Review Question - QID 218781

This patient with a history of breast cancer presenting with dyspnea, pleuritic chest pain, and sinus tachycardia has an acute pulmonary embolism. Raloxifene is a selective estrogen receptor modulator (SERM) that induces a hypercoagulable state, which can lead to an acute deep vein thrombosis or pulmonary embolism, collectively referred to as venous thromboembolic events (VTEs).

Pulmonary emboli commonly result from blood clots in the lower extremities, which can be the result of hypercoagulable states, vascular injury, or venous stasis. These are known as the Virchow triad. Risk factors for a hypercoagulable state include malignancy and use of certain medications. SERMs are a class of medications commonly used for the treatment of estrogen receptor-positive breast cancers. They exert mixed agonist-antagonist effects depending on the tissue. For example, tamoxifen is an antagonist in breast tissue (hence why it is used for breast cancer) but agonist at endometrial tissue, which increases the risk of endometrial hyperplasia and carcinoma. They exert an estrogen-like effect with respect to coagulation, inducing a hypercoagulable state. Tamoxifen's effect on hypercoagulability is more pronounced than that of raloxifene. VTEs resulting from SERM use are treated the same way as in patients without SERM use, namely with therapeutic anticoagulation (e.g., heparin).

Nicola et al. studied strategies for reducing VTEs in perioperative patients on tamoxifen. The authors found that a risk-stratifying algorithm for tamoxifen dosing in the perioperative period reduced the risk of VTE. They recommended that their risk-stratifying algorithm for perioperative tamoxifen use be adopted to reduce morbidity and mortality in these patients.

Incorrect Answers:
Answer 1: Atorvastatin is an HMG-CoA reductase inhibitor, which can cause the notable side effect of statin-induced myopathy. Statin-induced myopathy presents with proximal, symmetric weakness and soreness in the weeks to months after starting statin therapy. However, it can occur at any time during statin treatment. The treatment for this disorder is to discontinue the statin until symptoms resolve and then restart at a lower statin dose.

Answer 2: Levothyroxine is a form of hormone replacement for hypothyroidism. Levothyroxine can cause tachyarrhythmias, chest pain, tachycardia, and hypertension if used in excess. Patients may present with palpitations and hyperthermia.

Answer 3: Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor that commonly causes a chronic dry cough as a side effect. ACE inhibitors also block the breakdown of bradykinin and substance P, which then accumulate and cause a cough. In patients who develop this side effect, the ACE inhibitor can be changed to an angiotensin II receptor blocker (ARB).

Answer 4: Metformin most commonly causes stomach upset, nausea, and vomiting during initiation of treatment. These symptoms typically resolve within a week without further intervention and do not require dose modifications. Lactic acidosis is another rare side effect of metformin.

Bullet Summary:
Raloxifene is a selective estrogen receptor modulator that causes a hypercoagulable state, which can lead to venous thromboemboli.