Potassium-Sparing Diuretics

1

How do potassium-sparing diuretics work?

Potassium-sparing diuretics block the reabsorption of sodium through the epithelial sodium channel (ENaC) in exchange for potassium in the connecting tubule (CNT) and collecting duct (CD). Traditional potassium-sparing diuretics (amiloride, triamterene) directly block ENaC, and others block the mineralocorticoid receptor (MR [e.g., spironolactone, eplerenone]). Because a major action of the MR is to increase ENaC activity, MR antagonism acts indirectly by decreasing ENaC activity.

These diuretics may also have kidney-independent effects. ENaC is present in extra renal tissues such as the vascular endothelium, although the clinical effects of vascular ENaC are unclear. The MR is distributed throughout the body, and MR antagonists may contribute to cardiovascular protection via actions in the heart and vasculature.

2

Why is this class of diuretics called potassium-sparing diuretics?

Unlike diuretics that inhibit sodium transport in the proximal convoluted tubule, loop of Henle, or the distal convoluted tubule, potassium-sparing diuretics inhibit sodium reabsorption in the CNT and the CD. In the CNT and CD, sodium reabsorption occurs mainly via ENaC. As sodium is reabsorbed, the lumen becomes negative. The negative intraluminal voltage then favors potassium secretion from the cells of the CNT and CD to maintain electroneutrality ( Fig. 35.1 ). If sodium reabsorption in the CNT and CD is impaired, then potassium secretion is also impaired. Therefore diuretics that block the movement of sodium in the CNT and CD and decrease potassium secretion are called potassium-sparing diuretics .