Sulphamethoxazole

The concept of clinical synergism, which m be extremely difficult to demonstrate convincingly. Even with trimethoprim plus sulphamethoxazole, where tme synergism occurs in vitro, the optimum ratio of the two components may not always be present in vivo, i.e. at the site of infection in a particular tissue. 

Naisbitt, D.J., Fraser Gordon, S., Pirmohamed, M., Burkhart, C., Cribb, A.E., Pichler, W.J., and Kevin Park, B., Antigenicity and immunogenicity of sulphamethoxazole demonstration of metabolism-dependent haptenation and T-cell proliferation in vivo, Br. J. Pharmacol., 133, 295, 2001. 

In general, aromatic primary amino moiety (i.e., Ar-NH2), as present in a host of sulphadrugs viz., succinyl sulphathiazole, sulphamethoxazole, sulphaphenazole and other potent pharmaceutical substances, for instance sodium or calcium aminosalicylate, isocarboxazid, primaquine phosphate, procainamide hydrochloride, procaine hydrochloride and dapsone react with sodium nitrite in an acidic medium to yield the corresponding diazonium salts as expressed below ... 

Sulphadiazine Sulphathiazole Sulphamerazine Sulphamethazine Sulphamethoxazole Sulphadoxine Sulphaquinoxaline Sulphaphenazole Sulphasalazine 10-Desacetylbaccatine III Baccatine III Erythromycine... 

Co-trimoxazole consists of trimethoprim and sulphamethoxazole combined because of their synergistic antimicrobial effects. Trimethoprim is a folate antagonist that poses a teratogenic risk. 

Sulphonamide antimicrobial agents (Figure 8.22) such as sulphamethoxazole [21] are oxidized to protein-reactive cytotoxic metabolites in the liver and also other tissues. These include hydroxylamines and further products such as nitroso-deriva-tives. Sulphonamide drugs are linked with agranulocytosis, aplastic anaemia and... 

Antibiotics, e.g., peniciUin and streptomycin followed by long-term trimethoprim pins sulphamethoxazole... 

Fingerprint regions of two polymorphs (A B) of sulphamethoxazole. Spectra obtained by DRIFT. Reproduced with permission from Int. J. Pharmaceutics (see Reference 3). 

Wing LM, Miners JO. Cotrimoxazole as an inhibitor of oxidative drug metabolism effects of trimethoprim and sulphamethoxazole separately and combined on tolbutamide disposition. Br J Clin Pharmacol 1985 20(5) 482-5. 

Figure 7.12 Sequential blocking using sulphamethoxazole and trimethoprim...

Alfirevic A, Stalford AC, Vilar FJ et at. (2003) Slow acetylator phenotype and genotype in HIV-positive patients with sulphamethoxazole hypersensitivity. Br J Clin Pharmacol... 

Kernicterus (that may result from hyperbihrubinaemia) manifests as various neurological deficits, seizures, abnormal reflexes and eye movements. The blood-brain barrier of the neonate is not fully developed and unconjugated bilirubin can freely pass into the brain interstitium. Some medications, such as the antibiotic co-trimoxazole (a combination of trimethoprim and sulphamethoxazole) may induce this disorder in the infant, either when taken by the mother or if given directly to the infant, due to a displacement of bilirubin from binding sites on serum albumin, thus allowing unconjugated bihrubin to pass across the blood-brain barrier. 

Quantification. High Pressure Liquid Chromatography. The method referred to under Sulphamethoxazole may be used. 

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