This article seems pretty low on detail. Almost all of it seems to be talking about, well, not the drug in question.
What, exactly, does "10x more powerful" mean?
Potency? Presumably it'd then be prescribed in lower doses?
What, exactly, does "10x more powerful" mean?
Potency? Presumably it'd then be prescribed in lower doses?
https://www.statnews.com/wp-content/uploads/2016/09/Heroin-F...
http://mediad.publicbroadcasting.net/p/wosu2/files/styles/me...
https://twitter.com/davidjuurlink/status/859227636400349184?...
Hear, hear!
Especially in this context. I have a modest understanding of just a couple of these compounds. And that comes by way of chronic pain people in my life.
Over time, doing the work to better undestand these things has paid off. They, at times, get contradictory or just bad advice, or see something that makes them worry, or think they are in danger somehow.
It can be hard to get clarity, and know a change is thearaputic vs compliance related, for example.
Anyway, I just liked that you said that and followed up with super easy to understand information.
Illicit fentanyl and its derivatives are usually distributed in their pure form, to people who have no training in handling hazardous substances.
Sometimes first responders to fentanyl overdoses will not even be able to enter the room of the victim without hazmat suits, because accidentally breathing in fentanyl dust or touching a surface in which the dust has settled could kill them.
Everything I'm turning up suggests that, in the clinical setting, the "strength of opioids" is a statement about the relative size of the effective dose (in mg). Presumably that's correlated with molecular properties like the affinity, but I don't think that's what the article is talking about.
Edit: Since you edited your question I think you might want to look at opioid agonism across the range of receptors you should probably be able to find quite few NIH studies.
> The new, deadlier drugs are altered opioids that bind in more powerful ways to the brain’s receptors and get to the brain more quickly. The combination of factors can make them thousands of times more deadly.
> All opioids connect to particular brain and nervous system receptors that exist for the body’s natural painkiller, endorphins...
That is the only mention of the word "bind" and the article doesn't contain the word "affinity". It doesn't discuss the relationship between effective-dose-size and potential for addiction, except in cases where it seems to go in the opposite direction of what you suggested:
> Methadone is about three times stronger than morphine, but it does not produce a strong euphoric effect. It also lasts much longer and can address physical dependence on other opioids, making it the most common choice for treating opioid addiction.
Which of receptors the opioids can bind to and at what level also has impact on their addiction as many of these receptors regulate different functions iirc the ones that cause the most physical dependence are the strong Mu receptor agonists.
Oh gotcha, sorry about that. I edited my top-level comment fast, so I just assumed you hadn't had time to read the initial version.
> opioid agonism studies especially around addiction treatments where weak/partial agonists opioids are used to ease widthrawal symptoms without prolonging addiction.
OK, I spend 10 minutes Googling. I found a few authoritative lists of addictiveness that didn't seem to correlate with effective dose (which I am pretty confident is the measure of "power" being discussed in the article). And I couldn't find anything that asserted a reasonably robust correlation between effective dose size and addictiveness, whether mediated by agonism strength or otherwise. But I understand if you don't want to spend a bunch of time on this. Thanks.
All full Mu receptors agonists can cause severe physical dependency, the stronger the affinity the more they also can push out other opioids and natural occurring ones and as over time the opioids can actually affect the “shape” of the receptor this is essentially what causes the addiction since what your body produces like endorphine is no longer good enough for you.
So if this will be prescribed like fentanyl and other opioids this will be a problem the opioid epidemic didn’t happen because opioids were tightly prescribed and administered in controlled conditions it happened because you sprained your back and instead of some physiotherapy and a sauna you’ve been given a bottle of pills to chew on like candy.
Edit: realized that doesn't answer your question about the relationship between binding affinity, relative effective dose in mg/kg, etc. At least when medicinal chemists I work with say "10X stronger" they're referring to the binding affinity. Not sure about what it means in a person.
https://www.ctsi.ucla.edu/education/files/view/training/docs...
