Mechanism of Action

Both agents appear to affect Na+ reabsorption in the cortical collecting duct. A site in the connecting tubule also may be involved. Although amiloride has been more extensively studied than triamterene, both diuretics specifically block the apical membrane epithelial Na+ channel (ENaC) (Fig. 21-5).The reduced rate of Na+ reabsorption diminishes the gradient that facilitates K+ secretion. K+ secretion by the collecting duct principal cells is a passive phenomenon that depends on and is secondary to the active reabsorption of Na+.

In addition to their effects on distal Na+ and K+ transport, all of the K+-sparing diuretics inhibit urinary H+ secretion by the late distal tubule and cortical collecting duct. The mechanism of this inhibitory action is not totally clear.

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