08/06/2023
Aldosterone antagonists
EXAMPLES
Spironolactone, eplerenone or take a SEAT.
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* ATase in the collecting ducts, increasing excretion of Na* and
decreasing K* loss. Spironolactone, in particular, also acts on receptors in other tissues, including androgen receptors.
INDICATIONS
• 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)
CAUTIONS AND CONTRA- INDICATIONS
• Electrolyte disturbances (including hyperkalaemia and hyponatraemia)
• Caution in renal impairment
SIDE-EFFECTS
• Hyperkalaemia (K* sparing effect)
• GI disturbance
• Anti-androgenic effects (spironolactone - menstrual irregularities in females,
gynaecomastia and hypogonadism in males)
METABOLISM AND HALF-LIFE
Metabolised to active metabolites. ty of drug is 60-90 min
but ty of active metabolites is longer (up to 11 h).
MONITORING
Monitor plasma electrolytes for adverse effects as above.
DRUG INTERACTIONS
• Enhanced hypotensive effect with other antihypertensives
• Increased risk of hyperkalaemia with ACEls/ARBs and amiloride
• Increased risk of nephrotoxicity with NSAIDs
IMPORTANT POINTS
• Eplerenone is more selective than spironolactone and therefore causes fewer s*x hormone-related adverse effects
• Spironolactone may also be used in hypertension (unlicensed indication)
