Furosemide | Pharmacology Mentor

Generic Name

Furosemide

Mechanism

Inhibition of the Na⁺‑K⁺‑2Cl⁻ cotransporter (NKCC2) in the thick ascending limb reduces sodium, potassium, and chloride reabsorption.
The resulting increase in lumen‐side Na⁺ and Cl⁻ stimulates downstream water reabsorption via aquaporins, generating a marked diuretic effect.
Decreases interstitial fluid concentration → osmotic diuresis.
Decreases the glomerular filtration rate (GFR) through afferent arteriole vasoconstriction, which may lessen the rate of renal clearance of the drug.

Pharmacokinetics

Parameter	Typical value for oral/fixed‑dose	Clinical notes
Absorption	Oral bioavailability ≈ 30–70 %; peaks in 1–2 h	Poorer absorption in the presence of food or GI stasis
Distribution	Volume of distribution ~2 L/kg; ~30 % plasma protein bound	Central compartment rapidly equilibrates with loop tissue
Metabolism	Minimal hepatic metabolism	Excreted largely unchanged
Excretion	Renal elimination (≈ 80 %) via glomerular filtration and tubular secretion	Dose adjustments required in CKD; dose ~1/3 in ESRD

• Half‑life: 1–2 h (oral), 3–5 h (IV).
• Peak efficacy: 2–3 h post‑dose for oral; 30 min for IV.

Indications

Acute and chronic edema associated with:
Congestive heart failure
Hepatomegaly/cirrhosis
Nephrotic syndrome
Hypertension as monotherapy or combination therapy
Preoperative volume depletion prior to peritoneal dialysis
Acute tubular necrosis – diuretic therapy as rescue

Contraindications

Absolute contraindications:
Anuria or severe oliguria
Hypersensitivity to sulfonamides (contains sulfa moiety)
Relative contraindications:
Severe electrolyte/osmolality imbalance (hypo/hyperkalemia, hyponatremia)
Uncontrolled hypertension (may worsen)
Severe hepatic or renal dysfunction (dose adjustment needed)
Warnings:
Ototoxicity: especially at high IV doses, in renal insufficiency, or with concurrent aminoglycosides
Electrolyte disturbances: hypokalemia, hyponatremia, hypomagnesemia
Volume depletion can precipitate hypotension and renal injury

Dosing

Setting	Dose	Frequency	Notes
Acute IV	10–20 mg	30‑60 min IV push or infusion	Repeat to achieve desired diuresis
Acute IV (renal failure)	5–10 mg	30‑60 min	Avoid high single doses
Oral, acute	20–40 mg PO	Q6‑Q8h as needed	Use “split” dosing for higher total
Oral chronic	10–80 mg QD	TID or BID for high‑dose regimens	Start low, titrate to effect
Peritoneal dialysis pre‑dialysis	5–10 mg IV	1 h before dialysis	Prevents fluid accumulation

• Potassium supplementation often required to counteract hypokalemia.
• Avoid rapid IV administration; slow infusion to reduce ototoxicity risk.

Monitoring

Baseline: electrolytes (Na⁺, K⁺, Cl⁻, Mg²⁺, Ca²⁺), BUN/Cr, serum osmolality, blood pressure, hearing status (if high‑dose or IV).
Follow‑up:
Every 6–12 h in acute setting until diuresis stabilizes
Daily in chronic therapy: electrolytes, BUN/Cr, weight, office BP
Annual audiometry if prolonged high‑dose therapy

Clinical Pearls

“Potassium‑sparking”: Even small dose escalation can precipitate hypokalemia – routinely supplement or co‑prescribe potassium chloride or metolazone for long‑term diuresis.
Split dosing versus single dose: The total daily dose is often more important than the loading dose; splitting (Q12h) can improve tolerability while maintaining euvolemia.
Avoid concomitant NSAIDs when possible; they blunt renal perfusion and the diuretic response.
High‑dose IV safety: Administer at ≤0.5 mg/kg over 15–30 min to reduce auditory damage; avoid >1 mg/kg in rapid push.
Use with caution in pregnancy: Furosemide crosses the placenta and may reduce fetal renal perfusion; if needed, use the minimal effective dose and monitor fetal growth.
Non‑renal diuretics: Combine furosemide with a thiazide (e.g., hydrochlorothiazide) for "sequential nephron blockade" in refractory edema.
Dialysis timing: A small IV dose (5–10 mg) 1 h before peritoneal dialysis improves fluid removal and reduces ultrafiltration failure.

Reference: Clinical pharmacology literature and UpToDate® summaries on loop diuretics.