Pharmacology  ·  Cardiovascular

Loop Diuretics and Aldosterone Antagonists

Symptom control versus survival benefit — two diuretic classes with very different roles

• Loop diuretics block the sodium-potassium-2-chloride cotransporter in the thick ascending limb of the loop of Henle, producing rapid and substantial sodium and water loss — essential for relieving the congestion that causes dyspnea and edema, but they do not reduce mortality.
• Furosemide oral absorption is unreliable in decompensated heart failure because gut wall edema impairs drug uptake; intravenous administration bypasses this limitation, which is why IV furosemide is standard for hospitalized patients with significant fluid overload.
• Aldosterone antagonists block the mineralocorticoid receptor — their diuretic effect is mild, but they are one of the four survival pillars of guideline-directed medical therapy because aldosterone independently drives cardiac fibrosis and blocking this tissue-level effect reduces mortality.
• Spironolactone is the default aldosterone antagonist but also binds androgen and progesterone receptors, causing gynecomastia and breast tenderness; eplerenone is highly selective for the mineralocorticoid receptor and is substituted when these endocrine side effects occur.
• Loop diuretics lower potassium while RAAS blockers and aldosterone antagonists raise it — patients on all three classes together require regular potassium monitoring, and hypokalemia from loop diuretics increases arrhythmia risk.