Aldosterone antagonists

Competitive antagonist at intracellular aldosterone receptors in renal tubules causing reduced production of aldosterone-induced proteins....
Aldosterone antagonist...
  1. EXAMPLES: Spironolactone, eplerenone.
  2. MECHANISM OF ACTION: Competitive antagonist at intracellular aldosterone receptors in renal tubules causing reduced production of aldosterone-induced proteins.
    • This indirectly reduces activity of Na/K ATPase in the collecting ducts, increasing excretion of sodium and decreasing potassium loss.
    • Spironolactone, in particular, also acts on receptors in other tissues, including androgen receptors.
  • Congestive cardiac failure (spironolactone).
  • Oedema and ascites in liver disease (spironolactone).
  • Post-MI heart failure (eplerenone).
  • Nephrotic syndrome (spironolactone).
  • Primary hyperaldosteronism (including Conn’s syndrome) (spironolactone). 
  • Electrolyte disturbances (including hyperkalaemia and hyponatraemia).
  • Caution in renal impairment.
  • Hyperkalaemia (potassium sparing effect).
  • GI disturbance.
  • Anti-androgenic effects (spironolactone – menstrual irregularities in females, gynaecomastia and hypogonadism in males).
  • Metabolised to active metabolites. t½ of drug is 60–90 min but t½ of active metabolites is longer (up to 11 h).
  • Monitor plasma electrolytes for adverse effects as above.
  • Enhanced hypotensive effect with other antihypertensives.
  • Increased risk of hyperkalaemia with ACEIs/ARBs and amiloride.
  • Increased risk of nephrotoxicity with NSAIDs.
  • Eplerenone is more selective than spironolactone and therefore causes fewer sex hormonerelated adverse effects.
  • Spironolactone may also be used in hypertension (unlicensed indication).