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Additional information about the drug Furosemide


Furosemide, sold under the brand name Lasix among others, is a medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease.
Common side effects include low blood pressure with standing, ringing in the ears, and sensitivity to sunlight.
Furosemide was discovered in 1962
Contents
1 Medical uses
1.1 Kidney disease
1.2 Other information
2 Adverse effects
2.1 Interactions
3 Mechanism of action
4 Pharmacokinetics
5 Names
6 Veterinary uses
6.1 Horses
7 References
8 Further reading
9 External links
Medical uses
Furosemide (Lasix) for injection
Furosemide is primarily used for the treatment of edema, but also in some cases of hypertension (where there is also kidney or heart impairment).
Kidney disease
In chronic kidney diseases with hypoalbuminemia, it is used along with albumin to increase diuresis. It is also used along with albumin in nephrotic syndrome to reduce edema.
Other information
It is mainly excreted by tubular secretion in the kidney. In kidney impairment, clearance is reduced, increasing the risk of aderse effects. It can also cause kidney damage; this is mainly by loss of excessive fluid (i.e. dehydration), and is usually reversible.
Furosemide acts within 1 hour of oral administration (after IV injection, the peak effect is within 30 minutes). Diuresis is usually complete within 6–8 hours of oral administration, but there is significant variation between individuals.
Adverse effects
Furosemide also can lead to gout caused by hyperuricemia. Hyperglycemia is also a common side effect.
The tendency, as for all loop diuretics, to cause low serum potassium concentration ( hypokalemia ) has given rise to combination products, either with potassium or with the potassium-sparing diuretic amiloride ( Co-amilofruse ). Other electrolyte abnormalities that can result from furosemide use include hyponatremia, hypochloremia, hypomagnesemia, and hypocalcemia.
In the treatment of heart failure, many studies have shown that the long-term use of furosemide can cause varying degrees of thiamine deficiency, so thiamine supplementation is also suggested.
Although disputed,
Other precautions include: nephrotoxicity, sulfonamide (sulfa) allergy, and increases free thyroid hormone effects with large doses.
Interactions
Furosemide has potential interactions with these medications:
Aspirin and other salicylates
Other diuretics (e.g. ethacrynic acid, hydrochlorothiazide )
Synergistic effects with other antihypertensives (e.g. doxazosin )
Sucralfate
Potentially hazardous interactions with other drugs:
Analgesics : increased risk of kidney damage (nephrotoxicity) with nonsteroidal anti-inflammatory drugs ; antagonism of diuretic effect with NSAIDs
Antiarrhythmics: a risk of cardiac toxicity exists with antiarrhythmics if hypokalemia occurs; the effects of lidocaine and mexiletine are antagonized.
Antibacterials : increased risk of ototoxicity with aminoglycosides, polymyxins and vancomycin ; avoid concomitant use with lymecycline
Antidepressants : increased risk of hypokalemia with reboxetine; enhanced hypotensive effect with MAOIs ; increased risk of postural hypotension with tricyclic antidepressants
Antiepileptics : increased risk of hyponatremia with carbamazepine
Antifungals : increased risk of hypokalemia with amphotericin
Antihypertensives : enhanced hypotensive effect; increased risk of first dose hypotensive effect with alpha-blockers ; increased risk of ventricular arrhythmias with sotalol if hypokalemia occurs
Antipsychotics : increased risk of ventricular arrhythmias with amisulpride, sertindole, or pimozide (avoid with pimozide) if hypokalemia occurs; enhanced hypotensive effect with phenothiazines
Atomoxetine : hypokalemia increases risk of ventricular arrhythmias
Cardiac glycosides : increased toxicity if hypokalemia occurs
Cyclosporine : variable reports of increased nephrotoxicity, ototoxicity and hepatotoxicity
Lithium : risk of toxicity.
Mechanism of action
Main article: Loop diuretic
Furosemide, like other loop diuretics, acts by inhibiting the luminal Na-K-Cl cotransporter in the thick ascending limb of the loop of Henle, by binding to the chloride transport channel, thus causing sodium, chloride, and potassium loss in urine.
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. Because of 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.
Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors.
Pharmacokinetics
Molecular weight (daltons) 330.7
% Bioavailability 47-70%
Bioavailability with end-stage renal disease 43 – 46%
% Protein binding 91–99
Volume of distribution (L/kg) 0.07 – 0.2
Volume of distribution may be higher in patients with cirrhosis or nephrotic syndrome
Excretion
% Excreted in urine (% of total dose) 60 – 90
% Excreted unchanged in urine (% of total dose) 53.1 – 58.8
% Excreted in feces (% of total dose) 7 – 9
% Excreted in bile (% of total dose) 6 – 9
Approximately 10% is metabolized by the liver in healthy individuals, but this percentage may be greater in individuals with severe renal failure
Renal clearance (mL/min/kg) 2.0
Elimination half-life (hrs) 2
Prolonged in congestive heart failure (mean 3.4 hrs)
Prolonged in severe renal failure (4 – 6 hrs)
Time to peak concentration (hrs)
Intravenous administration 0.3
Oral solution 0.83
Oral tablet 1.45
The pharmacokinetics of furosemide are apparently not significantly altered by food.
No direct relationship has been found between furosemide concentration in the plasma and furosemide efficacy. Efficacy depends upon the concentration of furosemide in urine.
Names
Furosemide is the INN and BAN. The previous BAN was frusemide.
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, Furon, Furosedon, Fusid.frusone, Hydro-rapid, Impugan, Katlex, Lasilix, Lasix, Lodix, Lowpston, Macasirool, Mirfat, Nicorol, Odemase, Oedemex, Profemin, Rosemide, Rusyde, Salix, Seguril, Teva-Furosemide, Trofurit, Uremide, and Urex.
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 ( exercise-induced pulmonary hemorrhage ) by horses during races was discovered accidentally. In the United States of America, pursuant to the racing rules of most states, horses that bleed from the nostrils three times are permanently barred from racing. Clinical trials followed, and by decade’s end, racing commissions in some states in the USA 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”. Its use for this purpose is still prohibited in many other countries.
Furosemide is also used in horses for pulmonary edema, congestive heart failure (in combination with other drugs), and allergic reactions. Although 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 (pulmonary edema, pleural effusion, and/or ascites) in cats and dogs. It can also be used in an attempt to promote urine production in anuric or oliguric acute renal failure.
Horses
Furosemide is injected either intramuscularly or intravenously, usually 0.5-1.0 mg/kg twice/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. Excessive use of furosemide will most likely lead to a metabolic alkalosis due to hypochloremia and hypokalemia. 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, gastrointestinal 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 kidneys’ ability to excrete aspirin, so dosages will need to be adjusted if combined with that drug.
Furosemide may increase the risk of digoxin 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.

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