Colloquially acetaminophen/paracetamol and ibuprofen are "painkillers" but this is in a different class, it's amazing to have something which performs like the opioid pain relief but without at least some of the side effects.
It's the first non opioid painkiller applicable for situations like post operative use.
I'd have loved this after my hernia op, the last thing you need with that is opioid induced constipation.
Off topic complaint: I am guessing an absolutely massive amount of (admittedly minor in each instance) grief has been caused by the most widely deployed simple, inexpensive, useful and familiar drug unnecessarily having two different names acetaminophen / paracetamol. Finally figured this out this year (aged 64) after previously being confused why I couldn't find any damn paracetamol in pharmacies on my occasional visits to the US.
My wife and I got colds while vacationing in Edinburgh and had a heck of a time before realizing to ask for paracetamol rather than acetaminophen. Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
> Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
Yes, but:
> Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States. Notably, around 50% of these poisonings are unintentional, often resulting from patients misinterpreting dosing instructions or unknowingly consuming multiple acetaminophen-containing products.
There's an interesting thing too about metamizol. It's very popular here in Spain for some types of pain (for example, teeth related stuff or post-surgery) and it's used widely without much problem. In fact, it was the most sold medication in Spain in 2023 (sold under the Nolotil brand) [0]. But it's forbidden in places like the UK.
Thing is, as we are a popular destination with British tourists or even pensioners that live in the Mediterranean, we've found in the last years that British population is genetically more likely to have a very dangerous side effect, agranulocytosis, that could result in death.
Can't find the exact source (I'm on my phone), but seems like at least half of the metamizol related agranulocytosis cases in Spain have been of British origin, and several deaths have been reported. There's a ongoing legal process where at least 40 deaths are being investigated [1] and doctor have stopped providing metamizol to persons of British origin, and do it carefully for other persons.
So what was perfectly safe around here, was found quite dangerous for certain subset of the British population (no jokes about balconies, please).
Edit for some sources:
From 1998 to 2003, out of the 13 agranulocytosis cases from a hospital in Marbella, 8 were foreigner, and of those 5 were from the UK [2]. According to the ADAF association, out of the 45 deaths attributed to metamizol in Spain since 1996, only 8 of them were Spanish (they don't tell their sources in that article) [3]
I was under the impression that a lot of overdoses of acetaminophen are due to it being included in many different multiple-medicine cold/flu remidies, like cough syrup, NyQuil, decongestants, etc. So people end up exceeding the max dose accidentally when they take acetaminophen along with some of those other things.
Does the UK have rules that prevent mixing acetaminophen with other drugs? Its getting so its sometimes hard to find over the counter cold/flu medicines without acetaminophen
The UK rules apply to all medicines containing paracetamol.
Non-pharmacy retailers are only allowed to sell in packs of 16, and they'll usually only allow two packs of any paracetamol-containing medication to be sold at a time (eg. one cold/flu and one cough remedy).
If the name of the product doesn't already contain the word "paracetamol", then all of the packaging must prominently display "contains paracetamol" - so even small retailers that don't have computerised checkouts are expected to follow the same rules.
Deaths from paracetamol overdose fell by 43% (with a similar decrease in the rate of accidental poisonings) in the first 11 years after these changes were implemented: https://www.bmj.com/content/346/bmj.f403
My wife has negative reactions to it, which is extremely rare at normal doses (to the point many doctors don't believe her).
Trying to find medicine for her when she's sick is surprisingly time consuming as it is in so many things even vaguely related to treating cold / cough / flu symptoms.
As annoying as it is (and I agree it is fantastically annoying) much to my surprise admissions for paracetamol overdose to UK hospitals absolutely plummeted after purchasing restrictions were introduced.
Not sure what "plummeted" quantifies to in this context, but the US saw meaningful reductions in overdose treatments and calls to the poison control line after changing the labeling rules and a public education campaign. The cited study was even conducted before the full labeling rules change came into effect.
Teach a man why not to over-fish fish vs giving him a smaller amount of fish... or something.
The US doesn't have a significant problem with deliberate acetaminophen overdose as part of a suicide attempt, which is the problem the UK rules are meant to address.
Strictly speaking, if you wanted to solve intentional overdoses of acetaminophen, it appears that you could do it by presenting more appealing means of self-harm, like in the US. I'm pretty certain the availability of other lethal products (guns, really) directly correlates with whether OTC drug overdosing is a popular means of harm.
I'm willing to bet that handing out cyanide pills OTC would effectively eliminate intentional acetaminophen poisonings in the UK. Surprised the boffins at the NHS didn't think of it first if they really want to eliminate intentional overdoses! /s
There's some research to suggest if you make suicide a time consuming process some percentage of people who decide to do themselves in will reconsider while they're trying to carry out the act. I'm skeptical, but I understand the reasoning.
For those interested having done a brief literature search I've found a review article that paints the picture as much less clear than my categorical statement
I'm a big fan of paracetamol in terms of how well it works; 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.
Many very simple things can badly hurt or kill someone who doesn't take a few minutes to not be stupid about using them properly. Legislating with absurdities applied to all anything that possibly leads to completely individual harm because a few people can't take normal responsibility for themselves emphatically isn't reasonable.
It’s not theoretical. On one side of the ledger we have people dying horrible deaths, on the other side we have people who can’t have vast quantities of paracetamol on hand for no particular reason. If you do in fact need vast quantities of paracetamol for some reason, it can be prescribed.
The very idea that you should need special permission from some form of officialdom for having access to anything that is very widely useful but in all but a very, very small subset of select cases involving very, very few people who harm only themselves with its misuse is what's genuinely disgusting here.
The vast majority of adults should be able to live in a world where they're not treated like 10-year-old children for seeking a bit of modest pain relief for very common ailments.
I really hope I never find myself living in a society where your perspective dominates. I’d rather we took care of the weak than grumble about such an inconsequential inconvenience.
You used and descontextualizad the scariest number possible for whatever instinctively nannying nonsense reason of your own.
There were over 50,000 hospital emergency room visits, yes. However, bear in mind that many thousands of people visit emergency rooms for all kinds of unfounded reasons every year anyhow. Of those 50,000+ paracetamol-related visits (speaking of the United States here), less than 5% resulted in any need for hospitalization and only 450 or so deaths were registered in 2023, as a recent example year. These numbers out of an estimated 60 million individual uses PER WEEK by Americans according to the NIH.
For some perspective, accidents caused by "Fall involving ice-skates, skis, roller-skates or skateboards" in the U.S cause an average of 1000+ deaths per year.
Paracetamol can, just like many drugs, be dangerous, but if your criteria for paranoid restriction of something so commonly necessary and used without problems in the extreme absolute vast majority of cases are the numbers above, you'd better start banning one enormous shit list of completely innocuous activities and things that normal adults have access to before you reach something like paracetamol.
There seems to be a sort of mental illness prevalent in the kind of logic that equates any evidence of self-harm with a given product or thing with a rabid need to treat people like children in their access to it.
The entire adult population should not have to be treated like drooling morons in their very most basic personal medical choices because a completely minuscule percentage of the population lacks the mental capacity to read a basic safety label for a common medicine, or control their childrens' access to something that's easy to keep away from them.
“A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the US found that paracetamol was the cause of 41% of all cases” from https://en.m.wikipedia.org/wiki/Paracetamol_poisoning
> In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity.
10g is 20 pills of the highest strength you'll find in a regular store. Excedrin brand "Extra Strength" is half of that, you'd have to be eating 40+ pills in 24 hours, or 20+ pills per day on multiple consecutive days. Most acetaminophen pills have 100-200 mg of the active ingredient.
You're missing the context:
> Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity.[25] In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.[26]
So, it's not that acetaminophen will kill that easily. It's just that of the easily available ways to kill yourself, it's distinctly the one that destroys the liver quick.
It's unfortunately quite easy to do even inadvertently (not following dosage instructions) - doesn't take a lot.
The reason for the rule though was to combat its use in suicide attempts. They also have to be sold in blister packs here for the same reason, not the big bottles of Tylenol/Advil etc. that you get there (and we used to here) - relatively difficult to take several, requires more preparation than just chugging a bottle.
> the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid
Worse than that: it is effectively per day per shop. In a very short space of time I can buy two packs in Boots, two in Tesco, two in Sainsbury, ooh look another small Tesco I'll get two there as well, two from Savers, two from SuperDrug, …
Worse in what ways? I think it's a pretty neat feature of the design. If you just need some, you don't get a lot, and you don't get to buy a lot "just in case". If you truly need a lot, you can go though the hassle of going to multiple stores.
It's essentially just raising a barrier for (under normal circumstances) undesirable behavior.
It doesn't do what it is sold as doing¹ while causing a bit of faf.
The restriction is one of those put in place because someone somewhere want to be seen to be doing something.
> for (under normal circumstances) undesirable behavior.
Outside of a supply problem situation, which we don't have for that sort of thing and different at the time the change came in, why is it so undesirable?
--------
[1] Reducing accidental overdose rates², reducing people using out-dated-so-possibly-ineffective medicines, etc.
[2] Accidental overdose rates have fallen, but they have in many places without those restrictions, so I suspect that is a coincidence and probably more due to greater awareness³ of there being paracetamol or aspirin in other products and therefore the need to be careful what you take in combination.
To me it's really the principle of having lots of ridiculous rules that amount to a pile of little inconveniences all over every facet of modern life. It's not a logical reason to have a problem with it, but I would prefer to see a more logical set of rules that don't seem to be so ridiculous and maze like when you are doing something that is just slightly out of the norm.
Overdoses declined in the US, as well, where there are no limits on quantity, but there has been a campaign to educate and create better labeling practices for medication containing acetaminophen.
I think it's important to recognize that overdoses can be intentional or unintentional, and it isn't clear which ones will be affected by the policy of limiting purchase quantity per transaction.
The US went with the educational route - any product containing acetaminophen has “CONTAIN ACETAMINOPHEN - DO NOT COMBINE WITH OTHER PRODUCTS CONTAINING ACETAMINOPHEN”
Overdoses went down despite the fact I can buy $1,000 tablets for $5 at Costco.
That study is...not that rigorous, but I give them points for being clear about it.
"The downward step change was not apparent when the intervention point was moved back to the beginning of 1998."
"Despite the apparent benefits of the 1998 legislation, there continues to be a considerable number of deaths each year due to paracetamol poisoning"
"One limitation of this study was that we only used data for deaths for poisoning with paracetamol (with or without alcohol), in pure or compound form. We did not use data for deaths where paracetamol was consumed with other drugs."
They had to take the available data and massage it like a Thai masseuse to find what they were looking for.
Not to mention they estimate a decrease of 7 deaths per year, where the post-change level is 121 deaths per year. That's a 5% change, so it's not surprising they had to look at the data a number of ways to even find a change.
You don't need to take that much. LD50 is surprisingly close to the normal dose, and possible to do if you don't realise that cold remedies contain it (or that aminocetophen and paracetamol are the same thing!)
