Trimethoprim

UNDER REVIEW (September 2016)

Mechanism of Action:

Trimethoprim is an antibiotic that 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 (i.e. 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.

---

Drug specifics

Alternative drug name	not specified
Effects	Trimethoprim is commonly used for urinary- and respiratory-tract infections, and is also indicated for prostatitis, shigellosis, and invasive salmonella infections. It is sometimes used as long-term prophylaxis for patients at high risk of urinary oinfection.
Adverse actions	Common adverse effects include gastro-intestinal disturbances and rashes. Less commonly there is occasionally depression of haematopoiesis and patients on long term prophylaxis should be warned of potential warning signs.
Dose	200mg twice daily as a short course. Some patients at high risk of urinary infections are put on long term prophylaxis (100mg nocte).
Interactions	Trimethoprim is potentially teratogenic and should be avoided in the first trimester of pregnancy.
Contraindications	not specified
Comments	SULPHONAMIDE ANTIBIOTICS. Sulphonamides were one of the first group of antibiotics to be used but their importance has decreased as a result of increasing bacterial resistance and their replacement by antibacterials which are more active and less toxic. Sulfamethoxazole (sulphamethoxazole) and trimethoprim are used in combination (known as co-trimoxazole) because of their synergistic activity. However, co-trimoxazole is associated with rare but serious sulphonamide side-effects (e.g. Stevens-Johnson syndrome and blood dyscrasias, notably bone marrow depression and agranulocytosis). Co-trimoxazole remains drug of choice in Pneumocystis jiroveci (Pneumocystis carinii) pneumonia and is also indicated for toxoplasmosis and nocardiasis.
Contributors