Sulfonamides, Diaminopyrimidines, and Their Combinations

Abstract

The value of the sulfonamides as single antimicrobial agents has been greatly diminished both by widespread acquired resistance and by their relatively low potency compared to more modern antimicrobial drugs. However, when combined with antibacterial diaminopyrimidines such as trimethoprim, resistance occurs less frequently and thus their usefulness has been enhanced. This chapter discusses the chemistry, mechanism of action, antimicrobial activity, resistance, pharmacokinetic properties, drug interactions, toxicity and adverse effects, administration and dosage, and clinical applications of sulfonamides, diaminopyrimidines, and their combinations. Diaminopyrimidines interfere with folic acid production by inhibition of dihydrofolate reductase. Some diaminopyrimidines have marked specificity for bacterial dihydrofloate reductases (aditoprim, baquiloprim, ormetoprim, trimethoprim), others for protozoal enzymes (pyrimethamine), and others for mammalian enzymes (methyltrexate). Some diaminopyrimidines such as pyrimethamine have high activity against protozoa by inhibiting dihydrofolate reductase and thus preventing purine synthesis. These drugs are used in the treatment of systemic protozoal infections