Sulphonamide-trimethoprim

Sulphonamides Trimethoprim Chloramphenicol Erythromycin Fusidic acid sulphonamide... 

Cribb AE, Lee BL, Trepanier LA, et al. Adverse reactions to sulphonamide and sulphonamide-trimethoprim antimicrobials clinical syndromes and pathogenesis. Adverse Drug React Toxicol Rev 1996 15 9-50. 

PHENYTOIN CHLORAMPHENICOL, CLARITHROMYCIN, ISONI-AZID, METRONIDAZOLE, SULPHONAMIDES, TRIMETHOPRIM t phenytoin levels Inhibited metabolism Monitor phenytoin levels... 

ANTICOAGULANTS-ORAL METRONIDAZOLE, SULPHONAMIDES, TRIMETHOPRIM t anticoagulant effect Inhibition of CYP2C9-mediated metabolism of oral anticoagulants Monitor INR every 2-3 days... 

ANTIBIOTICS- SULPHONAMIDES, TRIMETHOPRIM ANTIMALARIALS -PYRIMETHAMINE T antifolate effect Additive effect Monitor FBC closely the effect may take a number of weeks to occur... 

The enzyme dihydrofolic acid (DHF) S5mthase (see below) converts p-aminobenzoic acid (PABA) to DHF which is subsequently converted to tetrahydric folic acid (THF), purines and DNA. The sulphonamides are structurally similar to PABA, successfully compete with it for DHF s)mthase and thus ultimately impair DNA formation. Most bacteria do not use preformed folate, but humans derive DHF from dietary folate which protects their cells from the metabolic effect of sulphonamides. Trimethoprim acts at the subsequent step by inhibiting DHF reductase, which converts DHF to THF. The drug is relatively safe because bacterial DHF reductase is much more sensitive to trimethoprim than is the human form of the enzyme. Both sulphonamides and trimethoprim are bacteriostatic. 

As on date, there exist a few typical sulphonamides and partieularly the sulphonamide-trimethoprim combinations which find their applications exclusively and most extensively for the management and treatment of the opportunistic infections in humans having AIDS. A few typical examples are as illustrated below ... 

Antibacterial drugs that inhibit nucleic acid synthesis sulphonamides, trimethoprim, quinolones and nitroimidazoles... 

McDonald M, Mannion C, Rafter P, A confirmatory method for the simultaneous extraction, separation, identification and quantification of tetracycline, sulphonamide, trimethoprim and dapsone residues in muscle by ultra-high-performance liquid chromatography-tandem mass spectrometry according to Commission Decision 2002/657/EC, J. Chromatogr. A 2009 1216 8110-8116. 

Fig. 5.16 A, some sulphonamides B, prontosil rabram C, unsubstituted diaminobenzylpyrimidines D, trimethoprim E, tetroxoprim F, dapsone.

Folate metabolism Sulphonamides (also ) Trimethoprim Pyrimethamine Trimetrexate / Inhibit folate synthesis Inhibits dihydrofolate reductase Inhibits dihydrofolate reductase Inhibits dihydrofolate reductase Not present in mammalian cells Mammalian enzyme not inhibited Mammalian enzyme not inhibited Toxicity overcome with leucovorin... 

Huovinen P., Sundstrom L., Swedberg G. Skold O. (1995) Trimethoprim and sulphonamide resistance. 

Noli, C., Koeman, J.P., andWillemse, T., A retrospective evaluation of adverse reactions to trimethoprim-sulphonamide combinations in dogs and cats. Vet. Q., 17, 123-128, 1995. 

Renew JE, Huang C-H (2004) Simultaneous determination of fluoroquinolone, sulphonamide, and trimethoprim antibiotics in wastewater using tandem solid phase extraction and liquid chromatography-electrospray mass spectrometry. J Chromatogr A 1042 113-121... 

Trimethoprim (TMP) and ormethoprim (OMP) are synergists of SAs that operate by a mechanism of competitive inhibition of dihydrofolate reductase. Sulphonamides (and their synergists) are widely used in farm animal feedstuff and fish cultures furthermore, they act as growth promoters at subtherapeutic concentrations. 

A wide range of compounds also inhibit a number of the enzyme systems that are involved in the biosynthesis of purines and pyrimidines in bacteria. For example, sulphonamide bacteriostatics inhibit dihydropteroate synthetase, which prevents the formation of folic acid in both humans and bacteria. However, although both mammals and bacteria synthesize their folic acid from PABA (Figure 7.12), mammals can also obtain it from their diet. In contrast, trimethoprim specifically inhibits bacterial DHF, which prevents the conversion... 

Absence of an enzyme or metabolic pathway Applies to some antibiotics and certain bacterial species, e.g. folate auxotrophs, trimethoprim and sulphonamides... 

Gram-negative bacteria Ampicillin, kanamycin, streptomycin, trimethoprim, chloramphenicol, tetracycline, sulphonamides... 

Humans cannot synthesise folic acid. Many bacteria, however, synthesise it from PABA this bacteria-specific pathway provides a target for synthetic antimicrobial agents like the sulphonamides and trimethoprim (Figure 20.4). Sulphonamides inhibit dihydropteroate syn-... 

Sulphonamides. Usually their names contain sulpha or sulfa. These drugs, and trimethoprim. 

Sulphonamides, amongst the first successful chemotherapeutic agents, now have their place in medicine mainly in combination with trimethoprim. Because of the risks of adverse drug reactions associated with their use, this is generally restricted to specific indications where other therapeutic agents have clearly inferior efficacy. Many sulphonamide compounds have been withdrawn from the market. Their individual names are standardised in the UK to begin with sulfa-. ... 

Co-trimoxazole, at first, very largely replaced the use of a sulphonamide alone. In turn, trimethoprim on its own is now used in many conditions for which the combination was originally recommended, and it may cause fewer adverse reactions (see below). The combination is, however, retained for ... 

Proguardl (t) 17 h) inhibits dihydrofolate reductase which converts folic to folinic acid, deficiency of which inhibits plasmodial cell division. Plasmodia, like most bacteria and unlike humans, cannot make use of preformed foUc acid. Pyrimethamine and trimethoprim, which share this mode of action, are collectively known as the antifols. Their plasmod-icidal action is markedly enhanced by combination with sulphonamides or sulphones because there is inhibition of sequential steps in folate synthesis (see Sulphonamide combinations, p. 231). 

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