Warfarin Flashcards
(29 cards)
What is the mechanism of action of warfarin?
Warfarin inhibits vitamin K epoxide reductase (which is required for converting vitamin K into its active state), preventing gamma carboxylation of vitamin K, reducing synthesis of vitamin K dependent clotting factors, II, VII, IX, and X, and the natural anticoagulation proteins C & S.
What are the main indications for warfarin therapy?
Atrial fibrillation, venous thromboembolism (VTE), DVT prophylaxis, mechanical heart valves, hypercoagulable disorders.
How is warfarin administered?
orally
What is Warfarin’s onset of action?
8-12 hours
Which clotting factors are inhibited by warfarin?
Factors II, VII, IX, X, and anticoagulants protein C and protein S.
Which coagulation pathway does warfarin impact most significantly?
Due to factor VII, the extrinsic pathway is most affected.
Why does warfarin initially increase thrombosis risk?
Protein C and S have shorter half-lives than clotting factors, leading to a temporary hypercoagulable state.
What test is used to monitor warfarin therapy?
Prothrombin Time (PT)/International Normalized Ratio (INR).
What is the therapeutic INR range for most indications?
INR 2.0–3.0 for most indications; 2.5–3.5 for mechanical heart valves.
What drugs increase warfarin effect (↑ INR)?
- CYP2C9 inhibitors (azoles, amiodarone).
- Microbiome alteration (Metronidazole, quinolones).
- Acetaminophen (reduces vitamin K recycling).
What medications can alter warfarin due to disturbances of the gut microbiome?
These medications can INCREASE the effectiveness of warfarin:
- Metronidazole
- Quinolones
How does amiodarone affect warfarin metabolism?
- Amiodarone inhibits CYP2C9, reducing warfarin metabolism and increasing INR.
- The warfarin dose should be reduced by 25-50%.
What medications can alter warfarin due to Cyp2C9 inhibition?
These medications can INCREASE the effectiveness of warfarin:
- Azoles
- Amiodarone
What medication is known to increase the effectiveness of warfarin due to increased vit K recycling?
Acetaminophen
What drugs decrease warfarin effect (↓ INR)?
When a patient is taking any of these medications or has these dietary practices, increase the dose of warfarin:
- CYP2C9 inducers (rifampin, phenobarbital, phenytoin, St. John’s Wort).
- Oral contraceptives.
- Green leafy vegetables (↑ vitamin K intake).
What dietary factors can reduce warfarin efficacy?
Increased vitamin K intake (e.g., green leafy vegetables) can decrease INR by increasing clotting factor synthesis.
How do NSAIDs interact with warfarin?
NSAIDs increase bleeding risk by inhibiting platelet function but do not affect INR.
What herbal supplements increase the bleeding risk associated with warfarin therapy?
Ginkgo biloba (unknown mechanism)
- Garlic
- Ginger
How does warfarin compare to heparin in onset of action?
Warfarin has a delayed onset (3-5 days) due to the need to deplete existing clotting factors, while heparin acts immediately.
What is the antidote for warfarin overdose?
- Limit or eliminate the dosage of warfarin.
- Give vitamin K (for mild elevations).
- Give fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) for life-threatening bleeding.
Why must warfarin be bridged with heparin in acute thromboembolism?
Due to initial warfarin-induced hypercoagulability from protein C depletion, heparin prevents early thrombosis. Warfarin induced skin necrosis (WISN), which is also prevented using a heparin bridge.
What genetic polymorphisms affect warfarin metabolism?
Polymorphisms in CYP2C9 (slower metabolism) and VKORC1 (altered warfarin sensitivity).
What conditions increase warfarin sensitivity?
Liver disease (reduced clotting factor synthesis), congestive heart failure (reduced metabolism), advanced age.
What is warfarin’s effect on pregnancy?
Warfarin is teratogenic (contraindicated in pregnancy) and can cause fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses).
