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Aldosterone antag: Side effects

An aldosterone antagonist is any of a number of diuretic drugs that antagonizes the effects of aldosterone at mineralocorticoid receptors. Examples include drugs such as spironolactone, epleronone, canrenone and finerenone.

Aldosterone activates mineralocorticoid receptors within the principal cells of the distal convoluted tubule and collecting duct of the nephron. This results in the upregulation and activation of N+/K+ pumps that function to pump three sodium ions out of the cell and into the interstitial fluid at the expense of two K+ ions which go the opposite way. Upregulation of the Na+/K+ pump results in a concentration gradient that ultimately gives rise to increased resorption of sodium ions (and water) from the tubule into the blood and the secretion of K+ ions into the urine.

The Randomized Aldactone Evaluation Study (RALES) and Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) established that spironolactone and eplerenone, respectively, increased survival in patients with severe CHF symptoms from LV systolic dysfunction occurring with minimal exertion or at rest (NYHA class III or IV) or CHF after an acute MI [1].

However, these drugs do not come without side effects. The major side effect of spironolactone, the most popular member of its class, include hyperkalemia, which when severe can result in cardiac myocyte membrane destabilization and arrhythmias (recommendation is to ensure patients have a baseline serum K+ < 5mEq/L before starting the drug). Hyperkalemia in patients treated with aldosterone antagonists has been shown to have an incidence of 10% in the community[2].

Spironolactone is structurally similar to progesterone and as such, patients who take this drug may suffer from sex-steroid receptor cross-reactivity, namely anti-progesterone and anti-androgen effects. These manifest as breast tenderness and gynecomastia for men. Spironolactone may also lower testosterone levels and its use is associated with sexual dysfunction and menstrual irregularities [3].