Sulphonamides

WIKIDRUGS ANTIBIOTICS

Sulphonamides are derivatives of sulphanilamide, an active metabolite of the pro-drug and dye prontosil.

Mechanism of Action

Sulphonamides act by competing with an essential precursor in folic acid synthesis in bacteria. Bacteria need to synthesise folic acid in order to grow as they are unable to obtain it from their 'diet' like mammals can. Since the bacteria is unable to synthesise RNA or DNA, due to it's lack of folic acid, it's growth is inhibited. As such sulphonamides are bacteriostatic.

Spectrum of Activity

These are generally broad spectrum antibiotics.

• They are active against aerobic gram-positive cocci and some rods.
• They are active against gram-negative rods, including enterobacteriaceae.
• They are active against the anaerobes, Actinomyces and Fusobacterium, but inactive against clostridial species and anaerobic cocci.
• Reistance is now widespread.
• Drugs which contain a PABA nuclear core, such as procaine, antagonise their actions.

Pharmacokinetic Considerations

• Sulphonamides are lipophilic weak acids of varying pKas.
• Most are absorbed readily from the gut, except Succinylsulphathiazole and Phthalylsuphathiazole.
• They tend to distribute widely throughout the body as the non-ionised form is able to cross cell membranes.
• The extent of binding to plasma proteins is very dependent on the individual drug and species involved and can vary between 20 and 90%.
• They are eliminate both by hepatic metabolism and renal excretion, the rate of both in each species and for each drug varies. This results in very different half-lives of each drug in each species.
• They are unable to work in pus or tissue debris as they contain thymidine and purines. This means that the bacteria can utilise these rather than folic acid for continued growth. This means that the drug will become obselete in such a circumstance.