The Sound of Evolution
Spironolactone
Mechanism of action:
Spironolactone is an aldosterone antagonist (aldosterone antagonist) and also a potassium-sparing diuretic (potassium-sparing diuretic). Spironolactone competitively blocks mineralocorticoid receptors in principal cells of the renal distal convoluted tubule and collecting duct, preventing aldosterone from increasing the gene expression of epithelial sodium channels (ENaC) and the Na+/K+-ATPase. This leads to decreased sodium and water reabsorption and reduced potassium and hydrogen ion excretion.
Reference(s):
1. Takamura N et al. (1997). Interactions of aldosterone antagonist diuretics with human serum proteins. Pharm Res.
2. LaCagnin LB et al. (1987). Conversion of spironolactone to 7 alpha-thiomethylspironolactone by hepatic and renal microsomes. Biochem Pharmacol.
3. Los LE et al. (1994). Hepatic metabolism of spironolactone. Production of 3-hydroxy-thiomethyl metabolites. Drug Metab Dispos.