4 ms·

It's not just anti-depressants, no? If I am mistaken, we do not know why plenty of medications work -- especially those within in the domain of mental disorder

It's not just anti-depressants, no? If I am mistaken, we do not know why plenty of medications work -- especially those within in the domain of mental disorders. For example, why does lithium work, amphetamines, etc.? Obviously, we know such medications work, but not the "how"/"why."

deleted 2y ago
[deleted]
vrc 2y ago
Tylenol is my favorite drug in this bucket
- hirvi74 2y ago
  I'll be the first to admit I know very little about acetaminophen, but what I know is that it can be good for breaking fevers and allegedly it's useful for pain relief (not my experiences)? I try my hardest to avoid it due to the associated hepatotoxicity which, to my understanding, is less likely/not observed in other NSAIDs.
  - gorlilla 2y ago
    It's not an NSAID at all, which have their own pitfalls with damage to the GI tract over time.
    - hirvi74 2y ago
      Huh, you are absolutely right. It's not an NSAID. Thank you for the correction. Sure, I do agree that NSAID have their own pitfalls. I am sure most, if not all, medications have pitfalls at some intersection between dosage and time. My understand of acetaminophen is that the line between therapeutic help and harm is rather small for compared to many other OTC medications. Just based off of a few brief searches it is recommended that an adult take no more than 2 tablets every 4 to 6 hours. One tablet is typically 325mg. According to this Harvard Health link [1]: "For the average healthy adult, the absolute maximum daily dose is no more than 4,000 milligrams (mg) from all sources. But in some people, doses close to the 4,000 mg daily limit for adults could still be toxic to the liver. It's safest to take only what you need, and to not exceed 3,000 mg a day whenever possible, especially if you use acetaminophen often." So, even with infrequent usage, and by following proper instructions, liver toxicity could still technically occur within just 24 hours of usage. How likely is it? Well, that I have not looked into. Overall, my point is: why risk even go down that road? Now, I could be wrong (again), but most research I have seen on the topic pertains to pain relief where Tylenol doesn't seem as effective as alternatives. Perhaps for other aliments it's better, but again, that begs the question -- better compared to what else and what are those risks? [1] https://www.health.harvard.edu/pain/acetaminophen-safety-be-cautious-but-not-afraid https://www.health.harvard.edu/pain/acetaminophen-safety-be-...
      - kranner 2y ago
        In India [1] the standard dose for acetaminophen has recently become 650mg, because the 500mg variant is price-controlled and allegedly one manufacturer spent roughly $ 120 million to market the 650mg variant to Indian doctors. [1] https://science.thewire.in/health/paracetamol-650-mg-drug-pricing/ https://science.thewire.in/health/paracetamol-650-mg-drug-pr...
      - OJFord 2y ago
        As I'm sure you know, the AI in NSAID is anti-flammatory; thus if you have some kind of non-inflammation pain, paracetamol (aka acetaminophen, Tylenol and other brands) is better. It's also better for lowering fever temperatures. Ibuprofen and other NSAIDs are also contraindicated by other medications, I'm sure there are some for paracetamol too, but I'm not aware of them vs. a few for ibuprofen. I think you're overstating the risk to your liver, it's not even a prescription drug in any country I'm aware of, there are guidelines and dosages stated for a very good reason, sure, but if you're not taking it routinely (rather just to address an occasional issue) it's fine. And if you are you should see a GP, but the outcome might still be that they agree and prescribe a daily dose. Ibuprofen should be taken with food to mitigate risk of stomach ulcers, but how many people follow that guidance? It's processed by and a toxin to kidneys instead of liver, can result in AKIs/renal failure, at least you have two of those I guess? Personally I take ibuprofen for a migraine etc., but paracetamol for a fever. Neither is happening frequently, so I don't worry about occasional use within the guidelines/on doctor advice of either of them.
        johnisgood 2y ago
        Might I add, if anyone is concerned about liver damage, just supplement NAC (n-acetyl-cysteine which is given for acetaminophen / paracetamol overdose), and milk thistle.
      - vidarh 2y ago
        Because NSAIDs can lead to erosion and bleeding in your gut. I've been told to avoid NSAIDs "forever", or at least until a gastroscopy has shown my stomach is fully recovered after using ibuprofen strictly within the dose limits. It's a known risk, and lowering the dose just reduces the odds - it doesn't remove the risk. Acetaminophen/paracetamol overdoses do happen, but they're rare and usually involve significant overdoses rather than minor accidental excess use. Their ability to bring down fevers etc. also tend to differ depending on source. Acetaminophen/paracetamol is usually the first recourse in hospitals etc. because as long as you dose it right, the odds it both works and doesn't incur harm are better.
