Furosemide

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Furosemide
Furosemide.svg
Furosemide-1Z9Y-3D-balls.png
Clinical data
Pronunciation /fjʊˈroʊsəˌmaɪd/
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration		 by mouth, IV, IM
ATC code C03CA01 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 43–69%
Metabolism liver and kidney glucuronidation
Onset of action 30 to 60 min (PO), 5 min (IV)[1]
Biological half-life up to 100 minutes
Excretion renal 66%, biliary 33%
Identifiers
CAS Number 54-31-9 YesY
PubChem (CID) 3440
DrugBank DB00695 YesY
ChemSpider 3322 YesY
UNII 7LXU5N7ZO5 YesY
KEGG D00331 YesY
ChEBI CHEBI:47426 YesY
ChEMBL CHEMBL35 YesY
ECHA InfoCard 100.000.185
Chemical and physical data
Formula C12H11ClN2O5S
Molar mass 330.745 g/mol
3D model (Jmol) Interactive image
  (verify)

Furosemide, sold under the brand name Lasix among others, is a medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease.[1] It may also be used for the treatment of high blood pressure. The amount of medication required depends on the person in question. It can be taken intravenously or by mouth. When taken by mouth it typically begins working within an hour while intravenously it typically begins working within five minutes.[1]

Common side effects include low blood pressure with standing, ringing in the ears, and sensitivity to the sun. Potentially serious side effects include electrolyte abnormalities, low blood pressure, and hearing loss. Blood tests are recommended regularly for those on treatment. Furosemide is a type of loop diuretic that works by decreasing the reabsorption of sodium by the kidneys.[1]

Furosemide was discovered in 1962.[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale price in the developing world is between 0.004 and 0.02 USD per day.[4] In the United States it is available as a generic medication and costs about 0.15 USD per day.[1] Furosemide is on the World Anti-Doping Agency's banned drug list due to concerns that it may mask other drugs.[5] It has also been used to prevent and treat race horses for exercise-induced pulmonary hemorrhage.[6][7]

Medical uses[edit]

Furosemide (Lasix) for injection

Furosemide is primarily used for the treatment of hypertension and edema.[8] It is the first-line agent in most people with edema caused by congestive heart failure.[8] It is also used for hepatic cirrhosis, renal impairment, nephrotic syndrome, in adjunct therapy for cerebral or pulmonary edema where rapid diuresis is required (IV injection), and in the management of severe hypercalcemia in combination with adequate rehydration.[9]

Kidney disease[edit]

In chronic kidney diseases with hypoalbuminemia, it is used along with albumin to increase diuresis. It is also used along with albumin in nephrotic syndrome to reduce edema. [10]

Other information[edit]

  • Excreted by tubular secretion, therefore in severe renal impairment (GFR 5–10 ml/min) lower doses are required due to accumulation in the body. It also can cause further renal damage and should be administered with caution.
  • Furosemide acts within 1 hour of oral administration (after IV peak effect within 30 minutes); diuresis is complete within 6 hours (for oral administration) and 2 hours (for IV administration).

Adverse effects[edit]

Although disputed,[11] it is considered ototoxic: "usually with large intravenous doses and rapid administration and in renal impairment".[12] Furosemide also can lead to gout caused by hyperuricemia. Hyperglycemia is also a common side effect.

The tendency, as for all loop diuretics, to cause low potassium levels (hypokalemia) has given rise to combination products, either with potassium itself (e.g. Lasix-K and Diumide-K Continus) or with the potassium-sparing diuretic amiloride (Co-amilofruse).

Interactions[edit]

Furosemide has potential interactions with these medications:[13]

Potentially hazardous interactions with other drugs:

Mechanism of action[edit]

Main article: Loop diuretic

Furosemide, like other loop diuretics, acts by inhibiting NKCC2, the luminal Na-K-Cl cotransporter in the thick ascending limb of the loop of Henle. 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 development of acidosis, as it is with the carbonic anhydrase inhibitors.

Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors.[14][15][16] Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors at µM concentrations, but not α1β2γ2 receptors.[14][16] During development, the α6β2γ2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide.[15]

Pharmacokinetics[edit]

  • Molecular weight (daltons) 330.7
  • % Protein binding 91–99
  • % Excreted unchanged in urine 80–90
  • Volume of distribution (L/kg) 0.07–0.2
  • Half-life – normal/ESRD (hrs) 0.5–2/9.7

Names[edit]

Furosemide is the INN and BAN.[17] The previous BAN was frusemide.

Some of the brand names under which furosemide is marketed include: Aisemide, Apo-Furosemide, Beronald, Desdemin, Discoid, Diural, Diurapid, Dryptal, Durafurid, Edemid, Errolon, Eutensin, Flusapex, Frudix, Frusetic, Frusid, Fulsix, Fuluvamide, Furesis, Furix, Furo-Puren, Furon, Furosedon, Fusid.frusone, Hydro-rapid, Impugan, Katlex, Lasilix, Lasix, Lodix, Lowpston, Macasirool, Mirfat, Nicorol, Odemase, Oedemex, Profemin, Rosemide, Rusyde, Salix, Teva-Furosemide, Trofurit, Uremide, and Urex.

