Talk:Carfentanil

Jurassic park reference

Is the t-rex reference really needed? Whats worse is that it's stated like it's fact, "it took 20mg to take down a t-rex", c'mon get real. Trivia sections SHOULD NOT be added to every single page. T-rex its so sexy dammit!

Mechanical ventilation, etc

I reverted this anon addition to the article: "(however, as the acute toxic effect of opioids is essentially a drug-induced apnea, artificial ventilation might have been sufficient to save the victims)." (referring to the Moscow theater crisis).

This is original research as there is no citation of the exact medical reasons for the deaths of the victims. While it could have been simple respiratory arrest secondary to opioid toxicity, that's speculation unless sourced. Given the immense potency of carfentanil and associated substances, it's possible that the victims received such a massive overdose that additional toxic effects were seen beyond respiratory depression. Again, this is original research so it's best to leave the article as is unless more detailed sources are found. --Bk0 15:49, 23 October 2005 (UTC)

This is anon speaking. I respectfully beg to disagree with your opinion. It is entirely unlikely that any other toxic effect beside respiratory arrest would be life-threatening after a carfentanil overdose. Contrary to your arguments, it is precisely the immense potency of carfentanil that makes it highly improbable that other effects were involved. Firstly, no drug of that potency is likely to have any significant non-receptor-mediated effects because of the extremely small amount of substance necessary to achieve lethal effects; secondly, fentanyl derivatives act essentially on the usual opiod receptors (mu receptors, mostly) and besides analgesia and some degree of sedation, apnea is the only significant effect of fentanyl derivatives that is in any way related to vital functions. To summarise, there's no reason to believe that apnea is not the primary (and probably only) cause of death in carfentanil intoxication. Therefore, if the Moscow victims suffered from carfentanil intoxication there is no reason to assume that they died from anything but respiratory arrest, and if they did, then artificial ventilation would have been life-saving, just as with any other victim of opioid overdose. 87.122.55.86

Basically, we're getting into sketchy territory here because carfentanil being the active constituent of the Moscow gas is speculation on behalf of a primary source. So we're speculating about unconfirmed speculation, which, if not strictly original research, is dangerous for an encyclopedia that's supposed to be completely verifiable. For instance, there's little or no credible evidence that the unnamed fentanyl analog (which may or may not be carfentanil) was the sole active constituent in the secret military gas. Therefore the assumption that respiratory arrest was the sole lethal effect is difficult to completely justify.

Perhaps a more cautiously worded addition would be better: "Assuming that carfentanil was the only active constituent (which has not been verified by the Russian military), the primary acute toxic effect to the theatre victims would have been drug-induced apnea..." --Bk0 18:51, 23 October 2005 (UTC)

I agree with you there and it would be fine with me to have the latter wording included, perhaps as "Assuming that carfentanil was the only active constituent (which has not been verified by the Russian military), the primary acute toxic effect to the theatre victims would have been opioid-induced apnea; in this case mechanical ventilation or treatment with opioid antagonists such as naloxone would have been life-saving for many or all victims." I would be happy to see that or a similar phrasing included but will leave it to you to actually make the edit. 87.122.4.185

Done. --Bk0 20:48, 23 October 2005 (UTC)

I have to disagree about respiratory effects being the only vital functions affected. Remifentanil causes significant bradycardia and hypotension in overdose, potentially making it lethal from a non-respiratory depression standpoint. The latter effect being highly likely to be µ receptor -mediated. Jkbayley (talk) 14:07, 4 September 2009 (UTC)

Besides this, a massive thorax rigor is a typical symptom at high doses, and if that happens, there is no chance to do artificial ventilation. It has to be reverted first by Naloxone or a strong muscle-relaxant like Rocuronium OR the patient has to be ECMOed! --37.201.111.25 (talk) 17:13, 7 October 2016 (UTC)

In the interest of readability and reducing the number of points in dispute, I trimmed verbiage I felt wasn't needed to convey what the sources said. I'd like to thank those of you with medical qualifications for bringing up points which the authors of the sources cited neglected to. I invite you all to review what I did and point out my mistakes.

While the Porton Down report was indeed primary research, it was also a report from Great Britain's chemical and biological defense laboratory on a unique opportunity to apply scientific analysis to artifacts present at an incident which was controversial on many points, not least the identity of the drugs used to subdue the Chechen terrorists and their hostages during the Moscow theater hostage crisis. The paper passed scientific peer review and was published in a WP:RS-compliant source. It conformed to the format required of biomedical journal articles, described methods and materials properly, and stated reasonable conclusions. For balance there's also a paper from the Annals of Emergency Medicine which does not attempt to identify the specific opioid agonists used, but does bring up lipophilicity and weight it more as a potential cause of lethalities among those exposed to the Russian riot control agent.

