Diuretics in the treatment of hypertension. Part 2: loop diuretics and potassium-sparing agents.

INTRODUCTION: Diuretics enhance the renal excretion of Na(+) and water due to a direct action at different tubular sites of the nephron where solute re-absorption occurs. AREAS COVERED: This paper focuses on the mechanism of action, pharmacodynamics, antihypertensive effects, adverse effects, interactions and contraindications of loop diuretics and potassium-sparing agents (including mineralocorticoid receptor antagonists (MRAs) and epithelial Na(+) channel blockers). EXPERT OPINION: Loop diuretics are less effective than thiazide diuretics in lowering blood pressure, so that their major use is in edematous patients with congestive heart failure (HF), cirrhosis with ascites and nephritic edema. MRAs represent a major advance in the treatment of resistant hypertension, primary and secondary hyperaldosteronism and in patients with systolic HF to reduce the risks of hospitalization and of premature death. Potassium-sparing diuretics when coadministered with diuretics (thiazides and loop diuretics) working at more proximal nephron locations reduce the risk of hypokalemia and hypomagnesemia and the risk of cardiac arrhythmias. At the end of the article, the basis for the combination of diuretics with other antihypertensive drugs to achieve blood pressure targets is presented.