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.
COX-1 is involved in the gastric mucosa, among other roles, which is why blocking it can cause stomach bleeding.
COX-2 is involved in maintaining the endothelium of blood vessels, and can increase stroke and infarction risk by stiffening and degrading the lining of the blood vessels over time.
Studies are a bit conflicting regarding whether blocking COX-1 or COX-2 is safer, as there seems to be downsides to both, and the difference in risk isn't that clear.
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.
I have never taken acetaminophen since then. If it's a low intensity pain, then I can handle it myself. If I need actual pain relief I'll use an NSAID.
Finding out later that paracetamol dosage is super close to overdose, and how it actually kills you... That put the tin hat on it.
I agree, paracetamol isn't perfect for every type of pain. NSAIDs help relieve pressure and can help, and opioids can waffle-stomp most pain but only for a little while and with dire risks of dependency, but for-purpose drugs like gabapentin are usually a lot more effective at blocking even high intensity neuropathic pain. Unlike NSAIDs, you can take them long term without needing a cocktail of PPIs to keep your stomach from imploding, and they're non-addictive.
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"]
To be fair though I really haven’t been involved with more than a handful of medications. I’m sure there’s many that work very crisply.
As an adult using it as a pain killer it has been ineffective.
(You might need a Time Machine first)
Any more and it's liver damage.
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 prescription.
Additionally, see https://www.medscape.com/viewarticle/422884 for Silymarin (which is found in Milk Thistle).
That said, do not exceed the maximum dose. Try ibuprofen, diclofenac, or whatever else, but they are not without risks either. For the record, acetaminophen is the only painkiller you can take on an empty stomach without it causing any GI issues.
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.
Ultimately, what one needs to do is just... not consume high amounts, or too frequently.
Trigger warning for self harm.
The real tragedies with acetaminophen are "cry-for-help" situations where someone thinks it is the same as aspirin, and swallows a handful, perhaps washing it down with alcohol. What might have been a suicide hesitation mark becomes an entry on a liver transplant list - if they are lucky. If you have children, make sure they know which one can be deadly, especially before going off to college.
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.
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. aspirin or ibuprofen and paracetamol is for more exceptional situations?
> Caffeine is supposed to reinforce the effect, but of course I had to avoid that to sleep.
If the goal was pain relief, you can combine ibuprofen and paracetamol. They can be staggered or taken together (in which case there's less duration coverage but some evidence that the combination works better than either separately).
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
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.
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.
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.
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.
I'd be interested to know if I'm wrong though.
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 dose for acetaminophen can be as small as 7. This is a much smaller ratio than for most other common over-the-counter drugs. There's not much room for error with acetaminophen.
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.
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.
Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.
It’s the exact opposite of what you claim. Cannabis is orders of magnitude less destructive to the body than paracetamol.
If you honestly believe what you wrote, you need to check your sources. There is a lot of drug war propaganda still out there.
Acetaminophen indeed has a shitty therapeutic index and cannabis in any (natural) form has basically no acute toxicity.
But i'd take 1g of acetaminophen daily for the rest of my life starting at age 1 instead of taking 1 cannabis joint equivalent every day. And that's even if we're talking edible form or vaping (i.e. not considering tars).
What about you?
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.
https://www.fda.gov/consumers/consumer-updates/dont-overuse-...
“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.
Would that not make it a very effective pain killer? /s
But seriously - you are not supposed to "feel" a drug. Opiates work on a much different mechanism, and you do "feel" them, but that is also the same mechanism that make them so addictive. What you want is a drug that helps you manage pain and not be addictive.