Loop Diuretics: Bumetanide
Indication
Bumetanide is commonly used in the management of edema secondary to congestive heart failure and hepatic or renal disease. It may also be used in the treatment of hypertensive patients.
Mechanism of Action
Bumetanide is a loop diuretic that is 40 times more potent than furosemide.4 Bumetanide functions through inhibition of reabsorption of sodium and chloride from the ascending loop of Henle. It interferes with the chloride-binding cotransport system (Na+-K+-2C1~ symporter) and halts salt transport in this segment. This action causes increased excretion of water, sodium, chloride, and potassium. The drug also inhibits calcium and magnesium reabsorption in the ascending limb by eliminating the transepithelial potential difference.
Dosing
Neonates:
Oral, I.M., I. V: 0.01 to 0.05 mg/kg/dose every 24 to 48 hours
Infants and children:
Oral, I.M., I.V.: 0.015 to 0.1 mg/kg/dose every 6 to 24 hours (maximum, 10 mg/day)
Continuous I.V. infusion: the total daily I.V. intermittent dose can be administered as a continuous infusion over 24 hours (5-50 µg/kg/h)
Adults:
Oral: 0.5 to 2mg/dose (maximum, 10 mg/day) once or twice daily
I.M., I.V.: 0.5 to 1 mg/dose (maximum, 10 mg/day)
Continuous I.V. infusion: 0.9 to 1 mg/hr
Pharmacokinetics
Bumetanide has an onset of action for oral or I.M. administration within 30 to 60 minutes after the initial dose and within a few minutes after the I.V. injection. The duration of action after a usual dose of the drug is 4 to 6 hours.
Bumetanide is almost completely absorbed from the gastrointestinal tract, with protein binding at 95%. The drug undergoes partial hepatic metabolism, with the majority of the drug eliminated as the parent molecule or as a metabolite in the urine. The half-life of bumetanide is 1 to 1.5 hours in adults and 2.5 hours in infants younger than 6 months of age.
Monitoring parameters: serum electrolytes, renal function, blood pressure Contraindications: anuria or increasing azotemia
Warnings/Adverse Effects
Warning: loop diuretics are potent agents. Excess amounts may lead to profound diuresis with fluid and electrolyte loss. Close medical supervision and dose evaluation is required. The injectable formulation of this drug contains benzyl alcohol and large amounts (>99mg/kg/d) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates. This syndrome consists of metabolic acidosis, respiratory distress, gasping respirations, central nervous system dysfunction, hypotension, and cardiovascular collapse. In vitro animal studies have shown that benzoate, a metabolite of benzyl alcohol, displaces bilirubin from protein binding sites. Avoid or use injection cautiously in neonates. In vitro studies using pooled sera from critically ill neonates have also shown bumetanide to be a potent displacer of bilirubin. Avoid use in neonates at risk for kernicterus. There is an increased risk of ototoxicity with rapid I.V. administration, renal impairment, excessive doses, and concurrent use with other ototoxins. Use with caution in patients with previous hypersensitivity reactions to sulfonamides or thiazides.
Adverse effects that may occur with bumetanide use include hypotension, chest pain, dizziness, headache, encephalopathy, vertigo, and potential rashes. Other effects may include urticaria, hypokalemia, nausea, pancreatitis, photosensitivity, diarrhea, dehydration, and decreased uric acid excretion. Hyponatremia, hypochloremia, arthritic pain, metabolic alkalosis, hypercalciuria, agranulocytosis, thrombocytopenia, hyperuricemia, and cramps have also been reported.
Drug-Drug Interactions
Hypotension may occur when bumetanide is used with other antihypertensive medications and angiotensin-converting enzyme (angiotensin-converting enzyme) inhibitors. NSAIDs decrease the effect of bumetanide. There is increased ototoxicity when bumetanide is used with aminoglycosides and ethacrynic acid; and drugs affected by potassium depletion, such as digoxin. With bumetanide administration, there is decreased glucose tolerance with antidiabetic agents; and decreased lithium excretion.
Poisoning Information
Symptoms of bumetanide overdose may include acute and profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume, and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting, and cramps. Decontamination using activated charcoal is recommended and other treatment is supportive and symptomatic. Replacement of fluid and electrolyte losses may be necessary.
Compatible Diluents/Administration
Administer undiluted by direct I.V. injection over 1 to 2 minutes; maybe diluted in D5W or normal saline and infused over 5 minutes; dilute in D5W to 0.024 mg/mL for continuous infusion.
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