Sulfonamides (FETT)

Antibacterials

TRIMETHOPRIM

Co-trimoxazole

Diaminopyrimidine derivatives

• Inhibition of bacterial folic acid synthesis

  • Sulfonamides inhibit dihydropteroate synthase.

  • Diaminopyrimidine derivatives inhibit dihydrofolate reductase (DHFR).

    • DHFR uses NADPH to reduce dihydrofolic acid to tetrahydrofolic acid (THF).

    • THF can be converted to methylene-THF.

    • Methylene-THF is an important cofactor for thymidylate synthetase, which catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).

• Both are bacteriostatic but become bactericidal when combined (sequential block of folate synthesis)

good

primarily renal (via tubular secretion)

• Shigella

• Salmonella

• Empiric treatment for simple UTI

• Prophylaxis and treatment of P. jirovecii

• Prophylaxis of toxoplasmosis

• Megaloblastic anemia

• Leukopenia, granulocytopenia (can be prevented with concomitant folinic acid administration)

• In high doses: hyperkalemia, particularly in HIV-positive patients [69]

• Artificially increased creatinine (despite unchanged GFR) [70]

• Children < 2 months of age

• Pregnant women

• Breastfeeding women

• Cautious use in people with

  • Hepatic failure

  • Renal failure

• Sulfonamides

  • Mutation in bacterial dihydropteroate synthase

  • Decreased uptake of sulfonamide

  • Increased para-aminobenzoate (PABA) synthesis