Abstract

Furosemide and ethacrynic acid are the most efficacious diuretics currently available. Even though the chemical structures of these compounds are dissimilar, their pharmacological actions are nearly indistinguishable. While the clinical literature suggests that there is a pharmacological difference between furosemide and ethacrynic acid, this finding has not been demonstrated in animals. In man both drugs produce chloriuresis and plasma volume reduction and both may produce metabolic alkalosis. However, the ability of furosemide to inhibit carbonic anhydrase and increase bicarbonate excretion may make it less likely to produce metabolic alkalosis. In order to demonstrate the pharmacological differences between the two drugs in dogs, the effects of equinatriuretic doses of furosemide and ethacrynic acid on the excretion of bicarbonate, chloride and potassium, on osmolality and on pH were determined. Plasma volume in anesthetized animals was maintained constant by varying the infusion rate of a balanced Tyrode's solution in normal animals and during alkalosis and acidosis. When sodium excretion increased from 1 to 40% of the filtered load, no quantitative differences between the effects of the two diuretics were seen on the excretion of chloride or potassium or on pH. In normal animals. when sodium excretion exceeded 30% of the filtered load, the effect of furosemide on bicarbonate excretion exceeded that of ethacrynic acid. During respiratory alkalosis, the effect of furosemide on bicarbonate excretion was greatly magnified. At 10% of filtered sodium excreted, the effect of furosemide on bicarbonate excretion was significantly greater than that produced by ethacrynic acid and the difference increased with increasing sodium excretion. There was no significant difference in the effect of the drugs in respiratory acidosis or metabolic alkalosis. The significantly greater effect of furosemide on bicarbonate excretion in normal animals and in respiratory alkalosis may help explain the clinical observation that furosemide has a lesser propensity to produce alkalosis than does ethacrynic acid. Furthermore, the data predict that ethacrynic acid would more markedly augment predisposing alkalosis than would furosemide.