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Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

societyforscience.org

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Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#101

Post by db48x »

Waterluvian wrote: post #94
AndrewDavis wrote: post #90

Earlier quoted context omitted.

Similar to you it is incredible at bringing down fever in my kid. I've seen my kid go from whimpering looking like death, to be crawling about playing happily again in half an hour. With the behaviour change tracking with her temperature coming down. As an adult using it as a pain killer it has been ineffective.

For me I’ve found it works incredibly well at killing a headache or outright stopping a scintillating migraine (especially when combined with caffeine). But for body aches and pains I also find it doesn’t do a whole lot, especially compared to ibuprofen.

That's because ibuprofen reduces inflammation but acetaminophen does not. Joint pain and other such aches are all accompanied by inflammation, but headaches are not.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#102

Post by AnthonBerg »

meew0 wrote: post #75
nandomrumber wrote: post #57

Can acetaminophen be packaged with n-acetyl cysteine to render it not rate limited by same?

The problem is that N-acetylcysteine tastes and smells awful (like farts/rotten eggs) and often causes nausea and vomiting as a side effect. The vast majority of people use acetaminophen in a safe way, and acetaminophen doesn't really have many side effects by itself, so you'd make life more unpleasant for a large number of people in order to prevent a tiny number of acute poisonings. Probably if this were implemente…

Experiences may vary; I’ve tasted and smelled NAC.

The smell is reminescent of a high-potency cannabis strain. (Sulfur-containing molecules.)

The taste is very acidic and a bit astringent.

Generally the smell and taste of something isn’t a concern with medication. I don’t think acetaminophen tastes great.

I’ve never encountered or seen the digestive issues that are often mentioned. I’ve seen other side effects which were noticeable – mast cell and histamine related I believe, kind of weird ones, like psoriasis kind of drying out a bit and the skin on the lips “refreshing” itself. (Really!) Subtle side effects and hard to put into words without making them seem bigger and weirder than they are, but NAC can nonetheless be a sort of histamine and mast cell “flusher”, so to speak and as it seems. Beneficial in the long run imo ime, but tricky to package universally.

Still, NAC is also tragically unknown and unused! There’s tons of fascinating literature on it. They fried rats’ brains with methamphetamine and fixed them with NAC; Brutal study, intriguing results on very significant mechanisms.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#103

Post by timr »

tomabuct wrote: post #95
timr wrote: post #59

Earlier quoted context omitted.

Meh. While I think the broad theme is fine (more access to education is generally good -- particularly when it comes to scientific literacy amongst the general public!), I think trying to encourage "research" in this way is largely pushing on a string. I can never figure out if this whole phenomenon of "science fairs" is just Kabuki theater for everyone involved, or if there's a core group of deeply deluded organizer…

Eh. Even if 1 in 10000000 of the kids that do "science fairs" end up in "science research" with at least one "scientific innovation", and the rest of them make $$$ in industry, that's them working. This comment is asinine on too many levels to fully rebut.

> This comment is asinine on too many levels to fully rebut.

Thanks. I mean, it's not like I have direct experience with this stuff or anything, as one of those 9,999,999 who spent years of my life doing science, only to end up in industry.

Also, it's not like we would do better by skipping the years of science and going directly to the productive part, or that those (now grown up) "kids" are encouraged to continue circling the airstrip of life by the funding programs that are happy to pay postdoc salaries -- postdocs being the best kind of cheap, indentured labor -- to keep the dream alive just a little bit longer. After all, walking away from a PhD/postdoc(s) is only just a bit harder than chewing off your own leg to escape a bear trap.

It's clearly much better to waste the time of our smartest people by injecting false economic incentives into the system in an effort to socially engineer some kind of scientific command economy. Let's grind those rocks, and turn the cheap gravel into concrete to build glorious future!

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#104

Post by foxwolf »

All my life, I've suffered from frequent (as in daily) headaches. I even have a photo of myself from my 10th birthday (or thereabouts), where you can visibly tell from how I'm holding my head that I had a headache. The nature and intensity of my headaches has changed over time.

In my 20's I discovered Excedrin (acetaminophen + caffeine) and, surprisingly, it not only worked, but worked very well. One tablet would kill most of headaches I was having at that time of my life in about 15 minutes.

Unfortunately, it stopped working for me by the time I was 30. It no longer has any noticeable effect.

Aspirin, Naproxen, Ibuprofin, and Tylenol 3 have no effect, either.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#105

Post by djmips »

foxwolf wrote: post #104

All my life, I've suffered from frequent (as in daily) headaches. I even have a photo of myself from my 10th birthday (or thereabouts), where you can visibly tell from how I'm holding my head that I had a headache. The nature and intensity of my headaches has changed over time. In my 20's I discovered Excedrin (acetaminophen + caffeine) and, surprisingly, it not only worked, but worked very well. One tablet would kil…

That is a tragedy. Sounds like you could use some precision medicine but it feels like that revolution is not happening fast though.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#106

Post by timr »

fc417fc802 wrote: post #88
timr wrote: post #59

Earlier quoted context omitted.

