Chemistry Structure and Mechanism of Action

Trimethoprim (Trimpex, Proloprim) is a structural analogue of the pteridine portion of dihydrofolic acid. It differs from the sulfonamides in that it acts at a second step in the folic acid synthetic pathway; that is, it competitively inhibits dihydrofolate reductase. This is the enzyme that catalyzes the reduction of dihydrofolic acid to tetrahydrofolic acid, the active form of folate. Dihydrofolate reductase is present in both mammalian tissue and bacteria, but 20,000 to 60,000 times more drug is required to inhibit the mammalian enzyme; this accounts for its selective toxicity against bacteria.

Trimethoprim-sulfamethoxazole (TMP-SMX) was introduced as a fixed dose combination in 1968. Tri-methoprim was added to sulfamethoxazole to synergisti-cally and sequentially inhibit bacterial synthesis of tetrahydrofolic acid. The combination was also designed to delay development of bacterial resistance. Sulfameth-oxazole was selected in part because it is a congener of the frequently used sulfisoxazole but exhibits slower enteric absorption and urinary excretion. Sulfamethoxazole has a half-life similar to that of trimethoprim.

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

Get My Free Ebook


Post a comment