dangerous and you don't need that much to overdose. The problem with the latter part of that post is, that person has taken two facts:
ethanol is a CYP inducer (actually outright wrong, in non-alcoholics it's an inhibitor of metabolism)
ethanol encourages the liver damage when taken with paracetamol (not disputing that)
and come to the conclusion that therefore CYP inducers plus paracetamol are dangerous. This is a massive leap of logic.

Longer version, what I actually posted (but it's screened cos I'm not her friend):
"I found this post via conuly. I am not sure you are correct about the pharmacology of paracetamol metabolism.

Acute ethanol use is an inhibitor of cytochrome p450 and is only an inducer in chronic usage. The reason for paracetamol-ethanol toxicity is not a CYP interaction per se, but saturation of the glucuronidation and sulfation alternative metabolism pathways causing paracetamol to be metabolised via CYP instead.

The significant thing is not induction or inhibition of CYP, but saturation of glutathione conjugation (which detoxifies NAPQI). Regarding specific agents, I looked them up in Stockley's Drug Interactions, which is our most common reference source for interactions:
"Heavy, but not moderate, tobacco smoking might increase the metabolism of paracetamol."
"It seems unlikely that specific foods, such as watercress and charcoal-broiled beef, would have a significant clinical effect, except perhaps cabbage and brussels sprouts if eaten to excess."
Insulin and paracetamol produces no results.

Paracetamol overdose is dangerous but I'm not at all convinced by the pharmacology of the risk factors you've posited. You've made the assumption that CYP induction causes paracetamol metabolism to proceed via CYP instead of the usual preferential glucuronidation/sulfation pathways, and I think that definitely needs a [citation needed]."