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PHARMACOLOGICAL TREATMENT OF HEART FAILURE (HF) - page 9 / 48

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Bumetanide, furosemide, and torsemide act at the loop of Henle (thus, they are called loop diuretics), whereas thiazides, metolazone, and potassium-sparing agents (e.g., spironolactone) act in the distal portion of the tubule. These 2 classes of diuretics differ in their pharmacologic actions.

The loop diuretics increase sodium excretion up to 20% to 25% of the filtered load of sodium, enhance free water clearance, and maintain their efficacy unless renal function is severely impaired.

In contrast, the thiazide diuretics increase the fractional excretion of sodium to only 5% to 10% of the filtered load, tend to decrease free water clearance, and lose their effectiveness in patients with moderately impaired renal function (creatinine clearance less than 30 mL per min).

Consequently, the loop diuretics are the preferred diuretic agents for use in most patients with HF. However, thiazide diuretics may be preferred in hypertensive HF patients with mild fluid retention because they confer more persistent antihypertensive effects.

Effect of diuretics in the management of HF

Controlled trials have demonstrated the ability of diuretic drugs to increase urinary sodium excretion and decrease physical signs of fluid retention in patients with HF17. In these short-term studies, diuretic therapy has led to a reduction in jugular venous pressures, pulmonary congestion, peripheral edema, and body weight, all of which was observed within days of initiation of therapy.

In intermediate-term studies, diuretics have been shown to improve cardiac function, symptoms, and exercise tolerance in patients with HF18. There have been no long-term studies of diuretic therapy in HF, and thus, their effects on morbidity and mortality are not known. When using diuretics in patients with HF, physicians should keep in mind the following considerations:

1. Diuretics produce symptomatic benefits more rapidly than any other drug for HF. They can relieve pulmonary and peripheral edema within hours or days, whereas the clinical effects of digitalis, ACE inhibitors, or beta-blockers may require weeks or months to become apparent.

2. Diuretics are the only drugs used for the treatment of HF that can adequately control the fluid retention of HF. Although both digitalis and low doses of ACE inhibitors can

17 Patterson JH, Adams KF, Jr., Applefeld MM, Corder CN, Masse BR. Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion. Torsemide Investigators Group. Pharmacotherapy 1994;14:514-21.

18 Wilson JR, Reichek N, Dunkman WB, Goldberg S. Effect of diuresis on the performance of the failing left ventricle in man. Am J Med 1981;70:234-9.

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