@Oddthinking One thing that really puzzles me about paracetamol prescriptions (the OTC part being another problem, indeed related to public health education): The geenral toxicity of it is long known, antidote regimens available with precise charts to guide the most inexperienced helper. Orally NAC is well tolerated as well, and it does blockto a large degree the ROS, glutathione depletion issues from paracetamol.

When I learned these facts it dawned immediately on me that both should be put into the same cap. That wasn't my original idea, and is also 'known' by now. As long as we keep from giving out advice, we might still share old ideas? In this case I just cannot fathom that combinations known to be quite toxic (ASS/APAP/caffeine, APAP/Hydrocodone etc) are apparently easy to market, no matter how much malpractice they present pharmacologically.

If someone has an educated guess to offer on why don't they just do that (combine APAP/NAC), please share.

@LangLangC I plead ignorance. If forced to guess, I would point at potential side effects - e.g. allergies or liver damage when consumed after alcohol.

@LangLangC By general toxicity, do you mean acute or chronic consumption?

Paracetamol plus alc is already a recipe for downfall, as is vicodin with alc. So I fail to see any inherent medical reason anyway. The most important complaints aaginst NAC are smell/taste (!), then gastrointestinal upset, even if injected (again: !).

By toxicity I mean the always occurring glutathione depletion. May be too small to matter in occasional low dose, but it's always there. (And of course just one, but an important aspect. Toxicity from other mechanisms just adds).

When I was 21, a friend of min who was an ambulance driver was despondent because he had picked up a teenager who accidentally swallowed too many paracetamol tablets - he wasn't diligent about how many he swallowed and lost track. The boy died.

NAC has its own profile of negs, but these seem quite small. It's even sold as a general supplement. Having the option to take pure para should of course remain. Further, emetic effect as an additional safeguard for (un)intentional overdose on para would be just a boon as well.

That anecdote has stuck with me. I have always been super diligent never to consume too many in a 24 hour period.

So when you talk about the acute toxicity, I nod as I know it is a serious problem, but once you are aware of it, easy to avoid.

But paracetemol is/was a very effective pain killer for me, and I am very glad it was available.

I didn't, however, know it had long term effects. (I was assured it was safe.)

@Oddthinking Had two similar ones over the years. One had consumed alcohol and para in a seemingly large temporal distance, the other just had a lot of head aches and swallowed a pill accordingly, apparently never exceeding the maximum dose. Two cases of liver damage followed.

@LangLangC Damn. (You are a medico of some kind?)

I'm noticing that Australian OTC Panadol contains 500mg per tablet. American Tylenol OTC ("Regular Strength") is 325mg per tablet. The daily maximum is 4g in Australia compared to 3-3.25g in the USA.

Apart from max-dose allowed safely: There is quite the different approach to 'pain' to observe between cultures. I notice some of that in the comments below the Q unfolding. I do not want to dismiss that people suffer actual pain. But two aspects should be analysed:

@Nat Depending on the framing on the question, it might be more successful on meta. Fewer questions and less possibility of drowning in questions related to the next Trump speech incident. It sounds like a very enjoyable read!

1. The 'guilt part': is anyone punished, did the person deserve the pain, doing something stupid, not following public health guidelines, was person too stupid? (Something extremely popular in the public, and open debates, especially in politics; and also diametrically opposed to any Hippocratic principles) The pain is there, and it's real, how to deal with it.

(Saying this of course as a lurker, not an active participant, although I have some experience elsewhere)

2. What is the actual biological function of 'pain'? 'Chronic pain' can be devastingly-hard-to-diagnose, or exlpain, just as migraines etc. But is this perhaps 'something useful' as well? Current self-optimisation reaction is: "pain presents itself, person needs pills, always" as if that were a natural law.

But often it is not overly hard to diagnose, only the pill being more convenient than eliminating the cause. Things like bad posture, dis-stress, overwork, and not in the least: diminished pain tolerance from cultural reasons, overindulgence on pain meds…

One such example is illustrated by "After Surgery in Germany, I Wanted Vicodin, Not Herbal Tea"

@LangLangC I just wish people were more aware of these. At least here (probably a different environment entirely) having these spelled out to them would help, I imagine. One patient has long-term consumption of codeine (disguised as buying Expectorant codeine) and the blood test results hinted at a damaged kidney. Liver damage seems to be more frequent as well, but I'm perhaps too sensitive to this stuff.

Back when doctors were trying to figure out the reason for my ESRD, they also asked if I took painkillers. Apparently when the cause is not sufficiently clear it's one of the common suspects.

The new thread was very nice, especially LangLangC's answer. Thank you!

@M.A.R. Well, don't get me started on cultural prejudices harming people… I am not saying there is no place for pain meds. But heroin is the perfect pain-killer, made medically <del>unavoidable</del> unavailable because of 'opium-dens'. Fentanyl is stronger, yes, but the therapeutic window? How many people could go live happy lives if treated against pain with ketamine or LSD (lots of class stuff actually). NO, because 'the hippies'.

@LangLangC strikethrough markdown in chat in enclosing text between three dashes

More than 80 years of societal damage and medically worse outcomes to blame on the generalised war on drugs. "Euphoria" listed as unwanted side-effect and reason for upgrading any drug's 'abuse potential'. Funny thing I observe: if in surgery standard anaesthesia has to be avoided and people do get a combo that involves ketamine, the requests for 'give me a painkiller' seem notably lower.

Oh? That's nice, thought people had to parse the tags themselves…

If there's anything I'm an expert at it is chat.SE quirks ;)

It is confusing that it differs from the main site.

@M.A.R. Truth be told, I sometimes wonder how people can get past 60. As seemingly everything hurts the kidneys…

About to enter the beautiful world of academia in about 10 days.

@M.A.R. And you don't mean the SE-site! (That'll be much quicker, I presume ;)

@LangLangC Was it Nixon? IIRC it was Nixon that tainted the image. Whatever that image was. I already have enough trouble catching up with the current US politics.

@M.A.R. Can't really blame it just on him. That's a widespread 'puritan' (ie anti-fun) sentiment, started in force in the 19th century (temperance etc). But curiously after multiple fact finding missions declaring the millennia old drugs cannabis to be GRAS, it was mainly on the insistence of one Egyptian doctor and local conference dynamics that it came under suspicion and onto the lists.

Again: you can 'abuse' just about anything and THC itself can be really quite nasty. But it is really just the WoD coupled with reductionist thinking that is still harming people. "Some people enjoy hemp" "We'll need to stop that!""But it's a known pain reliever and even listed in the European pharmacopeia's for centuries!" "Well, let's isolate one compound and try that on cancer patients…"

And all the while they kept on lying about it: "That's not part of our culture, completely alien, was only introduced by (Indians/Turks/Arabs: Europe; Mexicans/Blacks: US) recently…)" "Oh really? We can phrase our dismissal not just in-group/out-group style but with real xenophobia and racism? Then I am sold!"

@M.A.R. Not to justify Nixon, but to backup claims: Reading into the history of developments (eg doi.org/10.1080/00263206.2011.553890 ) is really illuminating when you see how modern prohibitionists argue.