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Clinical Experience With Intravenous Administration of Ethacrynic Acid FREE

George V. Irons, Jr., MD; Yi-Hong Kong, MD; William M. Ginn, Jr., MD; Edward S. Orgain, MD
[+] Author Affiliations

Reprint requests to Box 308, Duke University Medical Center, Durham, NC 27706 (Dr. Orgain).


From the Department of Medicine, Duke University School of Medicine, and the Cardiovascular Disease Service, Duke University Medical Center, Durham, NC.


JAMA. 1965;194(13):1348-1351. doi:10.1001/jama.1965.03090260008002
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The diuretic response to a single intravenous injection of ethacrynic acid was observed on 61 occasions in 31 edematous subjects. Maximal water, sodium, chloride, and potassium diuresis occurred within the first hour, and potassium diuresis continued into the following day. The average urine volume was 1,164 cc over the first three hours and 2,378 cc over 24 hours. Average urinary electrolyte losses for the first three hours were sodium, 114 mEq; chloride, 128 mEq; potassium, 25 mEq. For the subsequent 21 hours they were sodium, 49 mEq; chloride, 44 mEq; and potassium 43 mEq. No significant electrolyte alterations occurred after a single intravenous injection. An effective diuresis was achieved in spite of azotemia, hypochloremia, hyponatremia, and hypokalemia. The drug was particularly effective when administered to eight patients manifesting pulmonary edema on 12 occasions. No significant side effects were encountered.

