Trimethoprim
A dihydrofolate reductase inhibitor used alone for urinary tract infections and, with sulfamethoxazole, as co-trimoxazole.
Also called TMP (abbreviation).
Drug card
- How it works
- Blocking bacterial dihydrofolate reductase, so tetrahydrofolate is not made
- Used for
- Uncomplicated urinary tract infections
- Preventing repeat urinary tract infections
- Pneumocystis pneumonia, with sulfamethoxazole
- Known for
- High potassium (hyperkalemia)
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does trimethoprim work?
Binds bacterial dihydrofolate reductase far more tightly than the human enzyme, so bacteria cannot turn dihydrofolic acid into tetrahydrofolic acid and stop making nucleic acids. Sulfonamides strengthen it by blocking the step before.
Like other antibacterial folate antagonists: Bacteria must build their own folate to make the nucleic acids and proteins they grow on. These drugs block that pathway at two consecutive steps: sulfamethoxazole stops dihydrofolic acid being made, and trimethoprim stops it being turned into tetrahydrofolic acid. Given together as co-trimoxazole they act in synergy, and resistance develops more slowly than to either alone.
Uses
What is trimethoprim used for?
- Uncomplicated urinary tract infections
- Preventing repeat urinary tract infections
- Pneumocystis pneumonia, with sulfamethoxazole
Side effects
Side effects of trimethoprim
- High potassium (hyperkalemia)Known forSerious
- Rash
- Itching
- Nausea and vomiting
- Diarrhea
- Headache
- Megaloblastic anemia from low folateSerious
- Low white cells or plateletsSerious
- Low sodium (hyponatremia)Serious
- Aseptic meningitisSerious
- Cholestatic jaundiceSerious
- PancreatitisSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Watch potassium in kidney disease and with ACE inhibitors or other drugs that raise potassium.
- Contraindicated in megaloblastic anemia from folate deficiency; take care whenever folate may be low.
- Raises phenytoin levels by slowing its breakdown in the liver.
- Pregnancy: usually avoided in the first 12 weeks, as it can lower folate levels.
Good to know: Used on its own mainly for urinary infections; with sulfamethoxazole (co-trimoxazole) it also treats Pneumocystis pneumonia and gut infections.
Remember it
A way to remember it
Double lock on folate: SMX shuts step one, TMP shuts step two.
Sulfamethoxazole (SMX) blocks dihydropteroate synthase and trimethoprim (TMP) blocks dihydrofolate reductase, the next step in making folate. Two blocks in a row work in synergy and slow resistance, which is why they are given together as co-trimoxazole.
Written for biofideX
Its class
Antibacterial folate antagonists
Other antibacterial folate antagonists with a card:
Easily mixed up with antimetabolites and nitrofurans.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Trimethoprim tablets: label (DailyMed)
- Trimethoprim (NCI Thesaurus)
- Trimethoprim (NHS)
- Sulfamethoxazole and trimethoprim tablets: label (DailyMed)
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Antibiotics: DNA, folate and tuberculosis
Trimethoprim is one of 11 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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