indication

For the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Also for the treatment of hypertension alone or in combination with other antihypertensive agents.

pharmacology

Furosemide, a sulfonamide-type loop diuretic structurally related to bumetanide, is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome.

mechanism of action

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.

toxicity

Profound diuresis may cause fluid and electrolyte depletion. Excessive dehydration and potassium depletion may occur. Excessive diuresis may cause rapid weight loss, orthostatic hypotension or acute hypotensive episodes. May also cause tinnitus, reversible or permanent hearing loss or reversible deafness.

biotransformation

Only a small amount is hepatically metabolized to the defurfurylated derivative, 4-chloro-5-sulfamoylanthranilic acid.

absorption

60% absorbed in patients with normal renal function

half life

2 hours

route of elimination

Furosemide is excreted in urine. Significantly more furosemide is excreted in urine following the I.V. injection than after the tablet or oral solution.

drug interactions

Amikacin: Increased ototoxicity

Cisplatin: Increased ototoxicity

Colesevelam: Bile acid sequestrants such as colesevelam may decrease the absorption of loop diuretics such as furosemide. Monitor for decreased serum concentrations/therapeutic effects of loop diuretics if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Deslanoside: Possible electrolyte variations and arrhythmias

Digitoxin: Possible electrolyte variations and arrhythmias

Digoxin: Possible electrolyte variations and arrhythmias

Ethotoin: The hydantoin decreases the effect of furosemide

Fosphenytoin: The hydantoin decreases the effect of furosemide

Gentamicin: Increased ototoxicity

Ginseng: Ginseng decreases the therapeutic effect

Ibuprofen: The NSAID, ibuprofen, may antagonize the diuretic and antihypertensive effects of the loop diuretic, furosemide.

Indomethacin: The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.

Kanamycin: Increased ototoxicity

Mephenytoin: The hydantoin decreases the effect of furosemide

Netilmicin: Increased ototoxicity

Phenytoin: The hydantoin decreases the effect of furosemide

Streptomycin: Increased ototoxicity

Sulindac: The NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.

Tobramycin: Increased ototoxicity

Trandolapril: The loop diuretic, Furosemide, may increase the hypotensive effect of Trandolapril. Furosemide may also increase the nephrotoxicity of Trandolapril.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.