Talk:Warfarin

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[edit] 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)

[edit] 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)

[edit] 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

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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).

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)