A 65-year-old male comes to the emergency department with a two week history of progressive shortness of breath. He has been sleeping in a chair for the last three days because he cannot lie flat in bed. His past medical history is significant for hypertension, hyperlipidemia, coronary artery disease, and type 2 diabetes mellitus. He experienced a myocardial infarction two years ago but refused cardiac catheterization. His current medications are metoprolol, metformin, losartan, pioglitazone, atorvastatin, glyburide, and low-dose aspirin. He is a lifelong non-smoker. His blood pressure is 151/82 mmHg and his heart rate is 72/min, regular in rhythm. His oxygen saturation is 92% on room air. An S3 heart sound is present on cardiac auscultation. Bilateral crackles are heard on chest examination. There is 2+ symmetric bilateral pitting edema. EKG shows normal sinus rhythm with no acute ST segment or T wave changes. Cardiac enzymes are negative. Chest X-ray reveals increased interstitial markings with Kerley B lines and small bilateral pleural effusions. Which of the following medications most likely contributed to this patient's current condition?
A)Atorvastatin
B)Glyburide
C)Losartan
D)Metformin
E)Pioglitazone

Question

A 65-year-old male comes to the emergency department with a two week history of progressive shortness of breath.  He has been sleeping in a chair for the last three days because he cannot lie flat in bed.  His past medical history is significant for hypertension, hyperlipidemia, coronary artery disease, and type 2 diabetes mellitus.  He experienced a myocardial infarction two years ago but refused cardiac catheterization.  His current medications are metoprolol, metformin, losartan, pioglitazone, atorvastatin, glyburide, and low-dose aspirin.  He is a lifelong non-smoker.  His blood pressure is 151/82 mmHg and his heart rate is 72/min, regular in rhythm.  His oxygen saturation is 92% on room air.  An S3 heart sound is present on cardiac auscultation.  Bilateral crackles are heard on chest examination.  There is 2+ symmetric bilateral pitting edema.  EKG shows normal sinus rhythm with no acute ST segment or T wave changes.  Cardiac enzymes are negative.  Chest X-ray reveals increased interstitial markings with Kerley B lines and small bilateral pleural effusions.  Which of the following medications most likely contributed to this patient's current condition?
A)Atorvastatin
B)Glyburide
C)Losartan
D)Metformin
E)Pioglitazone

Quizplus · Accepted Answer

Explanation: This patient's orthopnea, hypoxia, bilateral crackles on exam, and chest radiograph findings are all consistent with pulmonary edema. Of the medications listed, the most likely to result in pulmonary edema is the PPAR-γ agonist pioglitazone, a member of the thiazolidinedione class. PPAR-γ receptors are present in the collecting tubule of the nephron, and stimulation by pioglitazone results in increased sodium reabsorption. This is the same channel via which aldosterone mediates its effects on sodium retention. Fluid retention can occur in 4-6% of patients on thiazolidinediones, but most of these patients likely have underlying heart failure. This patient's history of a myocardial infarct that was not followed by catheterization, as well as the presence of an S3 on physical exam, are highly suggestive of underlying heart failure. Given that the aldosterone channel is involved in mediating the sodium retention, treatment with an aldosterone inhibitor such as spironolactone may be particularly effective in removing the excess fluid. (Choice A) Fluid overload is not associated with statin medications such as atorvastatin. The most common side effects of statins include hepatotoxicity and muscle injury. (Choice B) Glyburide is a sulfonylurea medication and as such its most common side effect is hypoglycemia. (Choice C) ACE inhibitors or ARBs such as losartan are a key component of heart failure therapy and would not be expected to induce pulmonary edema in patients with underlying heart failure. (Choice D) There is no increased risk of fluid retention with metformin. However, metformin should be used with caution in patients with heart failure since lactic acidosis can result should the patient become hemodynamically unstable. Educational objective: The thiazolidinedione medications can result in fluid retention via PPAR-γ agonist effects on the renal collecting tubule resulting in sodium reabsorption. This effect is usually seen in patients with underlying heart failure. References: Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies. (http://www.ncbi.nlm.nih.gov/pubmed/17722967)

A 65-Year-Old Male Comes to the Emergency Department with a Two