Talk:Warfarin/Archive 1

Archive 1

Removed para:

I removed this:

"Warfarin was first developed for use as a rat poison (whence the proprietary name, from "war-faring" against rodents), where it kills by allowing any minor bleeding to continue unstopped until the animal dies. This use is declining as many rat populations have evolved resistance to warfarin.

It is also used medicinally, in much lower doses, as an anticoagulant."

Firstly, the rat poison element was already dealt with, lower down in the article. The duplciation was confusing.

Secondly, the name derivation is not what I and many others believe to be correct and contradicts the lower part of the article. You can't have both and I would want to see some good evidence for the "warfare" thing before accepting it. I think you will find that the Wisconsin Alumni version is generally held to be correct.

Is there any evidence for rats getting resistant to it? I don't see how this would work but if there is some evidence then we should have it in. 82.35.17.203 00:57, 2 Dec 2004 (UTC)

Restored immunity sentence (lower down) - there is plenty of evidence for this, sorry. Still don't see how it works! (i.e how does the warfarinised rat survive to pass on the immunity??) :) 82.35.17.203 01:07, 2 Dec 2004 (UTC)

Hi 82.35.17.203 - I'd suspect the aspect of 'warfaring' played a part in the choice of the acronym for the brand name; this sort of punning is popular in selection of brand names. As the use as a rodenticide preceeded medical use (and in the UK at least, is by far the better known of the uses), I think this should be mentioned higher up in the uses paragraph, rather than as a footnote in the history section. Sorry, I don't know how immunity in rats works; what little I do know is that resistance is conferred by a single recessive gene, and that animals inheriting double-recessive are stillborn (so warfarin-resistant rats have small litters; 'AA' rats live but are susceptible to warfarin poisoning, 'Aa' live and resist, and 'aa' are stillborn). I'm sure there's plenty of documentation available, I don't have it myself though - MPF 14:34, 11 Dec 2004 (UTC)

Hi. With the greatest of respect, your suspicion about the name doesn't add up to documentation of it. The Wisconsin thing is well-documented. I agree that the "warfare" idea is a cute pseudo-explanation, but I have yet to see any more to it than that. I disagree vehemently with your statement that its rodent-control use is "far better known" than the medical one, and I don't think you can assert this without evidence. It's quite simply a question of what you're already familiar with. There are increasing numbers of the elderly and not-so-elderly population on warfarin - those people, and their spouses, children, friends etc know what it is medically. I cannot see how one view can prevail without some evidence and I would be reluctant to alter the article based on a feeling that one of us has and another does not. Gonegonegone 17:52, 3 Feb 2005 (UTC)

Dead link

The link to the "Current Problems in Pharmacovigilance" article is dead. Can someone find a better ref? --Slashme 09:45, 16 March 2006 (UTC)

Yes. Google is your friend. JFW | T@lk 03:31, 17 March 2006 (UTC)

Inhibition by avocado, broccoli

The referenced article Interactions of Warfarin with Drugs and Food states that among the warfarin inhibitors are "foods high in vitamin K; and large amounts of avocado". This distinction is funny because avocados actually contain considerable amounts of vitamin K, though not quite as much as green leafy vegetables. In accordance with the referenced article, I added "foods high in vitamin K" as potential warfarin inhibitors to the "Interactions and contraindications" subsection, though I did not go so far and suggest that the warfarin-inhibiting effect of avocados and broccoli is solely due to their vitamin K content. Aragorn2 15:47, 20 April 2006 (UTC)

History and relevant trials

This page is really thin on the history and its increased acceptance as an anticoagulant. I've identified some papers that will provide historical information. Hopefully I can improve this today. JFW | T@lk 07:34, 1 June 2006 (UTC)

Purple toe

This was inserted:

Wardarin in some cases causes "Purple Toe Syndrome" in elderly people. Typically a purplish discoloration and pain may present in the feet and hands.

I've found a reference, but otherwise there's not a great deal I can find about the phenomenon. Moll S, Huffman J. Cholesterol emboli associated with warfarin treatment. Am J Hematol 2004;77:194-5. PMID 15389900. JFW | T@lk 20:41, 16 September 2006 (UTC)

Pesticide use

In the section "Pesticide use", you can find an information (not correct, by the way), that warfarin is no longer used as a rodenticide. It continues, that "superwarfarins", namely brodifacoum, replaced warfarin (I could provide bunch of links to online pest control stores that sells warfarin rodenticidal baits in my region, but I don't hold it for essential). And, as it goes:

"The active ingredient in rat poison is brodifacoum, which is sometimes referred to as a super-warfarin, because it is longer acting than the drug warfarin. It is both odorless and tasteless. It is effective when mixed with food bait, because the rodents will return to the bait and continue to feed over a period of days, until a lethal dose is accumulated (considered to be 1 mg/Kg/day over four to five days). It may also be mixed with talc and used as a tracking powder, which accumulates on the animal's skin and fur, and is subsequently consumed during grooming. The use as rat poison is now declining because many rat populations have developed resistance to warfarin.

The LD50 is 50–500 mg/kg. The IDLH value is 100mg/m3."

