A 72-year-old woman is brought to the emergency department due to severe shortness of breath, tachypnea, and pleuritic-type chest pain. She had a similar episode 3 weeks ago and has been treated with warfarin since then. The patient has several other medical conditions and is taking all her medications as recommended. On examination, her temperature is 36.7 C (98 F), blood pressure is 120/60 mm Hg, pulse is 118/min, and respirations are 28/min. Pulse oximetry is 93% on room air. Laboratory results are notable for the following: The patient's INR is subtherapeutic compared to her target INR range of 2.0-3.0 with warfarin. This patient is most likely taking which of the following additional medications?

Question

A 72-year-old woman is brought to the emergency department due to severe shortness of breath, tachypnea, and pleuritic-type chest pain.  She had a similar episode 3 weeks ago and has been treated with warfarin since then.  The patient has several other medical conditions and is taking all her medications as recommended.  On examination, her temperature is 36.7 C (98 F), blood pressure is 120/60 mm Hg, pulse is 118/min, and respirations are 28/min.  Pulse oximetry is 93% on room air.  Laboratory results are notable for the following:  The patient's INR is subtherapeutic compared to her target INR range of 2.0-3.0 with warfarin.  This patient is most likely taking which of the following additional medications?

Quizplus · Accepted Answer

11ec160b_3bd8_d497_9249_698392eb4fcb_MD0001_00 This patient with pleuritic chest pain, dyspnea, tachypnea, tachycardia, and hypoxia most likely experienced a recurrent pulmonary embolism (PE) in the setting of a subtherapeutic INR level, reflecting decreased warfarin efficacy. Warfarin is an oral anticoagulant that inhibits activation of vitamin K-dependent clotting factors, particularly factor VII. As a result, warfarin administration leads to prolongation of the prothrombin time (PT) and INR (ratio of a patient's PT compared to a normal control). In patients with atrial fibrillation, deep venous thrombosis, or PE who are taking warfarin for anticoagulation, the dose is usually adjusted to achieve a target therapeutic INR range (generally 2.0-3.0). Precise dosing of warfarin can be difficult due to its many interactions with other drugs that affect cytochrome P-450 activity, plasma protein binding, and/or gastrointestinal absorption. Warfarin elimination occurs primarily through hepatic metabolism by cytochrome P-450 enzymes. Drugs that increase P-450 activity, such as phenytoin, phenobarbital, and rifampin, increase warfarin elimination and decrease its anticoagulant activity (reflected as a subtherapeutic INR <2.0). Cholestyramine binds warfarin (and other drugs) in the intestine, thereby decreasing warfarin's therapeutic effect. (Choices A, C, and F) When used concurrently with warfarin, aspirin and other nonsteroidal anti-inflammatory drugs such as indomethacin increase the risk of bleeding due to antiplatelet effects and gastrointestinal ulceration. These drugs can also displace warfarin from plasma protein binding sites (increasing the concentration of free warfarin). Acetaminophen can interfere with vitamin K metabolism and enhance the effect of warfarin. (Choices B, D, and G) Both cimetidine and amiodarone inhibit the metabolism of warfarin, which can result in an increased PT/INR and bleeding risk. The interaction between amiodarone and warfarin is important because some patients with atrial fibrillation may be prescribed both medications. The commonly used antibiotics metronidazole and trimethoprim-sulfamethoxazole also inhibit warfarin metabolism. (Choices E and H) Benzodiazepines and opiates usually do not interact significantly with warfarin. Educational objective: Rifampin, phenobarbital, and phenytoin are potent enhancers of the cytochrome P-450 pathway; concurrent use of warfarin with these medications results in decreased efficacy of warfarin. In contrast, cimetidine, amiodarone, and trimethoprim-sulfamethoxazole inhibit warfarin metabolism, increasing the risk of bleeding.

A 72-Year-Old Woman Is Brought to the Emergency Department Due