About Furosemide

Description: Furosemide is a potent loop diuretic that acts on the kidneys to increase water loss from the body.
Systematic IUPAC Name: 4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoic acid
Formula: C12-H11-Cl-N2-O5-S
Pharmacotherapeutic Group: Cardiovascular system; High-Ceiling Diuretics
ATC vet code: C03CA01

Clinical Applications

Furosemide is widely recognised and used clinically in veterinary medicine as a loop diuretic and is the core diuretic recommended in ACVIM MMVD consensus protocols (Keene et al., 2019). Furosemide demonstrates a wide spectrum of pharmacologic activity. Typical applications include:

CHF (Congestive Heart Failure)
Pulmonary Oedema
Hypercalcemia
AKI (Acute Kidney Injury)
Hyperkalemia: Potassium excretion increases with dose
Antihypertensive Agent: Furosemide has a vasodilatory effect.
Bronchospasm: Furosemide can be inhaled to relieve dyspnea in patients with bronchospasm (Abbott and Kovacic, 2008).
Anticonvulsant: Furosemide shows promise as an adjunct to antiseizure therapy to help control epilepsy, status epilepticus, and acute ischemic damage related to seizures (Abbott and Kovacic, 2008).

General Actions

Diuresis: Furosemide demonstrates a wide spectrum of pharmacologic activity, but its principal action is a high-ceiling loop diuretic.
Vasodilation: Furosemide has a vasodilatory effect that precedes diuresis and may confer its immediate benefit in patients with volume overload (Abbott and Kovacic, 2008).

Mechanism of Action

High-Ceiling Loop Diuretic: A sulfamoyl-anthranilic acid derivative is a rapid-onset high-ceiling loop diuretic. Furosemide increases nephron filtration volume and impairs sodium, chlorine, and water re-absorption. (Abbott and Kovacic, 2008; Adin et al., 2017, 2003; Berg and Loew, 1977; Cohen et al., 1976; Ding et al., 2016; Harada et al., 2015; Hori et al., 2010, 2007; Lee et al., 1986; Ochoa et al., 2006; Raisbeck et al., 1983; Sayer et al., 2009; Scruggs and Rishniw, 2013; Uechi et al., 2003).

Metabolism and Excretion

Renal: The kidneys are responsible for 85% of total furosemide clearance, where about 43% of the drug undergoes renal excretion. More furosemide is excreted in urine following the I.V. injection than after the tablet or oral solution. Approximately 50% of the furosemide load is excreted unchanged in urine, and the rest is metabolised into glucuronide in the kidney.

Adverse Effects

Azotaemia: Elevations in BUN and creatinine are seen. Long-term outcomes do not show that azotaemic qualities have detrimental patient effects.
Dehydration: Due to the diuretic action of furosemide, there may be hemoconcentration and impairment of circulation.
Electrolyte Derangement: Electrolyte deficiency (including hypokalemia & hyponatremia) and dehydration may occur with prolonged treatment.

Sulphonomide Sensitivity: Cross-reactivity to sulfonamides is possible.

Contraindications

Circulatory Compromise: Do not use Furosemide in hypovolaemia, hypotension or dehydration.
Compromised Cardiac Output: A marked reduction in cardiac output can occur in animals with severe pulmonary disease, hypertrophic cardiomyopathy, pericardial or myocardial disorders, cardiac tamponade and severe hypertension.
Electrolyte Derangement: Do not use Furosemide where there is known or suspected electrolyte deficiency. Do not use it in the presence of anuria, depleted electrolytes, or significant dehydration.
Excessive Dose: Do not use 40 mg tablets in patients weighing less than 4 kg.
Excessive Water Access: Therapeutic efficacy may be impaired by increased drinking water intake. Water intake should be restricted during treatment where the animal's condition permits.
Hypersensitivity: Do not use in cases of hypersensitivity to furosemide, sulfonamides, or excipients.
Interactive Medications: Monitoring plasma potassium levels is advisable during prolonged combined therapy treatment with Cardiac Glycosides. Potassium supplements may be necessary. Allergic reactions have been associated with the use of Sulphonamides. Do not use concurrently with Aminoglycoside antimicrobials. Do not use concurrently with Cephalosporin antimicrobials.
Nephropathy: Do not use in animals with acute glomerular nephritis, renal failure with anuria, or electrolyte deficiency disease.