Veterinary uses[edit]

The diuretic effects are put to use most commonly in horses to prevent bleeding during a race. Sometime in the early 1970s, furosemide's ability to prevent, or at least greatly reduce, the incidence of bleeding (exercise-induced pulmonary hemorrhage) by horses during races was discovered accidentally. In the United States of America, pursuant to the racing rules of most states, horses that bleed from the nostrils three times are permanently barred from racing. Clinical trials followed, and by decade's end, racing commissions in some states in the USA began legalizing its use on race horses. On September 1, 1995, New York became the last state in the United States to approve such use, after years of refusing to consider doing so. 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.

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.

It is also used to treat congestive heart failure in cats and dogs (which experience fluid on the lungs) and complications from heartworm. It can be used in conjunction with an antibiotic and anti-inflammatory to treat this condition. It can also be used in an attempt to promote diuresis in anuric or oliguric acute renal failure.

Precautions, side effects, and administration for horses[edit]

Furosemide is injected either intramuscularly or intravenously, usually 0.5-1.0 mg/kg twice/day, although less before a horse is raced. As with many diuretics, it can cause dehydration and electrolyte imbalance, including loss of potassium, calcium, sodium, and magnesium. Excessive use of furosemide will most likely lead to a metabolic alkalosis due to hypochloremia and hypokalemia. 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 risk of kidney or ear damage), and trimethoprim sulfa (causes decreased platelet count). It may also cause interactions with anesthesics, so its use should be related to the veterinarian if the animal is going into surgery, and it decreases the kidneys' ability to excrete aspirin, so dosages will need to be adjusted if combined with that drug.

Furosemide may increase the risk of digoxin toxicity due to hypokalemia.

The drug is best not used during pregnancy or in a lactating mare, as it has been shown to be passed through the placenta and milk in studies with other species. It should not be used in horses with pituitary pars intermedia dysfunction (Cushings).

Furosemide is detectable in urine 36–72 hours following injection. Its use is prohibited by most equestrian organizations.

References[edit]

  1. ^ a b c d e "Furosemide". The American Society of Health-System Pharmacists. Retrieved Oct 23, 2015. 
  2. ^ Rang, Humphrey (2013). Drug discovery and development [electronic resource]. (2nd ed.). Edinburgh: Churchill Livingstone. p. Chapter 1. ISBN 9780702053160. 
  3. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  4. ^ "Furosemide". International Drug Price Indicator Guide. Retrieved 24 October 2015. 
  5. ^ "THE 2014 PROHIBITED LIST INTERNATIONAL STANDARD" (pdf). 2014. p. 5. Retrieved 24 October 2015. 
  6. ^ Sullivan, S; Hinchcliff, K (April 2015). "Update on exercise-induced pulmonary hemorrhage.". The Veterinary Clinics of North America. Equine Practice. 31 (1): 187–98. doi:10.1016/j.cveq.2014.11.011. PMID 25770069. 
  7. ^ Hinchcliff, KW; Couetil, LL; Knight, PK; Morley, PS; Robinson, NE; Sweeney, CR; van Erck, E (2015). "Exercise induced pulmonary hemorrhage in horses: American College of Veterinary Internal Medicine consensus statement.". Journal of veterinary internal medicine / American College of Veterinary Internal Medicine. 29 (3): 743–58. doi:10.1111/jvim.12593. PMID 25996660. 
  8. ^ a b "Furosemide". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  9. ^ Rossi S, ed. (2004). Australian Medicines Handbook 2004 (5th ed.). Adelaide, S.A.: Australian Medicines Handbook Pty Ltd. ISBN 0-9578521-4-2. 
  10. ^ BMC Nephrol. 2012 Aug 29;13:92. doi: 10.1186/1471-2369-13-92.The added-up albumin enhances the diuretic effect of furosemide in patients with hypoalbuminemic chronic kidney disease: a randomized controlled study. Phakdeekitcharoen B1, Boonyawat K Ann Pharmacother. 2003 May;37(5):695-700. Combined furosemide and human albumin treatment for diuretic-resistant edema. Elwell RJ1, Spencer AP, Eisele G
  11. ^ Rais-Bahrami K, Majd M, Veszelovszky E, Short B (2004). "Use of furosemide and hearing loss in neonatal intensive care survivors". Am J Perinatol. 21 (6): 329–32. doi:10.1055/s-2004-831887. PMID 15311369. 
  12. ^ BNF 45 March 2003
  13. ^ Brand name:Lasix - Generic name: Furosemide Prescription Drug Information, Side Effects - PDRHealth
  14. ^ a b Korpi ER, Kuner T, Seeburg PH, Lüddens H (1995). "Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor". Mol. Pharmacology. 47 (2): 283–9. PMID 7870036. 
  15. ^ a b Tia S, Wang JF, Kotchabhakdi N, Vicini S (1996). "Developmental changes of inhibitory synaptic currents in cerebellar granule neurons: role of GABA(A) receptor alpha 6 subunit". J. Neurosci. 16 (11): 3630–40. PMID 8642407. 
  16. ^ a b Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ (1996). "Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit". Mol. Pharmacol. 50 (3): 670–8. PMID 8794909. 
  17. ^ http://www.mhra.gov.uk/Howweregulate/Medicines/Namingofmedicines/ChangestomedicinesnamesBANstorINNs/index.htm

Further reading[edit]

  • Aventis Pharma (1998). Lasix Approved Product Information. Lane Cove: Aventis Pharma Pty Ltd.
  • Barbara Forney (2007). Understanding Equine Medications, Revised Edition (Horse Health Care Library). Eclipse Press. ISBN 1-58150-151-X. 

External links[edit]

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