TRIMETHOPRIM

• Learn PD and understand that it has synergism with sulfonamides.

Structure/Class	Trimethoprim is an inhibitor of dihydrofolate reductase
Pharmacodynamics	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. 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 Resistance is plasmid encoded, and due to: Reduced cell permeability Altered binding sites Overproduction of dihydrofolate reductase
Absorption/administration	PO and IV
Distribution	Well absorbed and distributes to all body tissue, including the CNS.
Metabolism
Excretion	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	Anaemia, leukopenia and granulocytopaenia (same with other anti-folate drugs) Also has other idiosyncratic reactions – N/V, vasculitis and renal damage.
Dosing/administration
Toxicology
Withdrawal syndrome
Special notes