General Description
Odorless white to slightly yellow crystalline powder. A diuretic drug. Almost tasteless.
Reactivity Profile
FUROSEMIDE(54-31-9) may undergo hydrolysis at sufficiently low pH. The pH of aqueous solutions should be maintained in the basic range to prevent hydrolysis. Alcohol has been shown to improve the stability of this compound. Incompatible with strong oxidizing agents .
Air & Water Reactions
Light sensitive. Air sensitive. Slightly soluble in water.
Fire Hazard
Flash point data for this chemical are not available; however, FUROSEMIDE is probably combustible.
Description
Furosemide (Item No. 26298) is an analytical reference standard categorized as a diuretic.
1 Formulations containing diuretics, including furosemide, have been misused in sports for weight reduction and as masking agents in humans and to prevent exercise-induced pulmonary hemorrhage in racehorses.
1,2 This product is intended for use in analytical forensic applications. This product is also available as a general research tool (Item No.
17273).
Originator
Lasix,Hoechst,W. Germany,1964
Manufacturing Process
10.8 grams of 3-sulfamyl-4,6-dichlorobenzoic acid (0.04 mol) and 11.7 grams
of furfurylamine (0.12 mol) are heated in 30 cc of diethyleneglycoldimethylether for 6 hours under reflux. When pouring the reaction mixture
into 300 cc of 1 N hydrochloric acid, the reaction product is immediately
separated off in the form of crystals. The light-yellow crude product is purified
by dissolving it in 100 cc of warm 1 N sodium bicarbonate solution,
precipitation by means of hydrochloric acid and subsequent recrystallization
from ethanol/water, with addition of charcoal. Colorless prisms are obtained
which decompose at 206°C while adopting a brown coloration, and with
evolution of gas.
Brand name
Lasix (Sanofi Aventis).
Therapeutic Function
Diuretic
Biological Activity
Loop diuretic that inhibits the Na + /2Cl - /K + (NKCC) cotransporter. Also acts as a non-competitive antagonist at GABA A receptors with ~ 100-fold greater selectivity for α 6-containing receptors than α 1-containing receptors.
Biochem/physiol Actions
Inhibits ion co-transport in the kidney.
Mechanism of action
Furosemide is a highly effective and quick-acting diuretic whose action, like all of the
examined loop diuretics, is associated with blocking reabsorption of ions in the ascending
bend of Henle’s loop. It is used for edema syndrome of various origins, edema of the lungs
and brain, chronic renal insufficiency, some forms of hypertonic crises, and poisoning by
barbiturates and other compounds excreted mainly with urine.
Clinical Use
Furosemide has a saluretic effect 8- to 10-fold that of the thiazide diuretics; however, it has a shorter duration of action (~6–8 hours). Furosemide causes a marked
excretion of sodium, chloride, potassium, calcium, magnesium, and bicarbonate ions, with as much as 25% of the filtered load of sodium excreted in response to initial
treatment. It is effective for the treatment of edemas connected with cardiac, hepatic, and renal sites. Because it lowers the blood pressure similar to the thiazide
derivatives, one of its uses is in the treatment of hypertension.
Side effects
Clinical toxicity of furosemide and other loop diuretics primarily involves abnormalities of fluid and electrolyte balance. As with the thiazide diuretics, hypokalemia is an
important adverse effect that can be prevented or treated with potassium supplements or coadministration of potassium-sparing diuretics. Increased calcium ion excretion
can be a problem for postmenopausal osteopenic women, and furosemide generally should not be used in these individuals. Hyperuricemia, glucose intolerance,
increased serum lipid levels, ototoxicity, and gastrointestinal side effects might be observed as well. Hypersensitivity reactions also are possible with furosemide (a
sulfonamide-based drug), and cross-reactivity with other sulfonamide containing drugs is possible.
Synthesis
Furosemide, 4-chloro-N-furfuryl-5-sulfamoylanthranylic acid (21.4.11), is
synthesized in a relatively simple manner from 2,4-dichlorobenzoic acid, which is converted
into 5-aminosulfonyl-4,6-dichlorobenzoic acid (21.4.10) during subsequent reaction
with chlorosulfonic acid and ammonia. Reacting this with furfurylamine gives
furosemide (21.4.11) .
Veterinary Drugs and Treatments
Furosemide is used for its diuretic activity in all species. It is used
in small animals
for the treatment of congestive cardiomyopathy,
pulmonary edema, hypercalcuric nephropathy, uremia, as adjunctive
therapy in hyperkalemia and, occasionally, as an antihypertensive
agent. In cattle,
it is approved for use for the treatment of
post-parturient udder edema. It has been used to help prevent or
reduce epistaxis (exercise-induced pulmonary hemorrhage; EIPH)
in racehorses.
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: increased risk of nephrotoxicity with
NSAIDs; antagonism of diuretic effect with
NSAIDs.
Anti-arrhythmics: risk of cardiac toxicity with
anti-arrhythmics if hypokalaemia occurs; effects of
lidocaine and mexiletine antagonised.
Antibacterials: increased risk of ototoxicity with
aminoglycosides, polymyxins and vancomycin; avoid
with lymecycline.
Antidepressants: increased risk of hypokalaemia with
reboxetine; enhanced hypotensive effect with MAOIs;
increased risk of postural hypotension with tricyclics.
Antiepileptics: increased risk of hyponatraemia with
carbamazepine; effects antagonised by phenytoin.
Antifungals: increased risk of hypokalaemia with
amphotericin.
Antihypertensives: enhanced hypotensive effect;
increased risk of first dose hypotensive effect
with alpha-blockers; increased risk of ventricular
arrhythmias with sotalol if hypokalaemia occurs.
Antipsychotics: increased risk of ventricular
arrhythmias with amisulpride or pimozide (avoid
with pimozide) if hypokalaemia occurs; enhanced
hypotensive effect with phenothiazines.
Atomoxetine: hypokalaemia increases risk of
ventricular arrhythmias.
Cardiac glycosides: increased toxicity if hypokalaemia
occurs.
Ciclosporin: variable reports of increased
nephrotoxicity, ototoxicity and hepatotoxicity.
Cytotoxics: concentration of furosemide increased
by dasabuvir, ombitasvir and paritaprevir - reduce
furosemide dose; increased risk of ventricular
arrhythmias due to hypokalaemia with arsenic
trioxide; increased risk of nephrotoxicity and
ototoxicity with platinum compounds.
Lithium: risk of toxicity.
Metabolism
Little biotransformation of furosemide takes place. It
is mainly eliminated via the kidneys (80-90%); a small
fraction of the dose undergoes biliary elimination and
10-15% of the activity can be recovered from the faeces.
storage
4°C, protect from light
References
[1]. hochman dw. the extracellular space and epileptic activity in the adult brain: explaining the antiepileptic effects of furosemide and bumetanide. epilepsia, 2012, 53 suppl 1: 18-25.
[2]. chen h, sun d. the role of na-k-cl co-transporter in cerebral ischemia. neurol res, 2005, 27(3): 280-286.
[3]. prandota j. furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases. am j ther, 2002, 9(4): 317-328.
