Aldosterone antagonists

Also known as

• Mineralocorticoid antagonists
• MRAs, MRCAs

 

Key examples

• Spironolactone
• Eplerenone

 

Common indications

1. Ascites and oedema due to liver cirrhosis: spironolactone is the first-line diuretic.
2. Chronic heart failure: of at least moderate severity or arising within 1 month of a myocardial infarction, usually as an addition to a β-blocker and an ACE inhibitor/angiotensin receptor blocker.
3. Primary hyperaldosteronism: for patients awaiting surgery or for whom surgery is not an option.

 

Mechanisms of action

• Aldosterone is a mineralocorticoid that is produced in the adrenal cortex. It acts on mineralocorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial sodium channels (ENaC). This increases the reabsorption of sodium and water (which elevates blood pressure) with the by-product of increased potassium excretion.
• Aldosterone antagonists inhibit the effect of aldosterone by competitively binding to the aldosterone receptor. This increases sodium and water excretion and potassium retention. Their effect is greatest in primary hyperaldosteronism or when circulating aldosterone is increased, e.g. in cirrhosis.

 

Important adverse effects

• An important adverse effect of aldosterone antagonists is hyperkalaemia, which can lead to muscle weakness, arrhythmias and even cardiac arrest. 
• Spironolactone causes gynaecomastia, which can have a significant impact on patient adherence. 
• Aldosterone antagonists can cause liver impairment and jaundice and are a cause of Stevens–Johnson syndrome (a T cell-mediated hypersensitivity reaction) that causes a bullous skin eruption.

 

Warnings

• Aldosterone antagonists are contraindicated in patients with severe renal impairment, hyperkalaemia and Addison’s disease (who are aldosterone deficient). 
• Aldosterone antagonists can cross the placenta during pregnancy and appear in breast milk so should be avoided where possible in pregnant or lactating women.

 

Important interactions

• The combination of an aldosterone antagonist with other potassium-elevating drugs, including ACE inhibitors and angiotensin receptor blockers, increases the risk of hyperkalaemia. 
• Nevertheless, when supported by appropriate monitoring, this may be a beneficial combination in the context of heart failure. 
• Aldosterone antagonists should not be combined with potassium supplements except in specialist practice.