A Comprehensive Review on Diuretics: Classification, Mechanisms, And Therapeutic Applications

Diuretics are a diverse class of agents that promote renal excretion of water and electrolytes, and they form a cornerstone of therapy for hypertension, heart failure and fluid overload states. This review summarizes renal physiology essential to diuretic action, and details each diuretic class: carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics, thiazide and thiazide-like diuretics, potassium‐sparing agents (aldosterone antagonists and ENaC inhibitors), vasopressin (V2) antagonists, and newer agents like SGLT2 inhibitors. We discuss mechanisms of action in relation to nephron segment and ion transport, with accompanying tables illustrating sites of action and pharmacologic effects. Clinical applications are covered – e.g. loop diuretics for acute pulmonary edema, thiazides for chronic hypertension, and spironolactone for resistant edema – as well as special situations (ICU fluid management, pregnancy, liver cirrhosis). Adverse effects (electrolyte disturbances, metabolic derangements, ototoxicity, gout, gynecomastia) and key drug interactions (e.g. thiazides with lithium, NSAIDs, ACE‐inhibitors) are reviewed. Recent trends are highlighted: SGLT2 inhibitors produce osmotic diuresis with cardio-renal benefit; vasopressin antagonists (e.g. tolvaptan) expand options for hyponatremia. Challenges such as diuretic resistance and unmet needs (e.g. diuretics that preserve renal function) are examined. Future perspectives include novel targets (WNK kinase inhibitors, design of metabolically neutral diuretics) and precision-medicine approaches. This synthesis integrates current guidelines and recent studies to provide clinicians with an up-to-date, mechanism-based understanding of diuretics (1–4).