Aldosterone antagonists, such as spironolactone and eplerenone, are potassium-sparing diuretics that block aldosterone at the mineralocorticoid receptor in the distal nephron. By reducing sodium and water reabsorption while conserving potassium, they play a key role in heart failure, resistant hypertension, and primary hyperaldosteronism. Clinically, they improve mortality in heart failure with reduced ejection fraction, making them much more than just “add-on” diuretics.

From a safety standpoint, the biggest concerns with aldosterone antagonists are hyperkalemia and renal function decline. These risks increase in patients with chronic kidney disease or when combined with ACE inhibitors, ARBs, or potassium supplements. Spironolactone can also cause endocrine-related adverse effects such as gynecomastia and menstrual irregularities, which is why eplerenone may be preferred in some patients.

Direct-acting vasodilators, most notably hydralazine and minoxidil, lower blood pressure by relaxing arteriolar smooth muscle and reducing systemic vascular resistance. Hydralazine is commonly used in heart failure in combination with nitrates, particularly in select patient populations, while minoxidil is reserved for severe, refractory hypertension due to its potency.

Despite their effectiveness, direct-acting vasodilators come with important clinical trade-offs. Reflex tachycardia and fluid retention are common, so they are typically prescribed alongside a beta blocker and a diuretic. Hydralazine is associated with drug-induced lupus, while minoxidil can cause significant edema and hypertrichosis, making careful patient selection and monitoring essential.

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