ALDOSTERONE ANTAGONIST...
EXAMPLES: Spironolactone, eplerenone.
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).
Tags:
Pharmacology