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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

#141

Post by AnthonBerg »

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…

Interesting!, thanks! NAC is all over the place; I didn’t know about this application.

And yeah I was 100% skeptical too!

Now I’m more sceptical of the kinda “nothing is known, nothing is knowable” angle, you know? There is so much knowledge, actionable, often unread, often unused.

(Have to mention it, if useful: Na—R-ALA (alpha lipoic acid) and ambroxol are kind of in the same vein. Ambroxol is strangely a sort of bromine counterpart to NAC and its sulfur atom. Sold as a mucolytic but is… alllll over the place. Funny how mucus, mucous membranes, the nervous system, and oxidation/redox stuff is all so adjacent it seems.

I have no idea why but after a severe period of stress, I happened to take Na-R-ALA as sometimes do and 60mg of ambroxol as mucolytic cough syrup. For a cough. And… the feeling was like in the movies where they stab someone with a giant syringe to revive them. Trainspotting or Pulp Fiction or whatever. I felt like I gasp-crawled out of a pit inside myself. It makes no sense. It was… a very distinct experience. And it didn’t seem like an airway clearance thing, more like my nervous system was refreshed.

So I hit the books. And it turns out ambroxol crosses the blood-brain barrier and is an antioxidant, and affects ion balance in neurons, and there are studies indicating it helps with… Parkinson’s and fibromyalgia (!!!). And those papers are pretty interesting and appear to be constructed on solid molecular biological premises.

idk)

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

#142

Post by Jolter »

mulderc wrote: post #138
Jolter wrote: post #113

Earlier quoted context omitted.

That’s a lot. I keep forgetting how many idiots are in the world. Some of those are probably intentional suicide attempts. What’s the maximum number of tablets for one purchase? Sweden has it regulated down to 14, because that’s just enough to not cause permanent damage in a depressed teenager.

My understanding is it isn’t so much people being idiots but that acetaminophen is in many products making it easy to overdose on when you are sick. https://www.fda.gov/consumers/consumer-updates/dont-overuse-...

Ah, I see,,, Wikipedia tells us:

“While a majority of adult overdoses are linked to suicide attempts, many cases are accidental, often due to the use of more than one paracetamol-containing product over an extended period.[106] […] Overdoses are frequently related to high-dose recreational use of prescription opioids, as these opioids are most often combined with paracetamol.[110] The overdose risk may be heightened by frequent consumption of alcohol.[111]“

So, combination drugs being used recreationally, yeah I guess I can believe that would lead to not keeping track of how much paracetamol you took today. And especially over time.

I figured it would be pretty hard to accidentally exceed 4000 mg in a day, but if you’re high on some stronger painkillers, which you’re developing some tolerance for, then it’s easy to just keeping taking more than you did last time.

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

#143

Post by cma »

shawabawa3 wrote: post #136
atombender wrote: post #121

Earlier quoted context omitted.

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%C…

I'm pretty sure ibuprofens risks are significantly higher than a 10-20% increased risk of dementia, it gives significantly increased risk of strokes iirc

I thought NSAIDs thinned blood more like apsirin and gave aneurysm risk instead of stroke, and the big risk was stomach bleeds.

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

#144

Post by Ey7NFZ3P0nzAe »

cluckindan wrote: post #76
Ey7NFZ3P0nzAe wrote: post #64

Earlier quoted context omitted.

Paracetamol is nicely synergic with all known painkillers. For example prescribing it with morphine leads to less morphine consumption. Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.

Prescribing cannabis for pain also leads to less morphine consumption.

