Furosemide works by decreasing the reabsorption of sodium by the kidneys.[4] Common side effects of furosemide injection include hypokalemia (low potassium level), hypotension (low blood pressure), and dizziness.[5]
Furosemide is primarily used for the treatment ofedema, but also in some cases ofhypertension (where there is also kidney or heart impairment).[14] It is often viewed as a first-line agent in most people with edema caused bycongestive heart failure because of its anti-vasoconstrictor and diuretic effects.[4][15] Compared with furosemide, however,torasemide (aka "torsemide") has been demonstrated to show improvements to heart failure symptoms, possibly lowering the rates of rehospitalization associated with heart failure, with no difference in risk of death.[16][17][18] Torsemide may also be safer than furosemide.[19][20] Providing self-administered subcutaneous furosemide has been found to reduce hospital admissions in people with heart failure, resulting in significant savings in healthcare costs.[21][22]
In chronic kidney diseases withhypoalbuminemia, furosemide is used along with albumin to increase diuresis.[24] It is also used along with albumin innephrotic syndrome to reduce edema.[25]
Furosemide is mainly excreted by tubular secretion in the kidney. In kidney impairment, clearance is reduced, increasing the risk of adverse effects.[4] Lower initial doses are recommended in older patients (to minimize side effects) and high doses may be needed inkidney failure.[26] It can also cause kidney damage; this is mainly by loss of excessive fluid (i.e., dehydration), and is usually reversible.[citation needed]
Furosemide acts within 1 hour of oral administration (after IV injection, the peak effect is within 30 minutes). Diuresis is usually complete within 6–8 hours of oral administration, but there is significant variation between individuals.[27]
The tendency, as for all loop diuretics, to cause low serum potassium concentration (hypokalemia) has given rise to combination products, either with potassium or with thepotassium-sparing diureticamiloride (Co-amilofruse). Other electrolyte abnormalities that can result from furosemide use include hyponatremia, hypochloremia, hypomagnesemia, and hypocalcemia.[31]
In the treatment of heart failure, many studies have shown that the long-term use of furosemide can cause varying degrees ofthiamine deficiency, sothiamine supplementation is also suggested.[32]
Furosemide is a known ototoxic agent generally causing transient hearing loss but can be permanent. Reported cases of furosemide-induced hearing loss appeared to be associated with rapid intravenous administration, high dosages, concomitant renal disease, and coadministration with other ototoxic medication.[33][34] However, a recently reported longitudinal study showed that participants treated with loop diuretics over 10 years were 40% more likely to develop hearing loss and 33% more likely of progressive hearing loss compared to participants who did not use loop diuretics.[35] This suggests the long-term consequences of loop diuretics on hearing could be a more significant than previously thought and further research is required in this area.
Other precautions include nephrotoxicity, sulfonamide (sulfa) allergy, and increased free thyroid hormone effects with large doses.[36]
Furosemide, like other loop diuretics, acts by inhibiting the luminalNa–K–Cl cotransporter in thethick ascending limb of theloop of Henle, by binding to the Na-K-2Cl transporter, thus causing more sodium, chloride, and potassium to be excreted in the urine.[38]
The action on the distal tubules is independent of any inhibitory effect on carbonic anhydrase or aldosterone; it also abolishes the corticomedullary osmotic gradient and blocks negative, as well as positive,free water clearance. Because of the large NaCl absorptive capacity of the loop of Henle, diuresis is not limited by the development of acidosis, as it is with the carbonic anhydrase inhibitors.[citation needed]
Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors.[39][40][41] Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors at μM concentrations, but not α1β2γ2 receptors.[39][41] During development, the α6β2γ2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide.[40]
The pharmacokinetics of furosemide are not significantly altered by food.[51]
No direct relationship has been found between furosemide concentration in the plasma and furosemide efficacy. Efficacy depends upon the concentration of furosemide in urine.[27]
The diuretic effects are put to use most commonly in horses to prevent bleeding during a race. In the United States of America, under the racing rules of most states, horses that bleed from the nostrils (exercise-induced pulmonary hemorrhage) three times are permanently barred from racing. Sometime in the early 1970s, furosemide's ability to prevent, or at least greatly reduce, the incidence of bleeding by horses during races was discovered accidentally. Clinical trials followed, and by the decade's end, racing commissions in some states in the USA began legalizing its use on race horses. In 1995,New York became the last state in the United States to approve such use, after years of refusing to consider doing so.[53] Some states allow its use for all racehorses; some allow it only for confirmed "bleeders". Its use for this purpose is still prohibited in many other countries.[citation needed]
Furosemide is also used in horses for pulmonary edema, congestive heart failure (in combination with other drugs), and allergic reactions. Although it increases circulation to the kidneys, it does not help kidney function and is not recommended for kidney disease.[54]
It is also used to treat congestive heart failure (pulmonary edema, pleural effusion, and/or ascites) in cats and dogs.[55]
Furosemide is injected eitherintramuscularly orintravenously, usually 0.5-1.0 mg/kg twice/day, although less before a horse is raced. As with many diuretics, it can causedehydration andelectrolyte imbalance, including loss ofpotassium,calcium,sodium, andmagnesium. Excessive use of furosemide will most likely lead to ametabolic alkalosis due tohypochloremia andhypokalemia. The drug should, therefore, not be used in horses that are dehydrated or experiencing kidney failure. It should be used with caution in horses with liver problems or electrolyte abnormalities. Overdose may lead to dehydration, change in drinking patterns and urination, seizures, gastrointestinal problems, kidney damage, lethargy, collapse, and coma.