The drawback of Ibuprofen is that it tends to cause damage to stomach and intestinal linings. That's why you are advised to take with food and/or lots of water. You don't want it absorbing all in one place. Long term use exacerbates the effect, making it more likely to cause ulcers and eventually internal bleeding. My partner ended up in the hospital with a serious internal bleed caused by taking Ibuprofen daily for chronic pain. I'm not saying don't use it, just be aware of the risks.
Ibuprofen is possibly worse than that, it seems that it may interfere with sex hormones. [1]
This 2017 study I found in 30s of searching is seemingly underpowered at n=30 or so, but the (preliminary) implication is awful enough that I won't give my boys ibuprofen at all. Out of abundance of caution.
They can have naproxen or acetaminophen instead -- we keep those out of reach and teach our children not to touch them without adults.
Ibuprofen is anti inflammatory which paracetamol isn't. IIRC this means ibuprofen can hide infections. I had a doctor friend who avoided its use as generic pain relief for that reason.
Again and again, this hepatologist makes his message clear: "Acetaminophen (Paracetamol) is the safest anti-fever and anti-pain medicine even among patients with liver disease. It is the first choice for fever and pain management even in advanced cirrhosis."
Look for some of his other posts on the topic for studies and citations.
You can buy two packs of 16 each, enough for 4 days usage at 2 per dose, 4 times per day, after which point if you still need them you maybe have a bigger problem. Or can just restock. What's "fantastically stupid" about it?
Naproxen works like acetaminophen, ibuprofen and others. Yet, it lasts several times longer thanks to its long half life. One naproxen replaces three or four acetaminophens.
There was no grief in my case. I was recently in Italy with my mother. With a picture of a Tylenol bottle, before I could even utter sto cercando..., the pharmacist quickly gave her a box of something. I think it was called panadol.
I have a few prescription medications that are called different things in the US. I thought it was fairly common knowledge with paracetamol, though. Tylenol being one of the common brands names.
Paracetamol was coined in 1956, acetaminophen was coined in 1955[1]. The world pharmaceutical stage was a bit less globalized back then, so splits in naming like this just happened. They're both contractions of the full chemical name, so it's hard to argue one is more correct than the other. At this point the names are too entrenched in their respective countries, so changing them would only cause mass confusion and likely overdoses due to people not understanding what they're taking.
Tylenol is slightly different in this case, as it is merely a brand name widely associated with their most commonly sold medicine. Tylenol does also make other medications, but the majority of it contains acetaminophen/paracetamol.
Acetaminophen and paracetamol are two names for the same generic chemical composition drug, which is why it is especially confusing. You can ask for aspirin or ibuprofen in any English speaking country, and they'll know what it is, but the world is divided on which of the two generic names to use: some acetaminophen, some paracetamol.
FWIW, acetaminophen was coined a year earlier than paracetamol, much like soccer was the accepted term far prior to football, but the Brits and a fair few other countries choose the later versions of the words.
I don't think that is correct re football. Football is an English invention.
It then split into Association Football and Rugby football.
From Association Football we get soccer. So Football was first then soccer.
e.g. The Football Association was formed in 1863 and the first international match in 1872 was billed as International Foot-ball Match and then in small writing (Association Rules) before the term soccer was used.
Ah you're right, I may have gotten my memory slightly mixed up. Even so, the name soccer (at least as a nickname) was formed in the UK, along with association football, both referencing the same thing, and which became more popular over time diverged across country lines, so the analogy isn't too poorly fitting at least!
>It's the first non opioid painkiller applicable for situations like post operative use.
Perhaps the first approved by FDA, I don't know. In many countries, metamizole is the first-line drug for postoperative pain.
(It should be noted that metamizole may very rarely cause agranulocytosis. It is suspected that the risk varies depending on the genetic makeup of the population, which would explain why it is banned in some countries but available OTC in others.)
From my limited experience of metamizole it feels a bit stronger than paracetamol/acetaminophen. Neat little drug if your genetics can take it.
Tangential: China technically banned metamizole due to the agranulocytosis scare, but somehow small clinics always have fresh stocks of this stuff. And their stocks don't look like my metamizole for horses! It's pressed out of the usual magnesium stearate instead of whatever rock-hard thing they use for animal drugs in China.
I had kidney stones last year, by far the most painful thing I have experienced, and got opioid based painkillers which made me constipated. To try and fix that I was eating some stoned prunes and it turns out one of them wasn't stoned and I damaged a tooth (it was weak anyway and needed replacement with an implant).
I received Ketorolac after a tooth replacement (airbags packs a good punch) and it was more effective than the 5mg baby sized morphine pills they prescribe nowadays.
It's a NSAIDs but it's not to hard on the stomach but it's somewhat hard on the kidneys. However Ketorolac is a dangerous drug if you don't follow the posology (don't take 2 pills at the same time, the therapeutic index is that narrow) or if your a poor metaboliser, it leads to kindey failure, stomach bleeding and other life threatening side effects. I would be surprised if that new pain killer was superior to this.
I am sure it's less dangerous but more effective I really doubt it.
AM404 really is the metabolite that keeps giving. The central nervous system system effects were fun too, acting on cannabinoid receptors and/or TRPV1 channels -- so either stony or spicy.
I would certainly consider ibuprofen a "painkiller", it works wonders when I get a headache. So the phrase "the first non-opioid pain reliever suitable for treating post-surgery pain" used later in the article should actually have been the title IMHO...
Interesting that for me ibuprofen doesn’t do absolutely anything (and I’m someone that avoided painkillers almost all my life) I take 1g pills and nothing.
Well, not nothing, my stomach clearly doesn’t like it and I feel it.
Human pain and painkillers response seems extremely variable across different subjects.
My family usually had paracetamol so I went till my early 20s without getting anything for pain or colds as it didn't do anything to me and it felt pointless. I mostly get headaches so discovering Ibuprofen was a life changer. I got a toothache that ibuprofen did nothing against so I tried paracetamol again, still no effects.
It is used surgically too (not just in childbirth as you might associate it) but it's a relatively risky procedure vs. a venous injection or pill to swallow.
Indeed. After my first bowel surgery, I woke up to a wall of pain — because the epidural did not work.
The intense pain caused me to throw up, repeatedly, which put strain on the fresh surgery and the stitches.
After what felt like an eternity, I myself noticed a wetness on my shoulder onto which a broken hose adaptor had leaked. After that was replaced, there were no further issues.
Thankfully, the stitches had held, and I didn't get a hernia.
Also, I did have to carry a pee-bag while the epidural was in, because the epidural made me lose control of my bladder. And the epidural itself left a scar.
Epidural is surely just the method of administration (into the spinal fluid) where the actual painkiller administered is opioids, though, right?
Meanwhile my understanding of Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) was that they were exactly that by definition - Anti-Inflammatories with pain being reduced by reducing the immediate cause of it, inflammation, not by interfering with the actual mechanisms of pain.
I guess one could consider general anaesthesia (laughing gas, ether, and more modern successors) to be "painkillers" too but they're obviously not quite the same category of thing.
Anyway, I enjoyed the article - it would be interesting to hear the author give their own reasons for not accounting for NSAIDs.
Paracetamol/acetaminophen is not an NSAID, though.
NSAID is effectively a shorthand for COX inhibitor; the term NSAID was coined at a time when the mechanism wasn't fully understood, and all other anti-inflammatories were steroids.
Paracetamol does target COX-2, but does so in a way that doesn't really have any effect on inflammation. Its main mechanism of action is as an AM404 inhibitor.
Opioid-induced constipation is easy to counteract, however, with the right form of magnesium, and/or laxatives. There are herbs that you could drink as a tea, too, for constipation.
If you ask me whether I choose pain or constipation, well, I am pretty sure you know the answer.
This constipation goes away once you stop, and everything depends on the dose and the frequency and duration of taking it.
There are also local anesthetics like the lidocaine family. Some of those are usable for post operative pain in the very short term, but obviously can't be administered orally. That presents a problem for most surgeries, since either they'll want to send the patient home or it's located somewhere that's hard to inject.
Depends on the country. In The Netherlands it's common to give opioids like oxy after surgery. I got like 20 pills after a minor wrist operation and didn't even need them.
Plus don't forget: even the "pain relief" provided by sticking a knife through your skin to the bone is addictive. So the side effect of addiction isn't going to go away.
> even the "pain relief" provided by sticking a knife through your skin to the bone is addictive
> the side effect of addiction isn't going to go away
While I agree with your conclusion itself, I disagree that the premise implies the conclusion. The main difference between suzetrigine and opioids, as explained in the article:
Crucially, opioids don’t just kill pain: they also incite pleasure.
When the mu opioid receptors present in the reward center of the
brain are activated, this reduces the secretion of a neurotransmitter
called GABA, which works to inhibit dopamine-producing neurons. As GABA
release declines, dopamine spikes, lighting up the reward center and
inducing pleasure.
The "pain relief" provided by sticking a knife though your skin to the bone is caused by endorphine, which functions similarly to opioids, and that's why it's addictive.
Since suzetrigine doesn't affect mu receptors in the brain, this mechanism doesn't apply.
But I'm almost sure it will have some other unintended side effects. Morphine had them, heroin had them, methadon had them... And each time the inventors were sure they didn't.
Some people pratice self-mutilation to relief their depression. 20 something years ago I frequented a girl who was full of scars under her clothes, she was pretty good at finding plausible excuses for the scars (plausible to a 20yr old ignorant about that practice), one day she confessed that she did this to herself and that she was unable to stop... It's not a memory I tought I would revisit but your question made me think of her and her dangerous mania.
Injuries generally cause brain to release endorphins, which in turn releases dopamine, causing addiction. For example, cutting is a common type of self-mutilation depressed people do. High-intensity exercise arguably also does the same thing - as your body is "microinjured" by strain, your brain releases endorphins to help with the pain, causing effects like "the runner's high".
Like for Aron Ralston, who was trapped under a rock and had to cut off his own leg to escape: would it have reduced his pain if he had stabbed himself in the shoulder to the bone?
Would this best be done with, say possibly, acupuncture needles or an ice pick, so as to minimize the damage and to maximize the relief?
Gunsmoke TV episode:
Doc: Well, Billy, we'll have to amputate your lower left leg - it's shot plumb thru with gangrene.
Billy: Will it hurt, Doc?
Doc: Hell yeah, it'll hurt! But thanks to Hacker News we have a new pain treatment: every time you yell. Chester here will stab your right leg to the bone with this h'yar ice pick. And Mary will hold a leather strap in your mouth so your teeth don't crack off! Don't forget to breathe.
Billy: I'm obliged and grateful to be part of your research program, Doc, but can't you instead just wait 10 minutes while I drink this here quart of whiskey and pass out? Then you can do as you wish.
Doc: Hell, no, time's a'wasting! Hold him down, fellas! Doctorin' progresses only a step at a time!
It very much oversimplifies the interaction between GABA and dopamine as effects of dopamine and the interaction with GABA varies much depending on the brain region and the specific receptor.
