Trimethoprim

From Wikipedia, the free encyclopedia

Trimethoprim chemical structure
Trimethoprim
Systematic (IUPAC) name
5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine
Identifiers
CAS number 738-70-5
ATC code J01EA01
PubChem 5578
DrugBank APRD00103
Chemical data
Formula C14H18N4O3 
Mol. weight 290.32 g/mol
Pharmacokinetic data
Bioavailability 90–100%
Metabolism hepatic
Half life 8–10 hours
Excretion renal 50–60%
Therapeutic considerations
Pregnancy cat.

B3(AU) C(US)

Legal status

S4(AU) POM(UK)

Routes Oral

Trimethoprim (INN) (IPA: [traɪˈmɛθəprɪm]) is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors. Trimethoprim was formerly marketed by GlaxoWellcome under trade names including Proloprim®, Monotrim® and Triprim®; but these trade names have been licensed to various generic pharmaceutical manufacturers. In clinical use it is often abbreviated TRI or TMP; its common laboratory abbreviation is W.

Contents

[edit] Mechanism of action

Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid. Tetrahydrofolic acid is an essential precursor in the de novo synthesis of the DNA nucleosides thymidine and uridine. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) and are thus dependent on their own de novo synthesis. Inhibition of the enzyme starves the bacteria of two bases necessary for DNA replication and transcription.

Tetrahydrofolate synthesis pathway
Tetrahydrofolate synthesis pathway

[edit] Co-trimoxazole

Trimethoprim is commonly used in combination with sulfamethoxazole, a sulfonamide antibiotic, which inhibits an earlier step in the folate synthesis pathway (see diagram above). This combination, also known as co-trimoxazole, TMP-sulfa, or TMP-SMX, results in a synergistic antibacterial effect by inhibiting successive steps in folate synthesis. Its use has been declining due to reports of sulfamethoxazole bone marrow toxicity.

[edit] Clinical indications

Trimethoprim, used as monotherapy, is indicated for the prophylaxis and treatment of urinary tract infections (cystitis). Co-trimoxazole, owing to its greater efficacy, is indicated for a wider range of infections. For example, it is used as prophylaxis in patients at risk for Pneumocystis jiroveci pneumonia (e.g. AIDS patients and those with some hematological malignancies), as therapy in Whipple's disease and certain other infections.

[edit] External links


Acne-treating agents (D10) edit
Topical agents: Azelaic acid, Benzoyl peroxide, Glycolic acid, Light therapy, Salicylic acid, Tea tree oil
Antibiotics: Clindamycin, Co-trimoxazole, Erythromycin, Sulfacetamide, Teicoplanin, Tetracyclines, Trimethoprim, Vancomycin
Hormonal: Antiandrogens, Contraceptives
Retinoids: Adapalene, Isotretinoin, Tazarotene, Tretinoin