Furosemide

Absorption

Furosemide, when administered orally, is absorbed from the gastrointestinal tract. The bioavailability of this medication can vary significantly across different oral dosage forms, with reported ranges from 10% to 90%. Specifically, when comparing oral tablets and oral solutions to an intravenous injection of the drug, the oral bioavailability is approximately 64% and 60%, respectively, of the intravenous administration. This indicates that the efficiency of absorption can differ based on the form in which furosemide is taken.

Toxicity

Clinical consequences from overdose depend on the extent of electrolyte and fluid loss and include dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia, hypochloremic alkalosis, hemoconcentration, cardiac arrhythmias (including A-V block and ventricular fibrillation). Symptoms of overdose include acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion. In cirrhotic patients, overdosage might precipitate hepatic coma.
In rats, the oral LD50, intraperitoneal LD50, and subcutaneous LD50 is 2600 mg/kg, 800 mg/kg, and 4600 mg/kg, respectively. The Lowest published toxic dose (TDLo) in a female is 6250 μg/kg.

Description

Furosemide, identified by Item No. 26298, is classified as a diuretic and serves as an analytical reference standard. It is important to note that formulations containing diuretics like furosemide have been known to be misused in sports for purposes such as weight reduction, as masking agents in humans, and to prevent exercise-induced pulmonary hemorrhage in racehorses.

This product, furosemide, is primarily intended for use in analytical forensic applications, where its properties can be utilized for detection and analysis in various testing scenarios. Additionally, it is available as a general research tool, offering versatility for scientists and researchers in different fields of study.

Chemical properties

white to light yellow crystal powde

Originator

Lasix,Hoechst,W. Germany,1964

The Uses of Furosemide

Furosemide inhibits ion co-transport in the kidney. Furosemide is used as a diuretic.

The Uses of Furosemide

diuretic, antihypertensive

The Uses of Furosemide

This compound belongs to the aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.

The Uses of Furosemide

An inhibitor of NKCC and a GABAA receptor antagonist.

Background

Furosemide is a potent loop diuretic that is derived from anthranilic acid. It functions by acting on the kidneys to inhibit electrolyte reabsorption and enhance the excretion of water, thereby increasing water loss from the body. This medication is particularly effective for treating edema that arises from a variety of clinical conditions, including congestive heart failure exacerbation, liver failure, renal failure, and high blood pressure.

Furosemide is known for its fast onset and short duration of action, making it a suitable choice for situations that require a drug with high diuretic potential. It has been used safely and effectively in both pediatric and adult patients. The drug's benefits are especially notable in clinical settings where a strong diuretic effect is needed.

What are the applications of Application

Furosemide is an inhibitor of NKCC and a GABAA receptor antagonist

Indications

Furosemide is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome, in adults and pediatric patients.
Oral furosemide is indicated alone for the management of mild to moderate hypertension or severe hypertension in combination with other antihypertensive medications.
Intravenous furosemide is indicated as adjunctive therapy in acute pulmonary edema when a rapid onset of diuresis is desired.
Subcutaneous furosemide is indicated for the treatment of congestion due to fluid overload in adults with NYHA Class II/III chronic heart failure. This drug formulation is not indicated for emergency situations or in patients with acute pulmonary edema.

Definition

A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration and anti-hypertensive agent.

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

General Description

Odorless white to slightly yellow crystalline powder. A diuretic drug. Almost tasteless.

Air & Water Reactions

Light sensitive. Air sensitive. Slightly soluble in water.

Reactivity Profile

Furosemide 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 Furosemide. Incompatible with strong oxidizing agents .

Hazard

Poison; moderately toxic; teratogen; questionable carcinogen; mutagen.

Fire Hazard

Flash point data for Furosemide are not available; however, Furosemide is probably combustible.

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.

Safety Profile

Poison by intravenous route. Moderately toxic by ingestion and intraperitoneal routes. Human systemic effects by intravenous route: change in the sensitivity of the ear to sound, tinnitus, unspecified effects on the heart, constriction of the arteries, a decrease in urine volume, interstitial nephritis, metabolic alkalosis, pulse rate decrease, fall in blood pressure. Ingestion can damage the liver. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic effects. Human mutation data reported. When heated to decomposition it emits very toxic fumes of Cl-, NOx, and SOx.

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.

storage

Store at RT

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.