Also honestly the conclusion is very much pseudosciencey, if it was so simple nobody would find benzos pleasurable except on withdrawal
Nociceptive pain being that by actual damage to tissue, as opposed to neuropathic pain like a headache or inflammation that you might take a (non-opioid!) NSAID for.
I'm a neuroscientist by training, and that doesn't match my understanding (although the definitions might have changed).
Inflammation would be an instance of nociceptive pain, and an NSAID would alleviate it by reducing the inflammation; and most tissue damage will result in inflammation.
Neuropathic pain, on the other hand, would be due to damage of the nerves themselves, and NSAIDs are completely useless here (ask anyone with sciatica or other nerve entrapment)
I'm happy to take that correction - I have no training in any relevant field - I was just trying to follow the description in TFA, which links indirectly to my link above in the second paragraph or so as 'nociceptive pain'; from which I inferred that's all it's talking about and existing non-opioids must therefore not target that.
Perhaps non-inflammatory (or generically) nociceptive pain killing is the point. (Which is getting a bit specific for such a broad title isn't it. Does 'painkiller' ordinarily have such a narrow meaning in your experience?)
Well my comment will still be here, and at least having the qualifier in the title is a pointer to look it up if needed, or to hint 'oh right ok it doesn't mean of all things, I guess paracetamol does not kill nociceptive pain, whatever that is'.
I guess that would make sense in a scientific paper or journal, but most people would have no idea what that means and just make for a confusing title that would turn people off from reading it. Almost everyone has heard of opiates in the evening news or social media.
And almost all those people have 'painkillers' such as paracetamol and ibuprofen in their cupboard, which they know not to be opiates.
The point isn't to accurately describe it as 'nociceptive' (which I've never heard of before either) and have that be understood, it's to qualify it such that it isn't confusing or sounding like an historical tale of how whatever the first NSAID/analgesic was came to be.
I think the medical community needs to take more seriously that different people have different pain tolerances.
My wife, daughter and I are very pain tolerant. Out of curiosity, I've turned down freezing for fillings and I even turned down some of pain meds before abdominal surgery. I've never taken the post op opioids, including when I had my impacted wisdom teeth removed.
My other kid, on the other hand, is a whimp. She gets anxious simply if I replace her earrings.
My use case for anesthesia is very different from my kid. I struggle to appreciate why anesthesia is even necessary beyond the need to restrain the patient.
My kid could go into a full blown panic attack from pain.
Yet I don't see anesthesiologists ever asking "how good are you with pain?"
wow I'm envious. I remember how much pimples hurt and I was astounded nobody warned me. This now makes me curious what the low pain tolerance to anxiety correlation is.
I think they're using it hyperbolically. As a parent (who also maybe has a high pain tolerance but I am a guy and we are famous for both thinking that and for not being pain tolerant) my daughter is currently like this including the earrings thing. It's more of a frustration but I know she will grow out of it as she's already gotten a lot better. I would imagine OP is in the same boat and is just letting off a little rhetorical steam.
You'd think my comment's thesis that folks with lower tolerances should be respected and treated differently would have given the rhetorical device away.
> Another example involves nerve growth factor inhibitors like tanezumab. Although tanezumab alleviated inflammatory pain from conditions like osteoarthritis, Phase III trials revealed an unfortunate side effect: rapidly progressive osteoarthritis. Researchers hypothesized that because patients felt so much better, they overused their arthritic joints, accelerating damage. Although further trials were conducted at lower doses and with restrictions, the FDA ultimately voted against its approval.
Really not sure how to feel about this part lol, I mean I get it, but at the same time this is very ugh.
That's a very real concern. A friend of mine has a higher than normal threshold for pain and have permanent injuries as a result. Among other things has walked around on a broken foot for months and failed to register a back injury. All of this then escalated to the point where she feels the pain, but the injuries have become permanent.
I have a similar condition. For me, the issue isn't so much the sensation of the permanent injuries themselves, but rather the constant physical fatigue that comes with them. Since doctors tend to rely heavily on those 1-to-10 pain scales with the little face expressions, it's incredibly hard to be taken seriously when your symptoms don't fit neatly into that system. What's frustrating is that people who can feel the pain early on often have a chance to prevent further damage. I couldn't and doctors couldn't even help me identify that I might have health issues.
I worry a lot about aging, and I'm also afraid of things like tumors or cancers that I might not feel until it's too late. As an example, I can't feel cavities forming and I didn't even notice my wisdom teeth piercing through my gums when I was a teen.
A rheumatologist explained to me that in people with chronic pain from things like arthritis, the brain's pain perception can become permanently altered to register pain that no longer "exists". She explained that the brain itself is really the source of the sensation of pain, and you don't necessarily need a "real" source producing a signal. So one should at least not ignore pain if one can avoid it.
Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening, which is the other "ugh" part to this.
That said, the article may not be fairly representing what happened in the first place, so...
>Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used.
Clicking "FDA" in the bit you quoted above takes you to a different page wherein the FDA laments the lack of data around the drug (eg, the "hypothesized mechanism"). It also suggests that the companies intend to work with the FDA more on this.
Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
> Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
Why do you present this as an either/or?
> Clicking "FDA" in the bit you quoted above takes you to a different page
Indeed, where I found that...
> That said, the article may not be fairly representing what happened in the first place, so...
...this is exactly what happened, i.e. I was successfully misled even before reaching your false dichotomy. Yay.
I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
I didn't intend to present it as an "either/or", though I can see how it can be read that way. I simply read you saying that they "completely prevent[ed]" something from coming to market when, perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That the "incomplete justification" you lamented may also have been how the FDA felt about the data provided to them.
It could also be for other reasons, absolutely! This is just one possibility that seems very obvious to me. There's no either/or from my end.
> I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
If I didn't already conclude that you presented a false dichotomy, why would I have inquired about why you did so? It's also not set in stone; from your reply I can just change my mind afterwards. But why do it in two rounds when I can do it in one?
I understand if I came across as hostile though, I admit it was sadly reflexive, and I apologize.
> perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it.
That's not a nuance I intended to disregard. Yes, I understand they can revisit the drug's approval later, didn't mean to suggest otherwise.
Especially when it's sometimes hard to read tone, even moreso from a stranger whose communication style we're unfamiliar with. Even harder still, comments online generally don't lend themselves well to nuance and assumptions can easily be made, such as my leaning too heavily on your use of the word "completely"! Should we hug it out?
Meanwhile, good old aspirin is not only an effective pain reliever but it has also been shown to reverse the effect of cartilage loss in osteoarthritis:
And that's not even taking into account its cardioprotective effects.
But hey, it can be hard on the stomach in SOME people so we developed alternatives with all sorts of nasty side effects, up to and including heart attacks and strokes (rofecoxib, valdecoxib, etc.) Hell, a decade ago, the FDA issued an advisory across the board that "Non-aspirin NSAIDS increase the risk of heart attacks and strokes":
Some day we will look back on the attempted replacement of aspirin with these other drugs the same way we now look back on the replacement of butter with margarine (and the replacement of saturated fats with trans fats more broadly).
I think your argument hinges on the implied idea that whoever makes up these entities (the FDA or otherwise) are intrinsically made of finer clay that the rest of us mere mortals.
For the avoidance of doubt, I'm not implying anything; I'm categorically stating it: experts are better than the hoi poloi. Always.
To continue my example of thalidomide, the FDA's Dr. Frances Oldham Kelsey prevented millions of American babies from being born with devastating deformities.
At the same time millions of American mothers and their GP's were clamoring for the anti-nausea drug that the British mother's were enjoying. And they too said the FDA was getting in their way.
Experts aren't "made of finer clay" : they just know a lot more than the populace about specific topics. There are other topics where I am the finer clay. See 'specialisation'.
The title... Confuses me. Especially with a handful on non-opiod painkillers sitting in my history. Gabapentin? Heck, ibuprofen?
Especially when the article itself compares it to ibuprofen:
> If paracetamol and ibuprofen are inadequate for pain relief, Journavx can now be prescribed as the next alternative treatment, instead of mild- to moderate-strength opioids.
"suitable for treating post-surgery pain" isn't something to cut, just for a better title. It just makes the clickbait stench of that first line even worse.
This is a better paracetamol. Which is awesome, and something we need. This is not a world first.
Gabapentin is an anticonvulsants. Ibuprofen and paracetamol are anti-inflammatory. While they are effective at reducing pain, they are technically not "pain killers". The title is therefore correct.
Interesting that the author chose that title despite the existence of NSAIDS [^1] and paracetamol(acetaminophen) - the latter of which they even mention (but only in the context of combination with opioids)
I'm always surprised that Kratom (https://en.wikipedia.org/wiki/Mitragyna_speciosa) doesn't come up more in these conversations. In addition to being a powerful painkiller, it helps manage opioid withdrawals.
I believe it's still somewhat legal for consumption in the U.S., though other countries have been moving to ban it to varying degrees, since it can be used recreationally, though it isn't known to produce the same intensity of euphoria as opioids, and can also be addictive, though I don't believe it to produce as severe withdrawals as opioids.
All in all I think it's a sadly understudied and underutilized medicine, which is the unsurprising result of pharmaceutical companies having less incentive to study plant medicines
The addiction is the kicker there. Kratom withdrawals/dependency isn't as bad as traditional opioids/opiates. But it's a magnitude of an order worse than nicotine/caffeine/etc. dependency and withdrawals for some people. And the full safety profile of people taking concentrated kratom extract for long periods of time isn't really known yet.
I'm really of the belief that the only reason kratom exploded in popularity the way it did was because it was a legal alternative to opiates. Not necessarily because it's an upgrade (or even sidegrade. ) If morphine could still be purchased in every corner store and pharmacy over the counter kratom extracts would never have blown up the way they did.
I don't feel the title is misleading, but it may be a cultural language difference.
The term 'painkiller' is reserved for strong pain relief, and wouldn't include things like ibuprofen. That made me think immediately of a non-opioid pain blocker not just a pain reliever.
>The term 'painkiller' is reserved for strong pain relief
Having claimed it was cultural. It have been helpful of you indicated which culture you felt this applied to.
In UK I'd say painkillers includes ibuprofen and paracetamol. I suppose with ibuprofen it's also referred to as an anti-inflammatory. Not sure how else one would refer to paracetamol other than with synonyms (analgesics) or euphemism (pain relief tablet).
Even in the UK it's not necessarily true. I wouldn't be surprised to hear it used that way, but I don't think my peer group in the UK would ever refer to NSAIDs as anything other than their brand or generic names.
I particularly disagree with the parent comment that calls this click bait. The topic's intrinsically interesting to anybody who'd be lured in by that title; it doesn't need "bait" and we all know NSAIDs exist.
The article's particularly good at citing its references inline, which I very much appreciated. Added this author to my RSS reader in fact.
The title is at the very least ambiguous. I expected an essay on the historic invention of NSAIDs/paracetamol as I also understand painkillers to include NSAIDs.
