A 65-year-old woman comes to the emergency department due to left leg pain and swelling for the past day. She has had no trauma or fever. The patient has a history of hypertension, congestive heart failure, type 2 diabetes mellitus, and osteoporosis. Family history is notable for breast cancer in her mother and sister. She takes multiple medications. Temperature is 37.8 C (100 F), blood pressure is 130/80 mm Hg, and pulse is 99/min. Pulse oximetry shows 98% on ambient air. The lungs are clear to auscultation, and heart sounds are normal without murmur. There is tenderness and edema of the left lower extremity up to the mid thigh. Venous Doppler ultrasonography reveals an occluding thrombus in the left femoral and popliteal veins. Which of the following pharmacotherapies most likely contributed to this patient's current condition?

Question

A 65-year-old woman comes to the emergency department due to left leg pain and swelling for the past day.  She has had no trauma or fever.  The patient has a history of hypertension, congestive heart failure, type 2 diabetes mellitus, and osteoporosis.  Family history is notable for breast cancer in her mother and sister.  She takes multiple medications.  Temperature is 37.8 C (100 F), blood pressure is 130/80 mm Hg, and pulse is 99/min.  Pulse oximetry shows 98% on ambient air.  The lungs are clear to auscultation, and heart sounds are normal without murmur.  There is tenderness and edema of the left lower extremity up to the mid thigh.  Venous Doppler ultrasonography reveals an occluding thrombus in the left femoral and popliteal veins.  Which of the following pharmacotherapies most likely contributed to this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3bc1_2eb9_9249_f9198c6c44ce_MD0001_00 Selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, are nonsteroidal compounds that bind to estrogen receptors and exhibit estrogen antagonist and agonist properties in a tissue-specific manner. Raloxifene has estrogen agonist activity on bone, inhibiting bone resorption and improving bone mineral density while exhibiting estrogen antagonist activity in the breast and endometrial tissue. Medicines with estrogen agonist activity, including SERMs, oral contraceptives, and hormone replacement therapy, cause a prothrombotic state and can increase the risk for venous thromboembolism (VTE). Proposed mechanisms include increased levels of clotting factors (eg, prothrombin; fibrinogen; factor VII, VIII, X) and activated protein C resistance. Current or prior thromboembolic disorders are contraindications to SERM use. (Choice A) Bisphosphonates (eg, alendronate) inhibit osteoclast-mediated bone resorption. Side effects include hypocalcemia, esophagitis, and osteonecrosis of the jaw. Bisphosphonates have no estrogenic activity and do not increase the risk for VTE. (Choice B) Thiazide diuretics (eg, chlorthalidone) inhibit Na⁺/Cl^- cotransporters in the distal convoluted tubule, decreasing reabsorption of Na⁺ and increasing reabsorption of calcium, which can be beneficial in patients with osteoporosis. Side effects include electrolyte abnormalities, hyperglycemia, and hyperlipidemia. (Choice C) Sodium-glucose cotransporter 2 inhibitors (eg, empagliflozin) reduce reabsorption of glucose in the proximal renal tubule, leading to urinary glucose excretion. Side effects include urinary tract and genital mycotic infections as well as hypotension. (Choice D) Glucagon-like peptide-1 (GLP-1) is released by the small intestine in response to food and induces glucose-dependent insulin release from pancreatic beta cells. GLP-1 agonists (eg, liraglutide) lower blood glucose with little hypoglycemia risk, but can cause gastrointestinal upset and weight loss. (Choice F) Sacubitril is a neprilysin inhibitor that increases atrial natriuretic peptide and brain natriuretic peptide levels (thereby promoting diuresis and vasodilation) in patients with heart failure. It is administered with an angiotensin II receptor blocker (valsartan) to offset the associated increase in angiotensin II levels. Side effects include cough, hyperkalemia, and renal impairment. (Choice G) Spironolactone is an aldosterone antagonist used in patients with heart failure. It has prominent anti-androgenic effects, which can lead to gynecomastia in male patients due to unopposed estrogenic effects on breast tissue. However, it has minimal effects on estrogen levels and does not increase the risk of VTE. Educational objective: Raloxifene is a selective estrogen receptor modulator (SERM) that has estrogen agonist activity on bone and decreases bone resorption. Medicines with estrogen agonist activity, including SERMs, oral contraceptives, and hormone replacement therapy, can increase the risk for venous thromboembolism. __________ References: Selective estrogen receptor modulators in menopause. (http://www.ncbi.nlm.nih.gov/pubmed/24346250)

A 65-Year-Old Woman Comes to the Emergency Department Due to Left