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Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

societyforscience.org

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

#81

Post by mjevans »

timr wrote: post #59
carlmr wrote: post #53

Earlier quoted context omitted.

>these kinds of science fairs are fundamentally about access. Completely agree there, which kind of brings me to a related thought: One thing I do wonder is, if you look at a few hundred years ago a lot of the inventors in math, physics, engineering, were a tiny group of people with access to resources and education. You're always reading the same names. It seems if we as a society could decide that science is more i…

Meh. While I think the broad theme is fine (more access to education is generally good -- particularly when it comes to scientific literacy amongst the general public!), I think trying to encourage "research" in this way is largely pushing on a string. I can never figure out if this whole phenomenon of "science fairs" is just Kabuki theater for everyone involved, or if there's a core group of deeply deluded organizer…

I suspect you're correct about basic / true research and discovery of 'the new'.

Also probably about that US Gov funding. I've heard it's more about knowing how to write a grant than it is about being worthy of getting one. Better direction, better active identification of candidates (instead of the passive system that's biased towards large players), better stability. All of those would help.

However, there's a _lot_ of stuff that would be within reach, were only enough mass manufacture involved to drive down the adoption cost and break through the catch 22. Many things only need for gathering the correct sort of people, giving them enough room to work on a clear goal, and seeing where things really are.

The big business problems with that are figuring out if the return is plausibly worth the investment, and feeding the baby long enough that it can become a working adult.

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

#82

Post by oliwarner »

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.

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

#83

Post by dmckeon »

hgomersall wrote: post #69
Ey7NFZ3P0nzAe wrote: post #61

Earlier quoted context omitted.

It's terrible that you are counting in tablets instead of actual amount of acetaminophen

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.

Tylenol markets a 650mg Extended Release for Arthritis and Joint Pain: https://www.tylenol.com/products/arthritis/tylenol-8hr-arthr... It is effective for me for general analgesia.

Trigger warning for self harm.

The real tragedies with acetaminophen are "cry-for-help" situations where someone thinks it is the same as aspirin, and swallows a handful, perhaps washing it down with alcohol. What might have been a suicide hesitation mark becomes an entry on a liver transplant list - if they are lucky. If you have children, make sure they know which one can be deadly, especially before going off to college.

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

#84

Post by johnisgood »

chistev wrote: post #58
dreamcompiler wrote: post #51

Earlier quoted context omitted.

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.

The maximum single dose of paracetamol is 1000 mg, and four doses (4000 mg) in 24 hours. Any more and it's liver damage.

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 prescription.

Additionally, see https://www.medscape.com/viewarticle/422884 for Silymarin (which is found in Milk Thistle).

That said, do not exceed the maximum dose. Try ibuprofen, diclofenac, or whatever else, but they are not without risks either. For the record, acetaminophen is the only painkiller you can take on an empty stomach without it causing any GI issues.

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

#85

Post by johnisgood »

shanemhansen wrote: post #23
fracus wrote: post #18

Earlier quoted context omitted.

I thought morphine didn't cause health damage to the human body apart from addiction and withdrawal symptoms.

Well it absolutely muddles your mind when you're on it and it causes constipation. It can also depress your respiratory system.

Not everyone experiences side-effects of opioids, in fact, they are not even THAT common. I do not experience euphoria, nausea, mental fog, or any sedation from ANY opioids. I experience constipation, but I am fine with that. Morphine might be more dulling (or foggy) than say, oxycodone, but it highly varies.

As for "depress your respiratory system", yeah, in high enough doses, or if you are especially sensitive to it.

Pharmaceutical opioids are pretty much safer than NSAIDs. The side-effects of NSAIDs are actually worse than the side-effect of opioids. You will not get ulcers, blood clots, stroke, heart issues, GI issues, and all sorts of other issues with opioids.

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

#86

Post by Waterluvian »

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.

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.

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

#87

Post by pests »

hgomersall wrote: post #69
Ey7NFZ3P0nzAe wrote: post #61

Earlier quoted context omitted.

It's terrible that you are counting in tablets instead of actual amount of acetaminophen

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.

I don’t think it is. Many combinations available in the USA.

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

#88

Post by fc417fc802 »

timr wrote: post #59
carlmr wrote: post #53

Earlier quoted context omitted.

>these kinds of science fairs are fundamentally about access. Completely agree there, which kind of brings me to a related thought: One thing I do wonder is, if you look at a few hundred years ago a lot of the inventors in math, physics, engineering, were a tiny group of people with access to resources and education. You're always reading the same names. It seems if we as a society could decide that science is more i…

Meh. While I think the broad theme is fine (more access to education is generally good -- particularly when it comes to scientific literacy amongst the general public!), I think trying to encourage "research" in this way is largely pushing on a string. I can never figure out if this whole phenomenon of "science fairs" is just Kabuki theater for everyone involved, or if there's a core group of deeply deluded organizer…

> 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.

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

#89

Post by Waterluvian »

hgomersall wrote: post #69
Ey7NFZ3P0nzAe wrote: post #61

Earlier quoted context omitted.

It's terrible that you are counting in tablets instead of actual amount of acetaminophen

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.

Do you guys have liquid forms, especially for children where the dosage is, obviously, entirely up to you?

One memory I have of visiting our U.S. head office with a bunch of UK people was the “we have to get to Target because they sell Tylenol in ungodly quantities.” And I thought bottles of 200 pills felt ridiculous up here in Canada.

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

#90

Post by AndrewDavis »

Waterluvian wrote: post #86
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.

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.

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.

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