Furosemide (Lasix®)

Based on "Treatment of Myocardial Ischemia and Hypertension"
written by Thomas Michel, MD, PhD, and Brian B. Hoffman, MD

Furosemide is a rapid acting sulfonamide loop diuretic. It causes strong diuresis and saluresis.

Furosemide "pros" and "cons"

Advantages:

• Very potent diuretic. Furosemide is effective even in patients with relatively severe renal failure. High-ceiling diuretics are the most efficacious medications available for inducing significant water and electrolyte excretion.
• Rapid onset of diuretic effect.
• No side effects unrelated to diuretic effect. Most adverse effects are due to abnormalities of fluid and electrolyte balance.
• Very useful in emergencies. Provides immediate symptomatic relief from dyspnea (shortness of breath), caused by pulmonary edema.
• Furosemide has a wide therapeutic index and is relatively non-toxic.

Disadvantages:

• Weak antihypertensive activity and short duration of blood pressure lowering effect.
• Very short half-life. Furosemide has short elimination half-life and prolonged-release preparations are not available. Consequently, often the dosing interval is too short to maintain adequate levels of loop diuretics in the tubular lumen.
• Most common side effects: fluid and electrolyte disturbances.
• Overdose can lead to water and electrolyte depletion.
• Ototoxicity (damage to the inner ear). High furosemide doses produce ototoxic effect (mostly reversible)2. Ototoxicity occurs most frequently with rapid intravenous administration. Bumetanide seems to be less ototoxic and can be used as an alternative in persons suffering from furosemide-induced ototoxicity3. Furosemide can increase the ototoxic potential of aminoglycoside antibiotics, especially in patients with impaired renal function.
• Variable and incomplete bioavailability from the oral dosing. Furosemide has a marked inter-individual bioavailability.
• Hypokalemia. Furosemide is a very potent loop diuretic and causes renal loss of potassium. The most common severe side effect is hypokalemia. Hypokalemia may lead to dangerous cardiac dysrhythmias.
• Hyperuricemia (high level of uric acid in the blood), occasionally leading to gout. Furosemide may inhibit the excretion of uric acid, resulting in hyperuricemia. Patients with a history of gouty arthritis attacks are particularly susceptible to attacks as a result of furosemide-induced hyperuricemia.
  Note: Hyperuricaemia is lower than with thiazides.
• Hyperglycemia (high blood glucose level) and carbohydrate intolerance, infrequently precipitating diabetes mellitus. Hyperglycemia is linked to diuretic-induced hypokalemia. Potassium deficiency leads to inhibition of insulin secretion.
  
  Hyperglycemia appears to result from inhibition of insulin secretion.
  Note: Hyperglycaemic action of furosemide is less marked than thiazides.
• Dyslipidemia - rise in total and LDL cholesterol and triglycerides with lowering of HDL.
• Compared to thiazides, furosemide seems to cause slightly fewer hypokalemias
  

FDA approved uses

• Hypertension (alone or in combination with other medications for lowering blood pressure).
• Edema resulting from heart failure, lever disease, and renal disease.

Off-label uses & therapeutic perspectives

• Hypercalcemia to increase calcium excretion.
• Asthma1 - furosemide works as bronchodilator in acute asthma attacks.

Onset of action

Diuresis:

• Oral tablets - 1 hour
• Intramuscular injection (IM) - 30 minutes
• Intravenous injection IV - ~5 minutes

Symptomatic improvement with acute pulmonary edema occurs within 15 to 20 minutes and prior to diuretic effect.

Peak effect: 1 to 2 hours (oral).

Duration of action

• Oral tablets - 6 - 8 hours
• Intravenous injection - 2 hours

Mechanism of action

1. Renal effects

Furosemide inhibits the activity of the Na+- K+-2Cl transporter in the Loop of Henle (a significant sodium and water reabsorption site). This results in a decreased absorption of water and increased production of urine.

Furosemide stimulates prostaglandin E2 production.

2. Antihypertensive effects

Furosemide lowers blood pressure by reducing extracellular fluid and plasma volumes.

3. Vascular effects

Furosemide produces peripheral vascular effects. Intravenous furosemide produces a rapid (within minutes) venodilation, particularly in patients with pulmonary edema4. Venodilation is mediated by local vascular prostaglandin synthesis.

Time to clear out of the system

The plasma half-life is nearly 0.5 to 2 hours in persons with normal renal function. In persons with renal insufficiency plasma half-life increases because both urinary excretion and renal conjugation decrease.

Contraindications

• Hypersensitivity to sulfonamides or furosemide
• Severe fluid or electrolyte depletion
• Anuria (absence of urine)

Historical note

The discovery of furosemide was based on the synthesis of a series of N-substituted -5halogen-2,4-disulphamoylanilines. Furosemide was discovered at Hoechst in Germany by Roman Muschaweck and his associates and patented in 19625.

Further reading

• Furosemide vs Torsemide

References

• 1. Pendino JC, Nannini LJ, Chapman KR, Slutsky A, Molfino NA. Effect of inhaled furosemide in acute asthma. J Asthma. 1998;35(1):89-93. PubMed
• 2. Rybak LP. Furosemide ototoxicity: clinical and experimental aspects. Laryngoscope. 1985 Sep;95(9 Pt 2 Suppl 38):1-14. PubMed
• 3. Prepageran N, Scott AR, Rutka JA. Ototoxicity of loop diuretics. Ontario: Hamilton; 2004.
• 4. de Berrazueta JR, González JP, de Mier I, Poveda JJ, García-Unzueta MT.Vasodilatory action of loop diuretics. J CardiovascPharmacol. 2007 Feb;49(2):90-5.
• 5. eds. R. Landau, B. Achilladelis, and A. Scriabine. Pharmaceutical Innovation: Revolutionizing Human Health. Chemical Heritage Press, Philadelphia, 1999
• 6. Murray MD, Haag KM, Black PK, et al. Variable furosemide absorption and poor predictability of response in elderly patients. Pharmacotherapy . 1997;17:98–106.

Published: October 16, 2017
Last updated: October 16, 2017 by eMedExpert staff