The bolded parts are related to the toxicity of warfarin, what, in this formulation of the sentences is confusing (first, it reffers to brodifacoum as the "active ingredient", than, gives values of toxicity that are reffered to warfarin). I found only acute LD₅₀ values for brodifacoum in the materials of th UN:

http://www.inchem.org/documents/pds/pds/pest57_e.htm

Rats (M) 0.27 mg/kg b.w. technical material

Mice (M) 0.40 mg/kg b.w. technical material

no data on cumulative toxicity; but, given the cumulative toxicity of warfarin, that is about one decimal magnitude higher than acute toxicity, the cumulative toxicity of brodifacoum would most likely be in order of tens of µg per kg b.w./day, or lower.

Thus, I add the known brodifacoum toxicity values.--84.163.124.102 23:31, 7 October 2006 (UTC)

Dangers

This section is missing! The current article reads more like an advertisement (minus the legally reqired listing of all side effects) than an encyclopedia article. There's no mentions of the many drug interactions that occur with warfarin or its toxicity to the liver, kidneys and pancreas. Warfarin is on the list of the top 10 medications found at autopsy. It also occupies the top 5 list of the most problematic drug-interactions in nursing homes: http://www.scoup.net/M3Project/topten/

The side effects of warfarin mirror the symptoms of diabetes and pancreatic disorders. Many websites advise people to ignore orange urine, but dark urine is listed as a serious side effect. It's also a common symptom of diabetes.

There is a growing concern with those who work with geriatric and diabetic patients about the prevalence of diabetes that develops in people on coumadin, but the medical-pharmaceutical industry isn't anywhere near investigating this. When they don't study the problem, then it doesn't exist....or does it?

Or the pregnancy danger -- The anticoagulant warfarin (COUMADIN) is a known teratogen, an agent that can disturb the development of the embryo and fetus and lead to birth defects. Warfarin taken by a woman during pregnancy can cause bleeding into the baby's brain (cerebral hemorrhage), underdevelopment (hypoplasia) of the baby's nose and stippling of the ends (the epiphyses) of the baby's long bones.

Elderly people might be extra-sensitive to the effects of Warfarin. Dentists need to be informed when a patient is taking this drug.

Anyway, if you are taking this drug, maybe you shouldn't be writing the article. It might make you feel better to minimize the dangers of this serious medication, but it's truly a conflict of interest. —Preceding unsigned comment added by 204.249.68.152 (talk • contribs)

Any article on Rx drugs deserves a "Side Effect" section, thats right. And for the side effects in this particular case: warfarin certainly is a potentially dangerous drug, it has a lot of drug-drug interactions, may seriously damage organism or even cause death -- but, to be honest, it saves much more lives than it destroys (in human medicine). It is the most used anticoagulant medication in various very serious health conditions, hence not surprisingly commonly found in autopsies. It is potentially hepatotoxic and pancreas toxic, but compared to other antivitamins, used in medicine (take a look just on methotrexate), it is very well tolerated by the most patients.

Nobody competent in knowledge disputes the teratogenic potential, along with other risks related to pregnancy (elevated risk of abortions, or intrauterine bleedings, for example) and every conscientious doctor, who's treating a woman in fertile age with warfarin, clarifies risks of gravidity with his/her patient and does every measure needed to insure an unplanned pregnancy does not occur during the warfarin treatment (e.g. providing contraception and/or appropriate gynecologic supervision to the women in fertile age); but the situation is similar with many other medications that are life-saving or absolutely necessary in certain conditions (e.g. certain (in fact most) antiepileptics or immunosuppressants). But I agree in this point with you, the risks of the medication should be properly discussed, in every article on drugs, not just this one. Fortunately, wikipedia is a dynamic medium, so we can compensate the shortcomings in it.--Spiperon 21:55, 19 October 2006 (UTC)

I am a little confused by 204.249.68.152's "if you are taking this drug, maybe you shouldn't be writing the article" - who is it directed at? Most of the editing here has been done by doctor types and other clever people with white coats, letters after the name etc - I'm the only editor who has ever said (probably not from this username) that I take this drug, and I don't think I can be accused of minimizing the dangers. It sounds like a slightly odd attitude, based on some misunderstanding perhaps. And no, I don't think there's a conflict of interest at all here. Applying this logic would lead to very little editing getting done anywhere on wikipedia! Everyone's got some interest in a topic, otherwise why bother to edit it? You just have to know your interest is there and be careful. The "It might make you feel better" bit is somewhat patronising, as well as inapplicable to what has actually happened here. I've contributed usefully to this article, not helped to make it a whitewash - something it is not. And yes, we do need a dangers section, that would be an excellent idea. But I am pretty clear about what danger I am in, and am not in! :) Gonegonegone 16:17, 20 October 2006 (UTC)

Injectable argument - discuss here?

Can the current argument over injectable warfarin not be solved in some slightly nmore grown-up fashion than the current multiple reversions, please? I thought that was what talk pages were for. It cannot be that difficult to produce and discuss the evidence, can it? (Also, while I am at it, you really need that second comma, if that bit is staying in. Not that my adding it is meant to endorse a position! :) ) 138.37.199.199 06:56, 3 July 2006 (UTC)

The multiple reversions are a spill-over from a chronic conflict on Parkinson's disease; please ignore Tojo or his many sockpuppets. Evidence is easily found by using Google. You are correct about the comma.