Paracetamol can be referred to as an antipyretic (fever reducing drug), and it's widely used for that in the same way ibuprofen is used as an anti inflammatory.
>The term 'painkiller' is reserved for strong pain relief
Maybe there's some very specific, limited medical context where this is the case but in common parlance it's not at all the case, search for "painkiller" in an online shop like Amazon and you'll find a whole lot of Paracetamol/Tylenol, and various NSAIDs (aspirin/ibuprofen) and manufacturers of those drugs actually use that specific term.
All dictionaries I've looked at (MW, OED, Cambridge) define painkiller broadly as any drug that relieves pain. Do you have a source for your claim that it's used narrowly? Here's mine: https://www.merriam-webster.com/dictionary/painkiller
Can you explain what the difference is? Would pain-relievers be substances that undo whatever is causing the pain, making them indirect, while painkillers act directly on the pain signals and their transmission?
It might be clickbait, but it's also pretty big news of a fairly universal topic and not in the vein of "This one secret that your doctor doesn't want to know!"
As someone else already mentioned in this thread, in Europe there is already metamizole which is used for post-surgery pain. Anyone knows if suzetrigine is more effective than metamizole?
The paragraph on the relation to Brugada Syndrome hits home, as I have that rare disease. What isn't clear is if it's safe for Brugada patients - a hell of a lot of drugs are not advisable for us. As I also have CRPS type II (complex regional pain syndrome) I'd like a non-narcotic strong pain killer that doesn't induce arrhythmia.
One thing people barely notice is how well the FDA is working.
A government agency with very high trust that partners with companies and helps to get things approved but only when they’re safe and has gotten more efficient since Covid is a rare and precious thing.
If you read the parts about the discovery, and how the trail went, you'll see how basic research into all kinds of things feed into innovations like this.
Which is why some bean counter or ideologue cutting this stuff will halt progress all over the place.
Everyone's pain tolerance is different. I am also very aware on stomach and kidney issues those drugs have.
Having said that, ketorolac is a very potent pain inhibitor, can be prescribed for 6 days, causes no dependence issues. Pretty sure can be prescribed more. Cheap, out of patent protection. Took it when broke my hand, it was a miracle of painkiller.
> Traditional opioids mimic opium, a compound found in the poppy plant that contains morphine.
Huh? How can a compound contain another compound. I thought opium was the term for an extract which contained opiates (compounds) and not the other way round.
In the original sentence, "contains morphine" is probably modifying "compound", not “poppy plant”
---
"Opium" is the dried latex (milky fluid) that comes from the seed capsules of the opium poppy (Papaver somniferum).
Opium contains ~12% morphine, ~2.5% codeine, and ~1.5% thebaine, all of which are analgesic alkaloids that act on the μ-opioid receptors. So opium itself is a cocktail of these, plus non-analgesics like noscapine (a cough suppressant) and papaverine (a vasodilator.)
Heroin is synthesized from morphine by acetylation.
Oxycodone is synthesized from thebaine in a more complex, multi-step process.
As for the terms "opiate" vs. "opioid", the terms are sometimes used interchangeably but "opiate" generally refers to naturally occurring chemical (morphine, codiene, thebaine, etc.) while "opioid" is a catch-all Heroin is often lumped in with the opiates since it is a simple synthesis; oxycodone could be called a "semi-synthetic" opioid, and fully synthetic opioids include fentanyl, methadone, and tramadol. Relative to morphine, codeine is about 1/10th the potency, heroin is 4x, fentanyl is 50-100x, and the veterinary analgesic carfentanil (given to elephants and rhinos) is 10,000x--yikes!
Two different meanings of the word. The article is using the traditional non-scientific meaning. Opium is a compound (as in a mixture), containing several different chemical compounds (as in molecules containing more than one element).
> At least 100 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin.[6] It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort,[7] and earlier in Echinacea.
Cannibinoid receptors are separate from opioid receptors.
Well then I hope the 111th non opioid painkiller works for you. I know people in chronic pain (my body isn’t exactly a picnic) and so far none of them have gotten hooked on oxy but it’s always looming.
According to our psychological theories any sufficiently fast acting and strong painkiller will be addictive as long as it removes or reduces any type of pain.
Seams strange if this one truly will not have "drug abuse" connected to it.
The impression I got from Wikipedia reading about this (suzetrigine) is that it’s not addictive because it acts on peripheral nerves and not directly in your brain
Given how scared people are of "addiction" the seller certainly would like that narrative and it might make sense from a withdrawal perspective. Which in turn has an effect on how addictive a drug is to a very large degree.
There are also lots of studies indicating that the speed of action of a drug is important for addiction. Which essentially boils down to the fact that the brain (beeing effected by operant conditioning) needs a drug response that is sufficiently noticeable to be connected to the action of taking the drug.
Colloquially acetaminophen/paracetamol and ibuprofen are "painkillers" but this is in a different class, it's amazing to have something which performs like the opioid pain relief but without at least some of the side effects.
It's the first non opioid painkiller applicable for situations like post operative use.
I'd have loved this after my hernia op, the last thing you need with that is opioid induced constipation.
Off topic complaint: I am guessing an absolutely massive amount of (admittedly minor in each instance) grief has been caused by the most widely deployed simple, inexpensive, useful and familiar drug unnecessarily having two different names acetaminophen / paracetamol. Finally figured this out this year (aged 64) after previously being confused why I couldn't find any damn paracetamol in pharmacies on my occasional visits to the US.
My wife and I got colds while vacationing in Edinburgh and had a heck of a time before realizing to ask for paracetamol rather than acetaminophen. Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
> Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
Yes, but:
> Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States. Notably, around 50% of these poisonings are unintentional, often resulting from patients misinterpreting dosing instructions or unknowingly consuming multiple acetaminophen-containing products.
Source: https://www.ncbi.nlm.nih.gov/books/NBK441917/#:~:text=Acetam...
There's an interesting thing too about metamizol. It's very popular here in Spain for some types of pain (for example, teeth related stuff or post-surgery) and it's used widely without much problem. In fact, it was the most sold medication in Spain in 2023 (sold under the Nolotil brand) [0]. But it's forbidden in places like the UK.
Thing is, as we are a popular destination with British tourists or even pensioners that live in the Mediterranean, we've found in the last years that British population is genetically more likely to have a very dangerous side effect, agranulocytosis, that could result in death.
Can't find the exact source (I'm on my phone), but seems like at least half of the metamizol related agranulocytosis cases in Spain have been of British origin, and several deaths have been reported. There's a ongoing legal process where at least 40 deaths are being investigated [1] and doctor have stopped providing metamizol to persons of British origin, and do it carefully for other persons.
So what was perfectly safe around here, was found quite dangerous for certain subset of the British population (no jokes about balconies, please).
Edit for some sources:
From 1998 to 2003, out of the 13 agranulocytosis cases from a hospital in Marbella, 8 were foreigner, and of those 5 were from the UK [2]. According to the ADAF association, out of the 45 deaths attributed to metamizol in Spain since 1996, only 8 of them were Spanish (they don't tell their sources in that article) [3]
--
I was under the impression that a lot of overdoses of acetaminophen are due to it being included in many different multiple-medicine cold/flu remidies, like cough syrup, NyQuil, decongestants, etc. So people end up exceeding the max dose accidentally when they take acetaminophen along with some of those other things.
Does the UK have rules that prevent mixing acetaminophen with other drugs? Its getting so its sometimes hard to find over the counter cold/flu medicines without acetaminophen
The UK rules apply to all medicines containing paracetamol.
Non-pharmacy retailers are only allowed to sell in packs of 16, and they'll usually only allow two packs of any paracetamol-containing medication to be sold at a time (eg. one cold/flu and one cough remedy).
If the name of the product doesn't already contain the word "paracetamol", then all of the packaging must prominently display "contains paracetamol" - so even small retailers that don't have computerised checkouts are expected to follow the same rules.
Deaths from paracetamol overdose fell by 43% (with a similar decrease in the rate of accidental poisonings) in the first 11 years after these changes were implemented: https://www.bmj.com/content/346/bmj.f403
I think it's less mixed in with other products than in the US (?)
My wife has negative reactions to it, which is extremely rare at normal doses (to the point many doctors don't believe her).
Trying to find medicine for her when she's sick is surprisingly time consuming as it is in so many things even vaguely related to treating cold / cough / flu symptoms.
Yes, but:
350 million people in this country.
As annoying as it is (and I agree it is fantastically annoying) much to my surprise admissions for paracetamol overdose to UK hospitals absolutely plummeted after purchasing restrictions were introduced.
Score one for the nanny state.
Not sure what "plummeted" quantifies to in this context, but the US saw meaningful reductions in overdose treatments and calls to the poison control line after changing the labeling rules and a public education campaign. The cited study was even conducted before the full labeling rules change came into effect.
Teach a man why not to over-fish fish vs giving him a smaller amount of fish... or something.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5676300/
The US doesn't have a significant problem with deliberate acetaminophen overdose as part of a suicide attempt, which is the problem the UK rules are meant to address.
Strictly speaking, if you wanted to solve intentional overdoses of acetaminophen, it appears that you could do it by presenting more appealing means of self-harm, like in the US. I'm pretty certain the availability of other lethal products (guns, really) directly correlates with whether OTC drug overdosing is a popular means of harm.
I'm willing to bet that handing out cyanide pills OTC would effectively eliminate intentional acetaminophen poisonings in the UK. Surprised the boffins at the NHS didn't think of it first if they really want to eliminate intentional overdoses! /s
There's some research to suggest if you make suicide a time consuming process some percentage of people who decide to do themselves in will reconsider while they're trying to carry out the act. I'm skeptical, but I understand the reasoning.
For those interested having done a brief literature search I've found a review article that paints the picture as much less clear than my categorical statement
https://pubmed.ncbi.nlm.nih.gov/17536874/
denmark has same rule, for same purpose and effect
I'm a big fan of paracetamol in terms of how well it works; 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/
Given how common accidental paracetamol overdose is I think it’s perfectly reasonable.
Many very simple things can badly hurt or kill someone who doesn't take a few minutes to not be stupid about using them properly. Legislating with absurdities applied to all anything that possibly leads to completely individual harm because a few people can't take normal responsibility for themselves emphatically isn't reasonable.
It’s not theoretical. On one side of the ledger we have people dying horrible deaths, on the other side we have people who can’t have vast quantities of paracetamol on hand for no particular reason. If you do in fact need vast quantities of paracetamol for some reason, it can be prescribed.
The very idea that you should need special permission from some form of officialdom for having access to anything that is very widely useful but in all but a very, very small subset of select cases involving very, very few people who harm only themselves with its misuse is what's genuinely disgusting here.
The vast majority of adults should be able to live in a world where they're not treated like 10-year-old children for seeking a bit of modest pain relief for very common ailments.
I really hope I never find myself living in a society where your perspective dominates. I’d rather we took care of the weak than grumble about such an inconsequential inconvenience.
This attitude is why your society arrests people for mean tweets.
