Description: Furosemide is a sulfonamide-derived loop diuretic used in the management of edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Other uses include mild to moderate hypertension and as an adjunct in hypertensive crisis and acute pulmonary edema. Furosemide is also useful in treating hypercalcemia, although it is not FDA approved for this indication. Furosemide is effective in managing edema associated with congestive heart failure, and it may be useful in patients who are unresponsive to other diuretics or who have severe renal impairment. Furosemide was approved by the FDA in 1966.

Mechanism of Action: Furosemide is a loop diuretic that acts to inhibit the reabsorption of sodium and chloride in the ascending limb of the loop of Henle by interfering with the chloride-binding of the Na+/K+/2Cl- cotransport system, altering electrolyte transfer in the proximal tubule. A profound diuresis results from the increased urinary excretion of sodium, chloride, potassium, and hydrogen ions. In addition, furosemide increases the excretion of calcium, magnesium, bicarbonate, ammonium, and phosphate. The diuresis caused by furosemide can lead to increased aldosterone production, resulting in increased sodium resorption, and increased potassium and hydrogen excretion. Excessive loss of these electrolytes can lead to metabolic alkalosis.

Furosemide's effectiveness is independent of the acid-base status of the patient. Renal vasodilation occurs following administration of furosemide; renal vascular resistance decreases, and renal blood flow is enhanced. Reduced peripheral vascular resistance and increased peripheral venous capacitance also occur, and the subsequent decrease in left ventricular filling pressure may contribute to the drug's beneficial effect in patients with congestive heart failure. Initially, diuretics lower blood pressure by causing hypovolemia (decreased plasma and extracellular fluid), a temporary increase in glomerular filtration rate, and a decreased cardiac output. Cardiac output eventually returns to normal, but peripheral resistance is now reduced, resulting in lower blood pressure. In general, diuretics worsen left ventricular hypertrophy (LVH) and glucose tolerance. In addition, loop diuretics have been associated with hypercholesterolemia and hypertriglyceridemia.

Pharmacokinetics: Furosemide is administered orally and intravenously. It is absorbed erratically following an oral dose, and food will delay this absorption but will not alter the diuretic response. Diuresis generally begins 30 to 60 minutes after oral administration and about 5 minutes after IV administration. The drug is 95% plasma protein-bound, crosses the placenta, and appears in breast milk.

Furosemide undergoes minimal metabolism in the liver, with 50—80% of a dose excreted in the urine within 24 hours. The remainder of the drug is eliminated through nonrenal mechanisms including excretion in the feces. In patients with significant renal impairment, nonrenal elimination can increase to 98%. The half-life of furosemide is approximately 0.5—1 hour.

•Special Populations: In neonates and in patients with renal and hepatic impairment, half-lives are prolonged. Larger doses may be necessary in patients with renal impairment.


Drug Information Provided by
Gold Standard, Inc. � 2007