Sulfamethoxazole is an antibiotic. The substance comes from the group of sulfonamides. Sulfamethoxazole inhibits the synthesis of folic acid by bacteria and thus has a bacteriostatic effect. It is used in solid combination with trimethoprim under the name cotrimoxazole.
What is sulfamethoxazole?
Sulfamethoxazole is a substance belonging to the group of sulfonamides. It is used as an antibiotic and is approved in fixed combination with trimethoprim for the treatment of bacterial urinary tract and respiratory tract infections. This fixed combination of the two drugs is in a 5:1 ratio and is known as cotrimoxazole. Specific indications include infections with Pneumocystis jirovecii, nocardia asteroides, Stenotrophomonas maltophilia.
Pharmacologic action
Sulfamethoxazole, like all substances in the sulfonamide group, is a synthetically produced substance. The action of sulfonamides is based on the fact that they prevent bacteria from producing folic acid. Folic acid is important for the production of nucleotides. As a result, the bacteria cannot reproduce because copying their genetic material is not possible without folic acid. Sulfonamides therefore have a bacteriostatic effect, since they do not kill the bacteria but prevent them from multiplying. Sulfamethoxazole in particular is a competitive antagonist of dihydropteroate synthase. Aminobenzoic acid (PABA) is a natural substrate of this enzyme. The enzymatic reaction inhibited by sulfamethoxazole is an important step in the synthesis of bacterial folic acid. Thus, it cannot be synthesized, resulting in the inability to copy the DNA of bacteria, since folic acid is required for DNA duplication. For humans, this inhibition is irrelevant, since they do not synthesize folic acid themselves, but absorb it through food. The plasma half-life of sulfamethoxazole is approximately nine to eleven hours.
Medical application and use
In fixed combination with trimethoprim, sulfamethoxazole is used under the name cotrimoxazole. Cotrimoxazole is indicated for upper and lower respiratory tract infections (except streptococcal angina), kidney and urinary tract infections, male and female reproductive tract infections, and gastrointestinal tract infections. In addition, it is approved for the treatment of brucellosis, nocardiosis, non-genuine mycotic mycetoma, and South American blastomycosis. Accordingly, in addition to its antibacterial activity, cotrimoxazole is also effective against some fungi. Treatment with cotrimoxazole is also possible as a therapeutic trial in the initial stage of granulomatosis with polyangiitis. However, in this indication the mechanism of action is not known. Another special indication, as mentioned above, is Pneumocystis jirovecii pneumonia.
Risks and side effects
The safety profile of the fixed combination of sulfamethoxazole with trimethoprim is considered good, and thus its use is safe. The side effects attributable to sulfamethoxazole are mainly skin problems, especially eczema. In addition to adverse effects on the skin, sulfamethoxazole can also cause leukopenia, anemia, thrombocytopenia, ataxia, convulsions, psychosis, depression, nausea, vomiting, loss of appetite, and diarrhea. In addition to the adverse effects caused by sulfamethoxazole, side effects may occur that are due to the trimethoprim. These include gastrointestinal problems, skin reactions, aseptic meningitis, increases in transaminases, bilirubin, creatine, and urea, minor changes in blood counts, and fever. Spermatogenesis may be impaired with prolonged use. In combination with trimethoprim, sulfamethoxazole causes prolongation of QT time. Therefore, cotrimoxazole must not be used concomitantly with other drugs that prolong the QT interval and must not be used in long-QT syndrome. Furthermore, cotrimoxazole must not be used in cases of known hypersensitivity to either drug, erythema exsudativum multiforme, existing blood count abnormalities, glucose-6-phosphate dehydrogenase deficiency, severe renal insufficiency, severe liver damage, porphyria, and in premature infants and neonates with hyperbilirubinemia.In mild renal and hepatic dysfunction and thyroid dysfunction and in neonates under 5 weeks of age, cotrimoxazole should be used only with special caution and supervision. Sulfamethoxazole potentiates the anticoagulant effect of 4-hydroxycoumarins and the blood glucose-lowering effect of sulfonylureas. In the case of cotrimoxazole, it should be noted that trimethoprim potentiates the effects of phenytoin, cardiac glycosides, and procainamide. In addition, plasma concentrations of methotrexate and the hormones of the contraceptive pill may be affected.