Since there seems to be an informed difference of opinion among you, perhaps we can make this a more scientifically literate discussion focusing more on carfentanil itself, than its use in the Moscow theater hostage crisis. That's more a footnote lately, anyway compared to the fact that people are now ordering carfentanil in kilo lots over the Internet from China. The RCMP seized a kilo of carfentanil in transit at Vancouver, packed in HP LaserJet toner cartridges. One of the Mounties' senior officers noted that it's difficult to see what anyone would do with 50 million lethal doses of carfentanil.

The one difficulty I see in prospect is WP:SYNTH, even if everyone here comes back with good sources. Do any of you know if there's a good review of the literature on carfentanil? I've researched the topic myself and only found a few isolated case reports of intoxication with Wildnil and other opioid agonists by wildlife and veterinary professionals. Those, of course, are also primary sources. It'd be great if someone, somewhere, did a review of the literature on carfentanil specifically, or as part of a discussion on treatment of intoxication with fentanyl analogues.

Thanks! loupgarous (talk) 20:45, 12 April 2017 (UTC)

Strongest opioid?

I'd just like to point out that Ohmefentanyl has an isomer (F9204) that is 13KX morphine. There is also an isomer mixture of Ohmefenanyl that has a reported potency in the region of 20-50KX morphine. More recent studies point to analogue such as fluoro-OMF that is even more potent. Perhaps a new section needs to be opened up to clarify this as clealry there are is some controversy over the strongest opioid or at the very least we are not 100% clear on the issue. (unsigned by Nuklear)

(moved from main article):
I think this whole page is full of bugs. It might be good reading for a very superficial account though. I have read the reference and no where does it provide conclusive evidence that the gas was infact carfentanil although I am not saying it wasnt, I am just saying that such claims should only be construed as being speculative. (unsigned by Nuklear)

Can you give more information on Ohmefentanyl and the related analogs you're talking about? Specifically, structural diagrams and citations would be preferable; you may want to consider creating articles about these compounds. Once we have sufficient sources for your claims I'll be happy to edit this article to include them. --Bk0 (Talk) 01:07, 9 December 2005 (UTC)

Actually I just clarrified with my friend and Ohmefentanyl is less potent than carfentanil whereas F9204 is more potent. However it is RTI-4614-4 (a racemic pair of the syn-diasteromers based on beta-hydroxy-3-methyl-fentanyl) that is most potent. I think that it has a potency in the range of 25 thousand times more than morphine.

Nuklear The British chemical and biological defense labs at Porton Down, England actually showed that residues on three British hostages' clothing and in one hostage's urine showed positive for carfentanil and remifentanil and negative for fentanyl, 3-methyl fentanyl and about five other fentanyl analogues. That demolishes the New York Daily News and Washington Post articles saying it was probably 3-methyl fentanyl, and is very embarrassing to the Russian Minister of Health at the time, who said it was fentanyl. Here's their article in the Journal of Analytical Toxicology, November 2012, pp 647–656 volume=36,issue=9 loupgarous (talk) 21:35, 12 April 2017 (UTC)

Weasel Words

It seems like most of the articles on Wikipedia have the "weasel words" tag... Does this article really need it? —Preceding unsigned comment added by 69.254.255.146 (talk) 00:15, 23 August 2009 (UTC)

The lead looks okay, it's the Moscow theatre bit that's the problem. 00:23, 23 August 2009 (UTC)

not sure how to edit this stuff, but why on earth would this drug have street names, espcially ones as ambiguous as those posted, listed under the main description? seems immoral and dangerous to me ..cc..

I concur we don't need to make this a "Shopper's Guide to Buying Fentanyl Analogues on the Street". I also think it's probably best to pare the Moscow theater hostage crisis mention to bare bones - like, "Richey and Timperley's group at Porton Down found carfentanil and remifentanil on hostages' clothes (and in one hostage's urine), didn't find fentanyl and 3-methyl fentanyl, so that's that."

As the guy who dropped that block of text in there, I'm more than happy for us to reach a concensus on paring the mention down to footnote size. I just agree with Mr. Weber (former Assistant SECDEF for for Nuclear, Chemical and Biological Defense Programs) that it's a good idea to make the public aware that Chinese firms are not just selling very toxic chemical over the Internet to people here, they're actively marketing carfentanil and other highly potent fentanyl analogues and offering advice to prospective customers on how to get it past Customs.