    - vrc 2y ago
      Prescription NSAIDs are one of the top 2-3 causes of adverse drug event hospitalizations in the US. Patients on opioids and NSAIDs lead to the highest rate of 10 day admissions. There is insufficient data capture of OTC drugs to factor them into this stat, I believe.
    - deleted 2y ago
      [deleted]
  - heavyset_go 2y ago
    NSAIDs tend to be taxing on the kidneys.
    - pitaj 2y ago
      Interestingly, this is not because of toxicity, but because of reduced bloodflow.
  - unsupp0rted 2y ago
    People are quick to break fevers, but probably shouldn’t, most of the time. Fevers are there to kill the virus. You only need to break them if they get high enough to pose a danger to the brain or other organs. Which is a lot higher than a low-grade fever.
devilbunny 2y ago
Amphetamines push catecholamines out of presynaptic neurons; that’s pretty settled. Here’s a fun one: we don’t know how general anesthetics work. From ether to desflurane to propofol, they all exhibit similar behavior, but we actually don’t know exactly what that mechanism is.
- Nasrudith 2y ago
  I thought we got a major hint of it being from disrupting nerve transmission mechanisms. Due to of all things anesthesizing plants with gases resulting in disruption of "conscious" behavior like facing towards sunlight or venus flytraps closing upon being touched.
  - devilbunny 2y ago
    Oh yeah, there are several plausible theories with decent evidence to support them, but nothing remotely definitive. Anesthesia is weird. I'm an anesthesiologist; believe me, there are tons of weird things about the human body that you learn from throwing various compounds at bodies and seeing what happens. Xenon is an effective (though expensive) anesthetic gas by itself. People of West African descent occasionally (~10-20%, usually on the lower end of that) have a hypersalivatory response to cholinergic stimulation. Drugs that should be fine and got approved but turn out to kill kids disproportionately (rapacuronium). Much of our practice is derived from "we've been doing this without too many bad effects for a long time with these drugs, so we're going to continue using them rather than try something new unless the new one brings something to the table that's a slam-dunk". Diethyl ether is slow, it smells awful, and it's flammable (and will form explosive peroxides if stored too long), but it's still a good anesthetic. If I had to re-create civilization from scratch, that would be one of the first drugs I tried to make.
    - bratwurst3000 2y ago
      would chloroform work as well? it is easyer to produce.
      - 2y ago
gofreddygo 2y ago
Classic property of medical science. The science of trials and errors. We know what works, under which conditions and doses and what side effects it may have. Thats useful, important and urgent with real consequences. The "why" costs money, resources and an itch for genuine curiosity and ingenuity with mostly negative returns. So it remains unknown, while we focus on the combining 2 or more things we already know and see where that can be sold. Another observation here is there's a lot of money riding on "pseudo science". See any superfood or beauty products for example. You take a data point that is demonstrated under certain conditions in a controlled environment. Make that single data point a centerpiece of evidence, tack the usual goop on it, market it, label it and place it on the front aisles of Trader Joe's. Now there's a lot of incentive to keep the "why" away from consumers walking those aisles.
- MetalGuru 2y ago
  God, what a depressing take
  - idrathernot 2y ago
    How is it depressing? If we waited for scientist's to fully understand the outcomes of their experiments prior to experimenting we’d still be living in caves. As long as the experimentation happens at a small enough scale, the “worst case” scenario is limited. What’s depressing is when things are scaled up in spite of an established body of evidence that such things are harmful.
    - mrguyorama 2y ago
      The depressing part is the billions wasted on supplements, "superfoods" and health drinks that have pretty much zero evidence of effect behind them. Turmeric is sold for like a dollar a pill. It's pure horseshit.
      - Modified3019 2y ago
        Consumers are lucky to get just horseshit instead of lead based yellow colorant.
jmcgough 2y ago
Here's an even better one - we don't know how alcohol works. I always assumed it was gabaergic in nature but it turns out that it's a really unusual drug with extremely weak binding, which is why it requires large amounts to have a psychoactive effect, making it challenging to use for binding studies.

