indication

For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections.

pharmacology

Sulfamethoxazole is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethoxazole is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA. Sulfamethoxazole is normally given in combination with Trimethoprim, a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either Trimethoprim or Sulfamethoxazole alone.

mechanism of action

Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.

toxicity

Sulfamethoxazole may cause nausea, vomiting, diarrhea and hypersensitivity reactions. Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency may also occur. Sulfamethoxazole may displace bilirubin from albumin binding sites causing jaundice or kernicterus in newborns.

biotransformation

Hepatic. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation, although the glucuronide conjugate has been identified.

absorption

Rapidly absorbed following oral administration. Also well-absorbed topically.

half life

10 hours

drug interactions

Chlorpropamide: Sulfonamide/sulfonylurea: possible hypoglycemia

Cyclosporine: The sulfonamide decreases the effect of cyclosporine

Methotrexate: The sulfamide increases the toxicity of methotrexate

Tobramycin: Increased risk of nephrotoxicity

Tolbutamide: Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Sulfamethoxazole. Consider alternate therapy or monitor for changes in Sulfamethoxazole therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.

Warfarin: Sulfamethoxazole may increase the anticoagulant effect of warfarin by decreasing its metabolism. Consider alternate therapy or monitor for changes in prothrombin time if sulfamethoxazole is initiated, discontinued or dose changed.