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Furosemide



Furosemide
Systematic (IUPAC) name
5-(aminosulfonyl)-4-chloro-2-
[(2-furanylmethyl)amino]benzoic acid
Identifiers
CAS number 54-31-9
ATC code C03CA01
PubChem 162482
DrugBank APRD00608
Chemical data
Formula C12H11ClN2O5S 
Mol. mass 330.745 g/mol
SMILES search in eMolecules, PubChem
Pharmacokinetic data
Bioavailability 43-69%
Metabolism hepatic and renal glucuronidation
Half life up to 100 minutes
Excretion renal 66%, biliary 33%
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)

Legal status

Prescription only

Routes Oral, IV, IM

Furosemide (INN) 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-Aventis under the brand name Lasix. 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.

Additional recommended knowledge

Contents

Mechanism of action

Main article: Loop diuretic

The name of lasix is derived as it "LAsts SIX hours" -- referring to its duration of action. Like other loop diuretics, furosemide acts by inhibiting the Na-K-2Cl symporter in the thick ascending 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.

Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors (Korpi et al, 1995, Tia et al, 1996, Wafford et al, 1996). Furosemide has been reported to reversibly antagonize GABA-evoked currents of alpha6 beta2 gamma2 receptors at microM concentrations, but not alpha1 beta2 gamma2 receptors (Korpi et al, 1995; Wafford et al, 1996). During development, the alpha6 beta2 gamma2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide (Tia et al, 1995).

Clinical use in humans

Furosemide, as a loop diuretic, is principally used in the following indications (Aventis, 1998):

  • Edema associated with heart failure, hepatic cirrhosis, renal impairment, nephrotic syndrome
  • Hypertension
  • Adjunct in cerebral/pulmonary edema where rapid diuresis is required (IV injection)

It is also sometimes used in the management of severe hypercalcemia in combination with adequate rehydration (Rossi, 2004).

Although disputed,[1] it is considered ototoxic: "usually with large parenteral doses and rapid administration and in renal impairment"[2]

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

Use in horses

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. 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). Clinical trials followed, and by decade's end, racing commissions in some states 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 that it increases circulation to the kidneys, it does not help kidney function, and is not recommended for kidney disease.

Precautions, side-effects, and administration

Furosemide is injected either IM or IV, usually 0.5-1.0 mg/lb 2x/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. It is especially important to prevent potassium loss, as it can cause serious problems. 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, GI problems, kidney damage, lethargy, collapse, and coma.

Furosemide should be used with caution when combined with corticosteriods (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 kidney's ability to excrete aspirin, so dosages will need to be adjusted if combined with that drug.

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 detectible in urine 36-72 hours following injection. Its use is prohibited by most equestrian organizations.

Drug Interactions

Furosemide has potential interactions with the following medications:[1]

Brand names

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

Founded around 1964.

References

  1. ^ 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. PMID 15311369.
  2. ^ BNF 45 March 2003

Further reading

  • Aventis Pharma (1998). Lasix Approved Product Information. Lane Cove: Aventis Pharma Pty Ltd.
  • Forney, Barbara C, MS, VMD. Equine Medications, Revised Edition. Blood Horse Publications. Lexington, KY. Copyright 2007.
  • Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
  • Korpi ER, Kuner T, Seeburg PH, Lüddens H (1995). "Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor". Mol. Pharmacol. 47 (2): 283-9. PMID 7870036.
  • 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.
  • 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.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Furosemide". A list of authors is available in Wikipedia.
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