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Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

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

#121

Post by atombender »

porphyra wrote: post #43

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'm a big fan of it in terms of efficacy; does wonders for headaches as well as joint aches.

My concern is about the relatively recent findings about potential Alzheimer risk [1]:

> During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10-1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97-1.16).

I don't follow the research closely enough to know if this is reliable evidence, but there are other studies showing the same thing.

Paracetamol also well known as mood-altering, apparently inhibiting empathy [2], which may be part of why it has an analgesic effect. That isn't as scary on a personal level, but imagine a society full of millions of people on paracetamol whose ability to feel empathy has been blunted.

[1] https://pubmed.ncbi.nlm.nih.gov/37633120/

[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC6455058/

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

#122

Post by [deleted] »

cess11 wrote: post #119
masklinn wrote: post #111

Earlier quoted context omitted.

> 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) That ain't much, I don't think I've seen boxes with that little around here. Normal packaging is 30~40, and you can get larger boxes, all without a script. Are the boxes that small because sweden tends to use an other analgesic as primary culturally e.g.…

Ibuprofen, naproxen and acetylsalicylic acid are also common. I prefer acetaminophen due to the main metabolite being a reuptake inhibitor of CB-active transmitters and I don't drink. I take maybe two-four grams per year, so your 40-pill box would last for a decade.

[deleted]

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

#123

Post by kyriakos »

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.

Same here I take it for migraines. Work's only if taken early when symptoms begin but it does work.

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

#124

Post by amelius »

AStonesThrow wrote: post #28
fracus wrote: post #18

Earlier quoted context omitted.

I thought morphine didn't cause health damage to the human body apart from addiction and withdrawal symptoms.

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).

Not just of the families and nurses.

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

#125

Post by Rastonbury »

AnthonBerg wrote: post #102
meew0 wrote: post #75

Earlier quoted context omitted.

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…

I take NAC to help with hangovers, I used to get smashing headaches and people would recommend random Korean and japanese 'hangover supplements', I was obviously very skeptical and googled every ingredient to check it is safe. The ones that worked had NAC or gluthanione. Looked into it and bought some and always take it when I drink or have panadol. Have not noticed any other subjective effects

Nausea or vomitting is rare, I imagine if it were common those hangover cure sellers would go out of business

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

#126

Post by laughingcurve »

timr wrote: post #37
ricardobeat wrote: post #11

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…

Thank god someone bothered to explain it to HN.

As someone getting a PhD at a top school and the first in my family to ever make it past high school I can assure you all these kids are raised from birth in a test tube by their parents.

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

#127

Post by amelius »

Rastonbury wrote: post #125
AnthonBerg wrote: post #102

Earlier quoted context omitted.

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…

I take NAC to help with hangovers, I used to get smashing headaches and people would recommend random Korean and japanese 'hangover supplements', I was obviously very skeptical and googled every ingredient to check it is safe. The ones that worked had NAC or gluthanione. Looked into it and bought some and always take it when I drink or have panadol. Have not noticed any other subjective effects Nausea or vomitting is…

> I was obviously very skeptical and googled every ingredient to check it is safe.

Did you check if drinking alcohol was safe? ;)

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

#128

Post by tialaramex »

oliwarner wrote: post #82
porphyra wrote: post #43

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.

"Therapeutic index" is a strange number to worry about. Those index scores are the balance between efficacy and toxicity. Acetaminophen is an effective analgesic, just toxic in large doses. It's perfect for lower intensity pain. It's non-addictive, doesn't have long term issues like NSAIDs. It's popular for a reason.

The effectiveness varies a lot. For me it works great, several other people I know get no effects at all from taking safe doses and of course excess doses are potentially extremely dangerous, extremely fast - about 2.5x the usual maximum dose causes liver failure in some people, that's barely more than "Oops, I already took that and I forgot" from a nasty death.

If it was discovered tomorrow rather than last century, it would never get OTC approval, because while for some people (like me) it's useful, the dangers are too high, so they'd definitely make it prescription-only. I'd probably still come back from any surgery with a bag of paracetamol because it's cheap and the surgeons can prescribe it to somebody it works on without worrying (it's not like an opioid, nobody is going to get unnecessary surgery so as to secure more paracetamol) but it would not be in cold & flu meds if they hadn't found it last century when they were more lax about safety.

[Edited to insert crucial omitted "not"]

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

#129

Post by Findecanor »

masklinn wrote: post #111
Findecanor wrote: post #109

Earlier quoted context omitted.

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…

> 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) That ain't much, I don't think I've seen boxes with that little around here. Normal packaging is 30~40, and you can get larger boxes, all without a script. Are the boxes that small because sweden tends to use an other analgesic as primary culturally e.g.…

> Are the boxes that small because sweden tends to use an other analgesic as primary culturally e.g. aspirin or ibuprofen and paracetamol is for more exceptional situations?

No, I'd say paracetamol is the most common. I think there was an increase in teenagers that tried to overdose on it to commit suicide some years ago. You could easily get 1000mg pills before that.

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