A 75-year-old woman on furosemide for heart failure develops severe hyponatraemia (Na+ 118 mEq/L). Her urine osmolality is 450 mOsm/kg. The physician suspects SIADH triggered by the loop diuretic. Furosemide treatment of SIADH paradoxically can help correct it. The mechanism is:

• A Furosemide blocks aquaporin-2 channels in the collecting duct, preventing water reabsorption
• B Furosemide promotes ADH secretion suppression through volume expansion of the central compartment
• C Furosemide competitively antagonises vasopressin V2 receptors in the collecting duct
• D Furosemide blocks the NKCC2 transporter in the thick ascending limb, reducing medullary hypertonicity and impairing free water concentration by ADH — making urine hypotonic — combined with high oral sodium intake to correct the deficit ✓

Explanation

Furosemide is used in SIADH management (along with fluid restriction and sodium supplementation) because it inhibits the Na-K-2Cl cotransporter (NKCC2) in the thick ascending limb of Henle. This disrupts the medullary concentration gradient necessary for ADH-driven water reabsorption in the collecting duct. With a reduced medullary osmotic gradient, ADH cannot maximally reabsorb free water, so the kidneys excrete more dilute urine (electrolyte-free water loss exceeds sodium loss). Combined with saline supplementation, this corrects hyponatraemia. Furosemide does not directly block aquaporins or V2 receptors; tolvaptan blocks V2 receptors.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.