Diuretics

Published on 07/02/2015 by admin

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Last modified 07/02/2015

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Diuretics

Thomas N. Spackman, MD, MS

Drugs that increase the excretion of sodium and water through the kidneys, termed diuretics, are classified on the basis of their site (Figure 99-1) or mechanism of action in the nephron. Diuretics are the recommended drugs for initial treatment of hypertension and are used in a variety of relative fluid-overload conditions, including heart failure, renal disease, and liver cirrhosis. Despite the lack of evidence that diuretic therapy prevents acute renal injury or improves outcome following injury or that diuretics reduce morbidity or mortality risk when used in chronic heart failure, they do provide symptomatic relief from fluid-overload syndromes.

Figure 99-1 Renal tubules showing the primary sites of diuretic action. (Netter illustration from www.netterimages.com. © Elsevier Inc. All rights reserved.)

Thiazide diuretics

Thiazides inhibit Na⁺ transport in the distal convoluted tubule and also in part of the cortical ascending limb of the loop of Henle. Water follows the salt that is not reabsorbed, causing the diuresis. Because the distal convoluted tubule accounts for only 5% or less of the total Na⁺ reabsorption, the diuretic effect is much weaker than that of loop diuretics. Because the Na⁺– Cl⁻ transporter is located on the luminal side of the tubule, thiazide diuretics are not effective at glomerular filtration rates of less than 30 mL/min.

Thiazides are rapidly and effectively absorbed from the gastrointestinal tract. They reach their peak action within a few hours and exert a diuretic effect for up to 12 h. Thiazides are most commonly used as initial treatment for hypertension. The early reduction in blood pressure is due to a reduction in blood volume. Chronic treatment results in blood pressure control through reduced vascular resistance despite return of fluid volumes to pretreatment levels.

The most common adverse effects of thiazides are dehydration and hypokalemia with metabolic alkalosis. Adverse effects unique to the use of thiazides include hypercalcemia and hyperuricemia from decreased renal excretion of Ca²⁺ and uric acid. Other adverse effects include hyperglycemia, hyponatremia, hypomagnesemia, fatigue, lethargy, hypersensitivity reactions, purpura, and dermatitis with photosensitivity.

Loop diuretics

Furosemide, bumetanide, torsemide, and ethacrynic acid are classified as loop diuretics because of their action in inhibiting the reabsorption of electrolytes in the thick ascending loop of Henle. They also exert a direct effect on electrolyte transport in the proximal tubule and cause renal cortical vasodilation and increased renal blood flow. The potent diuresis results in enhanced excretion of Na⁺, Cl⁻, K⁺, H⁺, Ca²⁺, Mg²⁺, , and . Cl⁻ excretion exceeds Na⁺ excretion. Excessive losses of K⁺, H⁻, , and Cl⁻, as well as rapid contraction of extracellular fluid volume, may result in metabolic alkalosis.

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