Diuretics
| Class / Subclass / Drug (brand name) | Usual Dose Range, mg / day | Daily Frequency |
| Thiazides | ||
| Chlorthalidone (Hygroton) | 12.5-25 | 1 |
| Hydrochlorothiazide (Microzide) | 12.5-25 | 1 |
| Indapamide (Lozol) | 1.25-2.5 | 1 |
| Metolazone (Zaroxolyn) | 2.5-5 | 1 |
| Loops | ||
| Bumetanide (Bumex) | 0.5-4 | 2 |
| Furosemide (Lasix) | 20-80 | 2 |
| Torsemide (Demadex) | 5-10 | 1 |
| Potassium sparing | ||
| Amiloride (Midamor) | 5-10 | 1 or 2 |
| Amiloride / hydrochlorothiazide (Moduretic) | 5-10 / 50-100 | 1 |
| Triamterene (Dyrenium) | 50-100 | 1 or 2 |
| Triamterene / hydrochlorothiazide (Dyazide) | 37.5-75 / 25-50 | 1 |
| Aldosterone antagonists | ||
| Eplerenone (Inspra) | 50-100 | 1 or 2 |
| Spironolactone (Aldactone) | 25-50 | 1 or 2 |
| Spironolactone / hydrochlorothiazide (Aldactazide) | 25-50 / 25-50 | 1 |
Thiazides are the preferred type of diuretic for treating hypertension, and all are equally effective in lowering blood pressure.
Potassium-sparing diuretics are weak antihypertensives when used alone but provide an additive hypotensive effect when combined with thiazide or loop diuretics. Moreover, they counteract the potassium- and magnesium-losing properties and perhaps glucose intolerance caused by other diuretics.
Aldosterone antagonists (spironolactone, eplerenone) are also potassium-sparing diuretics but are more potent antihypertensives with a slow onset of action (up to 6 weeks with spironolactone).
Acutely, diuretics lower blood pressure by causing diuresis. The reduction in plasma volume and stroke volume associated with diuresis decreases cardiac output and, consequently, blood pressure. The initial drop in cardiac output causes a compensatory increase in peripheral vascular resistance. With chronic diuretic therapy, the extracellular fluid volume and plasma volume return almost to pretreatment levels, and peripheral vascular resistance falls below its pre-treatment baseline. The reduction in peripheral vascular resistance is responsible for the long-term hypotensive effects. Thiazides lower blood pressure by mobilizing sodium and water from arteriolar walls, which may contribute to decreased peripheral vascular resistance.
When diuretics are combined with other antihypertensive agents, an additive hypotensive effect is usually observed because of independent mechanisms of action. Furthermore, many nondiuretic antihypertensive agents induce salt and water retention, which is counteracted by concurrent diuretic use.
Side effects of thiazides include hypokalemia, hypomagnesemia, hypercal-cemia, hyperuricemia, hyperglycemia, hyperlipidemia, and sexual dysfunction. Loop diuretics have less effect on serum lipids and glucose, but hypocalcemia may occur.
Hypokalemia and hypomagnesemia may cause muscle fatigue or cramps. Serious cardiac arrhythmias may occur, especially in patients receiving digitalis therapy, patients with LV hypertrophy, and those with ischemic heart disease. Low-dose therapy (e.g., 25 mg hydrochlorothiazide or 12.5 mg chlorthalidone daily) rarely causes significant electrolyte disturbances.
Potassium-sparing diuretics may cause hyperkalemia, especially in patients with chronic kidney disease or diabetes, and in patients receiving concurrent treatment with an ACE (angiotensin-converting enzyme) inhibitor, ARB (angiotensin II receptor blocker), NSAID (non-steroidal anti-inflammatory drug), or potassium supplement.
Eplerenone has an increased risk for hyperkalemia and is contraindicated in patients with impaired renal function or type 2 diabetes with proteinuria.
Spironolactone may cause gynecomastia in up to 10% of patients, but this effect occurs rarely with eplerenone.
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