The potassium-sparing diuretics consist of the following 4 medications–only some of which (spironolactone & eplerenone in the list below) are structurally similar.
Spironolactone is an antagonist of the aldosterone receptor, which like other steroid receptors is an intracellular receptor. The binding of spironolactone to the aldosterone receptor within collecting duct cells decreases the activity of apical ENac, thereby preventing Na reabsorption and K excretion. Although spironolactone on its own has a weak diuretic effect, when used in combination with other diuretics may be clinically useful in reducing edema. It also has well-documented beneficial effects in patients with congestive heart failure (see the 1999 RALES trial for details). Aside from having the obvious side effect of hyperkalemia, spironolactone also has anti-androgen activity based on its interaction with the androgen receptor, which prevents binding of dihydrotestosterone. Thus spironolactone is associated with the often unpleasant side effects of gynecomastia, decreased libido, testicular atrophy, and menstrual irregularities.
The drug eplerenone is structurally related to spironolactone, but has greater specificity for the aldosterone receptor (as opposed to the androgen receptor), thus allowing for its use as an effective K-sparing diuretic without the sex hormone side effects.
Both amiloride and triamterine work by direct inhibition of ENac.