Aldosterone receptor antagonists (ARAs), also known as mineralocorticoid receptor antagonists (MRAs), are a class of medications that block the effects of the hormone aldosterone. They are primarily used to manage conditions affecting the heart and blood vessels.
Understanding Aldosterone Receptor Antagonists
Aldosterone is a steroid hormone produced by the adrenal glands, located on top of the kidneys. It regulates the balance of salt (sodium) and water, impacting blood pressure and fluid volume. Aldosterone signals the kidneys to reabsorb sodium and water into the bloodstream, while increasing the excretion of potassium and hydrogen ions.
ARAs block aldosterone’s effects at mineralocorticoid receptors. This prevents sodium and water reabsorption in the kidneys, leading to increased excretion. This action reduces blood volume, decreasing blood pressure and fluid around the heart. ARAs also help the body retain potassium, counteracting aldosterone’s effect of increasing potassium excretion.
The two primary ARAs are Spironolactone and Eplerenone. Spironolactone is a non-selective antagonist, binding to mineralocorticoid, androgen, and progesterone receptors. Eplerenone is more selective, primarily binding to the mineralocorticoid receptor, which generally leads to fewer hormonal side effects.
Conditions Treated with Aldosterone Receptor Antagonists
In heart failure, ARAs are a standard therapy, especially for patients with reduced ejection fraction. Excess aldosterone can cause vascular stiffness, inflammation, and heart muscle enlargement. ARAs block these effects, reducing fluid buildup, improving heart function, decreasing hospitalizations, and prolonging life.
ARAs also manage high blood pressure, particularly when hypertension is difficult to control or when primary aldosteronism is suspected. They lower blood pressure by promoting the excretion of excess salt and water, reducing blood volume.
Primary aldosteronism is a condition where adrenal glands produce too much aldosterone, leading to high blood pressure and low potassium. ARAs are a cornerstone of treatment, countering elevated aldosterone.
ARAs also manage edema, or fluid retention, especially with severe liver disease like cirrhosis. In cirrhosis, fluid imbalances can cause significant fluid accumulation in the abdomen (ascites) and swelling. Spironolactone is a first-line treatment for ascites in cirrhotic patients.
Potential Side Effects and Important Considerations
The most common and serious side effect is hyperkalemia, or elevated potassium levels in the blood. Symptoms may include muscle weakness, fatigue, or an irregular heartbeat. Regular blood tests monitor potassium levels, typically within a week of starting treatment or adjusting the dose.
Kidney function also requires careful monitoring. ARAs can impact kidney function, and blood tests assess kidney health. A decline in kidney function may reduce potassium excretion, increasing hyperkalemia risk.
Specific side effects differ between Spironolactone and Eplerenone due to their selectivity. Spironolactone, being less selective, can cause hormonal side effects like gynecomastia (breast enlargement) in men, and menstrual irregularities or breast tenderness in women. These effects are often dose-dependent. Eplerenone, being more selective, generally has a lower incidence of these hormonal side effects.
Drug interactions are another important consideration. Combining ARAs with other medications that raise potassium levels, such as ACE inhibitors, ARBs, or NSAIDs, can further increase hyperkalemia risk.
Regular blood tests for potassium and kidney function are paramount to ensure safe use and identify issues early. Certain situations, such as pre-existing high potassium levels (typically above 5.0 mEq/L) or significant kidney impairment (e.g., a serum creatinine greater than 2.5 mg/dL for men or 2.0 mg/dL for women, or a glomerular filtration rate below 30 mL/min), may make these medications unsuitable.