> a few
Fifty thousand hospital visits per year
> isn’t reasonable
Fortunately this is not a popular opinion
You used and descontextualizad the scariest number possible for whatever instinctively nannying nonsense reason of your own.
There were over 50,000 hospital emergency room visits, yes. However, bear in mind that many thousands of people visit emergency rooms for all kinds of unfounded reasons every year anyhow. Of those 50,000+ paracetamol-related visits (speaking of the United States here), less than 5% resulted in any need for hospitalization and only 450 or so deaths were registered in 2023, as a recent example year. These numbers out of an estimated 60 million individual uses PER WEEK by Americans according to the NIH.
For some perspective, accidents caused by "Fall involving ice-skates, skis, roller-skates or skateboards" in the U.S cause an average of 1000+ deaths per year.
Paracetamol can, just like many drugs, be dangerous, but if your criteria for paranoid restriction of something so commonly necessary and used without problems in the extreme absolute vast majority of cases are the numbers above, you'd better start banning one enormous shit list of completely innocuous activities and things that normal adults have access to before you reach something like paracetamol.
There seems to be a sort of mental illness prevalent in the kind of logic that equates any evidence of self-harm with a given product or thing with a rabid need to treat people like children in their access to it.
The entire adult population should not have to be treated like drooling morons in their very most basic personal medical choices because a completely minuscule percentage of the population lacks the mental capacity to read a basic safety label for a common medicine, or control their childrens' access to something that's easy to keep away from them.
I’ve never heard of this particular overdose. In the US it’s completely unmonitored and I’ve never heard of an overdose. I’m genuinely surprised.
“A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the US found that paracetamol was the cause of 41% of all cases” from https://en.m.wikipedia.org/wiki/Paracetamol_poisoning
From that wikipedia page:
> In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity.
10g is 20 pills of the highest strength you'll find in a regular store. Excedrin brand "Extra Strength" is half of that, you'd have to be eating 40+ pills in 24 hours, or 20+ pills per day on multiple consecutive days. Most acetaminophen pills have 100-200 mg of the active ingredient.
You're missing the context:
> Intentional overdosing (self-poisoning, with suicidal intent) is frequently implicated in paracetamol toxicity.[25] In a 2006 review, paracetamol was the most frequently ingested compound in intentional overdosing.[26]
So, it's not that acetaminophen will kill that easily. It's just that of the easily available ways to kill yourself, it's distinctly the one that destroys the liver quick.
It's unfortunately quite easy to do even inadvertently (not following dosage instructions) - doesn't take a lot.
The reason for the rule though was to combat its use in suicide attempts. They also have to be sold in blister packs here for the same reason, not the big bottles of Tylenol/Advil etc. that you get there (and we used to here) - relatively difficult to take several, requires more preparation than just chugging a bottle.
> the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid
Worse than that: it is effectively per day per shop. In a very short space of time I can buy two packs in Boots, two in Tesco, two in Sainsbury, ooh look another small Tesco I'll get two there as well, two from Savers, two from SuperDrug, …
Worse in what ways? I think it's a pretty neat feature of the design. If you just need some, you don't get a lot, and you don't get to buy a lot "just in case". If you truly need a lot, you can go though the hassle of going to multiple stores.
It's essentially just raising a barrier for (under normal circumstances) undesirable behavior.
> Worse in what ways?
It doesn't do what it is sold as doing¹ while causing a bit of faf.
The restriction is one of those put in place because someone somewhere want to be seen to be doing something.
> for (under normal circumstances) undesirable behavior.
Outside of a supply problem situation, which we don't have for that sort of thing and different at the time the change came in, why is it so undesirable?
--------
[1] Reducing accidental overdose rates², reducing people using out-dated-so-possibly-ineffective medicines, etc.
[2] Accidental overdose rates have fallen, but they have in many places without those restrictions, so I suspect that is a coincidence and probably more due to greater awareness³ of there being paracetamol or aspirin in other products and therefore the need to be careful what you take in combination.
[3] Due to better labelling?
I think being able to buy a lot of medicine just in case is an amazing feature that makes me less dependent on the supply chain.
You can buy you entire year's supply of panadol by simply shop-hopping through the main street. What's the problem?
To me it's really the principle of having lots of ridiculous rules that amount to a pile of little inconveniences all over every facet of modern life. It's not a logical reason to have a problem with it, but I would prefer to see a more logical set of rules that don't seem to be so ridiculous and maze like when you are doing something that is just slightly out of the norm.
I did something similar when the whole household was coming down with Covid...
And yet the policy appears to have been effective in reducing overdoses.
Overdoses declined in the US, as well, where there are no limits on quantity, but there has been a campaign to educate and create better labeling practices for medication containing acetaminophen.
I think it's important to recognize that overdoses can be intentional or unintentional, and it isn't clear which ones will be affected by the policy of limiting purchase quantity per transaction.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5676300/
Based on what?
The US went with the educational route - any product containing acetaminophen has “CONTAIN ACETAMINOPHEN - DO NOT COMBINE WITH OTHER PRODUCTS CONTAINING ACETAMINOPHEN”
Overdoses went down despite the fact I can buy $1,000 tablets for $5 at Costco.
Based on studies⁰ that examined it.
The fact that another country had success with a different technique too doesn't mean it wasn't successful.
[0]: E.g. https://pubmed.ncbi.nlm.nih.gov/23393081/
That study is...not that rigorous, but I give them points for being clear about it.
"The downward step change was not apparent when the intervention point was moved back to the beginning of 1998."
"Despite the apparent benefits of the 1998 legislation, there continues to be a considerable number of deaths each year due to paracetamol poisoning"
"One limitation of this study was that we only used data for deaths for poisoning with paracetamol (with or without alcohol), in pure or compound form. We did not use data for deaths where paracetamol was consumed with other drugs."
They had to take the available data and massage it like a Thai masseuse to find what they were looking for.
Not to mention they estimate a decrease of 7 deaths per year, where the post-change level is 121 deaths per year. That's a 5% change, so it's not surprising they had to look at the data a number of ways to even find a change.
True, but paracetamol overdoses are not a fun death. Granted, you need to take a massive amount, but still.
You don't need to take that much. LD50 is surprisingly close to the normal dose, and possible to do if you don't realise that cold remedies contain it (or that aminocetophen and paracetamol are the same thing!)
I avoid it at all costs because of the possibility of liver damage. Ibuprofen seems to have the same effect without potentially serious side effects.
The drawback of Ibuprofen is that it tends to cause damage to stomach and intestinal linings. That's why you are advised to take with food and/or lots of water. You don't want it absorbing all in one place. Long term use exacerbates the effect, making it more likely to cause ulcers and eventually internal bleeding. My partner ended up in the hospital with a serious internal bleed caused by taking Ibuprofen daily for chronic pain. I'm not saying don't use it, just be aware of the risks.
https://pubmed.ncbi.nlm.nih.gov/9715832/
Ibuprofen is possibly worse than that, it seems that it may interfere with sex hormones. [1]
This 2017 study I found in 30s of searching is seemingly underpowered at n=30 or so, but the (preliminary) implication is awful enough that I won't give my boys ibuprofen at all. Out of abundance of caution.
They can have naproxen or acetaminophen instead -- we keep those out of reach and teach our children not to touch them without adults.
Perhaps there is some more recent research?
[1] https://www.pnas.org/doi/abs/10.1073/pnas.1715035115
And also kidney failure in prolonged use, usually in patients with any sort of previous kidney damage.
Ibuprofen is anti inflammatory which paracetamol isn't. IIRC this means ibuprofen can hide infections. I had a doctor friend who avoided its use as generic pain relief for that reason.
But for muscular/joint pain the anti-inflammatory aspect is a feature, not a bug. And I'd guess that's what most long term user's target is?
https://x.com/theliverdr/status/1908363713771425946
Again and again, this hepatologist makes his message clear: "Acetaminophen (Paracetamol) is the safest anti-fever and anti-pain medicine even among patients with liver disease. It is the first choice for fever and pain management even in advanced cirrhosis."
Look for some of his other posts on the topic for studies and citations.
People will still happily use paracetamol when drinking or "for hangover" (headache and all that), hitting their liver really hard. :(
I take the OG: Aspirin.
Ibuprofen and other NSAID result in a ton of hospitalizations each year due to gastric bleeding.
I know folks that got ulcers; from both ibuprofen, and Aleve.
I take acetaminophen, but only occasionally.
The LD50 is 10x the standard dose (5 g vs 0.5 g)
And the people that have serious toxicity at 5 g are likely already sensitive due to alcohol intake, malnutrition, etc.
For a healthy, well fed human who isn’t consuming alcohol the dose that causes serious issues is closer to 20x
You can buy two packs of 16 each, enough for 4 days usage at 2 per dose, 4 times per day, after which point if you still need them you maybe have a bigger problem. Or can just restock. What's "fantastically stupid" about it?
Wife: good day at the office dear?
Me: yep argued with some strangers on HN about how daft/wise UK's paracetamol laws are, highly fulfilling!
:-)
Naproxen works like acetaminophen, ibuprofen and others. Yet, it lasts several times longer thanks to its long half life. One naproxen replaces three or four acetaminophens.
How are you consuming a whole pack of paracetamol a day for that to be a problem?
> Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
Its introduction pretty effectively reduced the incidence of suicide attempts by overdose resulting in death or hospitalisation.
https://pubmed.ncbi.nlm.nih.gov/23393081/
(The tl;dr conclusion: it worked, consider going further.)
There was no grief in my case. I was recently in Italy with my mother. With a picture of a Tylenol bottle, before I could even utter sto cercando..., the pharmacist quickly gave her a box of something. I think it was called panadol.
Panadol is a household staple in Australia as well
I have a few prescription medications that are called different things in the US. I thought it was fairly common knowledge with paracetamol, though. Tylenol being one of the common brands names.
Don't forget people like to call it APAP too.
Paracetamol is the standard and WHO approved name used everywhere except certain parts of the US. It's ridiculous the FDA chose acetaminophen.
Paracetamol was coined in 1956, acetaminophen was coined in 1955[1]. The world pharmaceutical stage was a bit less globalized back then, so splits in naming like this just happened. They're both contractions of the full chemical name, so it's hard to argue one is more correct than the other. At this point the names are too entrenched in their respective countries, so changing them would only cause mass confusion and likely overdoses due to people not understanding what they're taking.
[1]: https://en.wikipedia.org/wiki/Paracetamol#Naming
What parts of the US use paracetamol? I’ve lived on both coasts and the Midwest and haven’t ever seen anything but acetaminophen.
Wikipedia has it's acetaminophen in United States, Canada, Japan, South Korea, Colombia and Venezuela
Can confirm it is called acetaminophen in Canada
I've live for all my life in a lot of places in the US and "Paracetamol" was never used. I'd never heard that term until this HN thread.
The overseas territories are split on which variant they use.
I had a really bad first few days visiting the US the first time because of this
Tylenol also. Virtually all drugs and chemical products go under a bunch of somewhat confusing names. I guess for marketing?