The safety profile of paracetamol is orders of magnitudes higher ghan cannabis though. It is still one of the, if not the, most heavily used and appreciated drug and can be taken at any age

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

#145

Post by Ey7NFZ3P0nzAe »

dreamcompiler wrote: post #140
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 not possible to state an absolute toxic dose in milligrams for everybody because it depends on things like your body mass, the preexisting condition of your liver, whether other liver-damaging drugs are on board, etc. In my case I was talking about 500 mg tablets which are commonly branded in the US as "Extra Strength Tylenol." The point I was trying to make is that the deadly dose divided by the therapeutic dos…

> It's not possible to state an absolute toxic dose in milligrams for everybody because it depends on things like your body mass, the preexisting condition of your liver, whether other liver-damaging drugs are on board, etc

Well yes it is possible to define an absolute toxic dose. 100 grams is an absolute toxic dose of acetaminophen in humans, 8294 tablets is not a dose.

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

#146

Post by Ey7NFZ3P0nzAe »

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.…

There are almost no situations were taking the recommended dosage of acetaminophen is harmful. It's either useless (won't help for a skin rash for example) or has positive effects.

There absolutely ARE situations where ibuprofen should not be used (kidney, infections, others), even at the usual dosage.

Hence I believe that it's a terrible idea to write on the internet "they can be staggered or taken together" as if they had a simimar safety profile

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

#147

Post by Ey7NFZ3P0nzAe »

hgomersall wrote: post #92
Waterluvian wrote: post #89

Earlier quoted context omitted.

Do you guys have liquid forms, especially for children where the dosage is, obviously, entirely up to you? One memory I have of visiting our U.S. head office with a bunch of UK people was the “we have to get to Target because they sell Tylenol in ungodly quantities.” And I thought bottles of 200 pills felt ridiculous up here in Canada.

Yeah, you can get lower doses. It turns out I was wrong and you can get 1g, but my understanding is it's not used in routine healthcare (for obvious reasons). https://bnf.nice.org.uk/drugs/paracetamol/medicinal-forms/#o... I'd be interested to know if I'm wrong though.

In france the usual dosage most of the time is 1g

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

#148

Post by Ey7NFZ3P0nzAe »

Findecanor wrote: post #109
hgomersall wrote: post #69

Earlier quoted context omitted.

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…

FYI in france no box is allowed to contain more than 1g. And in theory pharmacist should not accept selling more than 1 box, they tend to do though.

Can't put a source but I had lessons explaining that the US had insane rates of tylenol suicide, and that are apparently correlated with the size of boxes sold otc. Years ago many countries including france put a limit on the quantities sold at once and the suicides plummeted. The US didn't because of lobbies or something.

So sad and obvious.

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

#149

Post by tomabuct »

timr wrote: post #103
tomabuct wrote: post #95

Earlier quoted context omitted.

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 c…

Resentment is inherently anecdotal, but nevertheless a data point.

The issue with your argument is that you’re conflating two different points on the academic pipeline by shitting on high school science fairs because of the post-doc hellscape further down the line.

The latter is a special case of low wage, dead-end jobs that are inherent to capitalism, which can more generally leave anyone paralyzed in a vicious grind loop. Improving this may require capitalistic reform such as UBI and increased housing supply, but is the human condition of the quest for satisfaction in one’s niche.

The former is exposure to future possibilities that could satisfy the constraints of economic and intellectual well-being, likely through incremental progress but with the potential for breakthrough in either realm.

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

#150

Post by gus_massa »

throwawaymaths wrote: post #4

impressive for a high schooler but this just adds a protecting group onto tylenol. am i missing something? edit: oh i see. its really blurry but the silyl modified tylenol is predicted to have good trpv1 binding computationally. afaict no in vitro or in vivo studies were done. could be cool. not sure if diethylethynylphenylsilyl group has good Lipinski properties though (i suspect not) edit: s/aspirin/Tylenol

[Very good comment! I'd use the opportunity to add more questions.]

How expensive are the steps? They look like advanced steps that can be done in a lab to prepare a few micrograms, but I'm not sure if they can be scaled to industrial production.

Why silicon instead of just a carbon? Is it better blocking the docking? Is it better moving the orbital energy levels? Is it as safe as the poster claim?

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