Use of diuretics in Hypertension
Diuretics were the first drug class to show benefits in patients with hypertension, although they were usually used in combination with other agents, even in the early trials.
They primarily work by reducing extracellular sodium and volume, although some also have vasodilatory properties, perhaps at the calcium channel. Thiazide and thiazide-like diuretics act primarily in the distal convoluted tubule and are the most widely used, particularly in patients with normal renal function.
Today, diuretic doses are much lower than those used in early clinical trials. The lower doses reduce the incidence and severity of adverse effects, particularly hypokalemia, which is blamed for some of the long-term metabolic effects (diabetes, increased cholesterol) of thiazides. The BP-lowering effects of diuretics can be overcome with dietary or other sources of sodium and with the use of nonsteroidal antiinflammatory drugs (NSAIDs). Most authorities agree that chlorthalidone is both more potent in lowering BP and has a longer duration of action than HCTZ.
Diuretics that act primarily in the thick ascending limb of the loop of Henle, “loop diuretics,” are usually required for patients with Stage 4 and higher CKD. They are also often used for patients with heart failure. If short-acting furosemide or bumetanide is given once daily, fluid accumulation can occur during the 12 to 18 hours before the next dose, particularly if the evening meal contains most of the day’s dietary sodium. Most loop and thiazide diuretics are sulfonamides, so they are contraindicated in patients with true sulfa allergies. Oral ethacrynic acid is a sulfur-free loop diuretic.
The two mineralocorticoid receptor blockers, spironolactone and eplerenone, have largely been used in patients with heart failure or primary aldosteronism. However, the recent PATHWAY-2 randomized, crossover trial provided evidence that spironolactone is an effective add-on therapy for treatment-resistant hypertension across a spectrum of plasma aldosterone concentrations. An important safety consideration in the use of spironolactone is the risk of potentially fatal hyperkalemia; monitoring of serum potassium is essential.