I had personally never heard of IV warfarin. But have a look here and here. JFW | T@lk 08:47, 3 July 2006 (UTC)

Indeed, I also noticed that there is an entry in the United States Pharmacopeia for "Warfarin Sodium for Injection USP 29". It seems quite unusual though, because I can't see any rationale for the use of IV warfarin. -Techelf 10:17, 3 July 2006 (UTC)

Perhaps the patient is unable to take anything by mouth? Shimmin 11:19, 3 July 2006 (UTC)

I've never seen it given iv (I wonder if it's even on the formulary), but I guess it does exist. If someone can't take anything by mouth, there are other substitutes (which are more practical) like heparin or its derivatives. Andrew73 12:58, 3 July 2006 (UTC)

You (or a physician) can't deliberately interchange coumarine and heparine anticoagulants in all conditions, needing anticoagulant medication.--84.163.109.68 23:25, 22 March 2007 (UTC)

Clotcare

The link to this site has now been removed by several users. It is not a warfarin site - it is about VTE. The pages about warfarin consist of news items. It is unclear who runs it (a patient, a drug company?) It has some material with academic references, but I really doubt it is (1) unbiased, (2) reliable. It fails WP:EL in my view. JFW | T@lk 20:19, 6 March 2007 (UTC)

You are correct that ClotCare is not strictly a warfarin site - it deals with all topics relating to anticoagulation and antithrombotic therapy. However, the link provided is to the list of warfarin-related articles. These contain a wealth of information about the medical use of warfarin. All information is presented by anticoagulation and antithrombotic therapy experts from across the US and Canada. The author is provided with each posting and a biosketch of each editorial board member is available at http://www.clotcare.com/clotcare/eb.aspx. I invite you to review the information on ClotCare's world-class editorial board, which is composed of healthcare providers recognized as respected authorities in this field. Nearly half of them have served on the American College of Chest Physicians Consensus Conference on Antithrombotic Therapy. Also, most of the healthcare provider postings highlight new information and reference relevant print publications from major medical journals.

ClotCare subscribes to the HONCode standards for health information on the Web. The information on ClotCare is relevant and useful to anyone seeking information on warfarin as used medically. The information is current, continuously updated as new information develops in the field of anticoagulation and antithrombotic therapy, and it supplements the information on warfarin provided in Wikipedia. Further, ClotCare's Editorial Board responds to direct questions submitted by both patients and healthcare professionals such that an individual can always find the information he/she seeks. Additionally, the site is free and sells nothing.

If you have any questions, please let me know. Sincerely, Marie --Mbwalker 04:27, 7 March 2007 (UTC)

On closer reading + seeing the editorial board I guess this one qualifies well as a source for additional reading. Any thoughts from other editors? JFW | T@lk 04:53, 7 March 2007 (UTC)

I initially thought the link was spam too, but on closer examination it appears reputable. The edit summary "ClotCare is run by leading anticoagulation/antithrombotic therapy experts from the US and Canada. ClotCare has a wealth of warfarin-related info for patients and providers." looks exactly like spam. Dlodge 21:41, 23 March 2007 (UTC)

Interactions and contraindications

It seems this section (the latter half, anyway) would work more effectively as a table rather than a list. Every item in the list has the same type of data (the herb, beneficial effects/uses, potential conflicts) ... thoughts? 71.63.244.225 15:28, 3 June 2007 (UTC)

The historical Link

To my complete delight our librarian informed me that the 1959 historical article by KP Link was available free. It turns out that it contains a wealth of historical information, and effectively all the citation still needed for the historical section. The same edition (http://circ.ahajournals.org/content/vol19/issue1/) also contains historical content on heparin by McLean. More stuff to read... JFW | T@lk 08:36, 23 December 2007 (UTC)

Genomics

All very nice, those VKORC1 assays etc. But are they worth it? doi:10.1111/j.1538-7836.2007.02699.x JFW | T@lk 07:44, 20 August 2007 (UTC)

I cannot get the full text of your article, but this questions seems worth adding to the page. Also, note that the Kovacs algorithm probably correctly handles some of these patients based on 1) their prevalence being higher than the failure rate of the algorithm; 2) the dosing range suggested by the algorithm is flexible enough that it can handle the smaller variations due to genomics.Badgettrg 09:34, 3 October 2007 (UTC)

http://content.nejm.org/cgi/content/short/358/10/999 - VKORC1 is more important than CYP2C9 in determining initial response to warfarinisation. This probably needs working into the article when I get the fulltext. JFW | T@lk 09:13, 7 March 2008 (UTC)

PMID 18250228 - argh, now CYP4F2 has come to play. JFW | T@lk 19:46, 25 March 2008 (UTC)

Black box warning added to warfarin in the U.S.

This article (written by the FDA) is about the FDA adding a black box warning to Warfarin in 2006: [1]. Ksheka 11:21, 17 July 2007 (UTC)

Should be added to content...--Xris0 (talk) 22:39, 8 April 2008 (UTC)

GA push

Well, this article wasn't in bad shape to start with, and it has certainly benefited from WP:RxCOTM. Any suggestions for further improvement before GA nomination would be greatly appreciated; I'm sure we could even get this to FA with some more effort. Fvasconcellos (t·c) 15:27, 8 July 2008 (UTC)

Thanks for your excellent work. I think there are not that many remaining points. What we should perhaps be covering is:

• The MOA section is unreferenced.
• "Loading regiments" doesn't actually list how the regimens work, just which one is better.
• The drugbox lists some cytochrome P450 interactions but these (and their relative importance) are not discussed in the text - how does each enzyme participate in the metabolism of warfarin?
• Should we cite early clinical trials that established warfarin in the treatment for VTE and AF?
• Apart from the alleged Stalin case, are there any other historical warfarin poisoning cases that we should mention?

