Bumetanide and furosemide in heart failure

Abstract

We assessed the handling of and response to oral bumetanide (1.0 and 2.0 mg) and to furosemide (40 and 80 mg) in 20 patients with stable, compensated congestive heart failure (CHF), comparing the two drugs and, in addition, examining differences from normal subjects. Bumetanide and furosemide were similar in time course of absorption, but patients with CHF had considerably prolonged absorption compared to normal subjects causing attainment of lower peak concentrations of drug. In both CHF and normal subjects, more bumetanide than furosemide was absorbed. The elimination half-life of furosemide was approximately twice that of bumetanide, and both were about two times longer than respective values in normal subjects. "Dose"-response curves were shifted downward from normal with both drugs. In patients with CHF, overall response did not differ between bumetanide and furosemide. The two drugs exhibit subtle differences, the clinical importance of which appears to be negligible from this study. Importantly, however, both drugs showed delayed absorption causing attainment of peak urinary excretion rates of diuretic two- to threefold lower than in normal subjects. This effect along with the abnormal responsivity of the tubule may contribute to the "resistance" to oral doses of diuretics observed clinically even though no quantitative malabsorption of drug occurs.

Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

“…New hyponatremia was defined as a sodium level <135 mEq/L and new hypokalemia was defined as a serum potassium <3.5 mEq/L that developed during the course of the hospitalization (ie, patients with new electrolyte abnormalities who did not meet these criteria at admission). Loop diuretic doses were converted to intravenous furosemide equivalents with 1 mg bumetanide=20 mg torsemide=40 mg furosemide 16, 17. Peak diuretic dose was defined as the highest single intravenous (IV) dose of diuretic during the first 7 days of the hospitalization in IV furosemide equivalents.…”

The renin angiotensin aldosterone system and frusemide response in congestive heart failure.

“…Despite the proven efficacy of loop diuretics in patients with CHF, supranormal doses are typically required in order to achieve a natriuretic response [6][7][8][9]. The cause for resistance to these drugs is unknown.…”

“…The cause for resistance to these drugs is unknown. Prior studies have essentially excluded a pharmacokinetic cause [6][7][8][9]. Thus, some undefined pharmacodynamic abnormality is presumed culpable.…”

Mechanism and management of diuretic resistance in congestive heart failure

“…Some clinicians consider bumetanide to be more effective than furosemide in patients with CHF because of its better oral bioavailability. Both in normal subjects and in patients with CHF bumetanide has an 80% bioavailability compared to 40% for furosemide 12 . Although bumetanide is 40 times more potent than furosemide on a weight basis, both drugs are equally effective when equipotent doses are administered 13 .…”