Hyperaldosteronism

Question 1

Aldosterone antagonist (Spironolactone, epleronone)

Common indications

Answer 1

1. Ascites and oedema due to liver cirrhosis- spironolactone is the first-line diuretics
2. Chronic HF- of at least moderate severity or arising within 1 month of a MI, usually as an addition to BB and ACEI/ARB
3. Primary Hyperaldosteronism- For patients awaiting surgery or for whom surgery is not an option

Question 2

Aldosterone antagonist (Spironolactone, epleronone)

MOA

Answer 2

• 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

Question 3

Aldosterone antagonist (Spironolactone, epleronone)

Important adverse effects

Answer 3

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

Question 4

Aldosterone antagonist (Spironolactone, epleronone)

Warnings

Answer 4

• 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 pregnancy or lactating women

Question 5

Aldosterone antagonist (Spironolactone, epleronone)

Important interactions

Answer 5

• The combination of aldosterone antagonist with other potassium-elevating drugs, including ACEI and ARB, 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

Question 6

Aldosterone antagonist (Spironolactone, epleronone)

Administration and communication

Answer 6

• Spironolactone should generally be taken with food
• When starting treatment with spironolactone, particularly in high doses, it is particularly important to warn men about the possibility of growth and tenderness of tissue under the nipples and impotence
• Reassure them that such effects are benign and reversible, but acknowledge that they may be uncomfortable and embarrassing
• Ask patients to return if they have troublesome side effects, as these may respond to dose reduction
• Advise all patients that aldosterone antagonists can cause their potassium levels to rise and reinforce the importance of attending for blood tests

Question 7

Aldosterone antagonist (Spironolactone, epleronone)

Monitoring

Answer 7

• Efficacy should be monitored by patient report of symptoms and clinical findings, e.g. reduction in ascites, oedema and/or blood pressure
• Safety should be monitored by checking renal function and serum potassium concentration due to risk of renal impairment and hyperkalaemia