Furosemide

Furosemide is a widely used loop diuretic that acts primarily on the ascending limb of the loop of Henle in the nephron to promote the excretion of water, sodium, and chloride. It is a powerful diuretic commonly used in the treatment of edema associated with heart failure, liver cirrhosis, and kidney disease, as well as for managing hypertension, especially in patients with renal impairment or volume overload.

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Pharmacological Classification

• Therapeutic class: Diuretic, Antihypertensive

• Pharmacologic class: Loop diuretic

• ATC code: C03CA01

• Common brand names: Lasix (international), Frumex, Frusemide (UK/Australia)

• Formulations available: Oral tablets (20 mg, 40 mg, 80 mg), oral solution, injectable solution (10 mg/mL)

• Legal status: Prescription only (Rx)

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Mechanism of Action

Furosemide selectively inhibits the Na⁺-K⁺-2Cl⁻ symporter in the thick ascending limb of the loop of Henle, blocking the reabsorption of:

• Sodium (Na⁺)

• Chloride (Cl⁻)

• Potassium (K⁺)

This inhibition leads to:

• A significant natriuretic effect (loss of sodium and water)

• Increased diuresis (urine output)

• Reduced plasma volume

• Decreased preload and afterload

• Transient vasodilation

The net result is volume depletion, which helps reduce edema and lower blood pressure. Furosemide also increases calcium and magnesium excretion, contributing to its distinctive side effect profile compared to thiazide diuretics.

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Indications

1. Edema

• Due to congestive heart failure (CHF)

• Hepatic cirrhosis

• Renal disease, including nephrotic syndrome

• Pulmonary edema

2. Hypertension

• Particularly effective in chronic kidney disease (CKD)

• Used when thiazides are ineffective (e.g., GFR <30 mL/min/1.73 m²)

3. Hypercalcemia

• Promotes urinary calcium excretion; often used alongside isotonic saline

4. Forced Diuresis

• In cases of drug overdose or poisoning to enhance elimination

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Dosage and Administration

Oral Dose (Adults)

• Edema:

  • Initial: 20–40 mg once daily or divided twice daily

  • Titration: May be increased by 20–40 mg every 6–8 hours if needed

  • Maintenance: Commonly 40–120 mg/day in divided doses

• Hypertension:

  • Typical dose: 40 mg twice daily

  • Less commonly used first-line

Intravenous/Intramuscular Dose

• IV bolus: 20–40 mg slow injection

• May repeat every 1–2 hours, or use continuous infusion in acute settings (e.g., pulmonary edema)

Pediatric Dose

• Oral/IV: 1–2 mg/kg/dose every 6–12 hours; max 6 mg/kg/day

Special Considerations

• Always use the lowest effective dose to minimize electrolyte disturbances

• Avoid late dosing (after 4 PM) to reduce nocturia

• IV dose is approximately equivalent to oral, though bioavailability varies (50–70%)

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Pharmacokinetics

• Onset:

  • Oral: 30–60 minutes

  • IV: 5 minutes

• Duration:

  • Oral: ~6–8 hours

  • IV: ~2 hours

• Half-life: 1–2 hours (prolonged in renal failure)

• Bioavailability: 50–70% (high interindividual variability)

• Protein binding: ~95%

• Elimination: Primarily via kidneys (unchanged drug)

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Contraindications

• Hypersensitivity to furosemide or sulfonamides (rare cross-reactivity)

• Anuria (no urine output)

• Severe electrolyte depletion (especially hypokalemia, hyponatremia)

• Hepatic coma or pre-coma

• Volume depletion or dehydration

• Breastfeeding (excreted in milk and may inhibit lactation)

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Warnings and Precautions

Electrolyte Imbalances

• Hypokalemia, hyponatremia, hypocalcemia, and hypomagnesemia are common

• Can trigger arrhythmias, especially in patients on digoxin

• Monitor serum electrolytes regularly

Ototoxicity

• High doses or rapid IV infusion can cause hearing loss, sometimes irreversible

• Risk increased when combined with aminoglycosides

Volume Depletion

• Risk of hypotension, dizziness, prerenal azotemia, especially in elderly

Hyperuricemia

• May precipitate gout attacks

Hyperglycemia

• Can impair glucose tolerance; caution in diabetics

Photosensitivity

• Advise on sun protection

Sulfa Allergy

• Rare but possible cross-reaction in sulfonamide-sensitive individuals

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Adverse Effects

Common

• Increased urination (polyuria)

• Hypotension

• Dizziness

• Hypokalemia

• Dehydration

• Muscle cramps

Less Common

• Hyponatremia

• Hypomagnesemia

• Hypocalcemia

• Gout attacks

• Tinnitus

• Rash

Rare/Serious

• Ototoxicity (especially IV)

• Stevens-Johnson Syndrome (SJS)

• Blood dyscrasias (thrombocytopenia, agranulocytosis)

• Pancreatitis

• Interstitial nephritis

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Drug Interactions

Increased Nephrotoxicity/Ototoxicity

• Aminoglycosides (e.g., gentamicin)

• Cisplatin

Hypokalemia-Potentiated Toxicity

• Digoxin (↑ risk of arrhythmias)

• Antiarrhythmics (e.g., amiodarone, sotalol)

• Lithium (↓ renal clearance; toxicity risk ↑)

Antihypertensives

• Additive hypotensive effect with:

  • ACE inhibitors

  • Beta-blockers

  • Calcium channel blockers

  • Nitrates

NSAIDs

• May blunt diuretic and antihypertensive effect

• Can impair renal function when combined

SGLT2 Inhibitors

• Additive volume loss; monitor for dehydration and hypotension

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Monitoring Parameters

• Electrolytes: Na⁺, K⁺, Mg²⁺, Ca²⁺

• Renal function: BUN, creatinine, eGFR

• Volume status: BP, daily weights, intake/output

• Hearing (if on high-dose IV)

• Serum uric acid

• Blood glucose in diabetics

• Signs of dehydration or hypotension

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Use in Special Populations

Elderly

• Increased sensitivity; start at lower doses

• Monitor closely for orthostatic hypotension, falls

Pregnancy

• Use only if essential; may impair placental perfusion

• Category C (US); caution due to potential fetal toxicity

Lactation

• Contraindicated; may suppress lactation and is excreted in milk

Pediatrics

• Dosing based on weight; monitor for fluid/electrolyte shifts

Renal Impairment

• Effective even in low GFR

• Dose may need to be increased in renal failure due to decreased delivery to site of action

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Clinical Considerations

• Furosemide is particularly useful in acute pulmonary edema for its rapid IV action

• In chronic heart failure, furosemide improves symptoms (dyspnea, edema), but does not improve survival

• Used in combination with potassium-sparing diuretics (e.g., spironolactone) to reduce hypokalemia

• For resistant edema, IV infusion may be preferred over bolus

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Comparison with Other Diuretics

• Thiazide diuretics (e.g., hydrochlorothiazide, bendroflumethiazide):

  • Less potent, not effective when GFR <30 mL/min

  • More suitable for hypertension

• Spironolactone:

  • Potassium-sparing; beneficial in heart failure with reduced ejection fraction

  • Slower onset

• Torasemide:

  • Another loop diuretic; longer duration, more predictable absorption

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Patient Counseling Points

• Take early in the day to avoid nighttime urination

• Monitor weight daily; report >2 kg increase in 3 days

• Report symptoms of dehydration: dry mouth, dizziness, muscle cramps

• Eat potassium-rich foods unless otherwise instructed

• Avoid NSAIDs unless prescribed

• Do not stop suddenly without consulting your provider