A 63-year-old man comes to the emergency department due to muscle weakness with severe cramping in the lower extremities. The cramps are severe enough to disrupt his sleep. The patient also exercises daily but has had to suspend his exercise regimen in the last 3 days due to the symptoms. Past medical history is notable for hypertension, for which he was started on chlorthalidone and amlodipine 4 weeks ago. Blood pressure in the emergency department is 140/86 mm Hg and pulse is 90/min. The heart has a regular rate and rhythm, and he has palpable pedal pulses with no peripheral edema. Which of the following is the most likely cause of this patient's muscular symptoms?

Question

A 63-year-old man comes to the emergency department due to muscle weakness with severe cramping in the lower extremities.  The cramps are severe enough to disrupt his sleep.  The patient also exercises daily but has had to suspend his exercise regimen in the last 3 days due to the symptoms.  Past medical history is notable for hypertension, for which he was started on chlorthalidone and amlodipine 4 weeks ago.  Blood pressure in the emergency department is 140/86 mm Hg and pulse is 90/min.  The heart has a regular rate and rhythm, and he has palpable pedal pulses with no peripheral edema.  Which of the following is the most likely cause of this patient's muscular symptoms?

Quizplus · Accepted Answer

Thiazide diuretics lower blood pressure by decreasing intravascular volume, reducing cardiac output, and lowering systemic vascular resistance. Thiazides inhibit Na⁺/Cl⁻ co-transporters in the distal convoluted tubules, thereby decreasing reabsorption of Na⁺ and Cl⁻. The decrease in intravascular volume is partially attenuated by activation of the renin-angiotensin-aldosterone system. However, the rise in aldosterone secretion leads to increased urinary excretion of potassium and hydrogen ions, with resulting hypokalemia and metabolic alkalosis. Chlorthalidone appears to be more potent in lowering blood pressure than other thiazides (eg, hydrochlorothiazide) but is also associated with more metabolic abnormalities. Significant hypokalemia can cause muscle weakness, cramps, and possible rhabdomyolysis. (Choice A) Hypovolemia stimulates uric acid reabsorption in the proximal tubules. This can cause hyperuricemia and potentially precipitate a gout attack (acute monoarticular arthritis). (Choice B) Thiazides increase calcium reabsorption in the distal convoluted tubules, reducing urinary excretion of calcium and modestly raising serum calcium levels. They do not cause hypocalcemia. (Choice C) Thiazides decrease insulin secretion and peripheral uptake of glucose. This can cause hyperglycemia, not hypoglycemia. (Choice E) Thiazides can cause hyponatremia due to increased urinary excretion of sodium. Acute hyponatremia causes nausea, malaise, headache, and central nervous symptoms (eg, altered mental status, seizures). Muscle cramps are less common and usually seen with chronic hyponatremia. (Choice F) Hypophosphatemia can cause muscle weakness and paralysis but is not a side effect of thiazides. It is commonly seen with chronic alcohol use. Educational objective: Thiazide diuretics decrease intravascular fluid volume, which stimulates aldosterone secretion and leads to increased excretion of potassium and hydrogen ions in the urine. This results in hypokalemia and metabolic alkalosis. __________ References: Thiazides and the risk of hypokalemia in the general population. (http://www.ncbi.nlm.nih.gov/pubmed/25105457)

A 63-Year-Old Man Comes to the Emergency Department Due to Muscle