Review on Furosemide

Santosh B. Dighe, Sonawane Shubham Ramesh, Thete Bhati Sharad, Tarkase Sahil Bhausaheb

 Department Pharmacology, PRCOP Loni.

*Corresponding Author E-mail: shubhams2903@gmail.com

ABSTRACT:

Furosemide is a potent loop diuretic used to treat hypertension and edematous conditions associated with heart, renal, and hepatic failure. Its mode of action involves inhibiting chloride reabsorption in the ascending limb of the loop of Henle. However, the exact mechanism is not fully understood. Variability in response to furosemide can occur due to differences in fluid and electrolyte balance, as well as individual differences in drug metabolism and elimination. Both acute and delayed tolerance to furosemide have been reported. The drug is primarily eliminated via the kidneys, and its pharmacokinetics can be influenced by renal function. Furosemide has a high degree of plasma protein binding, limiting its distribution despite its low solubility in water. Variability in bioavailability is attributed to factors such as low solubility, presystemic metabolism, and site-specific absorption. The involvement of a nonspecific organic acid pump in the active secretion of furosemide to its site of action is mentioned. Overall, furosemide therapy requires individualized dosing and close monitoring due to its complex pharmacokinetics and potential for adverse effects.

KEYWORDS: Furosemide is a potent loop diuretic used for hypertension and edema.

INTRODUCTION:

Structure of furosemide:- 

Molecular weight: 330.745g/Mol.

Profile:

Furosemide is a potent loop diuretic which an anthranilic acid Furosemide is a potent loop diuretic used for hypertension and edema.

Its mode of action involves inhibiting chloride reabsorption in the loop of Henle

Variability in response can occur due to fluid/electrolyte balance and individual differences

Associated Conditions:

1. Edema

2. Body Fluid Retention

3. Acute pulmonary edema

4. Mild to moderate hypertension

5. Chest Congestion

6. Ascites

7. Cirrhosis.

Mechanism of Action:

· Furosemide mainly acts on the kidney which ultimately increases the water loss from body It blocks the tubular reabsorption of sodium and chloride

· In the proximal, distal tubule and also in the thick ascending loop of Henle. 

· The competitive inhibition of sodium-potassium-chloride cotransporters (NKCC2) occurs in the nephron and diuresis effect is achieved. 

· Increased excretion of water along with sodium, chloride, magnesium, calcium, hydrogen, and potassium ions is due to the inhibiting transport of sodium ion in basolateral  side.

Furosemide employ direct vasodilatory effect.

For increase in therapeutic effect in treatment of acute pulmonary edema. 

It reduce response of vasoconstrictors. Eg – Angiotensin II and noradrenaline.

It decrease the production of natriuretic hormone with vasoconstriction properties. 

Furosemide has main mechanism is its having inhibitory effect on carbonic anhydrase and aldosterone

Route of administration:

IV Peripherally or centrally, IM, Oral

1hour, not greater than 4mg/min

250mg to 50ML sodium chloride 0.9% or undiluted via CRIP (Cysteine-rich Intestinal protein).

Increased danger of ototoxicity and nephrotoxicity if infused at faster rate than approximately 4mg/min.

Pharmacokinetic Properties:-

· Absorption =

Tablet Oral administration.

Absorbs from GI track.

It display variable bioavailbility.

Bioavailability of Oral dosage form is ranging between 10 – 90%.

· Distribution:

After receiving 40mg of furosemide intravenously, the volume of distribution was 0.140L/kg in heart failure patients and 0.181L/kg in healthy individuals.

Protein

· Binding:

In healthy individuals, plasma concentrations between 1

- 400mcg/mL are roughly 91-99% bound. Around 2.3– 4.1% of the unbound fraction is present at therapeutic conc.

· Metabolism:

Furosemide is mostly metabolized in the liver and kidneys, with lower amounts occurring in both organs.

Approximately 85% of the entire clearance of furosemide is carried out by the kidneys, of which 40% is due to biotransformation.

Furosemide glucuronide, a pharmacologically active metabolite, and saluamine (CSA), also known as 4-chloro 5-sulfamoylanthranilic acid, are the two main metabolites of furosemide Concentrations. Mostly, furosemide binds to serum albumin.

Furosemide:

4-chloro-5-sulfamoylanthranilic acid.

Furosemide glucuronide

· Excretion:

Four thirds of the medicine is excreted via the kidneys, which account for 85% of the overall clearance of furosemide. Urine contains a significantly higher amount of furosemide after an intravenous injection than it does after an oral solution or pill. The kidneys metabolize the remaining 50% of the furosemide load into glucuronide and the remaining 50% is eliminated unaltered in the urine.

