Furosemide

Furosemide

Furosemide (INN, BAN)
Systematic (IUPAC) name
4-chloro-2-[(furan-2-ylmethyl)amino]- 5-sulfamoylbenzoic acid
Clinical data
AHFS/Drugs.com
Licence data US Daily Med:
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Legal status
  • (Prescription only)
Routes of
administration
Oral, IV, IM
Pharmacokinetic data
Bioavailability 43-69%
Metabolism hepatic and renal 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 Registry Number  Y
ATC code C03
PubChem CID:
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C12H11ClN2O5S
Molecular mass 330.745 g/mol
 Y   

Furosemide, sold under the brand name Lasix among others, is a medication used to treat health system.[3] The global wholesale price 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]

Contents

  • Medical uses 1
    • Kidney disease 1.1
    • Other information 1.2
  • Adverse effects 2
    • Interactions 2.1
  • Mechanism of action 3
  • Pharmacokinetics 4
  • Names 5
  • Veterinary uses 6
    • Precautions, side effects, and administration for horses 6.1
  • References 7
  • Further reading 8
  • External links 9

Medical uses

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

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

  • 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.

Adverse effects

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

Furosemide has potential interactions with these medications:[13]

Potentially hazardous interactions with other drugs:

Mechanism of action

Furosemide, like other loop diuretics, acts by inhibiting NKCC2, the luminal Na-K-2Cl symporter 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

  • 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/ESRF (hrs) 0.5–2/9.7

Names

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

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 (for their own protection), these rules do not apply in all countries. 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". However, its use for this purpose is still prohibited in many other countries, and veterinarians dispute its use for this problem.

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

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

  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. ed.). Edinburgh: Churchill Livingstone. p. Chapter 1.  
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  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.  
  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.  
  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.:  
  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.  
  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.  
  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.  
  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.  
  17. ^ http://www.mhra.gov.uk/Howweregulate/Medicines/Namingofmedicines/ChangestomedicinesnamesBANstorINNs/index.htm

Further reading

  • 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.  

External links

  • Lasix and horse bleeding
  • (Wind Publications)Furosemide in the Horse
  • U.S. National Library of Medicine: Drug Information Portal - Furosemide
  • Furosemide-A Practical Manual of Renal Medicine