Home
Up
Sulfadiazine
Sulfadimidine
Sulfadoxine
Sulfafurazole
Sulfamethizole
Sulfametopyrazine
Sulfasomidine
Sulfathiazole

Sulphonamides

The discovery of Prontosil in the 1930s was a major breakthrough in the treatment of bacterial infections. Activity of the dye is due to the release in vivo of sulphanilamide, an analogue of para-aminobenzoic acid (Figure 1), which is essential for bacterial folate synthesis. Most bacteria synthesize folic acid and cannot take it up from the environment. Mammalian cells, in contrast, use preformed folate and cannot make their own. Sulphonamides block an early stage in folate synthesis leading to various effects, including a failure to synthesize purine nucleotides and thymidine. Chemical modification of the sulphanilamide molecule resulted in the production of hundreds of different sulphonamides, which differ chiefly in their pharmacological properties.

Figure 1. Chemical structure of protonsil, the prodrug of sulphanylamide, a mimic of p-aminobenzoic acid

Sulphonamides have a broad antibacterial spectrum, but activity against enterococci, Pseudomonas aeruginosa, and anaerobes is poor. They are predominantly bacteriostatic, and their action rather slow. Resistance emerges rapidly, and bacteria resistant to one sulphonamide are cross-resistant to the others.

The emergence of resistant strains and the appearance of safer and more potent agents have relegated the sulphonamides to a minor place in therapy. They are still found in combination products with trimethoprim, pyrimethamine, and other diaminopyrimidines. Topical silver sulfadiazine is used in burns, but the activity probably owes as much to the silver as to the sulphonamide.

Most sulphonamides are well absorbed when given orally and are primarily excreted in the urines, partly in an antibacterially inactive acetylated form. The compounds diffuse relatively well into cerebrospinal fluid and are effective in eradicating susceptible strains of Neisseria meningitidis.
Less soluble sulphonamides (e.g. sulfathiazole and sulfadiazine) are prone to cause renal damage due to the deposition of crystals in the urinary collecting system. Sulfafurazole (known as sulfisoxazole in the USA), sulfadimidine (sulfamethazine), sulfasomidine (sulfisomidine), and sulfamethizole lack this side effect and are preferred in the treatment of urinary infection. Some sulphonamides are distinguished by long plasma half-life. Sulfametopyrazine (T = 60 h) and sulfadoxine (T = 120h) are excreted so slowly that they are given at weekly intervals.
 

       Hit Counter

 

Send mail to stefano.biondi@innovativesolution.it with questions or comments about this web site.
Copyright 2010 Innovative Solution di Biondi Stefano