Spironolactone is a specific antagonist of the mineralocorticoid receptor (MR) in the distal tubules and collecting ducts of the kidney. Binding to the mineralocorticoid receptor changes the conformation of the complex, rendering it unable to bind the mineralocorticoid receptor responsive element (MRE) on the DNA in the nucleus. Spironolactone thus counteracts the actions of aldosterone and has a natriuretic and potassium-sparing effect.
Hence, it is usually categorised as a potassium-sparing diuretics. Hyperkalaemia is the main adverse effect of spironolactone.
Because of its steroid structure, spironolactone can interfere with other steroids, causing symptoms like gynaecomastia, impotence, hirsutism, and menstrual disturbances. As with other potassium-sparing diuretics, GI complaints and CNS disturbances are also possible.
Spironolactone is often used in combination with other diuretics in the treatment of hypertension and oedema in heart failure. It is the drug of choice in the treatment of hyperaldosteronism and as a diuretic in liver cirrhosis.
Spironolactone is used in patients with hepatic disease for all the following EXCEPT:
What is true about potassium?
Extra info: Increased aldosterone secretion increases the tubular secretion of potassium, leading to hypokalaemia. Hyperkalaemia relaxes vascular smooth muscle and decreases cardiac contractility. This is why spironolactone is beneficial in CHF.