REFERENCES

Schultz, E.M., et al:  α-β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids: A New Class of Diuretics , J Med Pharm Chem 5:660-662 ( (May) ) 1962;.
Baer, J.E., et al:  A New Class of Diuretic-Saluretic Agents: The α-β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids , Pharmacologist 4:158, 1962;.
Komorn, R.M., and Cafruny, E.J.:  Ethacrynic Acid: Diuretic Property Coupled to Reaction With Sulfhydryl Groups of Renal Cells , Science 143:133-134 ( (Jan 10) ) 1964;.
Sperber, R.J.; DeGraff, A.C.; and Lyon, A.F.:  Diuretic Therapy: Part IX. Ethacrynic Acid , Amer Heart J 69:281 ( (Feb) ) 1965;.
Gussin, R.Z., and Cafruny, E.J.:  Effect of Ethacrynic Acid on Uptake of Mercury by Renal Cortical Slices , Fed Proc 23:438 ( (March) -April) 1964;.
Maher, J.F., and Schreiner, G.E.:  Studies on Ethacrynic Acid in Patients With Refractory Edema , Ann Intern Med 62:15-29 ( (Jan) ) 1965;.
Cafruny, E.J.:  Diuretics in Clinical Practice , Postgrad Med 35:246-251 ( (March) ) 1964;.
Cannon, P.J.; Ames, R.P., and Laragh, J.H.:  Methylenebutyryl Phenoxyacetic Acid , JAMA 185:854-863 ( (Sept 14) ) 1963;.
Cannon, P.J., et al:  "Contraction" Alkalosis Following Diuresis Induced by Ethacrynic Acid in Edematous Subjects , Fed Proc 23:306 ( (March) -April) 1964;.
Daley, D., and Evans, B.:  Diuretic Action of Ethacrynic Acid in Congestive Heart Failure , Brit Med J 2:1169-1171 ( (Nov 9) ) 1963;.
Cannon, P.J., et al:  Ethacrynic Acid: Effectiveness and Mode of Diuretic Action in Man . Circulation 31:5-18 ( (Jan) ) 1965;.
Schroder, G.; Sannerstedt, R.; and Werko, L.:  Clinical Experiences With Ethacrynic Acid, A New Non-Thiazide Saluretic Agent (MK-595) , Acta Med Scand 175:781-786 ( (June) ) 1964;.
Fisher, M.:  Ethacrynic Acid in Diabetes With Edema , Clin Res 12:252 ( (April) ) 1964;.
Bernstein, A., et al:  Ethacrynic Acid: A New Potent Diuretic , Amer J Med Sci 249:551-560 ( (May) ) 1965;.
Melvin, K.E.W.; Farrelly, R.O.; and North, J.D.K.:  Ethacrynic Acid: A New Oral Diuretic , Brit Med J 1:1521-1524 ( (June 8) ) 1963;.
Hagedorn, C.W.; Kaplan, A.A.; and Hulet, W.H.:  Diuresis in Nephrotic Syndrome With Ethacrynic Acid , Clin Res 12:47 ( (Jan) ) 1964;.
Maher, J.F., et al:  Effect of Ethacrynic Acid on Refractory Edema , Clin Res 12:70 ( (Jan) ) 1964;.
Brest, A.N., et al:  MK-595: Diuretic Assay and Renal Functional Response , Circulation 28:694 ( (Oct) ) 1963;.
Sperber, R.J., et al:  Ethacrynic Acid in Pathological Fluid Retention , JAMA 191:703-706 ( (March 1) ) 1965;.
Ledingham, J.G.G.:  Ethacrynic Acid Parenterally in the Treatment and Prevention of Pulmonary Edema , Lancet 1:952-954 ( (May 2) ) 1964;.
Baer, J.E.:  Ethacrynic Acid: Excretion and Distribution in the Dog , Pharmacologist 5:267, 1963;.
Goldberg, M., et al:  Effects of Ethacrynic Acid on Renal Diluting and Concentrating Mechanisms: Evidence for Site of Action in the Loop of Henle , J Clin Invest 43:201-216 ( (Feb) ) 1964;.
Earley, L.E., and Friedler, R.M.:  Renal Tubular Effects of Ethacrynic Acid , J Clin Invest 43:1495-1506 ( (July) ) 1964;.
Baer, J.E., et al:  2,3-Dichloro-4-(2-Methylenebutyryl)-Phenoxyacetic Acid (1): A Novel and Potent Diuretic-Saluretic Agent , Fed Proc 22:598 ( (March) -April) 1963;.
Schwartz, W.B., et al:  Effects of Chronic Hypercapnia on Electrolyte and Acid-Base Equilibrium: II. Recovery, With Special Reference to Influence of Chloride Intake , J Clin Invest 40:1238-1249 ( (July) ) 1961;.
Atkins, E.L., and Schwartz, W.B.:  Factors Governing Correction of Alkalosis Associated With Potassium Deficiency: Critical Role of Chloride in Recovery Process , J Clin Invest 41:218-229 ( (Feb) ) 1962;.
Beyer, K.H., et al:  Renotropic Characteristics of Ethacrynic Acid: A Phenoxyacetic Saluretic-Diuretic Agent , J Pharmacol and Exper Ther 147:1-22 ( (Jan) ) 1965;.

