A 56-year-old woman comes to clinic for follow-up of heart failure with reduced ejection fraction. Over the last 3 months, the patient has been hospitalized twice due to acute decompensation of heart failure that required treatment with intravenous furosemide. Since her most recent discharge, she has been taking high doses of oral furosemide, but she continues to have progressive lower extremity edema and weight gain. Serum creatinine is 1.2 mg/dL and serum potassium is 4.1 mEq/L. The patient is started on metolazone. The addition of metolazone is likely to assist in treating this patient because of which of the following effects of furosemide?

Question

A 56-year-old woman comes to clinic for follow-up of heart failure with reduced ejection fraction.  Over the last 3 months, the patient has been hospitalized twice due to acute decompensation of heart failure that required treatment with intravenous furosemide.  Since her most recent discharge, she has been taking high doses of oral furosemide, but she continues to have progressive lower extremity edema and weight gain.  Serum creatinine is 1.2 mg/dL and serum potassium is 4.1 mEq/L.  The patient is started on metolazone.  The addition of metolazone is likely to assist in treating this patient because of which of the following effects of furosemide?

Quizplus · Accepted Answer

11ec160b_3b92_7d45_9249_1d63cb66b96d_MD0001_00 This patient has decompensated heart failure with ongoing volume retention despite high doses of oral furosemide (ie, loop diuretic) therapy. Thiazide diuretics, especially metolazone, potentiate the diuretic effect of loop diuretics and can be helpful in treating refractory volume overload. Sodium is the major determinant of volume status. Loop diuretics function by inhibiting the Na-K-2Cl cotransporter in the ascending limb of the loop of Henle to block sodium absorption and encourage the excretion of sodium and water in the urine. However, the sodium excretion caused by loop diuretics is limited by the reabsorption of sodium in the distal convoluted tubule; the Na-Cl cotransporter in the distal tubule counteracts some of the effect of loop diuretics by absorbing much of the sodium that is not absorbed in the loop of Henle. Inhibition of the Na-Cl cotransporter with metolazone prevents reabsorption of the increased sodium delivered to the distal tubule, significantly increasing total sodium excretion. (Choice A) Loop diuretics inhibit calcium absorption in the loop of Henle, leading to increased calcium delivery to the distal tubule. However, calcium has minimal effect on volume status. Thiazide diuretics increase calcium absorption in the distal tubule, making up for some of the calcium loss caused by loop diuretics. (Choice C) Loop diuretics stimulate hydrogen ion excretion and bicarbonate reabsorption, creating a tendency toward metabolic alkalosis. Carbonic anhydrase inhibitors (eg, acetazolamide) block bicarbonate absorption in the proximal tubule and are sometimes used to minimize the metabolic alkalosis caused by loop diuretics. (Choice D) Both loop and thiazide diuretics increase the reabsorption of uric acid and, therefore, may increase the risk of gout attacks. (Choice E) Both loop and thiazide diuretics have minimal effect on tubular glucose reabsorption. Sodium-glucose cotransporter-2 inhibitors (eg, empagliflozin) block glucose resorption in the proximal tubule to lower serum glucose levels while also stimulating an osmotic diuresis. (Choice F) The increased distal tubular delivery of sodium caused by loop diuretics stimulates increased potassium secretion by the principal cells in the late distal tubule and collecting duct. This potassium loss is amplified with the addition of a thiazide diuretic. Potassium-sparing diuretics (eg, spironolactone) can help offset the potassium loss caused by loop and thiazide diuretics. Educational objective: Thiazide diuretics, especially metolazone, potentiate the diuretic effect of loop diuretics (eg, furosemide) by blocking the reabsorption of the increased distal tubular sodium delivery caused by loop diuretics. __________ References: Combination of loop diuretics with thiazide-type diuretics in heart failure. (http://www.ncbi.nlm.nih.gov/pubmed/21029871)

A 56-Year-Old Woman Comes to Clinic for Follow-Up of Heart