Generic Name

Bumetanide

Mechanism

• Inhibition of the Na⁺‑K⁺‑2Cl⁻ symporter in the thick ascending limb → ↓ Na⁺, K⁺, Cl⁻ reabsorption.
• Resulting osmotic water excretion produces a large diuretic response.
• Potent inhibitor compared to furosemide: ~10–20× higher potency at equivalent dosages, allowing a smaller oral dose for comparable effect.

Pharmacokinetics

• Absorption: Oral bioavailability 90–100 % (rapid absorption within 1 h).
• Distribution: High protein binding (~90 %); crosses the placenta; limited CNS entry.
• Metabolism: Minimal hepatic metabolism; mainly excreted unchanged by kidneys.
• Elimination: Renal clearance is the primary route; half‑life ≈1.5–2 h (oral); 4–5 h (IV).
• Kidney excretion: Requires functional glomerular filtration; accumulation in renal insufficiency.

Indications

• Edema associated with congestive heart failure, liver cirrhosis, nephrotic syndrome, or post‑operative states.
• Hypertension (adjuvant to other antihypertensives) in selected patients.
• Fluid overload in end‑stage renal disease (ESRD) when peritoneal dialysis is not available.

Contraindications

• Absolute contraindications: hypersensitivity to bumetanide or sulfonamide core; severe hyponatremia; severe renal failure (CrCl < 15 mL/min) unless dose‑adjusted and closely monitored.
• Caution: pregnancy (Category C), lactation, advanced liver disease, severe dehydration, and gout (risk of hyperuricemia).
• Warning: potential for ototoxicity (rare) when used with aminoglycosides or in patients with renal impairment.

Dosing

• Titration based on clinical response and monitoring parameters.
• Split doses (morning/afternoon) can reduce post‑dose orthostatic hypotension.

Adverse Effects

• Common: Hypotension, dizziness, dehydration, electrolyte disturbances (hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia), taste alterations, increased uric acid.
• Serious: Severe electrolyte depletion, ototoxicity (with aminoglycosides), rhabdomyolysis (rare), acute renal failure, allergic reactions, metabolic alkalosis, severe hyperglycemia in diabetics.

Monitoring

• Electrolytes: K⁺, Na⁺, Cl⁻, Mg²⁺, Ca²⁺ (baseline, 24 h, then every 48–72 h until stable).
• Renal function: BUN, creatinine, estimated CrCl (baseline, daily until steady, then periodic).
• Vital signs: BP, HR, orthostatic blood pressure.
• Fluid balance: Urine output (≥300 mL/h for ≥4 h), weight monitoring (daily).
• Metabolic panel: Glucose (for diabetic patients), lactate if clinically indicated.

Clinical Pearls

• Potency Advantage: 1 mg bumetanide ≈ 20–25 mg furosemide; use this when a small oral dose is desired for severe edema but avoid dose creep.
• Early Electrolyte Correction: Replace K⁺ and Mg²⁺ promptly when initiating therapy; consider potassium‑sparing diuretics or supplements to avoid hypokalemia‑induced arrhythmias.
• Renal Function Adjustments: In CKD or ESRD, start at the lowest dose (0.5 mg) and titrate slowly; monitor for accumulation because clearance declines with CrCl < 40 mL/min.
• Gout Considerations: Bumetanide can precipitate gout flare—screen serum uric acid and consider prophylactic allopurinol if needed.
• Ototoxicity Check: When co‑administered with aminoglycosides, monitor auditory function; limit bumetanide dose or consider alternative diuretic if high ototoxic risk.