I'll try to help if I can. JFW | T@lk 16:37, 8 July 2008 (UTC)

Warfarin and Contact Sports

There appears to be no real firm information on contact sports other than dont do it. Surely contact sports can not be totally banned. Can anyone pick this up and provide some more detail ?? —Preceding unsigned comment added by 212.159.102.122 (talk) 18:09, 10 October 2008 (UTC)

There is nothing on PubMed when searching for "warfarin and contact sports". However, warfarin increases bleeding risk. Therefore, anything that can lead to injury (such as contact sports) is routinely discouraged. Unless you can produce a useful source, I don't think we can qualify this statement any further. JFW | T@lk 19:59, 11 October 2008 (UTC)

Oversdose

Doesn't have much info about the treatment of warfarin overdose/toxicity. Use of Vit K iv/po/sc is not discussed or the use of FFP. --Doc James (talk) 16:12, 19 December 2008 (UTC)

Where Warfarin got its name

I am curious to figure out how to intelligently incorporate information about how Warfarin came by it's name. There are some notes among pages OTHER THAN the one for the drug, to the Wisconsin Alumni Research Foundation. But it is missed that WARFarin, as it happens, got its name from that foundation. —Preceding unsigned comment added by 69.129.193.254 (talk) 04:00, 3 March 2009 (UTC)

This is already covered in the article, in the history section. Is it not clear enough? Does it need more prominence? SNALWIBMA ( talk - contribs ) 09:27, 3 March 2009 (UTC)

African Americans? Or Africans?

The article reports a greater frequency of VKORC1 in African Americans, are we intentionally not saying Africans? Or would it be better to say people of African origin? Same rationale could apply to Asian Americans? Does a person of Han ancestry born in China respond differently to Warfarin than one born in San Francisco?192.138.62.36 (talk) 19:17, 10 March 2009 (UTC)

These results were obtained in African American people. They have been separated from West Africa for numerous generations and might have a completely different VKORC1 distribution from Africans. Similar studies are unlikely to be conducted in West Africa for a little while. JFW | T@lk 06:56, 11 March 2009 (UTC)

Warfarin Picture

Unfortunatley the picture used for Warfarin is different to that shown by PubChem. PubChem shows the hydroxyl group on the second benezene ring adjacent to the oxygen molecule in the ring, whereas the wikipedea picture shows it to be opposite the oxygen molecule. I would take a guess that PubChem is more correct. —The preceding unsigned comment was added by 86.151.218.18 (talk) 15:59, 21 April 2007 (UTC).

As the previous comment has pointed out, the structural formula in PubChem and the structural formula in the current Wikipedia entry differ. In addition, both these structural formulas differ from the ball-and-stick model shown in the Wikipedia entry. At first I thought these might represent errors, but it is likely that all three formulas are correct. They may well be tautomers i.e. isomers that spontaneously interconvert at room temperature. The interconversion between the Wikipedia and PubChem structural formulas would take place by the hydrogen spontaneously detaching from the hydroxyl at the top of the Wikipedia version and attaching to the double-bonded lactone oxygen at the bottom, and the electrons rearranging to accommodate, which would produce the PubChem form. Which tautomer predominates would depend on conditions such as temperature and pH. Though it disagrees with PubChem, the Wikipedia structural formula agrees with several other online sources I've looked at, e.g. "Chemical Stability of Pharmaceuticals", by Connors et al, ISBN ISBN 047187955X, 9780471879558. On page 805ff this book discusses these two tautomeric forms of warfarin. (The book is available on Google Book search as http://books.google.com/books?id=qw4P5AABgmEC&pg=PA804&lpg=PA804&dq=warfarin+lactone&source=bl&ots=7AFOsD7ult&sig=AAU3x3f8SGig4_XsapBk_T3CgiA&hl=en&ei=P58eSp6UAcyptgfNzcjsAw&sa=X&oi=book_result&ct=result&resnum=3#PPA806,M1). The ball-and-stick model on Wikipedia has a cyclic hemiketal structure that would result if the hydroxyl at the top of the Wikipeida structural formula lost its proton (which it would tend to do under neutral or alkaline conditions) then attacked the carbonyl carbon in C=0 group at the top of the molecule, closing a third ring and eventually picking up the lost proton on the carbonyl oxygen. The spontaneous formation of this cyclic hemiketal as a third tautomer is chemically plausible, but not mentioned in the book by Connors cited just above. CharlesHBennett (talk) 15:16, 28 May 2009 (UTC)

Warfarin

I have noticed in all articles about Warfarin, that there is no mention of these side affects...Nausea,Loss of appetite,shortness of breath...The last time I was on it, I lost 20 pounds in 6 months cause I could barely eat. The shortness of breath came later in the treatment...I am so nauseated when I stand up, I have to walk all hunched over, which cannot be good for my back...They only other alternative is Lovanox shots, which are so expensive, no one can afford it anyway, even if you can get the insurance company to pay for it..6/18/2009 Oldbat20 (talk) 02:01, 19 June 2009 (UTC)

These side effects are very uncommon, which is why they are not mentioned. Shame you didn't get on with it. There are other vitamin K antagonists that might be more suitable, rather than going straight onto LMWH injections. JFW | T@lk 06:03, 19 June 2009 (UTC)

