5 ms·

It's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of live

It's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of liver failure (especially if you also drink alcohol). Also it just doesn't work super well in my personal experience --- I hardly feel anything when I take it. And yet it's one of the most commonly taken medicines worldwide.

reedf1 1y ago
I take it mostly as an anti-pyretic (fever reducer). For which it is extremely effective. It's my drug of choice for colds, flu, etc.
- MichaelRo 1y ago
  Well, it doesn't work for high fever (> 39-40 Celsius). For that, I alternate Ibuprofen and sodium metamizole every 4 hours. For pain release, paracetamol it's very modest. Some effect for light head pain, zero for strong pain. Zero effect for strong back pain. Ibuprofen works better in all these cases but comes with stomach damage if taken for long.
  - Ey7NFZ3P0nzAe 1y ago
    Paracetamol is nicely synergic with all known painkillers. For example prescribing it with morphine leads to less morphine consumption. Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.
    - cluckindan 1y ago
      Prescribing cannabis for pain also leads to less morphine consumption.
      - Ey7NFZ3P0nzAe 1y ago
        The safety profile of paracetamol is orders of magnitudes higher ghan cannabis though. It is still one of the, if not the, most heavily used and appreciated drug and can be taken at any age
        cluckindan 1y ago
        That is untrue. Did you read the OP article? Just 10 standard 500mg tablets of paracetamol in 24h will cause irreversible liver damage. It’s the exact opposite of what you claim. Cannabis is orders of magnitude less destructive to the body than paracetamol. If you honestly believe what you wrote, you need to check your sources. There is a lot of drug war propaganda still out there.
        Ey7NFZ3P0nzAe 1y ago
        indeed I have not been specific enough: I meant "at therapeutic dosage". Thank you for keeping me in check! Acetaminophen indeed has a shitty therapeutic index and cannabis in any (natural) form has basically no acute toxicity. But i'd take 1g of acetaminophen daily for the rest of my life starting at age 1 instead of taking 1 cannabis joint equivalent every day. And that's even if we're talking edible form or vaping (i.e. not considering tars). What about you?
dreamcompiler 1y ago
Two tablets work great for me for headaches but results do vary. The danger zone for liver damage is roughly 14 tablets taken all at once. (Less if you've been drinking.) From what I'm told, acetaminophen overdose is quite an unpleasant way to die.
- chistev 1y ago
  The maximum single dose of paracetamol is 1000 mg, and four doses (4000 mg) in 24 hours. Any more and it's liver damage.
  - deleted 1y ago
    [deleted]
  - johnisgood 1y ago
    I will respond here with links, because my comments regarding NAC and silymarin are getting down-voted. https://emedicine.medscape.com/article/820200-treatment https://emedicine.medscape.com/article/820200-treatment - Treatment for liver damage is NAC (N-acetylcysteine) which is available as a supplement. > N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity https://www.ncbi.nlm.nih.gov/books/NBK537183/ https://www.ncbi.nlm.nih.gov/books/NBK537183/ Again, NAC is readily available without prescription. Additionally, see https://www.medscape.com/viewarticle/422884 https://www.medscape.com/viewarticle/422884 for Silymarin (which is found in Milk Thistle). That said, do not exceed the maximum dose. Try ibuprofen, diclofenac, or whatever else, but they are not without risks either. For the record, acetaminophen is the only painkiller you can take on an empty stomach without it causing any GI issues.
    - oliwarner 1y ago
      Acetylcysteine isn't magic though. It needs to be administered within 12h and 5% will have a severe anaphylactic-type reaction with risk of respiratory arrest. And the liver can still have been irreparably damaged due to other factors. In the context of this being a miserable way to kill yourself, it's absolutely awful because there is very much a cut off point where you will still be suffering immeasurable pain and no amount of NAC will save you.
Jolter 1y ago
But how many cases of poisoning occur each year?
- mulderc 1y ago
  “56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States” -Acetaminophen Toxicity Suneil Agrawal; Brian P. Murray; Babak Khazaeni. https://www.ncbi.nlm.nih.gov/books/NBK441917/ https://www.ncbi.nlm.nih.gov/books/NBK441917/
  - Jolter 1y ago
    That’s a lot. I keep forgetting how many idiots are in the world. Some of those are probably intentional suicide attempts. What’s the maximum number of tablets for one purchase? Sweden has it regulated down to 14, because that’s just enough to not cause permanent damage in a depressed teenager.
    - pixl97 1y ago
      Um. I could go to Walmart or Target and buy pounds of it.
    - mulderc 1y ago
      My understanding is it isn’t so much people being idiots but that acetaminophen is in many products making it easy to overdose on when you are sick. https://www.fda.gov/consumers/consumer-updates/dont-overuse-acetaminophen https://www.fda.gov/consumers/consumer-updates/dont-overuse-...
      - Jolter 1y ago
        Ah, I see,,, Wikipedia tells us: “While a majority of adult overdoses are linked to suicide attempts, many cases are accidental, often due to the use of more than one paracetamol-containing product over an extended period.[106] […] Overdoses are frequently related to high-dose recreational use of prescription opioids, as these opioids are most often combined with paracetamol.[110] The overdose risk may be heightened by frequent consumption of alcohol.[111]“ So, combination drugs being used recreationally, yeah I guess I can believe that would lead to not keeping track of how much paracetamol you took today. And especially over time. I figured it would be pretty hard to accidentally exceed 4000 mg in a day, but if you’re high on some stronger painkillers, which you’re developing some tolerance for, then it’s easy to just keeping taking more than you did last time.