If you didn't read the link to that Associated Press story on carfentanil, here it is.

I also went through the body of the text and changed passive voice constructions, subjunctivis, and other WP:WEASEL stuff to simple declarative statements today. loupgarous (talk) 21:02, 12 April 2017 (UTC)

Casualties vs Deaths

The Moscow Theater section previously said that there were over 125 confirmed casualties. Looking at the main article, there were about 130 deaths. As explained by Casualties, the term refers to deaths and injuries, not just fatalities, so 125 casualties is at best imprecise (how many of the casualties were fatalities), and at worst, a significant understatement of the number of casualties. I've corrected this to "deaths". The only verification I have for this is the main article; if this is not actually the case, please discuss here. Arathald (talk) 07:33, 4 August 2013 (UTC)

Heroin/carfentanil overdose deaths confirmed in Hamilton County, Ohio

According to the New York Times, September 5, 2016: http://www.nytimes.com/2016/09/06/us/ohio-cincinnati-overdoses-carfentanil-heroin.html

The above says that Naloxone will not work on this drug. But the below says it will. First responders need to know. https://www.dea.gov/divisions/hq/2016/hq092216.shtml rumjal 13:50, 7 March 2017 (UTC) — Preceding unsigned comment added by Rumjal (talk • contribs)

There's a lack of consensus in the medical literature whether you are best advised to use naloxone or naltrexone for intoxication with carfentanil and other large animal opioids. The only consensus there I've seen so far is you DON'T use diprenorphine, the antagonist you use in large animals for carfentanil, etorphine, etc. I've read short reviews of the literature by MDs writing up their treatment of wildlife and vet-med professionals who got stuck with large animal tranks and presented at their ERs for treatment, and no one I've read so far has said naloxone doesn't work.

Renarcosis seems to be another thing people can agree on with the more potent fentanyl analogues. Perhaps this is what someone saw after treating with naloxone, which doesn't mean Narcan doesn't work, just that you need to watch the patient and be ready to use it again. And again.

Anyone here have a good review of the literature on human intoxication with carfentanil yet? With the amount of this stuff being sold to North Americans from China, you'd think the case reports would be trickling in. loupgarous (talk) 21:18, 12 April 2017 (UTC)

Haven't seen one published yet. PMID 27495118 looks like the first study of metabolism in humans and explains the long duration. Probably nalmefene with its higher affinity and longer duration of action would be better than either naloxone or naltrexone for treatment of overdose. Meodipt (talk) 04:57, 13 April 2017 (UTC)

Thanks - this actually belongs in our article because it provides an alternate mechanism (to lipophilicity) for the comparatively long duration of action of carfentanil. I'll make it so.

Is there a journal article on nalmefene's advantages in treating carfentanil poisoning? While I agree that an opioid antagonist with a longer biological half-life and span of action would be better to treat OD or poisoning with any long-acting opiate agonist (due to the danger of renarcosis), it's WP:OR unless we can produce a notable and reliable source saying so.

But thanks to you, at least we can give readers a more complete picture of why carfentanil's longer-lasting and more dangerous than, say, fentanyl or the older opiate agonists. loupgarous (talk) 20:57, 23 April 2017 (UTC)

Second thoughts on that. Please read our article as it stands and help me decide if we need to get very far into the metabolic fate of carfentanil. Is it really of encyclopedic interest? loupgarous (talk) 00:21, 24 April 2017 (UTC)

Therapeutic index

At the end of the sentence referring to a "therapeutic index" of 10,060, I see a reference, #7.

Following the link, I see the phrase "The finding that the aerosol comprised carfentanil and remifentanil is consistent with the outcome arising from its use, for literature data suggest little margin of safety between their therapeutic and lethal doses in humans, and a high lethality in the absence of prompt and appropriate medical intervention.".

I Imagine that the difference (between "10,060" and "little margin") is that respiratory depression may not be fatal if respirations are supported until the drug wears off or an antidote is given. However, I don't see any reasonably authoritative reference to this difference. The difference is, in practice, one between extremely safe and extremely dangerous. This should call for more clarity than usual. Could the author of the '10,060' therapeutic index provide either a link to an accessible and responsible source or a summary of such, clarifying whether apnea is considered dangerous or just an inconvenience for the anesthesiologist? — Preceding unsigned comment added by Davidrei (talk • contribs) 19:16, 19 April 2017 (UTC)

Good catch. I cited that source, and later was troubled by this inconsistency in the article, too. They're criticizing the Russians on one hand for using a highly toxic opiate agonist like carfentanil, and on the other hand speculating that the Russians chose it because it's got a higher therapeutic index than fentanyl (implying the ratio between the therapeutic dose of this drug's 10,000 times lower than the toxic dose). The authors of that article say explicitly that carfentanil's not approved for human use at all, which means they can't be looking at it from a human clinical perspective - in human anesthesiology there is no such perspective. In veterinary use, this drug (marketed as "Wildnil") is used all over the world to immobilize large animals with no provision (or need) for mechanical ventilation or other external respiratory support.