Reproductive Safety

Pregnancy Avoid Use. Furosemide crosses the placenta. Embryotoxic effects (foetal urinary tract malformation) were seen in trials with laboratory animals at maternally non-toxic doses. However, some UK products are authorised for use during reproduction and lactation (SPC data).
Lactation: Avoid Use. Furosemide is excreted in milk and may affect nursing offspring. However, some UK products are authorised for use during reproduction and lactation (SPC data).
Male Fertility: Avoid Use. The effects are unknown (SPC data).
Female Fertility: Avoid Use. The effects are unknown (SPC data).
Neonates: Avoid Use. The effects are unknown (SPC data).

Overdose

Acute: Dehydration. Electrolyte and water imbalances. This may present as depressed mentation, akinesia, seizures, and cardiovascular collapse.
Chronic: Typically, electrolyte derangements such as hypokalemia are seen.

Potential Interactions

Anti-Arrhythmic Medications (including Amiodarone and Sotalol): Increased risk of cardiac toxicity because of Furosemide-induced hypokalaemia. Antagonism of effects of Lidocaine, Tocainide or Mexiletine possible.
Anti-Diabetic Medications: Antagonism of hypoglycaemic effects.
Anti-Hypertensive Medications: Enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors or Angiotensin II receptor antagonists can result in marked falls in blood pressure; Furosemide should be stopped or the dose reduced before starting an ACE inhibitor or Angiotensin II receptor antagonists. Increased risk of first-dose hypotension with post-synaptic alpha-blockers (e.g. Prazosin). Enhanced hypotensive effect with Phenothiazines.
Antihistamines: Hypokalaemia with increased risk of cardiac toxicity.
Antimicrobials: Increased risk of ototoxicity with Aminoglycosides, Polymixins or Vancomycin. Increased risk of nephrotoxicity with Aminoglycosides or Cefaloridine. Increased risk of hyponatraemia with Trimethoprim.
Anxiolytics and Hypnotics: Enhanced hypotensive effect of some agents.
Cardiac Glycosides: Increased risk of cardiac toxicity (because of Furosemide-induced hypokalaemia and electrolyte disturbances, including hypomagnesaemia).
Corticosteroids: Increased risk of hypokalaemia, sodium retention and possible antagonism of diuretic effect.
Cytotoxics: Increased risk of nephrotoxicity and ototoxicity with platinum compounds/Cisplatin.
NSAIDs: Increased risk of nephrotoxicity (especially with pre-existing hypovolaemia/dehydration. Indometacin and Ketorolac may antagonise the effects of Furosemide.
Oestrogens: Diuretic effect antagonised.
Other diuretics: Possible severe additive effect. Increased risk of hypokalaemia with Thiazide diuretics. Contraindicated concurrently with some potassium-sparing diuretic products (e.g. Amiloride/ Spironolactone) - increased risk of hyperkalaemia.
Potassium Salts: Contraindicated due to significant risk of hyperkalaemia.
Salicylates: Effects potentiated by Furosemide. Salicylic toxicity is increased.
Sympathomimetics: Increased risk of hypokalaemia with high doses of beta2 sympathomimetics.
Tetracyclines: Increased risk of azotaemia.
Torsades de pointes: Increased risk of cardiac toxicity when used alongside drugs that prolong Q-T interval because of Furosemide-induced hypokalaemia and other electrolyte disturbances.
Vasodilators: Enhanced hypotensive effect possible, e.g. with Hydralazine.

UK Formulations

Injection: 50 mg/ml Solution for Injection
Tablets: 10 mg, 20 mg, 40 mg tablets
Oral Liquids: 20 mg/5 ml Oral Solution and 10mg/ml Oral Solution