A 67-year-old man presents to the emergency department sudden onset of palpitation, shortness of breath, and dizziness which began 30 minutes ago. He has had similar episodes in the past but not as severe as this one. The patient reports that he has type 2 diabetes mellitus which is well-controlled and hypertension which is not currently being treated with medication. Blood pressure is 160/88 mmHg and heart rate is 140 beats/minute. Other vitals are within the normal range. Laboratory tests and an electrocardiogram are ordered, and the patient is diagnosed with atrial fibrillation. While discussing treatment options with the patient, he asks about warfarin side effects and drug interactions.
A) Alcohol
Cytochrome (CYP) P450 is a group of hemoprotein enzymes that are involved in many bodily homeostatic functions including drug metabolism. Alcohol in acute use can inhibit CYP 450 enzymes and thus decreases warfarin elimination from the body. This results in increased warfarin level in the blood.
Answer choice B: Carbamazepine, is incorrect. Carbamazepine is one of the CYP 450 inducers which means that it increases the expression level of CYP450 enzymes resulting in increased metabolism of warfarin and subsequently reducing the therapeutic level.
Answer choice C: Modafinil, is incorrect. Modafinil is a CYP inducer like carbamazepine.
Answer choice D: Phenytoin, is incorrect. Phenytoin is an anti-seizure medication that increases CYP 450 activity and reduces the therapeutic level of warfarin.
Answer choice E: Rifampin, is incorrect. This antibiotic is a known CYP 450 enzyme inducer.
Key Learning Point
Cytochrome 450 enzymes are a group of mostly liver enzymes that metabolize medications. Their action can be enhanced or inhibited by different chemicals, resulting in altered therapeutic dosages of many medications including warfarin. Alcohol inhibits cytochrome P450 enzymes and decreases warfarin elimination, leading to increased warfarin level in the blood and greater risk of bleeding.