I didn't analyze the issue closely, thinking "this is doubtless the therapeutic index in large animals, and no one bothers with providing respiratory support when using carfentanil to immobilize elephants and rhinos", and didn't want to get into WP:SYNTH trouble by disputing a published source, but it's confusing to both of us, and could confuse others reading the article. The main reason I cited the Porton Down paper was it was a source on the military use of carfentanil, and that comes up later in the article as well - it's a notable criticism of carfentanil.

I'll be WP:BOLD and remove the "therapeutic index" speculation from the article text, because I agree with your point. We can always revert that change if enough others disagree to change the consensus. loupgarous (talk) 21:28, 23 April 2017 (UTC)

I went over Riches, Timperley, et al's article and couldn't find the speculation on the therapeutic index of 10,060 for carfentanil (which is more than water's when you think about it.). I hesitate to say where I got it, because it's academic, I took that statement out of the article, but I have to step up and admit I screwed up. Thank you for drawing it to my attention! loupgarous (talk) 00:56, 24 April 2017 (UTC)

LD50 omits units

In the section "...Toxicity Levels" there are numbers for LD50 & AD50, but they are not associated with units, such as milligram/kg, microgram/kg, or nanogram/kg. That's an ambiguity factor of 10^6. Is it deliberate? (I prefer to be fully informed, but can imagine temporary alternatives). jimswen (talk) 18:04, 26 May 2017 (UTC) jimswen (talk) 18:04, 26 May 2017 (UTC)

Legitimate use?

Does anybody know if this drug has a legitimate medical or veterinary use? The article doesn't list any at present. I've seen unsubstantiated claims that it is used to knock out large animals such as elephants, but there are no reliable sources supporting this that I can find. Terms such as "elephant tranquiliser" or "horse tranquiliser" are often used in sensationalist tabloid stories about street drugs. --Ef80 (talk) 23:00, 1 August 2017 (UTC)

[1] Drugs.com says it has veterinary use in some countries. Sizeofint (talk) 01:00, 2 August 2017 (UTC)

I was wondering the same thing. As far as I've read, it is (legally) only used in vet offices for large animals like you said. Why is there no mention of what it purpose is in the article? It is being produced, there has to be a reason why they are producing it other than for illicit use.Zdawg1029 (talk) 06:00, 18 August 2017 (UTC)

The US National Library of Medicine's PubChem Open Chemistry Database's entry on carfentanil says "It is marketed under the trade name Wildnil as a general anaesthetic agent for large animals. Carfentanil is intended for large-animal use only as its extreme potency makes it inappropriate for use in humans". That's a good secondary source meeting WP:RS which describes carfentanil's legitimate veterinary use and also mentioning why it has no legitimate use in humans. loupgarous (talk) 17:24, 1 November 2017 (UTC)

Lethality reference is a dead link.

The boston globe reference to its lethality is a dead link. I found the link to the article here. https://www.bostonglobe.com/metro/2017/11/15/comparing-lethality-and-potency-opioid-drugs/6iEmKXzFDc2rjg9IIZeXWP/story.html I don't know enough about editing wikipedia to do it myself. — Preceding unsigned comment added by 2607:FCC8:C2C0:E2F0:5D76:91C0:71A1:AC18 (talk) 20:13, 9 February 2019 (UTC)

What is the lethal dose? Fentanyl is around 2 mg

2 milligrams of fentanyl, a lethal dose for most people. Carfentanil is lethal in much smaller amounts.

What is the lethal dose? And are there any photos on the Commons comparing the doses that can be used on Wikipedia? If not, someone needs to upload one. A comparison photo would be great. Like the one in the second reference:

References

-- Timeshifter (talk) 15:07, 20 May 2019 (UTC)

It's about 25% lower in rats according to https://www.who.int/medicines/access/controlled-substances/Critical_Review_Carfentanil.pdf — Preceding unsigned comment added by 83.226.146.180 (talk) 00:40, 5 July 2019 (UTC)

Source has photo from New Hampshire State Police Forensic Lab comparing lethal doses.

