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More about acetaminophen - Input Junkie
October 6th, 2013
11:59 am

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More about acetaminophen
Edited to add: This material is about the US. The laws are much more restrictive in (most of?) Europe, and I don't know about the rest of the world.

siderea took my post about Tylenol/acetaminophen/paracetamol and and ran with it.

Here's a prime bit, but really, read the whole thing and the comments:
3) Alcohol makes acetaminophen stronger, and lowers the fatal acetaminophen dose. Don't be drinking and taking acetaminophen.

3a) More specifically, acetaminophen is metabolized by CYP2E1 (among other CYP isoenzymes). Ethanol is a CYP2E1 inducer, and apparently, it's the metabolites of acetaminophen overwhelming the liver which is dangerous, so anything which increases the rate of CYP2E1 activity is dangerous with acetaminophen. You know what else is listed as a CYP2E1 inducer? Tobacco smoking.

3b) While we're at it, CYP1A2 and CYP2D6 are also involved. You know what interacts with CYP1A2 and CYP2D6? Everything. Inducers include tobacco, broccoli, brussel sprouts, Echinacea, chargrilled meat (hey, I'm just copying this from Wikipedia), cauliflower and insulin.

3c) Also, you'll want to have been very careful not to have inherited or mutated an extra copy (or multiple extra copies) of the gene for CYP2D6 (or presumably CYP1A2 or CYP2E1), something which it is speculated is the source of some people's unusually high susceptibility to acetaminophen overdose. Good luck with that.

4) There are legitimate reasons to prefer acetaminophen over ibuprofen and aspirin. You should know what they are if you're taking it, and you should take considered steps to prevent accidents. In a house with a child or other cognitively impaired party, it belongs in a locked medicine chest.

And I'm wondering whether having acetominiophen in prescription drugs which contain opiates might really be intentional murder. Or it might just be sloppiness-- opiates are bad, adding bad things to bad drugs might discourage use, fail to think about actual consequences because it's a bad drug.

Anyone else remember Triage? It was about a conspiracy of non-preference utilitarians who were using looser and looser standards to kill people who were "better dead".

This entry was posted at http://nancylebov.dreamwidth.org/1018386.html. Comments are welcome here or there. comment count unavailable comments so far on that entry.

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From:whswhs
Date:October 6th, 2013 04:27 pm (UTC)
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What is a non-preference utilitarian?
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From:nancylebov
Date:October 6th, 2013 04:32 pm (UTC)
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Approximately: A preference utilitarian thinks that the world is better if people get more of what they want. A non-preference utilitarian has some standard of better which doesn't reliably include what people want. It might be happiness, it might be lifespan, it might be something which isn't coming to mind at the moment.

I have no doubt that I've left out a lot of important philosophical details.
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From:whswhs
Date:October 6th, 2013 06:10 pm (UTC)
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It seems kind of weird to call it "utilitarianism" at all. I'm used to "utility" being defined as "people getting what they want." It's kind of an ethical analog of phenomenalism in metaphysics.
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From:ritaxis
Date:October 6th, 2013 04:54 pm (UTC)
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When I take acetaminophen, it is because it is the only over the counter pain reliever I am allowed to take because all the others -- aspirin and NSAIDs -- interact badly with a drug I have to take (yes, have to, just did a three-day experiment without it and it's definitely not optional). I am also allowed occasional use of opiates, but they don't really work anymore, which is sad, because I used to get a great effect from a fractional dose and I didn't have unpleasant side effects, so I loved them (and hardly ever used them). (Acetaminophen doesn't work all that well any more either. The only things that do work for my pain these days are targeted exercise and rest. It's really limiting)

I don't know if you've ever looked at the dosages on acetaminophen-opiate combinations, but they are low. And that is the point of those combinations. They are synergistic in their pain relief effects and you can use much, much smaller amounts of them to get the desired effect (unless you are like me and they just don't work for you). So, no, the people who create the combinations are not out to get the people who use them -- they're out to spare them the side effects of the drugs by enabling them to use smaller amounts.
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From:redbird
Date:October 6th, 2013 06:12 pm (UTC)
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Yes, there are sound arguments for the synergistic combinations. That said, it also feels like some people who are influencing policy are out to get the people who are using the medicine. Those arguments come out when people point out that not everyone can safely take acetaminophen at all, and that the synergy doesn't work for everyone, so non-acetaminophen versions of the drugs should also be available.

There are people who seem to believe that it's better [for whom?] if someone takes X mg of an opiate plus 500 mg of acetaminophen, than the exact same amount of opiate and no acetaminophen, and gets the same amount of pain relief. The claim is that knowing the acetaminophen is in there will convince the person to take less of the medication, even though they will get less of the drug that does help them, and so be in more pain: this is taken on faith to be desirable, by people who presumably don't realize that pain reduces quality of life and gets in the way of thinking clearly.

This involves a lot of othering of narcotics users, of course.

</rant>
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From:autopope
Date:October 6th, 2013 06:56 pm (UTC)
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The real problem is that we need better analgesics.

Ending the war on [some] drugs so that effective OTC opiates can be sold over the counter in pharmacies would be a good move. (There are effective cheap antidotes to opiate overdose available. Fixing a paracetamol overdose, on the other hand, means a hasty liver transplant if it's left more than about 6 hours. And those aren't guaranteed to be available, to say the least.)

But we also need more and better non-opiate analgesics that operate via different metabolic pathways from the regular NSAIDs like aspirin or ibuprofen, which have their own nasty failure modes -- some of them fatal (look at the history of COX2 inhibitors for an object lesson).

There was, for a while, a formulation of paracetamol combined with N-acetylcysteine, which acts as a competitor for NAPQI (the toxic metabolite which does the damage) -- this was available on prescription in the UK, for patients who needed an analgesic but were considered a suicide risk. It was then withdrawn from sale(!) due if I remember correctly to fear of litigation. Which is totally insane, in context ...
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From:whswhs
Date:October 6th, 2013 09:10 pm (UTC)
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The invention of better drugs that do more specifically what we want is certainly desirable, though the costs seem to be insanely high. Unfortunately, the drug that does specific thing X and does nothing else seems more like an sfnal marvelous invention than a real possibility. But it really would help, lacking that sort of progress, if we could declare peace on drugs and bring the troops home. Fear of opiates has to be one of the longest-lasting moral panics ever.
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From:autopope
Date:October 7th, 2013 08:11 am (UTC)
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The costs of new drug development are insanely high, but 98% of the costs are regulatory impositions. These have built up over the years due to (a) regulatory capture by the industry, and (b) industry incumbents -- merged into large multinationals -- who see high regulatory costs as a desirable barrier to entry by disruptive new incomers. Yes, we need safety standards and clinical trials; nobody wants to see a re-run of the elixir sulfanilamide or thalidomide disasters -- or of the Vioxx deaths. On the other hand, these standards are now killing people; for example, it's too expensive/non-cost-effective to develop new antibiotics commercially, and during the AIDS crisis it was necessary to introduce a fast-track to get anti-retrovirals onto the market fast enough to safe lives. Toxicity and side-effects have to take a back seat when dealing with an epidemic with a 100% mortality rate. So we really need to restore a sense of proportionality: but finding a safer replacement for an old time traditional remedy that is already dirt cheap isn't going to be very cost effective whatever we do to the framework.
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From:harvey_rrit
Date:October 6th, 2013 07:02 pm (UTC)
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Sounds like an expanded version of Ira Levin's DOCTOR COOK'S GARDEN.
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