Methotrexate
A folate antagonist that blocks DHFR, used for leukemia, lymphoma and other cancers and, once weekly at low dose, for arthritis and psoriasis.
Drug card
- Class
- Antimetabolite, and an antiproliferative immunosuppressant
- How it works
- Inhibiting dihydrofolate reductase so cells cannot make DNA building blocks
- Used for
- Acute lymphoblastic leukemia, including meningeal spread
- Non-Hodgkin lymphoma
- Breast cancer
- Squamous cell cancer of the head and neck
- Known for
- Bone marrow suppression and pancytopenia
- Liver fibrosis and cirrhosis with long-term use
- Pneumonitis
- Its name
- -trexate means a folic acid analogue (methotrexate type)
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does methotrexate work?
Binds and inhibits dihydrofolate reductase (DHFR), so dihydrofolate cannot be reduced to the tetrahydrofolate needed to make purines and thymidylate, and DNA synthesis and repair stall. Leucovorin (folinic acid) rescue is given after high doses. It is also immunosuppressive, by a mechanism that is unclear, and how it helps arthritis and psoriasis is not known.
Like other antimetabolites: Antimetabolites resemble natural molecules that cells use to build DNA and RNA, such as folate or the pyrimidine bases, closely enough to enter the same pathways. There they block a key enzyme or are built into the nucleic acid, so DNA synthesis fails. Actively dividing tissues feel it most: the tumor, bone marrow, the mouth and gut lining, and a developing fetus.
Uses
What is methotrexate used for?
- Acute lymphoblastic leukemia, including meningeal spread
- Non-Hodgkin lymphoma
- Breast cancer
- Squamous cell cancer of the head and neck
- Rheumatoid and polyarticular juvenile idiopathic arthritis
- Severe psoriasis
Side effects
Side effects of methotrexate
- Bone marrow suppression and pancytopeniaKnown forSerious
- Liver fibrosis and cirrhosis with long-term useKnown forSerious
- PneumonitisKnown forSerious
- Aplastic anemiaSerious
- Mouth ulcers (ulcerative stomatitis)
- Pulmonary fibrosisSerious
- Nausea, vomiting and abdominal discomfort
- Diarrhea and gut ulcerationSerious
- Kidney failure with high dosesSerious
- Severe skin reactions (such as SJS/TEN)Serious
- Seizures and leukoencephalopathySerious
- Lymphoma, which may regress when it is stoppedSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- For arthritis and psoriasis it is given once a week; mistaken daily dosing has caused deaths.
- Monitor blood counts and liver and kidney function; NSAIDs, PPIs, penicillins and probenecid raise its levels.
- Contraindicated in pregnancy for non-cancer uses; contraception is needed during and after treatment.
- Folic or folinic acid is given with low-dose arthritis treatment; avoid nitrous oxide, which deepens its folate block.
Remember it
A way to remember it
Antimetabolites are counterfeit parts on the DNA production line.
Methotrexate imitates folate and blocks DHFR; fluorouracil imitates uracil and blocks thymidylate synthase. Either way, dividing cells cannot make DNA.
Written for biofideX
Its name
-trexate means folic acid analogue (methotrexate type)
Methotrexate blocks dihydrofolate reductase, so cells lack the reduced folate they need to make DNA. Pemetrexed and raltitrexed end in -trexed, the stem for thymidylate synthase inhibitors.
- Every drug name stem
Its class
Antimetabolites
Other antimetabolites with a card:
Easily mixed up with alkylating agents, antibacterial folate antagonists and antiproliferative immunosuppressants.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Methotrexate injection: label (DailyMed)
- Methotrexate (NCI Thesaurus)
- About methotrexate (NHS)
- Side effects of methotrexate (NHS)
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.
Cancer chemotherapy
Methotrexate is one of 9 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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