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Schultz, E.M., et al:  α-β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids: A New Class of Diuretics , J Med Pharm Chem 5:660-662 ( (May) ) 1962;.
Baer, J.E., et al:  A New Class of Diuretic-Saluretic Agents: The α-β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids , Pharmacologist 4:158, 1962;.
Komorn, R.M., and Cafruny, E.J.:  Ethacrynic Acid: Diuretic Property Coupled to Reaction With Sulfhydryl Groups of Renal Cells , Science 143:133-134 ( (Jan 10) ) 1964;.
Sperber, R.J.; DeGraff, A.C.; and Lyon, A.F.:  Diuretic Therapy: Part IX. Ethacrynic Acid , Amer Heart J 69:281 ( (Feb) ) 1965;.
Gussin, R.Z., and Cafruny, E.J.:  Effect of Ethacrynic Acid on Uptake of Mercury by Renal Cortical Slices , Fed Proc 23:438 ( (March) -April) 1964;.
Maher, J.F., and Schreiner, G.E.:  Studies on Ethacrynic Acid in Patients With Refractory Edema , Ann Intern Med 62:15-29 ( (Jan) ) 1965;.
Cafruny, E.J.:  Diuretics in Clinical Practice , Postgrad Med 35:246-251 ( (March) ) 1964;.
Cannon, P.J.; Ames, R.P., and Laragh, J.H.:  Methylenebutyryl Phenoxyacetic Acid , JAMA 185:854-863 ( (Sept 14) ) 1963;.
Cannon, P.J., et al:  "Contraction" Alkalosis Following Diuresis Induced by Ethacrynic Acid in Edematous Subjects , Fed Proc 23:306 ( (March) -April) 1964;.
Daley, D., and Evans, B.:  Diuretic Action of Ethacrynic Acid in Congestive Heart Failure , Brit Med J 2:1169-1171 ( (Nov 9) ) 1963;.
Cannon, P.J., et al:  Ethacrynic Acid: Effectiveness and Mode of Diuretic Action in Man . Circulation 31:5-18 ( (Jan) ) 1965;.
Schroder, G.; Sannerstedt, R.; and Werko, L.:  Clinical Experiences With Ethacrynic Acid, A New Non-Thiazide Saluretic Agent (MK-595) , Acta Med Scand 175:781-786 ( (June) ) 1964;.
Fisher, M.:  Ethacrynic Acid in Diabetes With Edema , Clin Res 12:252 ( (April) ) 1964;.
Bernstein, A., et al:  Ethacrynic Acid: A New Potent Diuretic , Amer J Med Sci 249:551-560 ( (May) ) 1965;.
Melvin, K.E.W.; Farrelly, R.O.; and North, J.D.K.:  Ethacrynic Acid: A New Oral Diuretic , Brit Med J 1:1521-1524 ( (June 8) ) 1963;.
Hagedorn, C.W.; Kaplan, A.A.; and Hulet, W.H.:  Diuresis in Nephrotic Syndrome With Ethacrynic Acid , Clin Res 12:47 ( (Jan) ) 1964;.
Maher, J.F., et al:  Effect of Ethacrynic Acid on Refractory Edema , Clin Res 12:70 ( (Jan) ) 1964;.
Brest, A.N., et al:  MK-595: Diuretic Assay and Renal Functional Response , Circulation 28:694 ( (Oct) ) 1963;.
Sperber, R.J., et al:  Ethacrynic Acid in Pathological Fluid Retention , JAMA 191:703-706 ( (March 1) ) 1965;.
Ledingham, J.G.G.:  Ethacrynic Acid Parenterally in the Treatment and Prevention of Pulmonary Edema , Lancet 1:952-954 ( (May 2) ) 1964;.
Baer, J.E.:  Ethacrynic Acid: Excretion and Distribution in the Dog , Pharmacologist 5:267, 1963;.
Goldberg, M., et al:  Effects of Ethacrynic Acid on Renal Diluting and Concentrating Mechanisms: Evidence for Site of Action in the Loop of Henle , J Clin Invest 43:201-216 ( (Feb) ) 1964;.
Earley, L.E., and Friedler, R.M.:  Renal Tubular Effects of Ethacrynic Acid , J Clin Invest 43:1495-1506 ( (July) ) 1964;.
Baer, J.E., et al:  2,3-Dichloro-4-(2-Methylenebutyryl)-Phenoxyacetic Acid (1): A Novel and Potent Diuretic-Saluretic Agent , Fed Proc 22:598 ( (March) -April) 1963;.
Schwartz, W.B., et al:  Effects of Chronic Hypercapnia on Electrolyte and Acid-Base Equilibrium: II. Recovery, With Special Reference to Influence of Chloride Intake , J Clin Invest 40:1238-1249 ( (July) ) 1961;.
Atkins, E.L., and Schwartz, W.B.:  Factors Governing Correction of Alkalosis Associated With Potassium Deficiency: Critical Role of Chloride in Recovery Process , J Clin Invest 41:218-229 ( (Feb) ) 1962;.
Beyer, K.H., et al:  Renotropic Characteristics of Ethacrynic Acid: A Phenoxyacetic Saluretic-Diuretic Agent , J Pharmacol and Exper Ther 147:1-22 ( (Jan) ) 1965;.
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