Sulfonamides can be classified into two main categories based on their pharmacokinetic properties:
1.Short-acting sulphonamides:
These have a relatively short half-life and are quickly eliminated from the body.
Examples include sulfanilamide, sulfadiazine, and sulfisoxazole.
2.Intermediate and long-acting sulfonamides:
These have a longer half-life and are eliminated more slowly from the body.
Examples include sulfamethoxazole, sulfadimethoxine, and sulfamethoxypyridazine.
Sulfonamides can also be classified based on their clinical use:
1.Systemic sulfonamides:
Used for the treatment of various bacterial infections.
Examples include sulfadiazine and sulfamethoxazole.
2.Topical sulfonamides:
Used for the treatment of skin and eye infections.
Examples include sulfacetamide and mafenide.
Structure-Activity Relationship (SAR):
·The structure-activity relationship in sulfonamides can be summarized as follows:
The presence of the sulfonamide group (R-SO2-NH2) is essential for the antimicrobial activity of these drugs.
The substitution of an electron-withdrawing group at the para position of the benzene ring enhances the antibacterial activity.
The nature of the R group has a significant impact on the drug's pharmacokinetic properties, such as absorption, distribution, and elimination. Generally, more lipophilic R groups increase the half-life and protein binding of the drug.
The presence of a heterocyclic ring or an aromatic ring in the R group may improve the antibacterial activity and reduce the development of bacterial resistance.
Sulfonamides work by inhibiting the bacterial enzyme dihydropteroate synthase, which is involved in the synthesis of folate.
By blocking this enzyme, sulfonamides prevent the formation of folate, an essential cofactor for the synthesis of nucleic acids and proteins, ultimately leading to bacterial cell death.
Since human cells rely on preformed folate from dietary sources and do not synthesize it, sulfonamides selectively target the bacterial pathway without affecting human cells.
Sulphamethizole
Chemical formula:
C11H13N3O3S
Mechanism of action:
Sulphamethizole, like other sulfonamides, inhibits the bacterial enzyme dihydropteroate synthase, which is involved in the synthesis of folate. By blocking this enzyme, sulphamethizole prevents the formation of folate, an essential cofactor for the synthesis of nucleic acids and proteins, ultimately leading to bacterial cell death.
Uses:
Sulphamethizole is primarily used for the treatment of urinary tract infections caused by susceptible bacteria.
Side effects:
Common side effects include gastrointestinal disturbances (nausea, vomiting, diarrhea), rash, and hypersensitivity reactions. In rare cases, it may cause blood dyscrasias, such as hemolytic anemia, agranulocytosis, and thrombocytopenia, as well as kidney disorders like crystalluria or interstitial nephritis.