Furosemide

Abstract

The physiological effects of furosemide, a new diuretic agent chemically related to thiazide diuretics, have been evaluated in seven normal subjects and in 39 patients with edema of varied origin. The compound exhibited an unusually broad dose-response curve so that increasing diuresis could be induced with oral doses of from 40 mg once daily to 600 mg three times daily. At the higher dosages furosemide was significantly more effective than conventional thiazide diuretics and exhibited an order of potency which can be achieved with ethacrynic acid. In many of its diuretic properties furosemide resembled thiazide agents. The natriuresis and diuresis which it produced was associated with a disproportionate loss of chloride and potassium and the consequent production of degrees of hypokalemic alkalosis. However, physiological studies indicate that furosemide is qualitatively and quantitatively more similar to ethacrynic acid than to thiazide agents. Thus, furosemide, like ethacrynic acid and unlike thiazide diuretics acted to interfere with both urinary concentration (T c H H2 O ) during antidiuresis and to block urinary dilution (C H H2 O ) during water diuresis. It also caused a negative urinary hydrogen balance during diuresis. The data suggest that furosemide acts to block sodium chloride reabsorption in the ascending limb of Henle's loop and in more cortical distal diluting segments. The magnitude of its effects suggests that it also may interfere with proximal sodium chloride reabsorption. Ion exchange sodium reabsorptive mechanisms appear unaffected and become overactive during drug administration thereby accounting for the observed increases in potassium and hydrogen ion excretions. Because of its properties furosemide was especially useful intravenously as an adjunct in the treatment of acute pulmonary edema and for oral maintenance therapy in the treatment of difficult or refractory edematous patients, many of whom exhibit associated electrolyte derangements or azotemias. In these difficult situations, for maximum diuresis and to avoid problems associated with K + , H + and Cl - depletion, intermittent therapy added to a maintenance schedule which utilizes aldosterone antagonists or chloride and potassium supplements appears advisable. Furosemide, also like ethacrynic acid, was capable of adding to the natriuretic action of all other types of diuretic agents. This observation provides additional evidence for the existence of a number of different tubular transport processes located at different sites in the nephron which can participate in sodium conservation.