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Trimethoprim ( TMP ) is an antibiotic used mainly in the treatment of bladder infections.
Common side effects include nausea, changes in taste, and rash.
Trimethoprim was first used in 1962.
Contents
1 Medical uses
1.1 Spectrum of susceptibility
2 Side effects
2.1 Common
2.2 Rare
2.3 Contraindications
2.4 Liver and kidney problems
2.5 Pregnancy
3 Mechanism of action
4 History
5 See also
6 References
7 External links
Medical uses
It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species.
Resistance to trimethoprim is increasing, but it is still a first line antibiotic in many countries.
Spectrum of susceptibility
Cultures and susceptibility tests should be done to make sure bacteria is treated by trimethoprim.
Escherichia coli
Proteus mirabilis
Klebsiella pneumoniae
Enterobacter species
Coagulase-negative Staphylococcus species, including S. saprophyticus
Streptococcus pneumoniae
Haemophilus influenzae
Side effects
Common
Nausea
Change in taste
Vomiting
Diarrhea
Rash
Sun sensitivity
Itchiness
Rare
Can cause thrombocytopenia (low levels of platelets ) by lowering folic acid levels; this may also cause megaloblastic anemia.
Trimethoprim antagonizes the epithelial sodium channel in the distal tubule, thus acting like amiloride. This can cause increased potassium levels in the body ( hyperkalemia ).
Can compete with creatinine for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.
Use in EHEC infections may lead to an increase in expression of Shiga toxin.
Contraindications
Known hypersensitivity to trimethoprim
History of megaloblastic anemia due to folate deficiency
Liver and kidney problems
10-20% of trimethoprim is metabolized by the liver and the rest is excreted in the urine. Therefore, trimethoprim should be used with caution in individuals with kidney and liver impairments. Dosage adjustment is not needed for liver impairment but should be adjusted for kidney impairment.
Pregnancy
Based on studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.
The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.
Mechanism of action
Staphylococcus aureus DHFR in complex with NADPH and trimethoprim PDB entry 2W9G
Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF).
Tetrahydrofolate synthesis pathway
History
Trimethoprim was first used in 1962.
See also
Tetroxoprim
Iclaprim

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