Furosemide
Encyclopedia
Furosemide or frusemide (former BAN
British Approved Name
A British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...

) is a loop diuretic
Loop diuretic
Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency...

 used in the treatment of congestive heart failure and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

. It is most commonly marketed by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...

 under the brand name Lasix. It has also been used to prevent Thoroughbred
Thoroughbred
The Thoroughbred is a horse breed best known for its use in horse racing. Although the word thoroughbred is sometimes used to refer to any breed of purebred horse, it technically refers only to the Thoroughbred breed...

 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
World Anti-Doping Agency
The World Anti-Doping Agency , , is an independent foundation created through a collective initiative led by the International Olympic Committee . It was set up on November 10, 1999 in Lausanne, Switzerland, as a result of what was called the "Declaration of Lausanne", to promote, coordinate and...

's banned drug
Doping (sport)
The use of performance-enhancing drugs in sport is commonly referred to by the term "doping", particularly by those organizations that regulate competitions. The use of performance enhancing drugs is mostly done to improve athletic performance. This is why many sports ban the use of performance...

 list due to its alleged use as a masking agent for other drugs.

Medical uses

Furosemide is primarily used for the treatment of two conditions: hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

. It is the first line agent in most people with edema due to congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

.
  • Edema
    Edema
    Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

     associated with heart failure, hepatic cirrhosis
    Cirrhosis
    Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...

    , renal impairment, nephrotic syndrome
    Nephrotic syndrome
    Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....

  • Hypertension
    Hypertension
    Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

  • Adjunct in cerebral
    Cerebral edema
    Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...

    /pulmonary edema
    Pulmonary edema
    Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...

     where rapid diuresis
    Diuresis
    Diuresis may refer to:* Urine production, as an aspect of fluid balance* Excessive urine production - see polyuria* Immersion diuresis...

    , i.e. lowering body water content by inducing urination, is required (IV injection)


It is also sometimes used in the management of severe hypercalcemia in combination with adequate rehydration.

Adverse effects

Although disputed,
it is considered ototoxic: "usually with large parenteral doses and rapid administration and in renal impairment"
Furosemide also can lead to gout.

The tendency, as for all loop diuretics, to cause low potassium levels (hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...

) has given rise to combination products, either with potassium itself (e.g. Lasix-K) or with the potassium sparing diuretic of amiloride
Amiloride
Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...

 (Co-amilofruse
Co-amilofruse
Co-amilofruse is a non-proprietary name used to denote a combination of amiloride and the formerly named frusemide . Co-amilofruse in the treatment of fluid retention , either in the legs or on the lungs...

).

Interactions

Furosemide has potential interactions with the following medications:
  • Aminoglycoside
    Aminoglycoside
    An aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...

     antibiotics such as gentamicin
    Gentamicin
    Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...

  • Aspirin
    Aspirin
    Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

     and other salicylates
  • Other diuretics (e.g. ethacrynic acid
    Ethacrynic acid
    Etacrynic acid or ethacrynic acid , trade name Edecrin, is a loop diuretic used to treat high blood pressure and the swelling caused by diseases like congestive heart failure, liver failure, and kidney failure....

    , hydrochlorothiazide
    Hydrochlorothiazide
    Hydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...

    )
  • Indomethacin
  • Lithium
    Lithium pharmacology
    Lithium pharmacology refers to use of the lithium ion, Li+, as a drug. A number of chemical salts of lithium are used medically as a mood stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania, both acutely...

  • Synergistic effects with other antihypertensive
    Antihypertensive
    The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

    s (e.g. doxazosin
    Doxazosin
    Doxazosin mesylate, a quinazoline compound sold by Pfizer under the brand names Cardura and Carduran, is an α1a-selective alpha blocker used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia ....

    )
  • Sucralfate
    Sucralfate
    Sucralfate is a cytoprotective agent, an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Brand names include Sucramal in Italy; Carafate in U.S.A.; Pepsigard, Sucral, Sucrafil, Hapifate in India; Sutra or Musin in parts of South-East Asia; Sulcrate...


Mechanism of action

Furosemide, like other loop diuretics, acts by inhibiting NKCC2, the luminal Na-K-2Cl symporter
Na-K-2Cl symporter
The Na-K-Cl cotransporter is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells. There are two varieties, or isoforms, of this membrane transport protein, called NKCC1 and NKCC2. NKCC1 is widely distributed throughout the body; it has important...

 in the thick ascending limb of the loop of Henle
Loop of Henle
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer F. G. J...

. 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
Free water clearance
In the physiology of the kidney, free water clearance is the volume of blood plasma that is cleared of solute-free water per unit time. An example of its use is in the determination of an individual's state of hydration.-Overview:...

.

Due to 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 reabsorbtion in the loop, and by reducing this potential loop, diuretics cause an increase in Mg2+ and Ca2+ excretion. Prolonged use can cause significant hypomagnesemia
Hypomagnesemia
Hypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...

 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. Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors at µM concentrations, but not α1β2γ2 receptors. During development, the α6β2γ2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide.

Brand names

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, Trofurit, Uremide and Urex.
The name Lasix is derived from the phrase "lasts six (hours)" referring to its duration of action.
Intravenous and oral Lasix lasts two to four hours.

Veterinary uses

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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 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 (who expereince fluid on the lungs) due to complications from heartworms. It can be used in conjunction with an antibiotic and anti-inflamitory to treat this condition.

Precautions, side effects, and administration

Furosemide is injected either intramuscularly
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...

 (IM) or intravenously
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...

 (IV), usually 0.5-1.0 mg/kg 2x/day, although less before a horse is raced. As with many diuretics, it can cause dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...

 and electrolyte imbalance, including loss of potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

, calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

, sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

, and magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

. It is especially important to prevent potassium loss. Excessive use of furosemide will most likely lead to a metabolic alkalosis
Metabolic alkalosis
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*Alkalosis...

 due to hypochloremia
Hypochloremia
Hypochloremia is an electrolyte disturbance whereby there is an abnormally depleted level of the chloride ion in the blood.It rarely occurs in the absence of other abnormalities.It can be associated with hypoventilation....

 and hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...

. 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 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 kidney's ability to excrete aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

, so dosages will need to be adjusted if combined with that drug

Furosemide may increase the risk of digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...

 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.

Further reading

  • Aventis Pharma
    Aventis Pharma
    Aventis Pharma Limited , headquartered in Mumbai, is a part of Sanofi-Aventis group. Sanofi-Aventis and its 100% subsidiary Hoechst AG, are the major shareholders of Aventis Pharma Limited...

     (1998). Lasix Approved Product Information. Lane Cove: Aventis Pharma Pty Ltd.

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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