This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by STASON, W. B. Articles by LARAGH, J. H. Search for Related Content PubMed PubMed Citation Articles by STASON, W. B. Articles by LARAGH, J. H.

(Circulation. 1966;34:910.)
© 1966 American Heart Association, Inc.

---

Furosemide

A Clinical Evaluation of Its Diuretic Action

WILLIAM B. STASON M.D.¹; PAUL J. CANNON M.D.¹; HENRY O. HEINEMANN M D.¹; JOHN H. LARAGH M.D..¹

¹ From the Department of Medicine, Columbia University, College of Physicians and Surgeons, the Presbyterian Hospital, and the Francis Delafield Hospital, New York, New York.

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_HH2O) during antidiuresis and to block urinary dilution (C_HH2O) 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.

This article has been cited by other articles:

				K. A Wargo and W. M Banta A Comprehensive Review of the Loop Diuretics: Should Furosemide Be First Line? Ann. Pharmacother., November 1, 2009; 43(11): 1836 - 1847. [Abstract] [Full Text] [PDF]

				R. Koob and K. Prasad Acute Effects of Furosemide on Blood Electrolytes and Hemodynamics in Dogs Angiology, June 1, 1978; 29(6): 463 - 472. [Abstract] [PDF]

				R. K. Fuller, P. B. Khambatta, and G. C. Gobezie An Optimal Diuretic Regimen for Cirrhotic Ascites: A Controlled Trial Evaluating Safety and Efficacy of Spironolactone and Furosemide JAMA, March 7, 1977; 237(10): 972 - 975. [Abstract] [PDF]

				H. RUBINOFF Diuretics in Hypertension Ann Intern Med, September 1, 1973; 79(3): 455 - 455. [Abstract] [PDF]

				K. H. Olesen Dynamic Aspects of Volume and Osmoregulation in Congestive Heart Failure During Furosemide Diuresis Angiology, January 1, 1970; 21(1): 35 - 48. [PDF]

				L. F. Gregory Jr., R. R. Durrett, R. R. Robinson, and J. R. Clapp The Short-Term Effect of Furosemide on Electrolyte and Water Excretion in Patients With Severe Renal Disease Arch Intern Med, January 1, 1970; 125(1): 69 - 74. [Abstract] [PDF]

				R. G. MUTH Diuretic Properties of Furosemide in Renal Disease Ann Intern Med, August 1, 1968; 69(2): 249 - 262. [Abstract] [PDF]

				J. H. LARAGH The Proper Use of Newer Diuretics Ann Intern Med, September 1, 1967; 67(3_Part_1): 606 - 613. [Abstract] [PDF]