Fentanyl Is Now The Leading Cause Of US Overdose Deaths. By Dan Vergano. October 12, 2017. BuzzFeed. -- Timeshifter (talk) 02:56, 5 July 2019 (UTC)

2018 scientific info:

Postmortem Toxicology of New Synthetic Opioids. 26 October 2018. https://doi.org/10.3389/fphar.2018.01210. Frontiers in Pharmacology. From conclusion: "Postmortem concentrations seemed to correlate with their potency".

-- Timeshifter (talk) 15:25, 29 July 2019 (UTC)

Thanks for adding the reference you found to the caption at carfentanil. I have reworded it a bit further to indicate that there is uncertainty about the lethal dose. Can you have a look and see if you agree with the current text? Thanks, -- Ed (Edgar181) 17:38, 29 July 2019 (UTC)

I can't find this in the EMCDDA reference:

"The lethal dose range for carfentanil in humans is unknown"

Can you point me to the page number in the PDF:

http://www.emcdda.europa.eu/system/files/publications/9125/Risk%20assessment%20Carfentanil.pdf

-- Timeshifter (talk) 20:36, 29 July 2019 (UTC)

Sorry, I was looking at several documents and put the wrong source for the quote in the reference. I have corrected it now. It is https://www.dea.gov/press-releases/2016/09/22/dea-issues-carfentanil-warning-police-and-public -- Ed (Edgar181) 20:54, 29 July 2019 (UTC)

2 milligrams of fentanyl, a lethal dose for most people. Carfentanil is much more potent than fentanyl. A 2018 study of synthetic opioids states: "Postmortem concentrations seemed to correlate with their potency, although the presence of other CNS depressants, such as ethanol and benzodiazepines has to be taken into account."

(unindent). That article is from 2016. The article from Frontiers in Pharmacology is from Oct 2018. I think we should use that 2018 article conclusion below the photo caption. "Postmortem concentrations seemed to correlate with their potency." That is pretty definitive. It is not like there will be a double-blind controlled study to determine lethality in humans.

References

-- Timeshifter (talk) 21:48, 29 July 2019 (UTC)

The phrase you quote doesn't refer specifically to carfentanil - it's just a generalized conclusion about the opioid class as a whole. Also, the phrase "seemed to correlate" clearly expresses some uncertainty, and the remaining part of the statement that you don't quote "although the presence of other CNS depressants, such as ethanol and benzodiazepines has to be taken into account" introduces further uncertainty. It is not a definitive statement at all. It is still entirely consistent with the DEA's conclusion that "the lethal dose of carfentanil is uncertain". -- Ed (Edgar181) 00:20, 30 July 2019 (UTC)

I read most of the 2018 article and their data confirms what they said in the conclusion. They don't have a huge dataset since the lethal amounts per ml of blood is extraordinarily small, and that needs the right equipment to measure it. And they have to separate out the effect of other drugs in some cases. So I changed the wording in the caption here on the talk page to exactly quote what the article said. It is much more accurate than what you are saying. You are referencing an older article. That 2016 article did not have enough research back then to say anything more than "the lethal dose of carfentanil is uncertain". -- Timeshifter (talk) 01:06, 30 July 2019 (UTC)

That wording is accurate, but I think it misses making the point that carfentanil, specifically, is likely to have a lower lethal dose than the fentanyl shown. -- Ed (Edgar181) 01:29, 30 July 2019 (UTC)

The conclusion states the exact opposite. Have you read the 2018 article? -- Timeshifter (talk) 01:41, 30 July 2019 (UTC)

I think we are talking past each other here.  :/

Can you specify what wording in the 2018 article's conclusion you are referring to and specify which statement is an exact opposite of it? -- Ed (Edgar181) 01:59, 30 July 2019 (UTC)

Sorry. I misread what you wrote. I struck out my incorrect comment. I tried to clarify the caption further. -- Timeshifter (talk) 22:11, 30 July 2019 (UTC)

That wording is ok with me. (But my personal preference would be to have a simpler caption, and the details in the text.) -- Ed (Edgar181) 13:48, 31 July 2019 (UTC)

(unindent). I am trying to take my time. I don't work well when I am tired. :)

I found this related info:

• 13 July 2018: Notes from the Field: Overdose Deaths with Carfentanil and Other Fentanyl Analogs Detected — 10 States, July 2016–June 2017. Morbidity and Mortality Weekly Report (MMWR). Centers for Disease Control and Prevention. From the article: "Twelve states began reporting in August 2017, and 20 states and DC will begin reporting in August 2018."

-- Timeshifter (talk) 14:15, 1 August 2019 (UTC)