Thank you JFW for your reply...I tried to talk to the docs about other meds, but, they keep telling me that Warfarin and The shots are the only ones for these kinds of clots. However,my doc said they were working on something to replace Warfarin,but, it won't be ready for two years..man, that's to long to wait... lol

So I guess I will have to wait it out, if I don't starve to death by that time, or have respitory failure...sigh 6/19,2009Oldbat20 (talk) 14:26, 19 June 2009 (UTC)

You haven't told me the indication for your warfarin use. As I said, there are other oral vitamin K antagonists that work very similarly to warfarin and therefore don't require injections. I would recommend discussing this with your physician, because this is not actually the place to discuss your own health situation. Good luck. JFW | T@lk 09:35, 21 June 2009 (UTC)

misrepresentation of danger of low-molecular-weight heparin as a substitute during pregnancy?

The current article states in the section on pregnancy that "the risk of maternal hemorrhage with heparin use is high." This is imprecise and I think inaccurate. Current research (~10 years more recent than the 1995 citation that follows that statement) suggests that heparin is relatively safe and well-understood for use in pregnancy.

Relevant PubMed abstracts: http://www.ncbi.nlm.nih.gov/pubmed/18007136 http://www.ncbi.nlm.nih.gov/pubmed/19357505

At any rate, I'd like to see either more information here, or just take it out--as written, it doesn't really provide much information but it is frightening for someone who requires anticoagulation and hopes to carry a pregnancy to term in the future.76.210.76.166 (talk) 21:04, 26 April 2010 (UTC)

Agree. There is no reason this section needs to be scary. Risk of bleeding will of course be increased in pregnancy with any anticoagulant, and that's all that needs to be said. With careful monitoring most pregnancies do well. I've fixed it. The fix is shorter anyway. Wikipedia should not be a medical text or drug package insert; the medical management sections are just a very general outline description. SBHarris 00:19, 27 April 2010 (UTC)

Mismatched structures (cyclic hemiketal shown in one)

The line-drawing, and the 3d-mol-graphics of the structure don't quite match; it appears that they are (if I remember the terminology correctly?) tautomers of each other. The 4-hydroxy hydrogen shown in the line-drawing appears to have moved over to the methyl-C=O group, and a ring-closure has happened. Chemists may think this is trivial, the two structures probably are in equil in solution, but to the 'normal human' looking at the two structures, they appear confusing, and so would defeat the purpose of effective science communication; IMO. Having now seen the rest of the comments, I see this subject was brought up before; so I would like to emphasize my point is more about useful/effective communication to non-experts, rather than claiming which structure is 'correct'. I would only suggest the two representation be consistent? KingGeezer (talk) 15:09, 9 June 2010 (UTC)

You're right-- the ball and stick model should look like the line drawing and it doesn't. The ball and stick form probably IS a tautomer, like the cyclic hemiketal tautomers in ketone sugars like fructose. In coumadin, what is shown is also a cyclic hemiketal form where the coumarin 4' alcohol has attacked the ketone carbon in the 3' substituent, probably/possibly reversibly. But whether reversible or not, somebody needs to re-do the ball and stick model. Not least because it is surely 4-hydroxycoumarin ring-open form that is needed for the molecule to be active. How do we know? Because there is a whole class of 4-hydroxycoumarin anticoagulants, and many of them, for example phenprocoumon, have no chance of any hemiketal forming, because the 3-substituent contains no ketone! So if this ring-closed hemiketal forms for warfarin, it's incidental to the molecule's function, and has to be undone before the molecule is active as an enzyme inhibitor. SBHarris 17:49, 9 June 2010 (UTC)

I think this should be mentioned in the article text, where we can move the ball-and-stick model and provide a matching skeletal formula.

Ben (talk) 19:13, 19 June 2010 (UTC)

Okay. I'll move the ring-closed hemiketal down to its own thumb, until somebody can come up with a ball-and-stick for the active ring-open skeletal form in the userbox (which corresponds with the IUPAC name). If somebody wants to do a skeletal form form the ring-blocked hemiketal, they can do that also. SBHarris 20:40, 19 June 2010 (UTC)

I've just searched the literature with Web of Knowledge. The question of whether warfarin adopts a cyclic or open-chain form when it binds to the enzyme Vitamin K epoxide reductase (this is warfarin's mechanism of action) has been investigated quite extensively, including very recently. See the following papers for details: THEOCHEM (2010) 949, 41–51 and J. Phys. Chem. B (2007) 111, 10520–10528. The 2007 paper finds that warfarin is predominantly cyclic in non-polar environments and open-chain in polar environments. You might think, like I did initially, that this implies that in vivo, warfarin adopts the open-chain form, because biological cells are basically aqueous solutions and water is a polar solvent. However, I read the paper a little more carefully and the authors note that the part of Vitamin K epoxide reductase (VKOR) that warfarin binds to may be a hydrophobic environment. The structure of VKOR is not yet known, apparently.

Ben (talk) 10:21, 20 June 2010 (UTC)

See http://www.benjamin-mills.com/Wikipedia/warfarin-structures.pdf for a numbering system for the various isomeric forms of warfarin that have been postulated. 1 is the basic open-chain form found in polar solvents, 2 is the cyclic form found in the crystal structure and in non-polar solvents.