Tylenol is slightly different in this case, as it is merely a brand name widely associated with their most commonly sold medicine. Tylenol does also make other medications, but the majority of it contains acetaminophen/paracetamol.
Acetaminophen and paracetamol are two names for the same generic chemical composition drug, which is why it is especially confusing. You can ask for aspirin or ibuprofen in any English speaking country, and they'll know what it is, but the world is divided on which of the two generic names to use: some acetaminophen, some paracetamol.
FWIW, acetaminophen was coined a year earlier than paracetamol, much like soccer was the accepted term far prior to football, but the Brits and a fair few other countries choose the later versions of the words.
I don't think that is correct re football. Football is an English invention. It then split into Association Football and Rugby football.
From Association Football we get soccer. So Football was first then soccer.
e.g. The Football Association was formed in 1863 and the first international match in 1872 was billed as International Foot-ball Match and then in small writing (Association Rules) before the term soccer was used.
Ah you're right, I may have gotten my memory slightly mixed up. Even so, the name soccer (at least as a nickname) was formed in the UK, along with association football, both referencing the same thing, and which became more popular over time diverged across country lines, so the analogy isn't too poorly fitting at least!
>It's the first non opioid painkiller applicable for situations like post operative use.
Perhaps the first approved by FDA, I don't know. In many countries, metamizole is the first-line drug for postoperative pain.
(It should be noted that metamizole may very rarely cause agranulocytosis. It is suspected that the risk varies depending on the genetic makeup of the population, which would explain why it is banned in some countries but available OTC in others.)
From my limited experience of metamizole it feels a bit stronger than paracetamol/acetaminophen. Neat little drug if your genetics can take it.
Tangential: China technically banned metamizole due to the agranulocytosis scare, but somehow small clinics always have fresh stocks of this stuff. And their stocks don't look like my metamizole for horses! It's pressed out of the usual magnesium stearate instead of whatever rock-hard thing they use for animal drugs in China.
I broke a tooth because of kidney stones...
I had kidney stones last year, by far the most painful thing I have experienced, and got opioid based painkillers which made me constipated. To try and fix that I was eating some stoned prunes and it turns out one of them wasn't stoned and I damaged a tooth (it was weak anyway and needed replacement with an implant).
I received Ketorolac after a tooth replacement (airbags packs a good punch) and it was more effective than the 5mg baby sized morphine pills they prescribe nowadays.
It's a NSAIDs but it's not to hard on the stomach but it's somewhat hard on the kidneys. However Ketorolac is a dangerous drug if you don't follow the posology (don't take 2 pills at the same time, the therapeutic index is that narrow) or if your a poor metaboliser, it leads to kindey failure, stomach bleeding and other life threatening side effects. I would be surprised if that new pain killer was superior to this.
I am sure it's less dangerous but more effective I really doubt it.
Breaking news: turns out acetaminophen has an active metabolite that acts on... sodium channels.
https://medicalxpress.com/news/2025-06-acetaminophen-discove...
AM404 really is the metabolite that keeps giving. The central nervous system system effects were fun too, acting on cannabinoid receptors and/or TRPV1 channels -- so either stony or spicy.
I can't say it ever made me feel high, but acetaminophen has been long shown to have significant behavioral effects
https://pubmed.ncbi.nlm.nih.gov/27217114/
https://pubmed.ncbi.nlm.nih.gov/32888031/
My primary care doc doesn't want me taking either NSAIDS or acetaminophen so when I get asked at the urgent care what I take for pain I say "Nothing".
I would certainly consider ibuprofen a "painkiller", it works wonders when I get a headache. So the phrase "the first non-opioid pain reliever suitable for treating post-surgery pain" used later in the article should actually have been the title IMHO...
Interesting that for me ibuprofen doesn’t do absolutely anything (and I’m someone that avoided painkillers almost all my life) I take 1g pills and nothing.
Well, not nothing, my stomach clearly doesn’t like it and I feel it.
Human pain and painkillers response seems extremely variable across different subjects.
My family usually had paracetamol so I went till my early 20s without getting anything for pain or colds as it didn't do anything to me and it felt pointless. I mostly get headaches so discovering Ibuprofen was a life changer. I got a toothache that ibuprofen did nothing against so I tried paracetamol again, still no effects.
I also thought about epidural. Is that a non addictive way to give pain relief (extreme yes)
It is used surgically too (not just in childbirth as you might associate it) but it's a relatively risky procedure vs. a venous injection or pill to swallow.
Indeed. After my first bowel surgery, I woke up to a wall of pain — because the epidural did not work. The intense pain caused me to throw up, repeatedly, which put strain on the fresh surgery and the stitches.
After what felt like an eternity, I myself noticed a wetness on my shoulder onto which a broken hose adaptor had leaked. After that was replaced, there were no further issues. Thankfully, the stitches had held, and I didn't get a hernia.
Also, I did have to carry a pee-bag while the epidural was in, because the epidural made me lose control of my bladder. And the epidural itself left a scar.
Epidural is surely just the method of administration (into the spinal fluid) where the actual painkiller administered is opioids, though, right?
Meanwhile my understanding of Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) was that they were exactly that by definition - Anti-Inflammatories with pain being reduced by reducing the immediate cause of it, inflammation, not by interfering with the actual mechanisms of pain.
I guess one could consider general anaesthesia (laughing gas, ether, and more modern successors) to be "painkillers" too but they're obviously not quite the same category of thing.
Anyway, I enjoyed the article - it would be interesting to hear the author give their own reasons for not accounting for NSAIDs.
Paracetamol/acetaminophen is not an NSAID, though.
NSAID is effectively a shorthand for COX inhibitor; the term NSAID was coined at a time when the mechanism wasn't fully understood, and all other anti-inflammatories were steroids.
Paracetamol does target COX-2, but does so in a way that doesn't really have any effect on inflammation. Its main mechanism of action is as an AM404 inhibitor.
Opioid-induced constipation is easy to counteract, however, with the right form of magnesium, and/or laxatives. There are herbs that you could drink as a tea, too, for constipation.
If you ask me whether I choose pain or constipation, well, I am pretty sure you know the answer.
This constipation goes away once you stop, and everything depends on the dose and the frequency and duration of taking it.
There are also local anesthetics like the lidocaine family. Some of those are usable for post operative pain in the very short term, but obviously can't be administered orally. That presents a problem for most surgeries, since either they'll want to send the patient home or it's located somewhere that's hard to inject.
What kind of hernia ?
In the US it seems like they prescribe opioids like candy. I've never heard of opioids post hernia surgery in Europe.
I had open surgery for an inguinal hernia here in the UK. Was sent home with a box of Codeine, 15mg tablets, to go with the Paracetamol.
Plus some sachets of laxative for any constipation.
I don't want to be that guy, but UK barely counts in these kind of things, even more so nowadays.
There has been a huge opioid epidemic there as well.
Depends on the country. In The Netherlands it's common to give opioids like oxy after surgery. I got like 20 pills after a minor wrist operation and didn't even need them.
Right Side inguinal fixed with mesh. Yummy post op Opioids, bad constipation advice.
In Europe they almost never give you opioids. :|
I got morphine for an appendectomy in the UK.
[dead]
It will have different side effects.
Plus don't forget: even the "pain relief" provided by sticking a knife through your skin to the bone is addictive. So the side effect of addiction isn't going to go away.
> even the "pain relief" provided by sticking a knife through your skin to the bone is addictive
> the side effect of addiction isn't going to go away
While I agree with your conclusion itself, I disagree that the premise implies the conclusion. The main difference between suzetrigine and opioids, as explained in the article:
The "pain relief" provided by sticking a knife though your skin to the bone is caused by endorphine, which functions similarly to opioids, and that's why it's addictive.Since suzetrigine doesn't affect mu receptors in the brain, this mechanism doesn't apply.
But I'm almost sure it will have some other unintended side effects. Morphine had them, heroin had them, methadon had them... And each time the inventors were sure they didn't.
What is this thread? Sticking a knife through your skin to the bone kills pain and is addictive?
Some people pratice self-mutilation to relief their depression. 20 something years ago I frequented a girl who was full of scars under her clothes, she was pretty good at finding plausible excuses for the scars (plausible to a 20yr old ignorant about that practice), one day she confessed that she did this to herself and that she was unable to stop... It's not a memory I tought I would revisit but your question made me think of her and her dangerous mania.
20 something years ago I frequented a girl
LOL, this thread just keeps on delivering.
Happy that my clumsy writing brought you joy !
Clumsy? That's a great phrase.
It's a hyperbole.
Injuries generally cause brain to release endorphins, which in turn releases dopamine, causing addiction. For example, cutting is a common type of self-mutilation depressed people do. High-intensity exercise arguably also does the same thing - as your body is "microinjured" by strain, your brain releases endorphins to help with the pain, causing effects like "the runner's high".
Maybe they should have said something along the line "replaces the pain with a new one and gives you adrenalin that surpresses it and is addictive"
"There are more things in Heaven and Earth, Horatio, than are dreamt of in your philosophy."
And the Internet is the place where you get exposed to them at random.
Is this a useful first aid technique?
Like for Aron Ralston, who was trapped under a rock and had to cut off his own leg to escape: would it have reduced his pain if he had stabbed himself in the shoulder to the bone?
Would this best be done with, say possibly, acupuncture needles or an ice pick, so as to minimize the damage and to maximize the relief?
Gunsmoke TV episode:
Doc: Well, Billy, we'll have to amputate your lower left leg - it's shot plumb thru with gangrene.
Billy: Will it hurt, Doc?
Doc: Hell yeah, it'll hurt! But thanks to Hacker News we have a new pain treatment: every time you yell. Chester here will stab your right leg to the bone with this h'yar ice pick. And Mary will hold a leather strap in your mouth so your teeth don't crack off! Don't forget to breathe.
Billy: I'm obliged and grateful to be part of your research program, Doc, but can't you instead just wait 10 minutes while I drink this here quart of whiskey and pass out? Then you can do as you wish.
Doc: Hell, no, time's a'wasting! Hold him down, fellas! Doctorin' progresses only a step at a time!
+1! wtf!
It very much oversimplifies the interaction between GABA and dopamine as effects of dopamine and the interaction with GABA varies much depending on the brain region and the specific receptor. Also honestly the conclusion is very much pseudosciencey, if it was so simple nobody would find benzos pleasurable except on withdrawal
I think a better title here than:
> The first non-opoid [sic] painkiller
might be:
> The first non-opioid nociceptive pain-killer
Nociceptive pain being that by actual damage to tissue, as opposed to neuropathic pain like a headache or inflammation that you might take a (non-opioid!) NSAID for.
https://www.iasp-pain.org/resources/terminology/
I'm a neuroscientist by training, and that doesn't match my understanding (although the definitions might have changed).
Inflammation would be an instance of nociceptive pain, and an NSAID would alleviate it by reducing the inflammation; and most tissue damage will result in inflammation.