deleted 2y ago

[deleted]

vrc 2y ago

Tylenol is my favorite drug in this bucket

hirvi74 2y ago
I'll be the first to admit I know very little about acetaminophen, but what I know is that it can be good for breaking fevers and allegedly it's useful for pain relief (not my experiences)? I try my hardest to avoid it due to the associated hepatotoxicity which, to my understanding, is less likely/not observed in other NSAIDs.
- gorlilla 2y ago
  It's not an NSAID at all, which have their own pitfalls with damage to the GI tract over time.
  - hirvi74 2y ago
    Huh, you are absolutely right. It's not an NSAID. Thank you for the correction. Sure, I do agree that NSAID have their own pitfalls. I am sure most, if not all, medications have pitfalls at some intersection between dosage and time. My understand of acetaminophen is that the line between therapeutic help and harm is rather small for compared to many other OTC medications. Just based off of a few brief searches it is recommended that an adult take no more than 2 tablets every 4 to 6 hours. One tablet is typically 325mg. According to this Harvard Health link [1]: "For the average healthy adult, the absolute maximum daily dose is no more than 4,000 milligrams (mg) from all sources. But in some people, doses close to the 4,000 mg daily limit for adults could still be toxic to the liver. It's safest to take only what you need, and to not exceed 3,000 mg a day whenever possible, especially if you use acetaminophen often." So, even with infrequent usage, and by following proper instructions, liver toxicity could still technically occur within just 24 hours of usage. How likely is it? Well, that I have not looked into. Overall, my point is: why risk even go down that road? Now, I could be wrong (again), but most research I have seen on the topic pertains to pain relief where Tylenol doesn't seem as effective as alternatives. Perhaps for other aliments it's better, but again, that begs the question -- better compared to what else and what are those risks? [1] https://www.health.harvard.edu/pain/acetaminophen-safety-be-cautious-but-not-afraid https://www.health.harvard.edu/pain/acetaminophen-safety-be-...
    - kranner 2y ago
      In India [1] the standard dose for acetaminophen has recently become 650mg, because the 500mg variant is price-controlled and allegedly one manufacturer spent roughly $ 120 million to market the 650mg variant to Indian doctors. [1] https://science.thewire.in/health/paracetamol-650-mg-drug-pricing/ https://science.thewire.in/health/paracetamol-650-mg-drug-pr...
    - OJFord 2y ago
      As I'm sure you know, the AI in NSAID is anti-flammatory; thus if you have some kind of non-inflammation pain, paracetamol (aka acetaminophen, Tylenol and other brands) is better. It's also better for lowering fever temperatures. Ibuprofen and other NSAIDs are also contraindicated by other medications, I'm sure there are some for paracetamol too, but I'm not aware of them vs. a few for ibuprofen. I think you're overstating the risk to your liver, it's not even a prescription drug in any country I'm aware of, there are guidelines and dosages stated for a very good reason, sure, but if you're not taking it routinely (rather just to address an occasional issue) it's fine. And if you are you should see a GP, but the outcome might still be that they agree and prescribe a daily dose. Ibuprofen should be taken with food to mitigate risk of stomach ulcers, but how many people follow that guidance? It's processed by and a toxin to kidneys instead of liver, can result in AKIs/renal failure, at least you have two of those I guess? Personally I take ibuprofen for a migraine etc., but paracetamol for a fever. Neither is happening frequently, so I don't worry about occasional use within the guidelines/on doctor advice of either of them.
      - johnisgood 2y ago
        Might I add, if anyone is concerned about liver damage, just supplement NAC (n-acetyl-cysteine which is given for acetaminophen / paracetamol overdose), and milk thistle.
    - vidarh 2y ago
      Because NSAIDs can lead to erosion and bleeding in your gut. I've been told to avoid NSAIDs "forever", or at least until a gastroscopy has shown my stomach is fully recovered after using ibuprofen strictly within the dose limits. It's a known risk, and lowering the dose just reduces the odds - it doesn't remove the risk. Acetaminophen/paracetamol overdoses do happen, but they're rare and usually involve significant overdoses rather than minor accidental excess use. Their ability to bring down fevers etc. also tend to differ depending on source. Acetaminophen/paracetamol is usually the first recourse in hospitals etc. because as long as you dose it right, the odds it both works and doesn't incur harm are better.
  - vrc 2y ago
    Prescription NSAIDs are one of the top 2-3 causes of adverse drug event hospitalizations in the US. Patients on opioids and NSAIDs lead to the highest rate of 10 day admissions. There is insufficient data capture of OTC drugs to factor them into this stat, I believe.
  - deleted 2y ago
    [deleted]
- heavyset_go 2y ago
  NSAIDs tend to be taxing on the kidneys.
  - pitaj 2y ago
    Interestingly, this is not because of toxicity, but because of reduced bloodflow.
- unsupp0rted 2y ago
  People are quick to break fevers, but probably shouldn’t, most of the time. Fevers are there to kill the virus. You only need to break them if they get high enough to pose a danger to the brain or other organs. Which is a lot higher than a low-grade fever.