Ben (talk) 13:19, 20 June 2010 (UTC)

Slow effect

Isn't it rather the longish half life of the clotting factors that are responsible for the time it takes for warfarin effect to kick in? 62.16.221.174 (talk) 21:41, 30 January 2008 (UTC)

Yes, that's the case. Additionally, the initial procoagulant state is caused because protein C has a shorter half-life time (hours) in contrast to e.g. thrombin (days). --Firefly's luciferase (talk) 23:55, 28 November 2009 (UTC)

There are two unrelated reasons why warfarin has a slow onset of action. The first is related to its relatively long half-life (36 h). This means it takes about a week (4 warfarin elimination half-lives) to reach pharmacokinetic steady state. The second reason is the slow turnover of clotting factors. The apparent turnover time for the mix of clotting factors that influence the INR is about 14 h. If warfarin concentrations were raised to the target concentration rapidly e.g. by giving a loading dose then means it would take about 2 days (4 turnover half-lives) to reach pharmacodynamic steady state. Holford NH. Clinical pharmacokinetics and pharmacodynamics of warfarin. Understanding the dose-effect relationship. Clin Pharmacokinet. 1986;11(6):483-504. NHGH (talk) 23:43, 22 August 2010 (UTC)

Chemical Structure

The ball and stick model does not seem to match the chemical structure diagram.. note the OH group at the top of the 2nd ring in the chemical structure model.— Preceding unsigned comment added by 76.183.113.16 (talk • contribs)

The two chemical images actually do represent the same chemical compound, even though they differ in the way the atoms are connected. Warfarin can rapidly interconvert between the two. There is more discussion about it in the "Mismatched structures (cyclic hemiketal shown in one)" section above and in the "Molecular structure" section in the article. -- Ed (Edgar181) 11:20, 27 July 2011 (UTC)

I added an image tot he "Molecular structure" section to help illustrate this point. -- Ed (Edgar181) 11:32, 27 July 2011 (UTC)

Synthesis

I believe the first intermediate structure in the synthesis is incorrect. It should have a carbonyl at the alpha position of the sidechain. I don't have access to the full 1934 JACS article which is referenced for the synthesis, but looking at the first page I question if this is the correct reference for the synthesis of warfarin. Silverchemist (talk) 15:50, 6 August 2011 (UTC)

"Probable Interaction Between Warfarin and Marijuana Smoking"

This is my first post on wikipedia, so please excuse any style or other mistakes.

While doing research on Warfarin, I came across an article called "Probable Interaction Between Warfarin and Marijuana Smoking" which was published in The Annals of Pharmacotherapy - July/August 2009, Volume 43, No. 7/8. This article stronly suggests that smoking marijuana interacts with warfarin and and causes a great increase in clotting time and can result in serious health problems.

I would like to add this information to the drug interaction section of the Warfarin page; however, I just cannot fathom the instructions for editing an article. It was a struggle just to get to the talk page. Be that as it may, I believe that this information is so important I would hope someone could undertake the task of making this edit.

Thanks in advance for any assistance.

Zeemansatx (talk) 02:10, 16 November 2011 (UTC)

Thanks for pointing out this source (PMID 19531696), but it is a single case report that explicitly states that this is a novel observation. For a proper association, more data is required. The source is not a secondary source as advised by WP:MEDRS. JFW | T@lk 04:29, 16 November 2011 (UTC)

Despite my response, you decided to add a paragraph to the article. Case reports are not OK as sources. A decent secondary source is the minimum, especially in a large topic like this. Have a good look at WP:MEDRS, because it is a key guideline that everyone who makes edits to medical articles would do well to read. JFW | T@lk 08:31, 16 November 2011 (UTC)

Self monitoring

... seems to be okay - doi:10.1016/S0140-6736(11)61294-4 (Lancet meta-analysis) JFW | T@lk 23:14, 28 January 2012 (UTC)

Serum Albumin Binding

I thought that most warfarin binds to serum albumin, but this isn't mentioned at all, except to say that drugs that also bind to serum albumin will displace warfarin and can drastically affect INR. — Preceding unsigned comment added by 137.43.188.147 (talk) 16:44, 27 February 2012 (UTC)

Got a source? JFW | T@lk 19:01, 27 February 2012 (UTC)

Just added a section on alternatives

It cites James Gallagher (3 May 2012). "Aspirin is as 'good as warfarin' for most heart failure patients". BBC News. and reads as follows:

For the 75% of heart failure patients with a normal heart rhythm, aspirin may be an equally effective alternative. According to the British Heart Foundation, both warfarin and aspirin had risks and benefits, but a May 2012 study published in the New England Journal of Medicine showed "neither has an advantage over the other overall in preventing stroke or death in the long term", though the risks differ: while the "combined risk of death, stroke and major bleeding was the same for each drug," the risk of stroke is reduced more by the use of warfarin, and the risk of gastrointestinal haemorrhage is reduced more by aspirin. 67.101.5.179 (talk) 12:45, 3 May 2012 (UTC)

The problem with a section like this is that it violates WP:WEIGHT in WP:MEDRS. It is written as though warfarin were the standard of care already for patients with normal-rhythm heart failure, and aspirin is breathlessly presented as an alternative. In fact, warfarin has never been standard of care for these patients, and studies going back to 2004 (PMID 15215806) and a larger one in 2009 (PMID 19289640) found no particular benefit of warfarin over aspirin in treating them. This 2012 study in the NEJM is just more the same, showing the same. It's not news and it doesn't belong in the warfarin article. True Alternatives to warfarin are drugs that can be used in place of warfarin in places where warfarin is, or has been, standard of care, for example dabigatran/Pradaxa for Afib. Don't clutter this article with other stuff, looking at experimental alternatives to warfarin for uses it has never been proven for in the first place. SBHarris 18:07, 3 May 2012 (UTC)

Is this an advert ?

the disambiguation section at the top of this article says "This article is about the drug with the brandname Coumadin. For the anticoagulant rodenticide poisons often called "coumarins" or "coumadins", see 4-hydroxycoumarins."