Since pain relief opioids are full Mu receptor agonists the rest doesn’t really matter in the context of these articles this is accurate enough to be technically correct while not being generalized to all opioids such as low Ki opioids which are mixed agonists or antagonists which can be used to treat addiction and even overdose since they bind to they receptors but don't activate them fully or not at all which means that they block other opioids.
> no at the “effective” dose it likely won’t matter the problem is that effective dose is irrelevant in this case because we are talking about substance abuse.
Do you disagree with either of these?
1. In popular news coverage, or doctors talking with lay patients, the term "power" or "strength" of an opioid is shorthand for it's potency on normal (non-addicted) patients. That is, it is inversely related to the number of milligrams that must be administered to get effective pain relief for some fixed reference injury.
2. The potency of a drug is only weakly correlated with its potential for addiction. There are several opioids that are less potent than average but have a higher propensity for addiction than average, and vice versa.
Then there is agonism or antagonism which can be partial or full.
Full agonism is the "strongest" activation that doesn't have anything to do with affinity because it just means it fully activates the receptor, the affinity is how likely it will be bound to the receptors.
For opioids that are full agonists potency and affinity can be used essentially interchangeably these are all primary pain relief opioids and fully bind to the receptors in the same manner essentially, opioids which are mixed agonists or even antagonists such as those used to treat addiction or withdrawal can have very high affinity but low potency because while they bind to the receptor very strongly they don't fully activate it or even deactivate it but as their affinity is high they can beat other opioids to the binding and block the receptors.
As this drug is a replacement for fentanyl it's a full agonist opioid which means that if it's more potent it has to have a lower Ki value which means higher affinity at a matching ratio.
So, with oxycontin, you got a big effect at beginning, wearing off too soon, and craving another--all actions which are really good at reinforcing addiction.
If your binding strength is much better, wouldn't you get lower doses (less big effect at start), which are more effective (less craving), further apart in time (actually controlling the pain like it was supposed to). This seems like a huge win.
Fentanyl for example can administrated with a topical patch due to its relative strength to enable longer duration of pain relief, morphine would require an injection to be as effective.
The strengths you’re speaking of are potency. And even then, most addicts I know would rather have an unlimited supply of oxymorphone than fentanyl or any of the others. At a certain point, cost outweighs all of that.
There’s so much misinformation out there about these drugs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581407/
Yes is more to this than just affinity the type and level of the binding to each receptor is also important but on the grand scheme of things in this context it’s not because all the opioids which are primarily used for pain relief are full Mu receptor agonists which is when the simple affinity strength estimate is pretty much sufficient to estimate potency and potential harm.
Also last time I checked the potency is derived directly from the Ki value of the Mu receptor which represents the affinity (regardless of agonism) of the opioid, so these are essentially interchangeable.
This is the drug the article is talking about.
>Sufentanil (R30730, brand name Sufenta) is a synthetic opioid analgesic drug approximately 5 to 10 times more potent than its parent drug, fentanyl, and 500 times as potent as morphine. Structurally, sufentanil differs from fentanyl through the addition of a methoxymethyl group on the piperidine ring (which is believed to reduce duration of action[2]), and the replacement of the phenyl ring by thiophene. Sufentanil first was synthesized at Janssen Pharmaceutica in 1974.[3]
>Sufentanil is marketed for use by specialist centers under different trade names, such as Sufenta and Sufentil. Sufentanil with and without lidocaine or mepivacaine is available as a transdermal patch similar to Duragesic in Europe under trade names such as Chronogesic. It is available as a sublingual tablet under the trade name Dsuvia.[4]
>Currently sufentanil is the strongest opioid painkiller available for use in humans. Although stronger narcotic pain medications do exist, all medications stronger than sufentanil are approved for veterinary use only.
Non opioid pain killers like ibuprofen are usually 1/200-1/300th of morphine.
Marketing's probably up there.