Furosemide
[CAS# 54-31-9]

Identification

• Classification: API >> Urinary system medication >> Diuretic
• Name: Furosemide
• Synonyms: 5-(Aminosulfonyl)-4-chloro-2-((2-furanylmethyl)amino)benzoic acid; 4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid; 2-Furfurylamino-4-chloro-5-sulfamoylbenzoic acid
• Molecular Formula: C₁₂H₁₁ClN₂O₅S
• Molecular Weight: 330.74
• CAS Registry Number: 54-31-9
• EC Number: 200-203-6
• SMILES: C1=COC(=C1)CNC2=CC(=C(C=C2C(=O)O)S(=O)(=O)N)Cl

Properties

• Solubility: 66 mg/mL (DMSO), <1 mg/mL (water) (Expl.)
• Density: 1.6±0.1 g/cm³, Calc.^*
• Melting point: 220 °C (Expl.)
• Index of Refraction: 1.658, Calc.^*
• Boiling Point: 582.1±60.0 °C (760 mmHg), Calc.^*
• Flash Point: 305.9±32.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H315-H319-H335-H351-H360-H361
• Safety Statements: P203-P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	2	H361
Carcinogenicity	Carc.	2	H351
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H302
Germ cell mutagenicity	Muta.	2	H341
Reproductive toxicity	Repr.	1A	H360
Reproductive toxicity	Lact.	-	H362
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H312
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Carcinogenicity	Carc.	1B	H350
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Reproductive toxicity	Repr.	2	H361d

Discovery and Applications

Furosemide is a widely used diuretic, belonging to the class of loop diuretics. It is commonly used in the treatment of conditions such as heart failure, liver cirrhosis, and kidney disease, where fluid retention occurs. The compound's chemical structure is derived from the sulfonamide class of drugs, and it is known for its ability to prevent the reabsorption of sodium and chloride in the kidneys, thereby promoting increased urine output. Furosemide was first introduced in the 1960s and has since become an essential medication in the management of various cardiovascular and renal diseases.

The discovery of furosemide can be traced back to the efforts of researchers at the pharmaceutical company Hoechst AG in the early 1960s. They aimed to develop a more potent diuretic compared to existing thiazide diuretics. By synthesizing and testing various compounds, they found that furosemide exhibited a more powerful diuretic effect, particularly by acting on the loop of Henle in the kidney. This discovery was groundbreaking, as it provided a more effective treatment for patients with conditions such as congestive heart failure, where fluid retention often leads to swelling and shortness of breath.

Furosemide works by inhibiting the sodium-potassium-chloride symporter in the loop of Henle, a part of the nephron in the kidney. By blocking the reabsorption of sodium and chloride, furosemide increases the amount of water excreted in urine, thereby reducing fluid buildup in the body. This mechanism makes it highly effective in reducing edema, which is the accumulation of excess fluid in tissues. Additionally, furosemide helps lower blood pressure by reducing the total volume of fluid circulating in the bloodstream.

Furosemide is used in the treatment of various medical conditions, most notably in patients with heart failure, where it helps reduce pulmonary and peripheral edema. It is also employed in managing conditions like chronic kidney disease, liver cirrhosis, and hypertension, particularly when these conditions result in fluid retention. By eliminating excess fluid, furosemide helps alleviate symptoms such as swelling, shortness of breath, and elevated blood pressure.

In addition to its clinical uses, furosemide has found application in veterinary medicine for the treatment of similar conditions in animals, particularly in dogs with heart disease or edema. Its versatility and effectiveness in treating fluid retention-related conditions have made it one of the most commonly prescribed diuretics worldwide.

Despite its widespread use, furosemide must be prescribed and monitored carefully due to its potential side effects, including electrolyte imbalances, dehydration, and low blood pressure. Patients using furosemide are often monitored for changes in blood levels of sodium, potassium, and other electrolytes to avoid complications associated with these side effects.

In conclusion, furosemide is a potent loop diuretic with significant applications in the treatment of fluid retention and high blood pressure. Its discovery in the 1960s revolutionized the management of heart failure, kidney disease, and other conditions involving edema. Today, furosemide remains an essential medication in both human and veterinary medicine, playing a crucial role in improving patient outcomes by alleviating symptoms of fluid overload.

References

1979. Acetylsalicyclic acid restores acute insulin response reduced by furosemide in man. Diabetes, 28(9).
DOI: 10.2337/diab.28.9.841

1979. Time-dependent Changes in Prostaglandin Excretion in Response to Frusemide in Man. Clinical Science, 56(1).
DOI: 10.1042/cs0560077

1979. Effect of furosemide on canine splenic arterial blood flow. Research Communications in Chemical Pathology and Pharmacology, 23(3).
URL: https://pubmed.ncbi.nlm.nih.gov/461979