whymauri 1y ago
acetaminophen should not be an OTC drug
pipes 1y ago
Calpol in the UK, paracetamol for children in liquid form (which is British name for acetaminophen) works wonders for kids with a fever. I'm not exaggerating when I say that every doctor I've seen with my kids has said not to withhold it as it really helps with fever.
oliwarner 1y ago
"Therapeutic index" is a strange number to worry about. Those index scores are the balance between efficacy and toxicity. Acetaminophen is an effective analgesic, just toxic in large doses. It's perfect for lower intensity pain. It's non-addictive, doesn't have long term issues like NSAIDs. It's popular for a reason.
- Jolter 1y ago
  It’s cheap, too.
- raffraffraff 1y ago
  My family always had boxes of it around the place when I was growing up. Never really had much use for pain killers. But when I was in my early 20s, no money, not looking at myself, I cracked a tooth in half and it took a few days to see the dentist. It was excruciating. First thing I did, take paracetamol (our name for acetaminophen). It did absolutely nothing. The pain was like a lightning bolt from tooth to brain. After another 30 minutes, I couldn't handle it any more, went to the pharmacy and got aspirin. That worked within 20 minutes. I have never taken acetaminophen since then. If it's a low intensity pain, then I can handle it myself. If I need actual pain relief I'll use an NSAID. Finding out later that paracetamol dosage is super close to overdose, and how it actually kills you... That put the tin hat on it.
  - Jolter 1y ago
    Super close may be an exaggeration but could certainly be voted “most likely analgesic to let you take an intentional overdose”.
  - oliwarner 1y ago
    Neuropathic pain (which dental pain mostly is) is poorly handled. I agree, paracetamol isn't perfect for every type of pain. NSAIDs help relieve pressure and can help, and opioids can waffle-stomp most pain but only for a little while and with dire risks of dependency, but for-purpose drugs like gabapentin are usually a lot more effective at blocking even high intensity neuropathic pain. Unlike NSAIDs, you can take them long term without needing a cocktail of PPIs to keep your stomach from imploding, and they're non-addictive.
Waterluvian 1y ago
It’s unfortunate that it doesn’t work for you. Personally, I’ve never experienced a pharmaceutical that worked so reliably and predictably. It would bring a fever down in my kids when they were young without fail in about 25 minutes. To be fair though I really haven’t been involved with more than a handful of medications. I’m sure there’s many that work very crisply.
- AndrewDavis 1y ago
  Similar to you it is incredible at bringing down fever in my kid. I've seen my kid go from whimpering looking like death, to be crawling about playing happily again in half an hour. With the behaviour change tracking with her temperature coming down. As an adult using it as a pain killer it has been ineffective.
  - Waterluvian 1y ago
    For me I’ve found it works incredibly well at killing a headache or outright stopping a scintillating migraine (especially when combined with caffeine). But for body aches and pains I also find it doesn’t do a whole lot, especially compared to ibuprofen.
    - db48x 1y ago
      That's because ibuprofen reduces inflammation but acetaminophen does not. Joint pain and other such aches are all accompanied by inflammation, but headaches are not.
    - kyriakos 1y ago
      Same here I take it for migraines. Work's only if taken early when symptoms begin but it does work.
Ballas 1y ago
> I hardly feel anything when I take it. Would that not make it a very effective pain killer? /s But seriously - you are not supposed to "feel" a drug. Opiates work on a much different mechanism, and you do "feel" them, but that is also the same mechanism that make them so addictive. What you want is a drug that helps you manage pain and not be addictive.
atombender 1y ago
I'm a big fan of it in terms of efficacy; does wonders for headaches as well as joint aches. My concern is about the relatively recent findings about potential Alzheimer risk [1]: > During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10-1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97-1.16). I don't follow the research closely enough to know if this is reliable evidence, but there are other studies showing the same thing. Paracetamol also well known as mood-altering, apparently inhibiting empathy [2], which may be part of why it has an analgesic effect. That isn't as scary on a personal level, but imagine a society full of millions of people on paracetamol whose ability to feel empathy has been blunted. [1] https://pubmed.ncbi.nlm.nih.gov/37633120/ https://pubmed.ncbi.nlm.nih.gov/37633120/ [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC6455058/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6455058/
- shawabawa3 1y ago
  I'm pretty sure ibuprofens risks are significantly higher than a 10-20% increased risk of dementia, it gives significantly increased risk of strokes iirc
  - cma 1y ago
    I thought NSAIDs thinned blood more like apsirin and gave aneurysm risk instead of stroke, and the big risk was stomach bleeds.
    - atombender 1y ago
      NSAIDs are COX inhibitors which inhibit either COX-1, COX-2, or both. COX-1 is involved in the gastric mucosa, among other roles, which is why blocking it can cause stomach bleeding. COX-2 is involved in maintaining the endothelium of blood vessels, and can increase stroke and infarction risk by stiffening and degrading the lining of the blood vessels over time. Studies are a bit conflicting regarding whether blocking COX-1 or COX-2 is safer, as there seems to be downsides to both, and the difference in risk isn't that clear.

