Furosemide

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Furosemide
Systematic (IUPAC) name
4-chloro-2-(furan-2-ylmethylamino)- 5-sulfamoylbenzoic acid
Clinical data
Licence dataUS Daily Med:link
Pregnancy cat.C (AU) C (US)
Legal status Prescription only
RoutesOral, IV, IM
Pharmacokinetic data
Bioavailability43-69%
Metabolismhepatic and renal glucuronidation
Half-lifeup to 100 minutes
Excretionrenal 66%, biliary 33%
Identifiers
CAS number54-31-9 YesY
ATC codeC03CA01
PubChemCID 3440
DrugBankDB00695
ChemSpider3322 YesY
UNII7LXU5N7ZO5 YesY
KEGGD00331 YesY
ChEBICHEBI:47426 YesY
ChEMBLCHEMBL35 YesY
Chemical data
FormulaC12H11ClN2O5S 
Mol. mass330.745 g/mol
 YesY (what is this?)  (verify)
 
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Furosemide
Systematic (IUPAC) name
4-chloro-2-(furan-2-ylmethylamino)- 5-sulfamoylbenzoic acid
Clinical data
Licence dataUS Daily Med:link
Pregnancy cat.C (AU) C (US)
Legal status Prescription only
RoutesOral, IV, IM
Pharmacokinetic data
Bioavailability43-69%
Metabolismhepatic and renal glucuronidation
Half-lifeup to 100 minutes
Excretionrenal 66%, biliary 33%
Identifiers
CAS number54-31-9 YesY
ATC codeC03CA01
PubChemCID 3440
DrugBankDB00695
ChemSpider3322 YesY
UNII7LXU5N7ZO5 YesY
KEGGD00331 YesY
ChEBICHEBI:47426 YesY
ChEMBLCHEMBL35 YesY
Chemical data
FormulaC12H11ClN2O5S 
Mol. mass330.745 g/mol
 YesY (what is this?)  (verify)

Furosemide (INN/BAN[1]) or frusemide (former BAN) is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi under the brand name Lasix, and also under the brand names Fusid and Frumex.[2] It has also been used to prevent Thoroughbred and Standardbred race horses from bleeding through the nose during races.

Along with some other diuretics, furosemide is also included on the World Anti-Doping Agency's banned drug list due to its alleged use as a masking agent for other drugs.

Medical uses[edit]

Furosemide is primarily used for the treatment of hypertension and edema.[3] It is the first-line agent in most people with edema caused by congestive heart failure.[3] It is also used for hepatic cirrhosis, renal impairment, nephrotic syndrome, in adjunct therapy for cerebral/pulmonary edema where rapid diuresis is required (IV injection), and in the management of severe hypercalcemia in combination with adequate rehydration.[4]

Adverse effects[edit]

Although disputed,[5] it is considered ototoxic: "usually with large parenteral doses and rapid administration and in renal impairment".[6] 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) or with the potassium-sparing diuretic amiloride (Co-amilofruse).

Interactions[edit]

Furosemide has potential interactions with the following medications:[7]

Mechanism of action[edit]

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.

By inhibiting the transporter, the loop diuretics reduce the reabsorption of NaCl and also diminish the lumen-positive potential that derives from K+ recycling. This electrical potential normally drives divalent cation reabsorption in the loop, and by reducing this potential, loop diuretics cause an increase in Mg2+ and Ca2+ excretion. Prolonged use can cause significant hypomagnesemia in some patients. Since Ca2+ is actively reabsorbed in the distal convoluted tubule, loop diuretics do not generally cause hypocalcemia.

Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors.[8][9][10] Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors at µM concentrations, but not α1β2γ2 receptors.[8][10] During development, the α6β2γ2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide.[9]

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 (EIPH) 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. Despite the fact 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 canines (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 (IM) or intravenously (IV), 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.

Clinical use in kidney disease[edit]

Loop diuretic

Dose in normal renal function[edit]

Doses titrated to response.

Pharmacokinetics[edit]

Dose in renal impairment gfr (ml/min.)[edit]

Dose in patients undergoing renal replacement therapies[edit]

Important drug interactions[edit]

Potentially hazardous interactions with other drugs:

Route[edit]

Other information[edit]

Brand names[edit]

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, 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.

References[edit]

  1. ^ http://www.mhra.gov.uk/Howweregulate/Medicines/Namingofmedicines/ChangestomedicinesnamesBANstorINNs/index.htm
  2. ^ [1]
  3. ^ a b "Furosemide". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  4. ^ Rossi S, ed. (2004). Australian Medicines Handbook 2004 (5th ed.). Adelaide, S.A.: Australian Medicines Handbook Pty Ltd. ISBN 0-9578521-4-2. 
  5. ^ 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. 
  6. ^ BNF 45 March 2003
  7. ^ Brand name:Lasix - Generic name: Furosemide Prescription Drug Information, Side Effects - PDRHealth
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 

Further reading[edit]

External links[edit]