Neuropathic pain, on the other hand, would be due to damage of the nerves themselves, and NSAIDs are completely useless here (ask anyone with sciatica or other nerve entrapment)
I'm happy to take that correction - I have no training in any relevant field - I was just trying to follow the description in TFA, which links indirectly to my link above in the second paragraph or so as 'nociceptive pain'; from which I inferred that's all it's talking about and existing non-opioids must therefore not target that.
Perhaps non-inflammatory (or generically) nociceptive pain killing is the point. (Which is getting a bit specific for such a broad title isn't it. Does 'painkiller' ordinarily have such a narrow meaning in your experience?)
Will that terminology explanation be a subtitle? :)
Well my comment will still be here, and at least having the qualifier in the title is a pointer to look it up if needed, or to hint 'oh right ok it doesn't mean of all things, I guess paracetamol does not kill nociceptive pain, whatever that is'.
I guess that would make sense in a scientific paper or journal, but most people would have no idea what that means and just make for a confusing title that would turn people off from reading it. Almost everyone has heard of opiates in the evening news or social media.
And almost all those people have 'painkillers' such as paracetamol and ibuprofen in their cupboard, which they know not to be opiates.
The point isn't to accurately describe it as 'nociceptive' (which I've never heard of before either) and have that be understood, it's to qualify it such that it isn't confusing or sounding like an historical tale of how whatever the first NSAID/analgesic was came to be.
Also everyone heard of pain killers that are non-opioid, so you can't really get around explaining why this one is novel.
I think the medical community needs to take more seriously that different people have different pain tolerances.
My wife, daughter and I are very pain tolerant. Out of curiosity, I've turned down freezing for fillings and I even turned down some of pain meds before abdominal surgery. I've never taken the post op opioids, including when I had my impacted wisdom teeth removed.
My other kid, on the other hand, is a whimp. She gets anxious simply if I replace her earrings.
My use case for anesthesia is very different from my kid. I struggle to appreciate why anesthesia is even necessary beyond the need to restrain the patient.
My kid could go into a full blown panic attack from pain.
Yet I don't see anesthesiologists ever asking "how good are you with pain?"
wow I'm envious. I remember how much pimples hurt and I was astounded nobody warned me. This now makes me curious what the low pain tolerance to anxiety correlation is.
That the medical community acts as if you and I should be treated the same is insane to me.
read some books on parenting
Which ones worked for you?
My checkbook. It told me not to be a parent.
And I taught my bevy of child pickpockets to look for old people with checkbooks.
Thank you for forfeiting the evolution game.
Lol, why?
You were born with innate high pain tolerance, but your daughter is a whimp because she didn’t win genetic lottery like you?
I think they're using it hyperbolically. As a parent (who also maybe has a high pain tolerance but I am a guy and we are famous for both thinking that and for not being pain tolerant) my daughter is currently like this including the earrings thing. It's more of a frustration but I know she will grow out of it as she's already gotten a lot better. I would imagine OP is in the same boat and is just letting off a little rhetorical steam.
"I think they're using it hyperbolically."
You'd think my comment's thesis that folks with lower tolerances should be respected and treated differently would have given the rhetorical device away.
Yeah but have you considered they’re slow? Probably had bad parents.
Not slow, culturally inoculated hypersensitivity.
Wimp is a derogatory term with defined meaning. Try to educate yourself and your buddy before commenting something like that.
Or playful.
There’s always someone online who will assume the worst interpretation. It’s unfortunate.
> Another example involves nerve growth factor inhibitors like tanezumab. Although tanezumab alleviated inflammatory pain from conditions like osteoarthritis, Phase III trials revealed an unfortunate side effect: rapidly progressive osteoarthritis. Researchers hypothesized that because patients felt so much better, they overused their arthritic joints, accelerating damage. Although further trials were conducted at lower doses and with restrictions, the FDA ultimately voted against its approval.
Really not sure how to feel about this part lol, I mean I get it, but at the same time this is very ugh.
Well, pain exists for a reason for animals to pay attention to things that are harming the body.
If you remove the flag (pain), harm will continue.
That's a very real concern. A friend of mine has a higher than normal threshold for pain and have permanent injuries as a result. Among other things has walked around on a broken foot for months and failed to register a back injury. All of this then escalated to the point where she feels the pain, but the injuries have become permanent.
I have a similar condition. For me, the issue isn't so much the sensation of the permanent injuries themselves, but rather the constant physical fatigue that comes with them. Since doctors tend to rely heavily on those 1-to-10 pain scales with the little face expressions, it's incredibly hard to be taken seriously when your symptoms don't fit neatly into that system. What's frustrating is that people who can feel the pain early on often have a chance to prevent further damage. I couldn't and doctors couldn't even help me identify that I might have health issues.
I worry a lot about aging, and I'm also afraid of things like tumors or cancers that I might not feel until it's too late. As an example, I can't feel cavities forming and I didn't even notice my wisdom teeth piercing through my gums when I was a teen.
A rheumatologist explained to me that in people with chronic pain from things like arthritis, the brain's pain perception can become permanently altered to register pain that no longer "exists". She explained that the brain itself is really the source of the sensation of pain, and you don't necessarily need a "real" source producing a signal. So one should at least not ignore pain if one can avoid it.
My late wife took her own life because of Chronic Pain. She was told "The pain has become fixed in your perception".
Many years later we found that the actual cause was a Cerebrospinal Fluid (CSF) Leak.
After two failed surgeries to fix it, she had enough and checked herself out.
See our documentary Pain Warriors for the whole saga.
Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening, which is the other "ugh" part to this.
That said, the article may not be fairly representing what happened in the first place, so...
>Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used.
Clicking "FDA" in the bit you quoted above takes you to a different page wherein the FDA laments the lack of data around the drug (eg, the "hypothesized mechanism"). It also suggests that the companies intend to work with the FDA more on this.
Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
> Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
Why do you present this as an either/or?
> Clicking "FDA" in the bit you quoted above takes you to a different page
Indeed, where I found that...
> That said, the article may not be fairly representing what happened in the first place, so...
...this is exactly what happened, i.e. I was successfully misled even before reaching your false dichotomy. Yay.
>Why do you present this as an either/or?
>... your false dichotomy.
I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
I didn't intend to present it as an "either/or", though I can see how it can be read that way. I simply read you saying that they "completely prevent[ed]" something from coming to market when, perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That the "incomplete justification" you lamented may also have been how the FDA felt about the data provided to them.
It could also be for other reasons, absolutely! This is just one possibility that seems very obvious to me. There's no either/or from my end.
> I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
If I didn't already conclude that you presented a false dichotomy, why would I have inquired about why you did so? It's also not set in stone; from your reply I can just change my mind afterwards. But why do it in two rounds when I can do it in one?
I understand if I came across as hostile though, I admit it was sadly reflexive, and I apologize.
> perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it.
That's not a nuance I intended to disregard. Yes, I understand they can revisit the drug's approval later, didn't mean to suggest otherwise.
Gosh I hate natural language sometimes.
>Gosh I hate natural language.
Especially when it's sometimes hard to read tone, even moreso from a stranger whose communication style we're unfamiliar with. Even harder still, comments online generally don't lend themselves well to nuance and assumptions can easily be made, such as my leaning too heavily on your use of the word "completely"! Should we hug it out?
Hope you enjoy the rest of your day. :)
Cheers, no hard feelings.
> Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening
The more I learn about pharmacology, the more I realize this is the norm, rather than the exception.
In that case maybe, but there are plenty of cases where pain is not indicating harm and may actually prevent people from reducing harm.
Meanwhile, good old aspirin is not only an effective pain reliever but it has also been shown to reverse the effect of cartilage loss in osteoarthritis:
https://www.sciencedirect.com/science/article/abs/pii/S03785...
And that's not even taking into account its cardioprotective effects.
But hey, it can be hard on the stomach in SOME people so we developed alternatives with all sorts of nasty side effects, up to and including heart attacks and strokes (rofecoxib, valdecoxib, etc.) Hell, a decade ago, the FDA issued an advisory across the board that "Non-aspirin NSAIDS increase the risk of heart attacks and strokes":
https://www.fda.gov/drugs/drug-safety-and-availability/fda-d...
Some day we will look back on the attempted replacement of aspirin with these other drugs the same way we now look back on the replacement of butter with margarine (and the replacement of saturated fats with trans fats more broadly).
The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings.
The agency bears zero responsibility for the pain and suffering its caused by overcaution.
> The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings.
Thalidomide.
Patients (and often doctors) really don't have the skills or information to make an informed decision.
They can however have 'feelings'. This is not the same thing.
"This isn't FDA approved, and could come with risks. I have not seen any in my patients, but it is a possibility" is informed consent.
I think your argument hinges on the implied idea that whoever makes up these entities (the FDA or otherwise) are intrinsically made of finer clay that the rest of us mere mortals.
For the avoidance of doubt, I'm not implying anything; I'm categorically stating it: experts are better than the hoi poloi. Always.
To continue my example of thalidomide, the FDA's Dr. Frances Oldham Kelsey prevented millions of American babies from being born with devastating deformities.
At the same time millions of American mothers and their GP's were clamoring for the anti-nausea drug that the British mother's were enjoying. And they too said the FDA was getting in their way.
Experts aren't "made of finer clay" : they just know a lot more than the populace about specific topics. There are other topics where I am the finer clay. See 'specialisation'.
maybe they could lower the dosage in future studies? I'm sure they've considered that though and will take it into account.
The title... Confuses me. Especially with a handful on non-opiod painkillers sitting in my history. Gabapentin? Heck, ibuprofen?
Especially when the article itself compares it to ibuprofen:
> If paracetamol and ibuprofen are inadequate for pain relief, Journavx can now be prescribed as the next alternative treatment, instead of mild- to moderate-strength opioids.
"suitable for treating post-surgery pain" isn't something to cut, just for a better title. It just makes the clickbait stench of that first line even worse.
This is a better paracetamol. Which is awesome, and something we need. This is not a world first.
Gabapentin is an anticonvulsants. Ibuprofen and paracetamol are anti-inflammatory. While they are effective at reducing pain, they are technically not "pain killers". The title is therefore correct.
Is that true? That ibuprofen is only reducing my pain via reduced inflammation? I'm sure I've taken it for pain that isn't caused by inflammation.
Yes, but the parent isn't accurate about Paracetamol. It's not anti-inflammatory.
You can take them together within the stipulated limits for each, as one will reduce inflammation and the other will reduce the perception of pain.
Just have to be careful with the stomach when it comes to Ibuprofen... perhaps eat first.
Redescribing NSAIDs as "not technically painkillers", when that's one of their primary use cases, seems... Disingenuous at best.
Revisiting this, I also wouldn't call gabapentin an anti-convulsant. It's drug class is "gabapentinoid".
More often used for neuropathy than epilepsy (though used for both, due to how gabapentoids work.)
I found this New Yorker article to explain it well. https://www.newyorker.com/magazine/2025/06/02/the-radical-de...