Meh. While I think the broad theme is fine (more access to education is generally good -- particularly when it comes to scientific literacy amongst the general public!), I think trying to encourage "research" in this way is largely pushing on a string. I can never figure out if this whole phenomenon of "science fairs" is just Kabuki theater for everyone involved, or if there's a core group of deeply deluded organizer…

> not due to inequity, but because only someone well-off could devote their lives to something so erratic. Aren't those effectively the same thing? At least in the given context where society doesn't have the resources available for everyone to live like that.

Effectively the same in terms of distribution of outcome, perhaps, but it's a bit like saying that it's really unfortunate that poor people can't afford their own manicured gardens, peacock collection and garage full of antique race cars.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#107

Post by mancerayder »

foxwolf wrote: post #104

All my life, I've suffered from frequent (as in daily) headaches. I even have a photo of myself from my 10th birthday (or thereabouts), where you can visibly tell from how I'm holding my head that I had a headache. The nature and intensity of my headaches has changed over time. In my 20's I discovered Excedrin (acetaminophen + caffeine) and, surprisingly, it not only worked, but worked very well. One tablet would kil…

Have you ruled out head/neck muscle tightness due to jaw clenching? Have you tried muscle Botox injections? or seen a migraine specialist?

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#108

Post by mschuster91 »

carlmr wrote: post #53
timr wrote: post #37

Earlier quoted context omitted.

They aren't doing it on their own. Most of these kids are working with established researchers who give them the shape of the project, as well as the tools and the expertise to accomplish it. More recently the US scientific funding bodies have had summer programs for kids who wouldn't otherwise get that kind of access, but it's still the exception. It takes more than a summer to do this kind of work. Edit: quick sear…

>these kinds of science fairs are fundamentally about access. Completely agree there, which kind of brings me to a related thought: One thing I do wonder is, if you look at a few hundred years ago a lot of the inventors in math, physics, engineering, were a tiny group of people with access to resources and education. You're always reading the same names. It seems if we as a society could decide that science is more i…

> It seems if we as a society could decide that science is more important to us, with 8 billion people on earth, if we gave more access, time and incentives to people we should be able to increase the amount of scientific results exponentially.

Yep, but we collectively decided that it is more profitable to put the best minds that manage to survive the education trials to either shaving off 0.0000001 cents of each financial transaction and to still make billions of dollars off of that or to sell ads so people get convinced they need to buy something. And those that get dropped along the education pipeline, we either let them stay on the road side and let them rot in poverty or we just use them as yet another source of labor ready to be exploited.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#109

Post by Findecanor »

hgomersall wrote: post #69
Ey7NFZ3P0nzAe wrote: post #61

Earlier quoted context omitted.

It's terrible that you are counting in tablets instead of actual amount of acetaminophen

It's for this reason in the UK paracetamol (as we call acetaminophen) is only ever manufactured to 500mg tablets. I don't know if that is global.

Here in Sweden, a carton of 10 × 500 mg is the most you can find without a subscription. (Boxes of twice that amount is supposed to exists but I've never seen it)

Two years ago, I was prescribed the maximum dosage: 2 × 500 mg every six hours for a couple of months. Because it wears off more quickly than that, I tried to reduce it to one and a half pill more often but that wasn't enough to have any effect. Caffeine is supposed to reinforce the effect, but of course I had to avoid that to sleep.

I also got it as intravenous liquid at a time when I couldn't swallow.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#110

Post by oliwarner »

johnisgood wrote: post #84
chistev wrote: post #58

Earlier quoted context omitted.

The maximum single dose of paracetamol is 1000 mg, and four doses (4000 mg) in 24 hours. Any more and it's liver damage.

I will respond here with links, because my comments regarding NAC and silymarin are getting down-voted. https://emedicine.medscape.com/article/820200-treatment - Treatment for liver damage is NAC (N-acetylcysteine) which is available as a supplement. > N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity https://www.ncbi.nlm.nih.gov/books/NBK537183/ Again, NAC is readily available without pres…

Acetylcysteine isn't magic though.

It needs to be administered within 12h and 5% will have a severe anaphylactic-type reaction with risk of respiratory arrest. And the liver can still have been irreparably damaged due to other factors.

In the context of this being a miserable way to kill yourself, it's absolutely awful because there is very much a cut off point where you will still be suffering immeasurable pain and no amount of NAC will save you.

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