Furosemide (Frusemide)

💧 Loop diuretics such as Furosemide are powerful agents for rapid fluid removal. Their effect is dose-dependent and may be reduced in severe renal failure - sometimes requiring very high doses or continuous infusion. ⚠️ Do not use long-term for simple gravitational oedema; this usually responds to leg elevation, compression stockings, and improved mobility. Always 🔗 check the BNF entry here for up-to-date dosing and cautions.

🧬 Chemistry & Class

• Class: Loop diuretic (high-ceiling diuretic).
• Chemical name: 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid (an anthranilic acid derivative).
• Highly protein bound (≈95%) → secretion into tubular lumen depends on active transport rather than glomerular filtration.

⚙️ Mode of Action

• Inhibits the Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2) in the thick ascending limb of the loop of Henle.
• Blocks reabsorption of sodium, chloride, and potassium → osmotic water loss and increased urine output.
• Also enhances calcium and magnesium excretion.
• Venodilatory effect precedes diuresis (useful in acute pulmonary oedema to reduce preload).
• Dependent on renal blood flow - less effective in severe renal impairment unless very high doses or IV infusion used.

💊 Indications / Typical Doses

• Congestive cardiac failure (CCF/LVF): 20–80 mg OD/BD PO (titrate to response).
• Acute pulmonary oedema: 40–100 mg IV bolus over 20 mins, may repeat or switch to infusion if refractory.
• Chronic kidney disease: may require doses up to 250 mg/day or more (under specialist guidance).
• Hypertension: usually 20–40 mg OD PO, often with ACE inhibitor or ARB.
• Mild peripheral oedema: 20–40 mg OD PO or alternate days; combine with non-pharmacological measures (elevate legs, stockings, ambulation).

📊 Dose Range (check BNF / SPC)

🧠 Clinical Use & Pearls

• Give oral doses in the morning (and early afternoon if BD) to avoid nocturia.
• In acute LVF, venodilation provides rapid symptom relief even before diuresis begins.
• In advanced CKD, combine with a thiazide-type diuretic (e.g., metolazone) for synergistic effect - monitor closely for hypovolaemia and electrolyte loss.
• Always reassess the cause of oedema; chronic loop diuretic use without indication can worsen renal perfusion and cause hypotension.

⚠️ Contraindications & Precautions

• Avoid with ototoxic agents (e.g., aminoglycosides, cisplatin) - additive hearing loss risk.
• Monitor renal function (U&E, eGFR) and electrolytes - risk of AKI and hypokalaemia.
• Severe hypovolaemia or hypotension → hold until corrected.
• Hypokalaemia potentiates digoxin toxicity.
• Hypomagnesaemia and hypocalcaemia may cause arrhythmias.

💢 Side Effects

• Circulatory: volume depletion, orthostatic hypotension → syncope and falls (especially elderly).
• Electrolyte disturbances: ↓K⁺, ↓Mg²⁺, ↓Ca²⁺, ↑uric acid (gout), ↑glucose.
• Renal: pre-renal AKI, azotaemia, urinary retention (especially with prostate enlargement).
• Auditory: tinnitus and ototoxicity (esp. with high IV doses or aminoglycosides). In most cases, furosemide-induced ototoxicity is transient and reversible once the drug is stopped or the dose reduced. Hearing typically improves over hours to a few days. Furosemide inhibits NKCC transporters in the stria vascularis, disrupting the endocochlear potential. A rapid rise in plasma concentration causes an abrupt drop in cochlear potassium recycling. A slow infusion produces lower peak cochlear exposure even if the total dose is the same - so toxicity is much less likely.
• Endocrine/metabolic: hyperglycaemia, dyslipidaemia, gynaecomastia (rare cross-reactivity).

🤝 Drug Interactions

• Digoxin: ↑ toxicity due to hypokalaemia.
• ACE inhibitors/ARBs: ↑ risk of first-dose hypotension and renal dysfunction - monitor U&E.
• Lithium: ↓ clearance → lithium toxicity.
• NSAIDs: blunt diuretic response and ↑ nephrotoxicity (“triple whammy” with ACEi/ARB).
• Ototoxic drugs: aminoglycosides, vancomycin, cisplatin → additive auditory damage.

🧮 Monitoring

• Before starting: baseline U&E, eGFR, BP, weight, urine output.
• During treatment: monitor electrolytes (esp. K⁺, Na⁺, Mg²⁺) daily if IV, every few days if PO.
• Ongoing: weight trends and clinical response - aim for 0.5–1 kg/day fluid loss in acute overload.
• Check hearing if high-dose IV or prolonged infusion used.

📚 References

• BNF: Furosemide
• NICE NG106: Chronic heart failure in adults – management.
• NICE NG28: Type 2 diabetes in adults – diuretic therapy in hypertension/CKD.
• Renal Association 2024: Diuretic use in CKD guidelines.