Myocardial Infarction & Peripheral Vascular Diseases Q 18

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When caring for a patient who has started anticoagulant therapy with warfarin (Coumadin), the nurse knows not to expect therapeutic benefits for:

  

     A. At least 12 hours

     B. The first 24 hours

     C. 2-3 days

     D. 1 week

    

    

Correct Answer: C. 2-3 days

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The onset of action is typically 24 to 72 hours. A peak therapeutic effect is seen 5 to 7 days after initiation. However, the patient’s international normalized ratio (INR) may increase within 36 to 72 hours after initiating treatment. Warfarin is a once-daily oral medication. Warfarin administration can be at any time during the day, but recommendations are for administration in the afternoon or evening. By instructing patients to take warfarin later in the day, healthcare providers can have the opportunity to individualize a patient’s warfarin dose the same day based on their most current lab values.

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Option A: The dose-response of warfarin among patients is highly variable and depends on interpatient differences. Patient-specific factors such as drug metabolism, the presence of a vitamin K enriched diet, genetics, quantity of vitamin K-dependent clotting factors, concurrent disease states, binding proteins, concomitant drug interactions, laboratory testing, and medication adherence requires assessment when dosing warfarin.

Option B: The half-life of warfarin is generally 20 to 60 hours (mean: 40 hours). However, it is highly variable among individuals. The duration of action is 2 to 5 days. Hepatic metabolism, primarily through the CYP2C9 enzyme. Other minor enzymatic pathways for metabolism include CYP2C8, 2C18, 2C19, 1A2, and 3A4. Warfarin is primarily eliminated as metabolites by glomerular filtration in the kidney (92% via urine).

Option D: Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for activating the vitamin K available in the body. Through this mechanism, warfarin can deplete functional vitamin K reserves and therefore reduce the synthesis of active clotting factors. The hepatic synthesis of coagulation factors II, VII, IX, and X, as well as coagulation regulatory factors protein C and protein S, require the presence of vitamin K. Vitamin K is an essential cofactor for the synthesis of all of these vitamin K-dependent clotting factors.

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