Dr Sharon Rees @reesprescribe In the 1940s, after mouldy sweet clover led to haemorrhage in cattle, the cause was discovered to be a coumarin. It was used as rodenticide until licensed for human use in 1954 by Wisconsin Alumni Res Foundation (WARF), where it was launched as WARFarin #prescribing
Dr Sharon Rees @reesprescribe Until recently, #warfarin was the main oral anticoagulant in the world. New oral anticoagulants (NOACs) (eg dabigatran) introduced in 2008 have replaced #warfarin for some conditions, but #warfarin is still in use for original indications, including venous thromboembolism treatment and prevention, prophylaxis of embolism, atrial fibrillation, prosthetic heart valve and transient ischemic attacks #prescribing
Dr Sharon Rees @reesprescribe Vitamin K is needed to form many clotting factors. As vitamin K is recycled, it requires conversion back to its reduced active form. #Warfarin competes at vitamin K reductase binding site, so less active form is produced, lowering levels of factors II, VII, IX and X and proteins C and S, prolonging clotting time #prescribing
Dr Sharon Rees @reesprescribe Mechanism of action (continued): some drug-food interactions for #warfarin relate to changes in levels of vitamin K (eg green leafy veg) as higher/lower levels of vitamin K are in competition with #warfarin and can affect action #prescribing
Dr Sharon Rees @reesprescribe Problematic kinetics for #warfarin include high percentage of protein binding, narrow therapeutic index and two active isomers, which are each metabolised by different CYP450 enzymes, thus susceptible to individual variation. Some useful kinetics too; historically useful in chronic kidney disease (but not dialysis) as eliminated by metabolism #prescribing
Dr Sharon Rees @reesprescribe #Warfarin has multiple kinetic and dynamic drug-drug interactions including antiepileptics, corticosteroids, some antibiotics/antifungals, anti-platelets, alcohol, ginkgo biloba and St John's Wort. Genetic variations add to risks of over- and under-performance because of variable absorption and metabolism (eg CYP2C9 polymorphisms) #prescribing
Dr Sharon Rees @reesprescribe #Warfarin has some advantages over NOACs eg the ability to monitor anti-coagulation via INR testing assists concordance, safety netting and clinical efficacy. Also, overdose reversal by vitamin K (low cost compared with NOAC reversal agents). Serious adverse drug reactions include haemorrhage, fetal harm/death, rash, alopecia, blood disorders and hepatotoxicicity #prescribing
Dr Sharon Rees @reesprescribe There is so much to say about #warfarin, I'm finishing with an interesting fact. Coumarin is aromatic and occurs naturally in lavender, tonka beans (banned in US because of potential hepatic toxicity), cinnamon, green tea, cherries, carrots. However, it is virtually impossible to consume enough to be toxic #prescribing