I would have thought it should say something more like "This article is about the anti coagulent drug Warfarin and its use in medicine for humans. For the same chemical used as an anticoagulant rodenticide poison (also called "coumarins" or "coumadins"), see 4-hydroxycoumarins."

Obviously my wording is a bit slapdash - (maybe it's not the same chemical?) but I think it's better than advertising one brandname when the brand names are already present in the first line of the intro "Warfarin (also known under the brand names Coumadin, Jantoven, Marevan, Lawarin, Waran, and Warfant) is an anticoagulant. "

Can someone tidy that up ? EdwardLane (talk) 14:32, 19 May 2011 (UTC)

Removed "Coumadin" from disambiguation. Warfarin is sold under many brand names as well as generically, and this is not an advert for Bristol-Myers Squibb. BBODO (talk) 18:51, 4 September 2012 (UTC)

Why warfarin is not a vitamin K antagonist

Hi,

I changed the Wikipedia warfarin page to correct the erroneous assertion that warfarin is a vitamin K antagonist. Biosthmors reverted these changes it seems because he/she thought it was opinion.

It is not an opinion but is a fact if you try to understand the mechanism of action properly. Warfarin is an inhibitor of enzymes involved in the recycling of vitamin K from its inactive epoxide form to its active reduced form. This reduces the formation of active vitamin K which leads to its anticoagulant effect. The true mechanism of action is already explained in the warfarin page and it should be clear from that description that warfarin does not antgonize vitamin K. Indeed if vitamin K is given to someone who has been overcoagulated the effects of warfarin are antagonised. Warfarin does not in any way inhibit the action of vitamin K as a co-factor for formation of coagulation factors.

I am well aware that the clinical literature describes warfarin as a vitamin K antagonist. But this is because the authors of this literature are pharmacologically ignorant and do not understand what the term antagonist means.

Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: n.holford@auckland.ac.nz http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

NHGH (talk) 21:08, 5 October 2012 (UTC)

Thank you for sharing your knowledge here. The use of the word "unfortunately" was advancing an opinion, so I've reworded that part. Biosthmors (talk) 21:01, 8 October 2012 (UTC)

Good catch. These drugs are vitamin K recycling antagonists that end up depleting available vitamin K. That is why they can always be completely reversed by giving fresh vitamin K, and even the most "potent" ones don't take any MORE vitamin K to do that (which presumbly they would do, if they were in fact true pharmacological antagonists). Instead, the more potent drugs in this class (the so called super-coumarins in rodenticides) require administration of reversal-amounts of vitamin K (no more), but for far longer, since the potency simply relates to residence time in the body, not potency of action at the enzyme.

I've changed the lede to explain this fine point where it first occurs so the confusion is is not prolonged past the lede. This doesn't take that much space. I'll do the same for the vitamin K antagonist article lede, too. Thank you, Dr. Holford. SBHarris 22:26, 8 October 2012 (UTC)

Not found in reference provided

I didn't find the claim in the reference for the following text, and I think it should be done before reinsertion:

• "Under normal pharmacological therapy the drugs are administered to decrease the circulating concentration of the clotting factors they affect by 50%."

Mikael Häggström (talk) 15:11, 17 November 2012 (UTC)

That's okay, a better reference would have been required anyway. JFW | T@lk 21:57, 18 November 2012 (UTC)

Shorten Intro!

I suggest to shorten the introduction. It contains way too many details, e.g. on the mechanism of blood coagulation; most of that stuff can be moved to the sections below. Peteruetz (talk) 16:37, 22 May 2014 (UTC)

I was thinking the same thing and was looking here if there was a discussion for doing this. Blue Rasberry (talk) 21:22, 28 July 2014 (UTC)

Bee Stings

Could someone with real expertise discuss how this medicine interacts with bee stings ? Web postings seem consistently that there is an an increase in the adverse reaction that becomes geometrically worse with each additional sting. John5Russell3Finley (talk) 16:45, 25 August 2013 (UTC)

Nothing to find on Pubmed about this interaction, so unlikely that it will be discussed in the article. JFW | T@lk 17:10, 19 November 2014 (UTC)

Self-monitoring guideline

UK BCSH guideline on self-monitoring doi:10.1111/bjh.13070 JFW | T@lk 17:10, 19 November 2014 (UTC)

Interaction of Warfarin with Lovanox

Is there any negative interaction with the anticoagulant Lovanox? I am not a medical professional or a pharmacologist. I have been prescribed Lovanox for a Vinus procedure that will take place on January 23,2015. I was hospitalized in March, 2003 with a Deep Vein Thrombosis. I was placed on a Heparin Drip followed by bridging to Warfarin. The treatment I was given at that time was evidently successful. When I was discharged from the hospital, I still had the thrombosis in my right thigh. Over time the thrombosis disappeared. Warfarin has continued to protect me for many years from blood clots. I am a little apprehensive about taking a different anticoagulant. One example that came to my attention recently was the danger some people encountered with the new anticoagulant that does not require monitoring by blood sample. Do you have any suggestions?98.192.87.234 (talk) 21:36, 19 January 2015 (UTC)

