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Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

societyforscience.org

51–60 of 160 posts

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

#51

It's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of liver failure (especially if you also drink alcohol). Also it just doesn't work super well in my personal experience --- I hardly feel anything when I take it. And yet it's one of the most commonly taken medicines worldwide.

Two tablets work great for me for headaches but results do vary. The danger zone for liver damage is roughly 14 tablets taken all at once. (Less if you've been drinking.) From what I'm told, acetaminophen overdose is quite an unpleasant way to die.

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

#53
post #37

Earlier quoted context omitted.

Reversible computing, materials science, genetic research… it’s insane that these kids are doing this level of work in high school.

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 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.

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

#54
post #44

It's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of liver failure (especially if you also drink alcohol). Also it just doesn't work super well in my personal experience --- I hardly feel anything when I take it. And yet it's one of the most commonly taken medicines worldwide.

I take it mostly as an anti-pyretic (fever reducer). For which it is extremely effective. It's my drug of choice for colds, flu, etc.

Well, it doesn't work for high fever (> 39-40 Celsius). For that, I alternate Ibuprofen and sodium metamizole every 4 hours.

For pain release, paracetamol it's very modest. Some effect for light head pain, zero for strong pain. Zero effect for strong back pain. Ibuprofen works better in all these cases but comes with stomach damage if taken for long.

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

#55
post #49

Earlier quoted context omitted.

Nurses in palliative care and hospice are well-known to generously administer morphine in increasing doses, because it eventually takes away all the pain and suffering (of the families and nurses).

That’s a controversial take

Which part? This is definitely a common practice.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4594093/

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

#56
post #3

She didn't even break the top 10 in this content: https://www.societyforscience.org/regeneron-sts/2025-student... I'm impressed beyond words by these kids, though I think I'd give her the top prize. Watching my grandfather's final days taken away from him by the effects of morphine has always made me wish so much that we had much more effective non-narcotic painkillers

> Watching my grandfather's final days taken away from him by the effects of morphine

Those were not prbly his final days. he was artifically kept alive by modern medicine. Those final days are not natural part of dying.

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

#58

It's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of liver failure (especially if you also drink alcohol). Also it just doesn't work super well in my personal experience --- I hardly feel anything when I take it. And yet it's one of the most commonly taken medicines worldwide.

Two tablets work great for me for headaches but results do vary. The danger zone for liver damage is roughly 14 tablets taken all at once. (Less if you've been drinking.) From what I'm told, acetaminophen overdose is quite an unpleasant way to die.

The maximum single dose of paracetamol is 1000 mg, and four doses (4000 mg) in 24 hours.

Any more and it's liver damage.

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

#59
post #53
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…

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 organizers who really believe that they're Making A Difference (tm) in scientific research, and are just completely blind to the career prospects of actual young scientists [1].

Time and experience has shown that "scientific innovation" cannot be made to happen faster by throwing more money at it, and a promising young person would be much better off by putting their talents to use doing something less random [2]. You can produce more good research in aggregate (maybe), but only in the same way that you can find more gold by crushing more rocks. Either way, you have to crush the rocks.

For example, the US government dramatically increased grad school funding through the 80s-2000s, and the primary outcome was an employment crisis amongst PhDs in the sciences. In the 40s-70s it was fairly straightforward to establish a career in research, but these days it's Hunger Games. I sort of fundamentally believe that the reason most science came out of the European aristocracy was not due to inequity, but because only someone well-off could devote their lives to something so erratic. Science is an avocation, not a vocation.

Science fairs and the like are a weird little subculture of college-application polishers, in part because nobody in their right mind actually wants to become a scientist. I think it's a safe bet that the young woman in this article ends up doing something more lucrative with her life (and good for her, if she does).

[1] Or even more cynically: the organizers do know, and are doing it because it builds their own careers.

[2] Or at least, with a higher alpha.

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

#60

I'm not an expert in pharmaceutical chemistry, but this looks like a series of relatively complex and low yield reactions. Would it be likely that this would push the price of this product beyond what is reasonable for a general use drug?

The starting point is ~free (like 2 or 4 cents retail per dose for generic in the US). Given my relatively light usage of pain drugs, I would certainly pay 10x that for reduced toxicity. And then it isn't necessarily the case that the identified reactions are the most cost effective available.

If you have light usage, do you need reduced toxicity?

Acetaminophen's effective dose is pretty close to the dangerous dose, but I would take light use to mean you take something maybe once a month max and only a single dose (or maybe even just one pill when the dose is two pills). At that level of use, I don't think you're at risk of anything.

Otoh, if the title is accurate and it can be more effective at pain release and less damaging to the liver, that would be great for people who experience pain frequently.

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