Potent inhibitor of bacterial dihydro folate reductase
Pharmacokineetics
Absorption and distribution Trimethoprim is well absorbed from the gastrointestinal tract. Because the drug is a weak base, so higher concentration will be trapped in acidic prostatic and vaginal fluids. It is also penetrate the cerebrospinal fluid.
MOA
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Trimethoprim competitively inhibits dihydrofolate reductase, the enzyme that catalyzes the reduction of dihydrofolic acid (folic acid) to tetrahydrofolic acid (folinic acid) leading to decreased tetrahydrofolic acid coenzyme required for purine and pyrimidine synthesis. The bacterial reductase has a much stronger affinity for trimethoprim than does the mammalian enzyme, which accounts for the selective toxicity of the drug.
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The antibacterial spectrum of trimethoprim is similar to that of sulfamethoxazole. However, trimethoprim is 20- to 50-fold more potent than the sulfonamides. Trimethoprim may be used alone (although fluoroquinolones are preferred) in the treatment of UTIs , Prostatitis
Antibacterial spectrum
Similar to sulfonamide and more potent.
It can be used alone in treatment of acute urinary tract infection, bacterial prostatitis (fluoroquinolones are preferred) and vaginitis.
Adverse Effects
1-Hypersensitivity to trimethoprim.
2-It produces the effects of folic acid deficiency which include megalobastic anaemia, leucopenia, and granulocytopenia especially in pregnant patients and those having very poor diets. These blood disorders may be reversed by the simultaneous administration of folinic acid, which does not enter bacteria
3-Possible teratogenic risk in pregnancy: Trimethoprim is contraindicated in pregnancy because it is a folate antagonist.