Furosemide should be used with caution when combined with corticosteroids (as this increases the risk of electrolyte imbalance), aminoglycoside antibiotics (increases the risk of kidney or ear damage), and trimethoprim sulfa (causes decreased platelet count). It may also cause interactions with anesthetics, so its use should be related to the veterinarian if the animal is going into surgery, it decreases the kidneys' ability to excreteaspirin, so dosages will need to be adjusted if combined with that drug.
Furosemide may increase the risk ofdigoxin toxicity due to hypokalemia.
It is recommended that furosemide not be used during pregnancy or in a lactating mare, as it is passed through the placenta and milk in studies with other species. It should not be used in horses withpituitary pars intermedia dysfunction (Equine Cushing's Disease).
Furosemide is detectable in urine 36–72 hours following injection. Its use is restricted by most equestrian organizations.
US major racetracks ban the use of furosemide on race days.[56]
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Sullivan S, Hinchcliff K (April 2015). "Update on exercise-induced pulmonary hemorrhage".The Veterinary Clinics of North America. Equine Practice.31 (1):187–198.doi:10.1016/j.cveq.2014.11.011.PMID25770069.
^Täger T, Fröhlich H, Seiz M, Katus HA, Frankenstein L (July 2019). "READY: relative efficacy of loop diuretics in patients with chronic systolic heart failure-a systematic review and network meta-analysis of randomised trials".Heart Failure Reviews.24 (4):461–472.doi:10.1007/s10741-019-09771-8.PMID30874955.S2CID77394851.
^Miles JA, Hanumanthu BK, Patel K, Chen M, Siegel RM, Kokkinidis DG (June 2019). "Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis".Journal of Cardiovascular Medicine.20 (6):379–388.doi:10.2459/JCM.0000000000000794.PMID30950982.S2CID96436158.
^Abraham B, Megaly M, Sous M, Fransawyalkomos M, Saad M, Fraser R, et al. (January 2020). "Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure".The American Journal of Cardiology.125 (1):92–99.doi:10.1016/j.amjcard.2019.09.039.PMID31699358.S2CID207937875.
^Kitsios GD, Mascari P, Ettunsi R, Gray AW (April 2014). "Co-administration of furosemide with albumin for overcoming diuretic resistance in patients with hypoalbuminemia: a meta-analysis".Journal of Critical Care.29 (2):253–259.doi:10.1016/j.jcrc.2013.10.004.PMID24268626.
^Favrelière S, Delaunay P, Lebreton JP, Rouby F, Atzenhoffer M, Lafay-Chebassier C, et al. (June 2020). "Drug-induced hearing loss: a case/non-case study in the French pharmacovigilance database".Fundamental & Clinical Pharmacology.34 (3):397–407.doi:10.1111/fcp.12533.PMID31912913.S2CID210087413.
^abKorpi ER, Kuner T, Seeburg PH, Lüddens H (February 1995). "Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor".Molecular Pharmacology.47 (2):283–289.PMID7870036.
^abWafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ (September 1996). "Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit".Molecular Pharmacology.50 (3):670–678.PMID8794909.
^AMA Department of Drugs: Drug Evaluations Subscription, American Medical Association, Chicago, IL, 1990.
^Knoben JE & Anderson PO (Eds): Handbook of Clinical Drug Data, 6th. Drug Intelligence Publications, Inc, Hamilton, IL, 1988.
^abcdeGilman AG, Rall TW, Nies AS, et al. (1990).Goodman and Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York, NY: Pergamon Press.
^abcdeKelly MR, Cutler RE, Forrey AW, Kimpel BM (February 1974). "Pharmacokinetics of orally administered furosemide".Clinical Pharmacology and Therapeutics.15 (2):178–186.doi:10.1002/cpt1974152178.PMID4812154.S2CID74223978.
^Verbeeck RK, Patwardhan RV, Villeneuve JP, Wilkinson GR, Branch RA (June 1982). "Furosemide disposition in cirrhosis".Clinical Pharmacology and Therapeutics.31 (6):719–725.doi:10.1038/clpt.1982.101.PMID7075120.S2CID27659838.
^Chaturvedi PR, O'Donnell JP, Nicholas JM, Shoenthal DR, Waters DH, Gwilt PR (March 1987). "Steady state absorption kinetics and pharmacodynamics of furosemide in congestive heart failure".International Journal of Clinical Pharmacology, Therapy, and Toxicology.25 (3):123–128.PMID3557737.
This article incorporates text from this source, which is in thepublic domain.
