Furosemide 

is a loop diuretic medication used to treat fluid build-up due to heart failure, liver

scarring, or kidney disease.[1] It may also be used for the treatment of high blood pressure.[1] It can be
taken by injection into a vein or by mouth.[1] When taken by mouth, it typically begins working within
an hour, while intravenously, it typically begins working within five minutes.[1]
Common side effects include feeling lightheaded with standing, ringing in the ears, and sensitivity to
light.[1] Potentially serious side effects include electrolyte abnormalities, low blood pressure,
and hearing loss.[1] Blood tests are recommended regularly for those on treatment.[1] Furosemide is a
type of loop diuretic that works by decreasing the reabsorption of sodium by the kidneys.[1] Common
side effects of furosemide injection include hypokalemia (low potassium level), hypotension (low
blood pressure), and dizziness.[2]
Furosemide was patented in 1959 and approved for medical use in 1964.[3] It is on the World Health
Organization's List of Essential Medicines.[4] In the United States, it is available as a generic
medication.[1] In 2019, it was the seventeenth most commonly prescribed medication in the United
States, with more than 28 million prescriptions.[5][6] It is on the World Anti-Doping Agency's banned
drug list due to concerns that it may mask other drugs.[7] It has also been used in race horses for the
treatment and prevention of exercise-induced pulmonary hemorrhage.[8][9]

Furosemide is primarily used for the treatment of edema, but also in some cases
of hypertension (where there is also kidney or heart impairment).[10] It is often viewed as a first-line
agent in most people with edema caused by congestive heart failure because of its anti-
vasoconstrictor and diuretic effects.[11][1] Compared with furosemide, however, torasemide (aka
"torsemide") has been demonstrated to show improvements to heart failure symptoms, possibly
lowering the rates of rehospitalisation associated with heart failure, with no difference in risk of
death. [12][13][14] Torsemide may also be safer than furosemide.[15][16]
Furosemide is also used for liver cirrhosis, kidney impairment, nephrotic syndrome, in adjunct
therapy for swelling of the brain or lungs where rapid diuresis is required (IV injection), and in the
management of severe hypercalcemia in combination with adequate rehydration.[17]

Kidney disease[edit]
In chronic kidney diseases with hypoalbuminemia, furosemide is used along with albumin to
increase diuresis.[18] It is also used along with albumin in nephrotic syndrome to reduce edema.[19]

Other information[edit]
Furosemide is mainly excreted by tubular secretion in the kidney. In kidney impairment, clearance is
reduced, increasing the risk of adverse effects.[1] Lower initial doses are recommended in older
patients (to minimize side-effects) and high doses may be needed in kidney failure.[20] It can also
cause kidney damage; this is mainly by loss of excessive fluid (i.e., dehydration), and is usually
reversible.[citation needed]
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.[21]
Adverse effects[edit]
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.[22]
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.[23]
Furosemide is a known ototoxic agent generally causing transient hearing loss but can be
permanent. Reported cases of furosemide induced hearing loss appeared to be associated with
rapid intravenous administration, high dosages, concomitant renal disease and coadministration with
other ototoxic medication.[24][25] However, a recently reported longitudinal study showed that
participants treated with loop diuretics over 10 years were 40% more likely to develop hearing loss
and 33% more likely of progressive hearing loss compared to participants who did not use loop
diuretics.[26] This suggests the long-term consequences of loop diuretics on hearing could be a more
significant than previously thought and further research is required in this area.  
Other precautions include: nephrotoxicity, sulfonamide (sulfa) allergy, and increases free thyroid
hormone effects with large doses.[27]

Interactions[edit]
Furosemide has potential interactions with these medications:[28]

 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[edit]
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 more
sodium, chloride, and potassium to remain in the urine.[29]
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.[30][31]
[32]
 Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors
at μM concentrations, but not α1β2γ2 receptors.[30][32] During development, the α6β2γ2 receptor increases
in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide.[31]

Pharmacokinetics[edit]
 Molecular weight (daltons) 330.7
 % Bioavailability 47-70%
o Bioavailability with end-stage renal disease 43 - 46%[33][34]
 % Protein binding 91–99[35]
 Volume of distribution (L/kg) 0.07 – 0.2[36][37]
o Volume of distribution may be higher in patients with cirrhosis or nephrotic syndrome[36]
 Excretion
o % Excreted in urine (% of total dose) 60 - 90[36][37]
o % Excreted unchanged in urine (% of total dose) 53.1 - 58.8 [38]
o % Excreted in feces (% of total dose) 7 - 9[21]
o % Excreted in bile (% of total dose) 6 - 9[37]
 Approximately 10% is metabolized by the liver in healthy individuals, but this percentage may be
greater in individuals with severe kidney failure [37]
 Renal clearance (mL/min/kg) 2.0[36]
 Elimination half-life (hrs) 2[35]
o Prolonged in congestive heart failure (mean 3.4 hrs)[36][39]
o Prolonged in severe kidney failure (4 - 6 hrs)[40] and anephric patients (1.5-9 hrs)[37]
 Time to peak concentration (hrs)
o Intravenous administration 0.3[41]
o Oral solution 0.83[35]
o Oral tablet 1.45[35]
The pharmacokinetics of furosemide are apparently not significantly altered by food.[42]
No direct relationship has been found between furosemide concentration in the plasma and
furosemide efficacy. Efficacy depends upon the concentration of furosemide in urine.[21]

Names[edit]
Furosemide is the INN and BAN.[43] The previous BAN was frusemide.
Brand names under which furosemide is marketed include: Aisemide, Apo-Furosemide, Beronald,
Desdemin, Discoid, Diural, Diurapid, Dryptal, Durafurid, Edemid, Errolon, Eutensin, Flusapex,
Frudix, Frusemide, 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.