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| {{drugbox |
| | #REDIRECT [[Furosemide#Pharmacology]] |
| | IUPAC_name = 5-(aminosulfonyl)-4-chloro-2-<br>[(2-furanylmethyl)amino]benzoic acid
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| | image = furosemide-2D-skeletal.png
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| | image2 = furosemide-3D-vdW.png
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| | CAS_number = 54-31-9
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| | ATC_prefix = C03
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| | ATC_suffix = CA01
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| | PubChem = 162482
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| | DrugBank = APRD00608
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| | smiles = NS(=O)(=O)c1cc(C(O)=O)c(NCc2occc2)cc1Cl
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| | C = 12 |H = 11 |Cl = 1 |N = 2 |O = 5 |S = 1
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| | molecular_weight = 330.745 g/mol
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| | bioavailability = 43-69%
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| | protein_bound =
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| | metabolism = hepatic and renal [[glucuronidation]]
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| | elimination_half-life = up to 100 minutes
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| | excretion = renal 66%, biliary 33%
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| | pregnancy_AU = C
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| | pregnancy_US = C
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| | legal_status = Rx-only
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| | routes_of_administration = Oral, [[Intravenous therapy|IV]], [[Intramuscular injection|IM]]
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| }}
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| {{CMG}}
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| ==[[Furosemide (patient information)|For patient information, click here]]==
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| '''Furosemide''' ([[International Nonproprietary Name|INN]]) or '''frusemide''' (former [[British Approved Name|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'''.
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| Along with some other diuretics, furosemide is also included on the [[World Anti-Doping Agency]]'s [[doping (sport)|banned drug]] list due to its alleged use as a masking agent for other drugs.
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| ==Mechanism of action==
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| {{main|Loop diuretic}}
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| 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.
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| 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).
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| ==Clinical use in humans==
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| Furosemide, as a loop diuretic, is principally used in the following indications (Aventis, 1998):
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| * [[Edema]] associated with [[heart failure]], hepatic [[cirrhosis]], [[renal impairment]], [[nephrotic syndrome]]
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| * [[Hypertension]]
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| * Adjunct in [[cerebral edema|cerebral]]/[[pulmonary edema]] where rapid [[diuresis]] is required ([[intravenous|IV]] injection)
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| It is also sometimes used in the management of severe [[hypercalcemia]] in combination with adequate rehydration (Rossi, 2004).
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| Although disputed,<!--
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| --><ref name="AmJPerinatol2004-Rais-Bahrami">{{cite journal | author = Rais-Bahrami K, Majd M, Veszelovszky E, Short B | title = Use of furosemide and hearing loss in neonatal intensive care survivors. | journal = Am J Perinatol | volume = 21 | issue = 6 | pages = 329-32 | year = 2004 | id = PMID 15311369}}</ref>
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| it is considered [[ototoxic]]: ''"usually with large parenteral doses and rapid administration and in renal impairment"''<!--
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| --><ref>[[British National Formulary|BNF]] '''45''' March 2003</ref>
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| 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]]).
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| ==Use in horses==
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| 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|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.
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| 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.
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| ===Precautions, side-effects, and administration===
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| 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.
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| 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. | |
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| 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).
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| Furosemide is detectible in urine 36-72 hours following injection. Its use is prohibited by most equestrian organizations.
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| ==Drug Interactions==
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| Furosemide has potential interactions with the following medications:[http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/las1220.shtml]
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| * [[Aminoglycoside]] [[antibiotics]] such as [[Gentamicin]]
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| * [[Aspirin]] and other salicylates
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| * Other diuretics (e.g. [[Ethacrynic acid]])
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| * [[Indomethacin]]
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| * [[Lithium pharmacology|Lithium]]
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| * Synergistic effects with other [[antihypertensive]]s (e.g. [[Doxazosin]])
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| * [[Sucralfate]]
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| ==Brand names==
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| 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
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| Founded around 1964.
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| ==References==
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| {{reflist|2}}
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| ==Further reading==
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| * Aventis Pharma (1998). ''Lasix Approved Product Information''. Lane Cove: Aventis Pharma Pty Ltd.
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| * Forney, Barbara C, MS, VMD. ''Equine Medications, Revised Edition.'' Blood Horse Publications. Lexington, KY. Copyright 2007.
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| * Rossi S (Ed.) (2004). ''[[Australian Medicines Handbook]] 2004''. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
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| * {{cite journal |author=Korpi ER, Kuner T, Seeburg PH, Lüddens H |title=Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor |journal=Mol. Pharmacol. |volume=47 |issue=2 |pages=283-9 |year=1995 |pmid=7870036 |doi=}}
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| * {{cite journal |author=Tia S, Wang JF, Kotchabhakdi N, Vicini S |title=Developmental changes of inhibitory synaptic currents in cerebellar granule neurons: role of GABA(A) receptor alpha 6 subunit |journal=J. Neurosci. |volume=16 |issue=11 |pages=3630-40 |year=1996 |pmid=8642407 |doi= |url=http://www.jneurosci.org/cgi/content/full/16/11/3630}}
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| * {{cite journal |author=Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ |title=Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit |journal=Mol. Pharmacol. |volume=50 |issue=3 |pages=670-8 |year=1996 |pmid=8794909 |doi=}}
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| ==External links==
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| * [http://www.thinkythings.org/horseracing/lasixinfo.html Lasix and horse bleeding]
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| * [http://www.wada-ama.org/rtecontent/document/list_2005.pdf "Diuretics and other masking agents"] ([[Portable Document Format|PDF]]) – Part S5 of the World Anti-Doping Agency's ''2005 Prohibited List. International Standard.''
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| {{Antihypertensives and diuretics}}
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| [[Category:Loop diuretics]]
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