· Half life:

The 40mg dose of furosemide had a half-life of 4hours after oral administration and 4.5hours after intravenous treatment. After parenteral injection, furosemide has a terminal half-life of about two hours. Patients with severe renal failure may see a rise in the terminal half-life of up to 24hours.

· Clearance:

After 400mg of furosemide was injected intravenously, the plasma clearance was 2.34mL/kg/min in healthy participants and 1.23mL/kg/min in patients with heart failure.

Pharmacodynamic Properties:

· Furosemide treats edema and hypertension brought on by renal illness, cirrhosis, and congestive heart failure, including the nephrotic syndrome.

· Strong loop diuretic furosemide increases the amount of Na+ and water excreted by the kidneys by preventing their reabsorption from the loop of Henle, the proximal and distal tubules.

It affects the renal filtrate’s composition indirectly while acting directly on the nephron’s cells. In the end, furosemide causes the kidneys to produce more urine.

· Furosemide coupled to proteins is transported to the kidneys

· where it is actively released by nonspecific organic transporters that are expressed at the luminal site of action.

· After oral administration, the diuretic action starts to take effect in one to one and a half hours and within the first two hours, the peak effect is achieved. After oral administration, the effects typically persist between four and six hours, although they can last up to eight hours.

Drug Interaction:

Drug interactions that could be dangerous.

1) Drug: Drug interactions:

Ex - Aminoglycoside antibiotics, Ethacrynic acid, Salicylates, Cisplatin, Tubocurarine, Succinylcholine, Lithium,

Angiotensin converting enzyme (ACE) inhibitors,

Angiotensin II receptor blockers (ARBs),

Ganglionic or peripheral adrenergic blocking drugs,

Norepinephrine, Sucralfate, Chloral hydrate, Phenytoin,

Methotrexate, Cyclosporine, Thyroid hormones, Acetylsalicylic acid, and Nonsteroidal anti-inflammatory drugs (NSAIDs).

Antihypertensive:

Increased risk of ventricular arrhythmias with Sotalol if hypokalaemia occurs; enhanced hypotensive effect; increased risk of first-dose hypotensive effect with alphablockers.

Antipsychotics:

Amisulpiride, Sertindole, or Pimozide increase the risk of ventricular arrhythmias (avoid Pimozide if hypokalaemia occurs); phenothiazines have an elevated hypotensive impact.

Atomoxetine:

Ventricular arrhythmias are more likely in hypokalaemia.

Cardiac glycosides:

Heightened toxicity in the event of hypokalaemia.

Antibacterial:

Increased risk of ototoxicity with vancomycin and aminoglycosides avoid concurrent use with lymecycline.

2) Food Interaction:

Steer clear of long-term or excessive alcohol intake. The risk of orthostatic hypotension is increased by alcohol.

Don’t use organic liquorice. Steer clear of liquorice in excess as it can cause hypokalaemia.

Increase your intake of foods high in potassium. Potassium depletion may result from this drug. Foods high in potassium include orange juice and bananas.

Doses:

The usual initial dose of furosemide is 20 to 40 mg given as a single dose, injected intramuscularly or intravenously.

Hypertension:

Adult: 40-80mg daily Oedema associated with heart failure.

Adult: Initially 20mg daily or 40 mg once daily.

Severe case: 600mg.

Child: 1-3mg/kg daily.

Adverse effect:

· Profound ECFV depletion- extracellular Fluid volume concentration depletion.

· Hypokalaemia.

· Hypocalcemia

· Metabolic alkalosis

· Hypomagnesia 

· Hyperglycaemia

· Ototoxicity

Furosemide may cause serious side effects including:

· Increased urination,

· Thirst,

· Muscle cramps,

· Itching,

· Rashes, 

· Weakness,

· Dizziness,

· Spinning sensation (vertigo),

· Diarrhea

· Stamach pain

· Constipation

Toxicity:

Toxicity with furosemide manifests as extensions of its diuretic activity. The main signs and symptoms of overdose with furosemide are blood volume reduction, dehydration, electrolyte imbalance, hypotension, hypochloremic alkalosis, and hypokalaemia.

Treatment of overdose is supportive, and it consists of replacing excessive fluid and electrolyte losses. Clinicians should frequently determine serum electrolytes, arterial blood gas analysis, and blood pressure. In addition, providers must assure adequate drainage in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy). Haemodialysis does not accelerate furosemide elimination.

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Received on 11.03.2024      Revised on 04.01.2025 Accepted on 15.05.2025   Published on 22.07.2025 Available online from July 26, 2025 Res.J. Pharmacology and Pharmacodynamics.2025;17(3):188-192. DOI: 10.52711/2321-5836.2025.00031 ©A and V Publications All right reserved
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