reedf1 1y ago

I take it mostly as an anti-pyretic (fever reducer). For which it is extremely effective. It's my drug of choice for colds, flu, etc.

MichaelRo 1y ago
Well, it doesn't work for high fever (> 39-40 Celsius). For that, I alternate Ibuprofen and sodium metamizole every 4 hours. For pain release, paracetamol it's very modest. Some effect for light head pain, zero for strong pain. Zero effect for strong back pain. Ibuprofen works better in all these cases but comes with stomach damage if taken for long.
- Ey7NFZ3P0nzAe 1y ago
  Paracetamol is nicely synergic with all known painkillers. For example prescribing it with morphine leads to less morphine consumption. Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.
  - cluckindan 1y ago
    Prescribing cannabis for pain also leads to less morphine consumption.
    - Ey7NFZ3P0nzAe 1y ago
      The safety profile of paracetamol is orders of magnitudes higher ghan cannabis though. It is still one of the, if not the, most heavily used and appreciated drug and can be taken at any age
      - cluckindan 1y ago
        That is untrue. Did you read the OP article? Just 10 standard 500mg tablets of paracetamol in 24h will cause irreversible liver damage. It’s the exact opposite of what you claim. Cannabis is orders of magnitude less destructive to the body than paracetamol. If you honestly believe what you wrote, you need to check your sources. There is a lot of drug war propaganda still out there.
        Ey7NFZ3P0nzAe 1y ago
        indeed I have not been specific enough: I meant "at therapeutic dosage". Thank you for keeping me in check! Acetaminophen indeed has a shitty therapeutic index and cannabis in any (natural) form has basically no acute toxicity. But i'd take 1g of acetaminophen daily for the rest of my life starting at age 1 instead of taking 1 cannabis joint equivalent every day. And that's even if we're talking edible form or vaping (i.e. not considering tars). What about you?

