Potentiated sulphonamides:

• Combination of sulphonamides with 2,4-diaminopyrimidine and related agents
• Combination commonly used are sulphamethoxazole & trimethoprim, Sulphadiazine & trimethoprim, sulphadimethoxine & ormetoprim.

Mechanism of action:

• Combination of sulphonamide with 2,4-diaminopyrimidine results in synergistic effect via blockade of sequential steps in synthesis of tetrahydrofolate.
• Sulphonamide inhibit PABA utilization whereas diaminopyrimidine inhibits synthesis of tetrahydrofolic acid by inhibiting enzyme dihydrofolate reductase.

Advantages of using these potentiated sulphonamides are they becomes bactericidal and MIC of both drugs reduced by several folds against a wide variety of pathogenic organism. This reduces the dose of sulphonamide required for therapeutic effects. It also broadens the antibacterial spectrum and reduces chances of bacterial resistance to drugs.

Trimethoprim-sulphamethoxazole/cotrimoxazole:

• Combination of trimethoprim with sulphamethoxazole is called cotrimoxazole or TMP-SMX.
• Widely used in therapeutics in veterinary medicine.

Antibacterial spectrum:

• Antibacterial spectrum is broad and includes many gram-positive and gram-negative organism.
• Gram-positive which are susceptible to cotrimoxazole include streptococci and many strains of staphylococcus and nocardia.
• Gram-negative includes Enterobacteriaceae but pseudomonas aeruginosa is resistant.
• Protozoa like coccidia and toxoplasma are also affected.

Resistance:

• Resistance develops slowly than to trimethoprim and sulphamethoxazole when used alone
• Resistance usually develops due to acquisition of plasmid that codes for altered DHFRase.

Pharmacokinetics:

• Absorption is rapid with peak blood levels occurring between 1-4 hrs after oral administration
• Trimethoprim metabolized by oxidation followed by conjugation
• Sulphamethoxazole is primarily acetylated and conjugated with glucuronic acid.
• Both parent drugs and their metabolites are excreted in urine.

Side effects/Adverse effects:

• Skin toxicity
• Trimethoprim increase G.I and hemolytic effects of sulphonamide
• Keratoconjunctivitis sicca
• Hepatitis
• Vomiting
• Diarrhoea
• Anorexia, hemolytic anemia and fever
• Acute type I and type III hypersensitivity
• In Doberman, it may cause transient arthritis
• Cats: Salivation, frothing, anemia, anorexia
• Horse: Transient pruritis

Contraindications and precautions:

• In hypersensitive animal
• In patients with renal insufficiency, hepatopathies, blood dyscrasia
• In pregnant animals
• Animals must be allowed free access to water on potentiated sulphonamide therapy.

Indications:

• Upper and lower respiratory tract infection
• Renal and urinary tract infections
• Septicemia
• Coccidiosis in small animals

Dose:

Dogs: 30 mg/kg, PO or IV, 2 times daily

Cattle: 25-50 mg/kg, IV or IM, once daily

Others potentiated sulphonamides: