Furosemide - Drug Monograph

Introduction

Furosemide is a potent loop diuretic widely used in clinical practice for its ability to promote significant fluid and electrolyte excretion. First introduced in the 1960s, it remains a cornerstone therapy for various conditions involving fluid overload. As a sulfonamide derivative, furosemide acts specifically on the thick ascending limb of the loop of Henle, making it one of the most effective diuretics available.

Mechanism of Action

Furosemide inhibits the Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle, preventing sodium and chloride reabsorption. This action creates a hypertonic medullary interstitium, impairing the kidney's ability to concentrate urine and promoting excretion of water, sodium, chloride, potassium, calcium, and magnesium. The drug increases renal prostaglandin activity, contributing to its vasodilatory effects.

Indications

• Edema associated with congestive heart failure, cirrhosis, and renal disease
• Hypertension (often in combination with other antihypertensive agents)
• Acute pulmonary edema
• Hypercalcemia
• Ascites
• Nephrogenic diabetes insipidus (off-label)

Dosage and Administration

• Heart failure: 20-80 mg daily, may increase to 600 mg daily in severe cases
• Hypertension: 20-80 mg daily in divided doses
• Maximum single dose: 200 mg

• IV/IM: 20-40 mg, may repeat in 2 hours if needed
• Continuous IV infusion: 10-40 mg/hour after loading dose

• Renal impairment: Higher doses may be required
• Hepatic impairment: Use with caution due to electrolyte disturbances
• Elderly: Start with lower doses due to increased sensitivity
• Pediatrics: 1-2 mg/kg/dose every 6-12 hours

Pharmacokinetics

Contraindications

• Anuria unresponsive to furosemide trial
• Hypersensitivity to sulfonamides or furosemide
• Hepatic coma or severe electrolyte depletion
• Concomitant use with ethacrynic acid (increased ototoxicity risk)

Warnings and Precautions

• Volume depletion: May cause profound diuresis with water and electrolyte depletion
• Ototoxicity: Risk increases with rapid IV administration, high doses, renal impairment
• Hypotension: May occur, especially in volume-depleted patients
• Renal function: May cause azotemia in patients with renal impairment
• Hepatotoxicity: Rare cases of idiosyncratic hepatitis reported
• Photosensitivity: May increase sensitivity to sunlight
• Systemic lupus erythematosus: May exacerbate or activate

Drug Interactions

• Aminoglycosides: Increased risk of ototoxicity and nephrotoxicity
• Digoxin: Hypokalemia may potentiate digoxin toxicity
• Lithium: Reduced renal clearance leading to lithium toxicity
• NSAIDs: May diminish diuretic and antihypertensive effects
• Probenecid: Inhibits diuretic response
• ACE inhibitors/ARBs: Increased risk of hypotension and renal impairment
• Antidiabetic agents: May alter glucose control

Adverse Effects

• Polyuria, nocturia
• Hypokalemia (10-50%)
• Hyponatremia
• Hypochloremia
• Hypocalcemia
• Hypomagnesemia
• Hyperuricemia
• Orthostatic hypotension
• Dizziness, headache

• Ototoxicity (usually reversible)
• Severe electrolyte imbalances
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Pancreatitis
• Aplastic anemia
• Thrombocytopenia
• Interstitial nephritis

Monitoring Parameters

• Daily weights and intake/output measurements
• Serum electrolytes (Na, K, Cl, Mg, Ca) at baseline and regularly during therapy
• Renal function (BUN, creatinine)
• Blood pressure (standing and supine)
• Hearing assessment in high-risk patients
• Blood glucose levels in diabetic patients
• Uric acid levels
• Signs of volume depletion

Patient Education

• Take in morning to avoid nighttime urination
• Report signs of electrolyte imbalance (muscle cramps, weakness, dizziness)
• Monitor weight daily at same time with same scale
• Maintain adequate fluid intake unless otherwise directed
• Avoid sudden position changes to prevent dizziness
• Use sunscreen and protective clothing due to photosensitivity risk
• Do not take NSAIDs without consulting healthcare provider
• Report hearing changes or ringing in ears immediately
• Follow prescribed dietary recommendations, especially regarding potassium intake

References

1. Brater DC. Pharmacology of diuretics. Am J Med Sci. 2000;319(1):38-50. 2. Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-143. 3. Sica DA, Gehr TW. Diuretic combinations in refractory oedema states: pharmacokinetic-pharmacodynamic relationships. Clin Pharmacokinet. 1996;30(3):229-249. 4. FDA Prescribing Information: Furosemide Tablets and Injection. 2021. 5. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th edition. 6. UpToDate: Furosemide drug information. Accessed January 2024. 7. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int Suppl. 2012;2(5):337-414.