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Mechanism of action of diuretics

INTRODUCTION

Diuretics are among the most commonly used drugs. They act by diminishing sodium reabsorption at different sites in the nephron, thereby increasing urinary sodium and water losses. The ability to induce negative fluid balance has made diuretics useful in the treatment of a variety of conditions, particularly edematous states and hypertension.

A review of the mechanism and time course of action of diuretics will be presented here. Diuretic dosing and adverse effects are discussed separately. (See "Loop diuretics: Maximum effective dose and major side effects" and "Time course of loop and thiazide diuretic-induced electrolyte complications".)

MECHANISM OF ACTION

The diuretics are generally divided into four major classes, which are distinguished by the site at which they impair sodium reabsorption [1,2]:

  • Loop diuretics act in the thick ascending limb of the loop of Henle
  • Thiazide-type diuretics in the distal tubule and connecting segment (and perhaps the early cortical collecting tubule)
  • Potassium-sparing diuretics in the aldosterone-sensitive principal cells in the cortical collecting tubule
  • Acetazolamide and mannitol act at least in part in the proximal tubule

To appreciate how diuretics act, it is first necessary to review the general mechanism by which sodium is reabsorbed. Each of the sodium-transporting cells contains Na-K-ATPase pumps in the basolateral membrane [3]. These pumps perform two major functions: they return reabsorbed sodium to the systemic circulation; and they maintain the cell sodium concentration at relatively low levels. The latter effect is particularly important since it allows filtered sodium to enter the cells down a favorable concentration gradient via carrier-mediated transport.

         

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Literature review current through: Aug 2014. | This topic last updated: Oct 8, 2013.
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