Sulphonamides

Introduction

Sulphonamides are derivatives of sulphanilamide, an active metabolite of the pro-drug and dye prontosil. Commonly used ones are: sulphadiazine, sulphaquinoxaline, sulphadimethoxine, sulphadoxine and sulphanilamide.

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 bacterium is unable to synthesize RNA or DNA, due to its lack of folic acid, its 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.
• Resistance 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.

Side Effects and Contraindications

Major reactions to sulphonamides are uncommon but the following are the most common of the side effects recorded:

• Rapid intravenous injection can lead to muscle weakness, ataxia and collapse. This has only been recorded in cattle and horses.
• They can precipitate in tubular fluid resulting in renal tubular damage.
• Dobermans have had serious allergic reactions to them including immune-mediated polyarthritis, thrombocytopenia and haemolytic anaemia.
• Severe hepatotoxicity has been noted in some dogs.
• Long dosage regimens of Sulphonamides have resulted in keratoconjunctivitis sicca/'dry eye' in dogs.
• Sulphonamides inhibit thyroid gland function and so mild signs of hypothyroidism have been seen in dogs that have had intesive dosage regimens.

Hepatotoxicity

• some of these casue hepatic necrosis in susceptible animals
• has been associated with a reduced capability of detoxifying the metabolites
• Doberman Pinscher breed appears to be susceptible

Sulphonamides Learning Resources
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