They act at the level of the distal part of the nephron increasing the urinary elimination of sodium and reducing that of potassium which explains their name potassium-sparing diuretics.
One distinguishes two types of distal diuretics: aldosterone antagonists and those which have effects rather similar to those of antialdostérones but which act by different mechanisms.
Aldosterone induces the retention of sodium and the elimination of potassium ( See “Mineralocorticoid: Aldosterone and Antagonists”).
Aldosterone antagonists currently used are spironolactone (Aldactone*) and potassium canrenoate which acts after its conversion into canrenone. They have effects opposite to that of aldosterone, they increase the elimination of sodium and decrease that of potassium and magnesium whose plasma concentration tends to rise. They are hyperkalemic diuretics.
Aldosterone antagonists are without effect in a surrenalectomized animal or in a subject not secreting aldosterone. They could inhibit the transport of aldosterone in the cytosol of the epithelial cells of the nephron. They could also decrease aldosterone synthesis. Aldosterone antagonists have a slow and delayed effect.
They have a positive inotropic action in addition.
Because of their chemical steroidal structure aldosterone antagonists can give endocrine adverse effects, erectile dysfunction and gynecomastia in men, menstruation disorders and amenorrhea in women.
They are indicated for the treatment of primary hyperaldosteronism and edema secondary to cirrhosis, nephrotic syndrome or congestive heart failure and essential arterial hypertension.
Eplerenone (Inspra*) is a new anti-aldosterone whose properties are closely related to those of spironolactone.
Amiloride and triamterene
Amiloride is not an aldosterone antagonist, because its effects are preserved in the absence of aldosterone secretion. It induces, by a direct mechanism at the distal portion of the renal tubule, an increase in urinary excretion of sodium and decrease in magnesium and potassium excretion by inhibiting the exchange Na+/K+. Its mechanism of action is still poorly understood, it initially inhibits sodium reabsorption and secondarily potassium excretion.
Amiloride (Midamor*) is an hyperkalemic diuretic often used in combination with an hypokalemic thiazide diuretic to reduce the risk of hypokalemia.
It decreases the urinary calcium loss.
Amiloride was proposed in aerosol for the treatment of cystic fibrosis where an excessive sodium absorption and a defect of chloride secretion induce a dryness of the bronchial membranes.
The effects of triamterene (Dyrenium*) are quite similar to those of amiloride. Triamterene is released on the market in combination with a thiazide diuretic. It can give urinary calculuses.