Lovanox is a form of heparin called enoxaparin, usually used in a hospital and followed by warfarin I think. Monitored in the same or similar way. But this is not the place to ask patient-care questions. There's many sites on the web with information or consult your healthcare professional. juanTamad 05:08, 20 January 2015 (UTC) — Preceding unsigned comment added by Jtamad (talk • contribs)

Warfarin and schizophrenia

There is a scientific paper on the effects of warfarin on schizophrenia patients - is this relevant? — Preceding unsigned comment added by Kiwishake (talk • contribs) 01:03, 21 September 2015 (UTC)

What's the source and what does it conclude? Attaboy (talk) 03:57, 21 September 2015 (UTC)

Benefits?

I created a Research for benefits section based on two meta-analyses that reported lower cancer incidence for people on long-term vitamin K antagonists. David notMD (talk) 11:36, 22 September 2020 (UTC)

Stalin

It has been suggested that warfarin was used in Stalin's case. I want proof. — Preceding unsigned comment added by 2A00:23C4:7C87:4F00:6423:90DD:6C6E:5AEA (talk) 13:07, 11 August 2020 (UTC)

Death and state funeral of Joseph Stalin describes a history of hypertension, and a stoke as the cause of death. However, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228382/ raises the possibility that deliberate warfarin poisoning may have been the precipitating cause, evidence cited including that he was vomiting blood in days between the stoke and his death. David notMD (talk) 11:41, 22 September 2020 (UTC)

Dietary restrictions

In the sentence "In addition, food that contains large quantities of vitamin K1 will reduce the warfarin effect, I'd like to add "In Japan, for example, patients taking warfarin are prohibited from eating nattō, a common ferment soybean product with very high levels of vitamin K2". I can't find an explicit source, but I know this from, um, personal experience. Any opinions? --Calton | Talk 10:22, 27 February 2021 (UTC)

What

What on earth happened to the Talk page? I am sure one existed before??? 138.37.188.109 11:39, 29 Nov 2004 (UTC)

Bleeds

I felt that Axel's latest edit seemed to slightly understate the risk from a bleed. I'd hate the article to wrongly reassure someone with a bleed that as they are mostly not important they shouldn't do anything about it. So I have reworded it. The bad news is that my reword is clunky and needs sorting out but I am currently at a loss as to how to do this and not lose the meaning further, so I think I will leave it and hope that someone else will have a go. And where the h*ll is the Talk page??? :) 138.37.188.109 11:46, 29 Nov 2004 (UTC)

I cannot find an old talk page. Are you perhaps confusing it with a different page? I rephrased your edit. JFW | T@lk 12:55, 29 Nov 2004 (UTC)

You may be right - I did think there was one, but who knows what I have been bleeding into? :) (me again but not same IP, confusingly)

Thanks for the rephrase. It's good with one reservation on text and one language. The only lang prob is that ppl are going to misread "proportion" and the singular verb as a mistake. Your English is correct, but I would put money that they'll think it's wrong. :) On text, I still think that what is slightly missing is the message (which for DEEPLY personal reasons I wanted in! :) ) saying "don't assume that ANY bruising and bleeding is trivial unless someone with the right letters after their name has said so, you prat!" - but more nicely! <g> 138.37.188.109

Foreign usage

I live in Sweden. After a pulmonary embolism, I was put on 2.5mg warfarin sodium (Nycomed Waran), in the form of small green tablets. Dosage is monitored with an INR target in the rang 2-3. I'm interested in how this relates to the (presumably American) variants listed.

The listed variants are based on the British presentation. I'm not sure what the tablet colours are in Sweden. Please find out & add it to the article! JFW | T@lk 02:10, 30 Jan 2005 (UTC)

Yeah, you bet they're the UK colours! :) Actually we should have said this. I suppose I naively hoped there might be some international co-ordination in the colours ... tsk! I will edit the caption to include this - if we then find out there are 8 million different colour ranges we should maybe include this in the article. Of course, you could always start the Swedish warfarin page off! :) Green, eh? Wow ... Gonegonegone 17:43, 3 Feb 2005 (UTC)

Lead ("blood thinner")

In the lead it says:

Warfarin, sold under the brand name Coumadin among others,[1] is a medication that is used as an anticoagulant (blood thinner).[5]

but later on, under the Mechanism of Action section:

While warfarin is one of several drugs popularly referred to as a "blood thinner", this is a misnomer since it does not affect the viscosity of blood.[72]

Does this mean that the drug is often incorrectly used (or at least labeled) as a blood thinner or is the lead referring to a source that is incorrectly describing the drug as a blood thinner? Or just a technically on what "anticoagulant" means exactly as it might not technically always thin the blood and therefore just remove the brackets after anticoagulant in the lead. Lead also has one other mention about the drug as a blood thinner. Might be better if one of the two sections are edited to clarify.86.139.229.85 (talk) 01:40, 20 October 2021 (UTC)

Good point, I've addressed this in both places. Best wishes, Pol098 (talk) 17:48, 18 February 2023 (UTC)