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How Does Spironolactone Work?
Spironolactone competes with aldosterone to bind to the mineralocorticoid receptor (also known as the aldosterone receptor), which is expressed in the distal convoluted tubule cells of the kidney. The binding of spironolactone to the receptor inhibits aldosterone-dependent sodium–potassium exchange, leading to excretion of sodium and water and retention of potassium. Spironolactone is considered to be a weak diuretic and is usually administered with another drug that targets the proximal tubules in order to increase diuresis. In some patients, the use of spironolactone may cause hyperkalemia. Spironolactone is nonselective — it binds androgen and progesterone receptors, leading to off-target effects such as gynecomastia.