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Rifampin
11%
21/188
Trimethoprim-sulfamethoxazole
50%
94/188
Griseofulvin
13%
24/188
Phenobarbital
7%
14/188
St. John’s wort
10%
19/188
Select Answer to see Preferred Response
This patient likely developed a supratherapeutic INR after taking the sulfonamide antibiotic trimethoprim-sulfamethoxazole for cellulitis. P450 inhibitors such as sulfonamides will decrease P450-mediated warfarin breakdown, leading to an increase in INR. Warfarin is an anticoagulant that inhibits vitamin K epoxide reductase, thereby interfering with gamma-carboxylation of clotting factors II, VII, IX, X, and proteins C and S in the liver. Clinically, warfarin is used to provide chronic anticoagulation for patients with deep venous thrombosis (DVT), pulmonary embolism, prosthetic heart valves, and atrial arrhythmias such as atrial fibrillation. The INR is a blood test used to monitor the effects of warfarin and ensure that it is in a therapeutic range. A normal INR is 1.0 and the therapeutic range is typically 2.0-3.0. When INR changes abruptly, one should always consider the cytochrome P450 system because its metabolism can be affected by drugs that inhibit or induce P450. P450 inhibitors such as sulfonamides will decrease warfarin degradation, leading to an increase in INR. Likewise, P450 inducers will increase warfarin degradation, leading to a decrease in INR. Incorrect Answers: Answer 1: Rifampin is an antibiotic used to treat conditions such as tuberculosis and leprosy. It is a P450 inducer and would likely decrease INR in a patient taking warfarin. Answer 3: Griseofulvin is an oral antifungal agent used to treat dermatophytoses such as ringworm. It is a P450 inducer and would likely decrease INR in a patient taking warfarin. Answer 4: Phenobarbital is a barbiturate drug used to treat epilepsy. It is a P450 inducer and would likely decrease INR in a patient taking warfarin. Answer 5: St. John’s wort is a medicinal herb that is occasionally used to treat major depressive disorder. It is a potent P450 inducer and would likely decrease INR in a patient taking warfarin. Bullet Summary: Warfarin is an anticoagulant that inhibits gamma-carboxylation of vitamin K-dependent clotting factors. Its metabolism can be affected by drugs that interfere with the cytochrome P450 system.
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