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Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

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Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#111

Post by masklinn »

Findecanor wrote: post #109
hgomersall wrote: post #69

Earlier quoted context omitted.

It's for this reason in the UK paracetamol (as we call acetaminophen) is only ever manufactured to 500mg tablets. I don't know if that is global.

Here in Sweden, a carton of 10 × 500 mg is the most you can find without a subscription. (Boxes of twice that amount is supposed to exists but I've never seen it) Two years ago, I was prescribed the maximum dosage: 2 × 500 mg every six hours for a couple of months. Because it wears off more quickly than that, I tried to reduce it to one and a half pill more often but that wasn't enough to have any effect. Caffeine is…

> Here in Sweden, a carton of 10 × 500 mg is the most you can find without a subscription. (Boxes of twice that amount is supposed to exists but I've never seen it)

That ain't much, I don't think I've seen boxes with that little around here. Normal packaging is 30~40, and you can get larger boxes, all without a script.

Are the boxes that small because sweden tends to use an other analgesic as primary culturally e.g. aspirin or ibuprofen and paracetamol is for more exceptional situations?

> Caffeine is supposed to reinforce the effect, but of course I had to avoid that to sleep.

If the goal was pain relief, you can combine ibuprofen and paracetamol. They can be staggered or taken together (in which case there's less duration coverage but some evidence that the combination works better than either separately).

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#113

Post by Jolter »

mulderc wrote: post #68
Jolter wrote: post #67

Earlier quoted context omitted.

But how many cases of poisoning occur each year?

“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/

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.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#114

Post by Jolter »

oliwarner wrote: post #82
porphyra wrote: post #43

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.

"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.

It’s cheap, too.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#115

Post by johnisgood »

oliwarner wrote: post #110
johnisgood wrote: post #84

Earlier quoted context omitted.

I will respond here with links, because my comments regarding NAC and silymarin are getting down-voted. https://emedicine.medscape.com/article/820200-treatment - Treatment for liver damage is NAC (N-acetylcysteine) which is available as a supplement. > N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity https://www.ncbi.nlm.nih.gov/books/NBK537183/ Again, NAC is readily available without pres…

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…

I did not say it is magic. At any rate, silymarin is actually "magic". It may help you regenerate parts of your liver. See the link I mentioned.

Ultimately, what one needs to do is just... not consume high amounts, or too frequently.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#116

Post by raffraffraff »

oliwarner wrote: post #82
porphyra wrote: post #43

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.

"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.

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.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#117

Post by fc417fc802 »

timr wrote: post #106
fc417fc802 wrote: post #88

Earlier quoted context omitted.

> not due to inequity, but because only someone well-off could devote their lives to something so erratic. Aren't those effectively the same thing? At least in the given context where society doesn't have the resources available for everyone to live like that.

Effectively the same in terms of distribution of outcome, perhaps, but it's a bit like saying that it's really unfortunate that poor people can't afford their own manicured gardens, peacock collection and garage full of antique race cars.

Only someone well off could devote the necessary resources to have a garage full of antique race cars.

People who can afford a garage full of antique race cars only exist due to inequity.

What's the difference between those statements? As far as I can tell the latter includes the former while adding an implicit assumption about total available resources versus total population.

Apologies if it seems like I derailed things. Your comment was interesting but I didn't understand (still don't) the significance of the distinction you went out of your way to draw there. That said, I think the trailing remark that "only someone well-off could devote their lives to something so erratic" really hits the nail on the head. Even today you can see elements of that, for example on certain parts of youtube. People with excessive expendable income occasionally do some really impressive stuff.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#118

Post by Jolter »

raffraffraff wrote: post #116
oliwarner wrote: post #82

Earlier quoted context omitted.

"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.

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.…

Super close may be an exaggeration but could certainly be voted “most likely analgesic to let you take an intentional overdose”.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#119

Post by cess11 »

masklinn wrote: post #111
Findecanor wrote: post #109

Earlier quoted context omitted.

Here in Sweden, a carton of 10 × 500 mg is the most you can find without a subscription. (Boxes of twice that amount is supposed to exists but I've never seen it) Two years ago, I was prescribed the maximum dosage: 2 × 500 mg every six hours for a couple of months. Because it wears off more quickly than that, I tried to reduce it to one and a half pill more often but that wasn't enough to have any effect. Caffeine is…

> Here in Sweden, a carton of 10 × 500 mg is the most you can find without a subscription. (Boxes of twice that amount is supposed to exists but I've never seen it) That ain't much, I don't think I've seen boxes with that little around here. Normal packaging is 30~40, and you can get larger boxes, all without a script. Are the boxes that small because sweden tends to use an other analgesic as primary culturally e.g.…

Ibuprofen, naproxen and acetylsalicylic acid are also common.

I prefer acetaminophen due to the main metabolite being a reuptake inhibitor of CB-active transmitters and I don't drink. I take maybe two-four grams per year, so your 40-pill box would last for a decade.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#120

Post by Ballas »

porphyra wrote: post #43

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.

> 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.

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