Interesting that the author chose that title despite the existence of NSAIDS [^1] and paracetamol(acetaminophen) - the latter of which they even mention (but only in the context of combination with opioids)
Did I miss something?
EDIT: answered in sibling post, thanks @ggm!
[1]: Non Steroidal Anti-Inflammatory Drugs
I'm always surprised that Kratom (https://en.wikipedia.org/wiki/Mitragyna_speciosa) doesn't come up more in these conversations. In addition to being a powerful painkiller, it helps manage opioid withdrawals.
I believe it's still somewhat legal for consumption in the U.S., though other countries have been moving to ban it to varying degrees, since it can be used recreationally, though it isn't known to produce the same intensity of euphoria as opioids, and can also be addictive, though I don't believe it to produce as severe withdrawals as opioids.
All in all I think it's a sadly understudied and underutilized medicine, which is the unsurprising result of pharmaceutical companies having less incentive to study plant medicines
Because it's an opioid?
It's not though
The addiction is the kicker there. Kratom withdrawals/dependency isn't as bad as traditional opioids/opiates. But it's a magnitude of an order worse than nicotine/caffeine/etc. dependency and withdrawals for some people. And the full safety profile of people taking concentrated kratom extract for long periods of time isn't really known yet.
I'm really of the belief that the only reason kratom exploded in popularity the way it did was because it was a legal alternative to opiates. Not necessarily because it's an upgrade (or even sidegrade. ) If morphine could still be purchased in every corner store and pharmacy over the counter kratom extracts would never have blown up the way they did.
Johns Hopkins: "Kratom (Mitragyna speciosa): Pharmacology and use of a naturally occurring atypical opioid."
From your link "Kratom contains over 50 alkaloids—primarily mitragynine and 7-hydroxymitragynine—which act as partial agonists at μ-opioid receptors"
Cheese acts on opioid receptors also... we wouldn't call it an opioid
You don't get withdrawals from cheese, and the cure for these withdrawals isn't Suboxone
This is clickbait, there are at least two classes of non opioid painkillers in use since a long time. https://en.wikipedia.org/wiki/Analgesic
I don't feel the title is misleading, but it may be a cultural language difference.
The term 'painkiller' is reserved for strong pain relief, and wouldn't include things like ibuprofen. That made me think immediately of a non-opioid pain blocker not just a pain reliever.
>The term 'painkiller' is reserved for strong pain relief
Having claimed it was cultural. It have been helpful of you indicated which culture you felt this applied to.
In UK I'd say painkillers includes ibuprofen and paracetamol. I suppose with ibuprofen it's also referred to as an anti-inflammatory. Not sure how else one would refer to paracetamol other than with synonyms (analgesics) or euphemism (pain relief tablet).
Even in the UK it's not necessarily true. I wouldn't be surprised to hear it used that way, but I don't think my peer group in the UK would ever refer to NSAIDs as anything other than their brand or generic names.
I particularly disagree with the parent comment that calls this click bait. The topic's intrinsically interesting to anybody who'd be lured in by that title; it doesn't need "bait" and we all know NSAIDs exist.
The article's particularly good at citing its references inline, which I very much appreciated. Added this author to my RSS reader in fact.
The title is at the very least ambiguous. I expected an essay on the historic invention of NSAIDs/paracetamol as I also understand painkillers to include NSAIDs.
Paracetamol can be referred to as an antipyretic (fever reducing drug), and it's widely used for that in the same way ibuprofen is used as an anti inflammatory.
ibuprofen is also antipyretic
>The term 'painkiller' is reserved for strong pain relief
Maybe there's some very specific, limited medical context where this is the case but in common parlance it's not at all the case, search for "painkiller" in an online shop like Amazon and you'll find a whole lot of Paracetamol/Tylenol, and various NSAIDs (aspirin/ibuprofen) and manufacturers of those drugs actually use that specific term.
> The term 'painkiller' is reserved for strong pain relief,
In which dialect of English do you think this is true?
New England style American English
All dictionaries I've looked at (MW, OED, Cambridge) define painkiller broadly as any drug that relieves pain. Do you have a source for your claim that it's used narrowly? Here's mine: https://www.merriam-webster.com/dictionary/painkiller
How about metamizole? That is a painkiller (at least according to wikipedia), and it is definitely not an opioid or an NSAID.
Can you explain what the difference is? Would pain-relievers be substances that undo whatever is causing the pain, making them indirect, while painkillers act directly on the pain signals and their transmission?
It might be clickbait, but it's also pretty big news of a fairly universal topic and not in the vein of "This one secret that your doctor doesn't want to know!"
This news article claims that the results of the Phase II trials where not great?
https://www.painnewsnetwork.org/stories/2024/12/23/more-lack...
As someone else already mentioned in this thread, in Europe there is already metamizole which is used for post-surgery pain. Anyone knows if suzetrigine is more effective than metamizole?
Anyone better than me in pharmacology able to explain how suzetrigine compares to (high dosage?) ambroxol?
They are both Nav1.8 blockers, but in Germany you can get lots of ambroxol for cheap and OTC.
Oh ambroxol is very interesting! And a cheap generic
Really appreciate you mentioning it
https://pmc.ncbi.nlm.nih.gov/articles/PMC6494067/
Ambroxol has many interesting fringe applications.
It potentiates antibiotic effect in lung infections, including tuberculosis, treats painful hyperacusis, trigeminal neuralgia, neuropathic pain, parkinson, gaucher disease...
...and what's this? We have a surprise guest!
Ambroxol significantly reduces snoring and thus suddenly becomes a candidate for a medication half the population should take!
https://www.researchgate.net/publication/314424871_Evaluatio...
It's one of those drugs that deserves way bigger interest than it gets.
grain of salt with this because it's LLM and needs verification
https://images2.imgbox.com/e1/b7/YaB8gjLI_o.png
but apparently the problem with ambroxol vs suzetrigine
is it is not as selective on the ion channel and not as strong (needs megadose to do similar)
I cannot remember the drugs offhand but this is the same problem with other old generics for other kinds of targets
suzetrigine won't be generic for years which is a shame
Too bad its generic I guess. The cynic in me says that's why it doesn't get the interest it deserves
While suzetrigine is fascinating and great to see development in that field
technically Low‐Dose-Naltrexone (aka LDN) is not an opioid and reduces pain
(however it does it by modulating opioid receptors so okay I guess it's opioid-related)
found more background here
https://www.newyorker.com/magazine/2025/06/02/the-radical-de...
We'll have to see how this pans out, once people start getting it prescribed.
If you want to see what a "non-addictive" painkiller is like, watch Dopesick.
The paragraph on the relation to Brugada Syndrome hits home, as I have that rare disease. What isn't clear is if it's safe for Brugada patients - a hell of a lot of drugs are not advisable for us. As I also have CRPS type II (complex regional pain syndrome) I'd like a non-narcotic strong pain killer that doesn't induce arrhythmia.
One thing people barely notice is how well the FDA is working.
A government agency with very high trust that partners with companies and helps to get things approved but only when they’re safe and has gotten more efficient since Covid is a rare and precious thing.
If you read the parts about the discovery, and how the trail went, you'll see how basic research into all kinds of things feed into innovations like this.
Which is why some bean counter or ideologue cutting this stuff will halt progress all over the place.
Everyone's pain tolerance is different. I am also very aware on stomach and kidney issues those drugs have.
Having said that, ketorolac is a very potent pain inhibitor, can be prescribed for 6 days, causes no dependence issues. Pretty sure can be prescribed more. Cheap, out of patent protection. Took it when broke my hand, it was a miracle of painkiller.
Other comments have mentioned NSAIDs, but also there's nitrous oxide, ethanol, meditation, etc.
This is a silly headline.
It should have "suitable for treating post-surgery pain" added to it - that qualification is in the body of the article.
I'd say "suitable for treating post-surgery pain for US patients", because the rest of us get metamizole for that a lot of the time.
> Traditional opioids mimic opium, a compound found in the poppy plant that contains morphine.
Huh? How can a compound contain another compound. I thought opium was the term for an extract which contained opiates (compounds) and not the other way round.
In the original sentence, "contains morphine" is probably modifying "compound", not “poppy plant”
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"Opium" is the dried latex (milky fluid) that comes from the seed capsules of the opium poppy (Papaver somniferum).
Opium contains ~12% morphine, ~2.5% codeine, and ~1.5% thebaine, all of which are analgesic alkaloids that act on the μ-opioid receptors. So opium itself is a cocktail of these, plus non-analgesics like noscapine (a cough suppressant) and papaverine (a vasodilator.)
Heroin is synthesized from morphine by acetylation.
Oxycodone is synthesized from thebaine in a more complex, multi-step process.
As for the terms "opiate" vs. "opioid", the terms are sometimes used interchangeably but "opiate" generally refers to naturally occurring chemical (morphine, codiene, thebaine, etc.) while "opioid" is a catch-all Heroin is often lumped in with the opiates since it is a simple synthesis; oxycodone could be called a "semi-synthetic" opioid, and fully synthetic opioids include fentanyl, methadone, and tramadol. Relative to morphine, codeine is about 1/10th the potency, heroin is 4x, fentanyl is 50-100x, and the veterinary analgesic carfentanil (given to elephants and rhinos) is 10,000x--yikes!
Two different meanings of the word. The article is using the traditional non-scientific meaning. Opium is a compound (as in a mixture), containing several different chemical compounds (as in molecules containing more than one element).
This sentence confused me too!
Typo in title
s/opoid/opioid/
Paracetamol etc is an opiod?
No. Not even the 100th.
Wikipedia:
> At least 100 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin.[6] It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort,[7] and earlier in Echinacea.
Cannibinoid receptors are separate from opioid receptors.
They give me massive anxiety.
Well then I hope the 111th non opioid painkiller works for you. I know people in chronic pain (my body isn’t exactly a picnic) and so far none of them have gotten hooked on oxy but it’s always looming.
Please name them.
decaf anyone?
[flagged]
And then the story begins when the creator announces that everyone who took it will die within a month...
According to our psychological theories any sufficiently fast acting and strong painkiller will be addictive as long as it removes or reduces any type of pain.
Seams strange if this one truly will not have "drug abuse" connected to it.
The impression I got from Wikipedia reading about this (suzetrigine) is that it’s not addictive because it acts on peripheral nerves and not directly in your brain
Given how scared people are of "addiction" the seller certainly would like that narrative and it might make sense from a withdrawal perspective. Which in turn has an effect on how addictive a drug is to a very large degree.
Yeah, the lack of addictiveness was one used to promote the spiffy new drug heroine over the addictive morphine.
I am very curious about these theories, can you refer them?
Operant conditioning https://en.wikipedia.org/wiki/Operant_conditioning
There are also lots of studies indicating that the speed of action of a drug is important for addiction. Which essentially boils down to the fact that the brain (beeing effected by operant conditioning) needs a drug response that is sufficiently noticeable to be connected to the action of taking the drug.