Lasix: The Basics of Furosemide

Consider prescribing furosemide – a water pill – to patients with heart failure, liver disease and kidney disease.

How It Works
Furosemide, sold under the brand name Lasix, is a loop diuretic that blocks the sodium-potassium-chloride transporter in the ascending limb of the loop of Henle. This blockade results in decreased reabsorption of sodium, chloride, and water [1]. Diuresis starts within 30 minutes of intravenous administration and peaks in 1 to 2 hours. In addition to diuretic effects, furosemide also induces more rapid vascular changes within 15 minutes of intravenous administration, causing venodilation of the pulmonary vasculature and reducing pulmonary congestion [2]. Furosemide is the most well known and widely used of the loop diuretics which include bumetanide, torsemide, and ethacrynic acid.

Major Indications
Furosemide is used primarily in the treatment of acute and chronic heart failure, as well as cirrhosis, nephrotic syndrome, and other states characterized by fluid overload. It is used in the treatment of hypertension and for hyperkalemia in concert with other potassium-lowering agents. Furosemide has been traditionally used in hypercalcemia for its calcium-lowering effects, but has largely been supplanted by the more effective bisphosphonates [3].

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Notable History
Furosemide was discovered in 1962 [4]. It is on the World Health Organization’s list of essential medications, the medications most important to a basic health system. Furosemide is also on the list of drugs banned in athletic competition, due to concerns that it may mask the presence of other performance-enhancing drugs. Furosemide’s brand name Lasix comes from the fact that the drug, when given orally, “lasts six” hours.

Recently In The News For
The treatment of acute decompensated heart failure (ADHF) is rapidly evolving. ADHF traditionally was thought to be caused by fluid overload. This view has been challenged more recently as evidence has pointed more to changes in vascular reactivity and fluid redistribution as culprits [5,6]. As such, diuretics are taking a back seat to treatments with immediate vascular effects, such as nitrates and noninvasive positive pressure ventilation [7,8]. Upcoming studies will hopefully clarify the hierarchy of diuretics and other treatment modalities in the management of acute decompensated heart failure.

Adverse Events
The more common adverse events are generally predictable based on the mechanism of action, and include hypotension, fluid and electrolyte depletion, and acute renal failure. Potassium levels, kidney function, and urine output should be monitored during aggressive diuresis. Hyperuricemia and gouty attacks have also been reported with furosemide use. Furosemide has the potential to be ototoxic and is associated with reversible and irreversible hearing loss, particularly with rapid intravenous administration and high doses [9].

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Cautions
Furosemide should not be used in anuric patients. Furosemide contains a sulfonamide chemical group, but the risk of cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides has been shown in multiple studies to be extremely unlikely and administration of furosemide to sulfa-allergic patients is probably safe [10].

Dosing Adjustments
The ACC/AHA 2013 heart failure guidelines recommend initial dosing of 20-40 mg by mouth once or twice daily to a maximum total daily dose of 600 mg for chronic heart failure [11]. For acute pulmonary edema, the initial IV dose is 20-40 mg which may be repeated or increased by 20 mg/dose every 1-2 hours until urine output increases and dyspnea improves. For patients in de-compensated heart failure who take furosemide daily, the initial recommended IV dose should be ≥ 2.5 times the maintenance oral dose [12]. Furosemide may also be given as a continuous IV infusion, though a recent study showed no difference in symptom resolution when furosemide infusion was compared to bolus dosing [13].

Cost
The cost of Furosemide 20 mg tablets is $14.30 U.S dollars per 100 tablets. A 40 mg dose of IV Furosemide costs $9.86 [14].

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REFERENCES

1. Lexicomp Online. Furosemide: Drug information. www.uptodate.com. Accessed February 8, 2016.
2. Cotter G, Metzkor E, Kaluski E, Faigenberg Z, Miller R, Simovitz A, Shaham O, Marghitay D, Koren M, Blatt A. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. The Lancet [Internet]. 1998;351(9100):389-93.
3. Brater DC. Mechanism of action of diuretics. www.uptodate.com. Accessed February 8, 2016.
4. Rang, Humphrey (2013). Drug discovery and development [electronic resource]. (2nd ed.). Edinburgh: Churchill Livingstone. p. Chapter 1. ISBN 9780702053160.
5. Zile MR, Bennett TD, St John Sutton M, Cho YK, Adamson PB, Aaron MF, Aranda JM,Jr, Abraham WT, Smart FW, Stevenson LW, Kueffer FJ, Bourge RC. Transition from chronic compensated to acute decompensated heart failure: Pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation [Internet]. 2008 Sep 30;118(14):1433-41.
6. Fallick C, Sobotka PA, Dunlap ME. Sympathetically mediated changes in capacitance: Redistribution of the venous reservoir as a cause of decompensation. Circ Heart Fail [Internet]. 2011 Sep;4(5):669-75.
7. Frontin P, Bounes V, Houze-Cerfon CH, Charpentier S, Houze-Cerfon V, Ducasse JL. Continuous positive airway pressure for cardiogenic pulmonary edema: A randomized study. Am J Emerg Med [Internet]. 2011 Sep;29(7):775-81.
8. Levy P, Compton S, Welch R, Delgado G, Jennett A, Penugonda N, Dunne R, Zalenski R. Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: A feasibility and outcome analysis. Ann Emerg Med [Internet]. 2007;50(2):144-52.
9. Lexicomp Online. Furosemide: Drug information. www.uptodate.com. Accessed February 8, 2016.
10. Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, Bilker WB, Pettitt D. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med [Internet]. 2003;349(17):1628-35.
11. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL. 2013 ACCF/AHA guideline for the management of heart failure: A report of the american college of cardiology Foundation/American heart association task force on practice guidelines. J Am Coll Cardiol [Internet]. 2013;62(16):e147-239.
12. Collucci WS. Treatment of acute decompensated heart failure: Components of therapy. www.uptodate.com. Accessed February 8, 2016.
13. Felker GM, Lee KL, Bull DA et al NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med [Internet]. 2011 Mar 3;364(9):797-805.
14. Lexicomp Online. Furosemide: Drug information. www.uptodate.com. Accessed February 8, 2016.