devilbunny 2y ago

Amphetamines push catecholamines out of presynaptic neurons; that’s pretty settled. Here’s a fun one: we don’t know how general anesthetics work. From ether to desflurane to propofol, they all exhibit similar behavior, but we actually don’t know exactly what that mechanism is.

Nasrudith 2y ago
I thought we got a major hint of it being from disrupting nerve transmission mechanisms. Due to of all things anesthesizing plants with gases resulting in disruption of "conscious" behavior like facing towards sunlight or venus flytraps closing upon being touched.
- devilbunny 2y ago
  Oh yeah, there are several plausible theories with decent evidence to support them, but nothing remotely definitive. Anesthesia is weird. I'm an anesthesiologist; believe me, there are tons of weird things about the human body that you learn from throwing various compounds at bodies and seeing what happens. Xenon is an effective (though expensive) anesthetic gas by itself. People of West African descent occasionally (~10-20%, usually on the lower end of that) have a hypersalivatory response to cholinergic stimulation. Drugs that should be fine and got approved but turn out to kill kids disproportionately (rapacuronium). Much of our practice is derived from "we've been doing this without too many bad effects for a long time with these drugs, so we're going to continue using them rather than try something new unless the new one brings something to the table that's a slam-dunk". Diethyl ether is slow, it smells awful, and it's flammable (and will form explosive peroxides if stored too long), but it's still a good anesthetic. If I had to re-create civilization from scratch, that would be one of the first drugs I tried to make.
  - bratwurst3000 2y ago
    would chloroform work as well? it is easyer to produce.
    - 2y ago

gofreddygo 2y ago

Classic property of medical science. The science of trials and errors. We know what works, under which conditions and doses and what side effects it may have. Thats useful, important and urgent with real consequences. The "why" costs money, resources and an itch for genuine curiosity and ingenuity with mostly negative returns. So it remains unknown, while we focus on the combining 2 or more things we already know and see where that can be sold. Another observation here is there's a lot of money riding on "pseudo science". See any superfood or beauty products for example. You take a data point that is demonstrated under certain conditions in a controlled environment. Make that single data point a centerpiece of evidence, tack the usual goop on it, market it, label it and place it on the front aisles of Trader Joe's. Now there's a lot of incentive to keep the "why" away from consumers walking those aisles.

MetalGuru 2y ago
God, what a depressing take
- idrathernot 2y ago
  How is it depressing? If we waited for scientist's to fully understand the outcomes of their experiments prior to experimenting we’d still be living in caves. As long as the experimentation happens at a small enough scale, the “worst case” scenario is limited. What’s depressing is when things are scaled up in spite of an established body of evidence that such things are harmful.
  - mrguyorama 2y ago
    The depressing part is the billions wasted on supplements, "superfoods" and health drinks that have pretty much zero evidence of effect behind them. Turmeric is sold for like a dollar a pill. It's pure horseshit.
    - Modified3019 2y ago
      Consumers are lucky to get just horseshit instead of lead based yellow colorant.

jmcgough 2y ago

Here's an even better one - we don't know how alcohol works. I always assumed it was gabaergic in nature but it turns out that it's a really unusual drug with extremely weak binding, which is why it requires large amounts to have a psychoactive effect, making it challenging to use for binding studies.