dreamcompiler 1y ago

Two tablets work great for me for headaches but results do vary. The danger zone for liver damage is roughly 14 tablets taken all at once. (Less if you've been drinking.) From what I'm told, acetaminophen overdose is quite an unpleasant way to die.

chistev 1y ago
The maximum single dose of paracetamol is 1000 mg, and four doses (4000 mg) in 24 hours. Any more and it's liver damage.
- deleted 1y ago
  [deleted]
- johnisgood 1y ago
  I will respond here with links, because my comments regarding NAC and silymarin are getting down-voted. https://emedicine.medscape.com/article/820200-treatment https://emedicine.medscape.com/article/820200-treatment - Treatment for liver damage is NAC (N-acetylcysteine) which is available as a supplement. > N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity https://www.ncbi.nlm.nih.gov/books/NBK537183/ https://www.ncbi.nlm.nih.gov/books/NBK537183/ Again, NAC is readily available without prescription. Additionally, see https://www.medscape.com/viewarticle/422884 https://www.medscape.com/viewarticle/422884 for Silymarin (which is found in Milk Thistle). That said, do not exceed the maximum dose. Try ibuprofen, diclofenac, or whatever else, but they are not without risks either. For the record, acetaminophen is the only painkiller you can take on an empty stomach without it causing any GI issues.
  - oliwarner 1y ago
    Acetylcysteine isn't magic though. It needs to be administered within 12h and 5% will have a severe anaphylactic-type reaction with risk of respiratory arrest. And the liver can still have been irreparably damaged due to other factors. In the context of this being a miserable way to kill yourself, it's absolutely awful because there is very much a cut off point where you will still be suffering immeasurable pain and no amount of NAC will save you.

Jolter 1y ago

But how many cases of poisoning occur each year?

mulderc 1y ago
“56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States” -Acetaminophen Toxicity Suneil Agrawal; Brian P. Murray; Babak Khazaeni. https://www.ncbi.nlm.nih.gov/books/NBK441917/ https://www.ncbi.nlm.nih.gov/books/NBK441917/
- Jolter 1y ago
  That’s a lot. I keep forgetting how many idiots are in the world. Some of those are probably intentional suicide attempts. What’s the maximum number of tablets for one purchase? Sweden has it regulated down to 14, because that’s just enough to not cause permanent damage in a depressed teenager.
  - pixl97 1y ago
    Um. I could go to Walmart or Target and buy pounds of it.
  - mulderc 1y ago
    My understanding is it isn’t so much people being idiots but that acetaminophen is in many products making it easy to overdose on when you are sick. https://www.fda.gov/consumers/consumer-updates/dont-overuse-acetaminophen https://www.fda.gov/consumers/consumer-updates/dont-overuse-...
    - Jolter 1y ago
      Ah, I see,,, Wikipedia tells us: “While a majority of adult overdoses are linked to suicide attempts, many cases are accidental, often due to the use of more than one paracetamol-containing product over an extended period.[106] […] Overdoses are frequently related to high-dose recreational use of prescription opioids, as these opioids are most often combined with paracetamol.[110] The overdose risk may be heightened by frequent consumption of alcohol.[111]“ So, combination drugs being used recreationally, yeah I guess I can believe that would lead to not keeping track of how much paracetamol you took today. And especially over time. I figured it would be pretty hard to accidentally exceed 4000 mg in a day, but if you’re high on some stronger painkillers, which you’re developing some tolerance for, then it’s easy to just keeping taking more than you did last time.

whymauri 1y ago

acetaminophen should not be an OTC drug

pipes 1y ago

Calpol in the UK, paracetamol for children in liquid form (which is British name for acetaminophen) works wonders for kids with a fever. I'm not exaggerating when I say that every doctor I've seen with my kids has said not to withhold it as it really helps with fever.

