Everything about Trimethoprim totally explained
Trimethoprim (
INN) 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's often abbreviated
TRI or
TMP; its common laboratory abbreviation is
W.
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 nucleotide
thymidine. Bacteria are unable to take up folic acid from the environment (for example the infection host) and are thus dependent on their own
de novo synthesis. Inhibition of the enzyme starves the bacteria of nucleotides necessary for
DNA replication.
Co-trimoxazole
Trimethoprim was 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 an in vitro
synergistic antibacterial effect by inhibiting successive steps in folate synthesis. This claimed benefit wasn't seen in general clinical use.
Its use has been declining due to reports of sulfamethoxazole
bone marrow toxicity, resistance and lack greater efficacy in treating common urine and chest infections, and
side effects of antibacterial sulfonamides. As a consequence, the use of co-trimoxazole was restricted in 1995.
Clinical indications
Trimethoprim, used as
monotherapy, is indicated for the
prophylaxis and treatment of
urinary tract infections (
urethritis).
Co-trimoxazole, with its greater efficacy against a limited number of bacteria, remains indicated for some infections; for example, it's used as prophylaxis in patients at risk for
Pneumocystis jirovecii pneumonia (for example
AIDS patients and those with some
hematological malignancies) and as therapy in
Whipple's disease.
Footnotes
Further Information
Get more info on 'Trimethoprim'.
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