• Learn PD and understand that it has synergism with sulfonamides.
  1. Trimethoprim is an inhibitor of dihydrofolate reductase
Pharmacodynamics pharmacodynamics

  1. Trimethoprim is a bacteriostatic drug, but it is used synergistically with sulfonamides because they inhibit sequential steps in DNA synthesis. This combination then becomes bactericidal.
  2. Indications as follows:
    • Oral trimethoprim – treat UTI
    • Bactrim has a broad spectrum of uses: PCP pneumonia, bacterial diarrhea (treat salmonella and shigella) and UTI/prostatitis.
    • IV Bactrim is used to treat severe PCP pneumonia.
    • Pyremethamine/sulfonamides used to treat leishmaniasis/toxoplasmosis
  3. Resistance is plasmid encoded, and due to:
    • Reduced cell permeability
    • Altered binding sites
    • Overproduction of dihydrofolate reductase
  1. PO and IV
  1. Well absorbed and distributes to all body tissue, including the CNS.
  1. By renal mechanisms
    • Dose needs to be reduced in renal impairment.
    • It is a weak base, and therefore tends to concentrate in urine (which is a weak acid). This property increases its activity in prostatic and vaginal fluids.
Adverse events
  1. Anaemia, leukopenia and granulocytopaenia (same with other anti-folate drugs)
  2. Also has other idiosyncratic reactions – N/V, vasculitis and renal damage.
Withdrawal syndrome
Special notes