Bumetanide Mechanism of Action
Bumetanide inhibits sodium and chloride reabsorption in the thick ascending limb of the loop of Henle by blocking the Na+-K+-2Cl- cotransporter, producing potent natriuresis and diuresis. 1
Primary Site of Action
The major site of bumetanide action is the ascending limb of the loop of Henle, where it blocks sodium reabsorption as demonstrated by marked reduction of free-water clearance during hydration and tubular free-water reabsorption during hydropenia. 1
Bumetanide inhibits the Na+-K+-2Cl- cotransporter system that moves sodium, potassium, and chloride across cell membranes in the thick ascending loop of Henle. 2
The drug is somewhat more chloruretic than natriuretic, as reabsorption of chloride in the ascending limb is also blocked by bumetanide. 1
Secondary Site of Action
Bumetanide has an additional minor action in the proximal tubule, as evidenced by phosphaturia during bumetanide-induced diuresis (since phosphate reabsorption occurs largely in the proximal tubule). 1, 3
This proximal tubular activity is further supported by the reduction in renal clearance of bumetanide by probenecid, which is associated with diminished natriuretic response. 1
This proximal tubular effect does not appear related to carbonic anhydrase inhibition. 1
Electrolyte Effects
Potassium excretion is increased by bumetanide in a dose-related fashion, though bumetanide is less potent than furosemide regarding urinary potassium excretion effects. 1, 4
Bumetanide decreases uric acid excretion and increases serum uric acid levels. 1
The drug causes calciuria, phosphaturia, and minimal bicarbonaturia. 3
Pharmacological Potency
Bumetanide is approximately 40-50 times more potent than furosemide on a milligram-for-milligram basis, with 1 mg bumetanide having diuretic potency equivalent to approximately 40 mg furosemide. 1, 4, 5, 2
Of the loop diuretics available for clinical use, bumetanide is the most powerful, with in vitro transport inhibitory potency approximately 50-fold that of furosemide. 2
Clinical Pharmacodynamics
Diuresis starts within minutes following intravenous injection and reaches maximum levels within 15 to 30 minutes. 1
After oral administration, peak effects occur at approximately 30 minutes. 4, 3
The duration of action persists for 4 to 6 hours (or 3 to 6 hours per some sources). 6, 4
The drug produces increased fractional delivery of sodium chloride to the distal tubule and natriuresis approaching 20% of the filtered load of sodium. 3