Sulfanilamide

Absorption

Sulfonamides are absorbed through the vaginal mucosa. There are no pharmacokinetic data available describing how much of an intravaginal dose reaches the systemic circulation.

Toxicity

Oral, mouse LD50 = 3700 mg/kg; Intravenous, mouse LD50 = 621 mg/kg; Oral, rabbit LD50 = 1300 mg/kg. Side effects include itching, burning, skin rash, redness, swelling, or other sign of irritation not present before use of this medicine and long-term use of sulfonamides may cause cancer of the thyroid gland.

Description

Sulfanilamide was one of the earliest sulfonamide antimicrobials. It was first synthesized in 1908 by P. Gelmo and first used as a chemotherapeutic agent in 1935 by G. Domagk, J. Trefouel, and T. Trefouel. They thought that the drug was a complex sulfonamide; but it was later shown that its metabolite, sulfanilamide, was the true active substance.

Indications

For the treatment of vulvovaginitis caused by Candida albicans.

Background

Sulfanilamide is a molecule containing the sulfonamide functional group attached to an aniline.

Preparation

Sulfonamide is synthesized from acetanilide by chlorosulfonation, amination, hydrolysis, and neutralization:
Acetanilide is reacted with chlorosulfonic acid at 40～50℃, then cooled, slowly added to water for acid decomposition, precipitated at the same time, dried and filtered to obtain p-acetamidobenzenesulfonyl chloride, and then subjected to ammoniation, and the amination temperature is controlled at 40～ 45 ℃, and then hydrolyzed, acidified to obtain sulfonamide.

Antimicrobial activity

Sulfanilamide is a sulfonamide antibiotic. It is bacteriostatic against Streptococci in vitro at a concentration of 20 μg/ml and inhibits the growth of 106 clinically isolated strains of Gonococcus. Sulfanilamide reduces the concentration of Streptococcus in rabbit plasma ex vivo following four doses of 20 ml of a 2% sulfanilamide solution. Sulfonamide class antibiotics, of which sulfanilamide is a member, are bacteriostatic and inhibit bacterial synthesis of dihydrofolic acid by competing with 4-aminobenzoic acid for binding to dihydropteroate synthase. Formulations containing sulfanilamide have been used to treat T. vaginalis infections.

Pharmacokinetics

Sulfanilamide is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

The Uses of Sulfanilamide

Sulfanilamide was one of the earliest sulfonamide antimicrobials. It was first synthesized in 1908 by P. Gelmo and first used as a chemotherapeutic agent in 1935 by G. Domagk, J. Trefouel, and T. Trefouel. They thought that the drug was a complex sulfonamide; but it was later shown that its metabolite, sulfanilamide, was the true active substance.

Overdose

There are no reports of sulfanilamide overdose. Vaginal sulfanilamide is systemically absorbed through the vaginal mucous membranes. Excessive use of sulfanilamide vaginal cream may intensify its side effects, which should resolve with discontinuation of the drug. Long term use of sulfanilamide can cause cancer of the thyroid gland.