oliwarner 1y ago

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

Jolter 1y ago
It’s cheap, too.
raffraffraff 1y ago
My family always had boxes of it around the place when I was growing up. Never really had much use for pain killers. But when I was in my early 20s, no money, not looking at myself, I cracked a tooth in half and it took a few days to see the dentist. It was excruciating. First thing I did, take paracetamol (our name for acetaminophen). It did absolutely nothing. The pain was like a lightning bolt from tooth to brain. After another 30 minutes, I couldn't handle it any more, went to the pharmacy and got aspirin. That worked within 20 minutes. I have never taken acetaminophen since then. If it's a low intensity pain, then I can handle it myself. If I need actual pain relief I'll use an NSAID. Finding out later that paracetamol dosage is super close to overdose, and how it actually kills you... That put the tin hat on it.
- Jolter 1y ago
  Super close may be an exaggeration but could certainly be voted “most likely analgesic to let you take an intentional overdose”.
- oliwarner 1y ago
  Neuropathic pain (which dental pain mostly is) is poorly handled. I agree, paracetamol isn't perfect for every type of pain. NSAIDs help relieve pressure and can help, and opioids can waffle-stomp most pain but only for a little while and with dire risks of dependency, but for-purpose drugs like gabapentin are usually a lot more effective at blocking even high intensity neuropathic pain. Unlike NSAIDs, you can take them long term without needing a cocktail of PPIs to keep your stomach from imploding, and they're non-addictive.

Waterluvian 1y ago

It’s unfortunate that it doesn’t work for you. Personally, I’ve never experienced a pharmaceutical that worked so reliably and predictably. It would bring a fever down in my kids when they were young without fail in about 25 minutes. To be fair though I really haven’t been involved with more than a handful of medications. I’m sure there’s many that work very crisply.

AndrewDavis 1y ago
Similar to you it is incredible at bringing down fever in my kid. I've seen my kid go from whimpering looking like death, to be crawling about playing happily again in half an hour. With the behaviour change tracking with her temperature coming down. As an adult using it as a pain killer it has been ineffective.
- Waterluvian 1y ago
  For me I’ve found it works incredibly well at killing a headache or outright stopping a scintillating migraine (especially when combined with caffeine). But for body aches and pains I also find it doesn’t do a whole lot, especially compared to ibuprofen.
  - db48x 1y ago
    That's because ibuprofen reduces inflammation but acetaminophen does not. Joint pain and other such aches are all accompanied by inflammation, but headaches are not.
  - kyriakos 1y ago
    Same here I take it for migraines. Work's only if taken early when symptoms begin but it does work.

Ballas 1y ago

> I hardly feel anything when I take it. Would that not make it a very effective pain killer? /s But seriously - you are not supposed to "feel" a drug. Opiates work on a much different mechanism, and you do "feel" them, but that is also the same mechanism that make them so addictive. What you want is a drug that helps you manage pain and not be addictive.

atombender 1y ago

I'm a big fan of it in terms of efficacy; does wonders for headaches as well as joint aches. My concern is about the relatively recent findings about potential Alzheimer risk [1]: > During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10-1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97-1.16). I don't follow the research closely enough to know if this is reliable evidence, but there are other studies showing the same thing. Paracetamol also well known as mood-altering, apparently inhibiting empathy [2], which may be part of why it has an analgesic effect. That isn't as scary on a personal level, but imagine a society full of millions of people on paracetamol whose ability to feel empathy has been blunted. [1] https://pubmed.ncbi.nlm.nih.gov/37633120/ https://pubmed.ncbi.nlm.nih.gov/37633120/ [2] https://pmc.ncbi.nlm.nih.gov/articles/PMC6455058/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6455058/

shawabawa3 1y ago
I'm pretty sure ibuprofens risks are significantly higher than a 10-20% increased risk of dementia, it gives significantly increased risk of strokes iirc
- cma 1y ago
  I thought NSAIDs thinned blood more like apsirin and gave aneurysm risk instead of stroke, and the big risk was stomach bleeds.
  - atombender 1y ago
    NSAIDs are COX inhibitors which inhibit either COX-1, COX-2, or both. COX-1 is involved in the gastric mucosa, among other roles, which is why blocking it can cause stomach bleeding. COX-2 is involved in maintaining the endothelium of blood vessels, and can increase stroke and infarction risk by stiffening and degrading the lining of the blood vessels over time. Studies are a bit conflicting regarding whether blocking COX-1 or COX-2 is safer, as there seems to be downsides to both, and the difference in risk isn't that clear.