Furosemide, a loop diuretic, inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron. Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron, furosemide is a very potent diuretic.
Furosemide (Lasix) may promote excretion of magnesium. It increases excretion of water by interfering with the chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule.
For these reasons, oral replacement should be given in the asymptomatic patient, preferably with a sustained-release preparation, given the ability of magnesium to induce diarrhea. Bioavailability of oral preparations is assumed to be 33% in the absence of intestinal malabsorption. Several preparations are available: Mag-Ox 400, containing magnesium oxide; Slow-Mag, containing magnesium chloride; and Mag-Tab, containing magnesium lactate. These preparations provide 5-7 mEq (2.5-3.5 mmol or 60-84 mg) of magnesium per tablet. Six to 8 tablets should be taken daily in divided doses for severe magnesium depletion. Two to 4 tablets may be sufficient for mild, asymptomatic disease. Mag-Ox 400 contains 242 mg (20 mEq) of elemental magnesium, but absorption is less efficacious.