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The first non-opoid painkiller

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Re: The first non-opoid painkiller

#41

Post by dudeinjapan »

echelon_musk wrote: post #14

> 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!

Re: The first non-opoid painkiller

#42

Post by dakial1 »

perching_aix wrote: post #38

> 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 lo…

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.

Re: The first non-opoid painkiller

#43

Post by perching_aix »

gorjusborg wrote: post #34
Snoozus wrote: post #5

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.

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?

Re: The first non-opoid painkiller

#44

Post by perching_aix »

dakial1 wrote: post #42
perching_aix wrote: post #38

> 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 lo…

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.

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...

Re: The first non-opoid painkiller

#45

Post by CjHuber »

bheadmaster wrote: post #21
spwa4 wrote: post #17

Earlier quoted context omitted.

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: Crucially, opioids don’t just kill pain: they also incite pleasure. When the mu opioid recep…

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

Re: The first non-opoid painkiller

#46

Post by lr4444lr »

perching_aix wrote: post #38

> 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 lo…

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.

Re: The first non-opoid painkiller

#47

Post by Findecanor »

OJFord wrote: post #31
bravesoul2 wrote: post #29

Earlier quoted context omitted.

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.

Re: The first non-opoid painkiller

#48

Post by nick__m »

ggm wrote: post #2

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.

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.

Re: The first non-opoid painkiller

#49

Post by ta20240528 »

lr4444lr wrote: post #46
perching_aix wrote: post #38

> 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 lo…

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.

Re: The first non-opoid painkiller

#50

Post by jjulius »

perching_aix wrote: post #44
dakial1 wrote: post #42

Earlier quoted context omitted.

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.

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"?

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