Methotrexate vs 5-fluorouracil and capecitabine
How to tell Methotrexate and 5-fluorouracil and capecitabine apart when a board question makes them look alike.
Methotrexate blocks DHFR and uses leucovorin rescue; 5-FU/capecitabine block thymidylate synthase and leucovorin strengthens 5-FU binding.
Side by side
Folate antagonist that inhibits dihydrofolate reductase; leucovorin rescues toxicity.
Fluoropyrimidines inhibit thymidylate synthase; capecitabine is oral 5-FU prodrug with hand-foot syndrome clue.
Methotrexate depletes reduced folate pools needed for thymidine and purine synthesis.
5-FU metabolites inhibit thymidylate synthase and impair DNA synthesis; capecitabine converts to 5-FU.
High-dose methotrexate plus leucovorin rescue, mucositis, myelosuppression, or hepatotoxicity points methotrexate.
Colorectal chemotherapy with leucovorin enhancement, DPD toxicity concern, or hand-foot syndrome points fluoropyrimidine.
The trap
Both affect thymidine synthesis, but the rescue/enhancement role of leucovorin separates them quickly.
The repair move
For antimetabolites, ask which enzyme is hit and whether leucovorin is rescue or amplifier.
Try a free question
CoreA patient receives high-dose methotrexate and then leucovorin rescue is scheduled. Which enzyme target explains the rescue strategy?
Show answer and explanation
Answer: A. Dihydrofolate reductase. Methotrexate inhibits dihydrofolate reductase; leucovorin bypasses the blocked folate step to rescue normal cells.
Why the other choices are tempting
- B. 5-FU inhibits thymidylate synthase; leucovorin can enhance 5-FU binding rather than rescue it.
- C. Topoisomerase II is targeted by drugs such as etoposide/anthracyclines.
- D. Microtubule effects point to taxanes or vinca alkaloids.
- E. Proteasome inhibition points to bortezomib-type therapy.
Flashcards
Tap a card to flip it.
What is the fastest separator for Methotrexate vs 5-fluorouracil and capecitabine?
Methotrexate blocks DHFR and uses leucovorin rescue; 5-FU/capecitabine block thymidylate synthase and leucovorin strengthens 5-FU binding.
What clue should make you choose Methotrexate?
Folate antagonist that inhibits dihydrofolate reductase; leucovorin rescues toxicity.
Quick answers
What is the fastest way to tell Methotrexate from 5-fluorouracil and capecitabine?
Methotrexate blocks DHFR and uses leucovorin rescue; 5-FU/capecitabine block thymidylate synthase and leucovorin strengthens 5-FU binding.
What is the key clue for Methotrexate?
Folate antagonist that inhibits dihydrofolate reductase; leucovorin rescues toxicity.
What is the key clue for 5-fluorouracil and capecitabine?
Fluoropyrimidines inhibit thymidylate synthase; capecitabine is oral 5-FU prodrug with hand-foot syndrome clue.
What is the common trap with Methotrexate vs 5-fluorouracil and capecitabine?
Both affect thymidine synthesis, but the rescue/enhancement role of leucovorin separates them quickly.