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nbme24/Block 4/Question#44

A 71-year-old woman with non-Hodgkin lymphoma is ...

Leucovorin

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submitted by sajaqua1(204),

This answer rests on the difference between Folate and Leucovorin. Intrathecal methotrexate is given to block dihydrofolate reductase (DHFR) from making folic acid into DHF, and then turning that DHF into THF. This is done to prevent the production of downstreamn products necessary for metabolism including DNA synthesis. Leucovorin (also called 5-formy-lTHF) can be used to sidestep this product by being put into play downstream. See the diagram here: https://www.emed.com.au/folic-acid-and-fertility-doing-more-harm-than-good/ Folate is listed as Folic Acid, methotrexate interferes with DHFR, and Leucovorin is 5-formyl-THF. There is also further description here: https://www.drugbank.ca/drugs/DB00158

Why does this not simply undo the action of methotrexate? This is because many cancers do not have the reduced folate carrier. So the cancers pick up folate and methotrexate, and their DNA synthesis is reduced. Meanwhile other healthy cells can pick up the Leucovorin and stave off some of the worst effects. Remember, leucovorin cannot be given intrathecally.

https://www.d.umn.edu/~jfitzake/Lectures/DMED/Antineoplastics/DNASynthesisInhibitors/Methotrexate/LeucovorinRescue.html





 +1  upvote downvote
submitted by medstruggle(6),

Why do you give IV leucovorin with intrathecal methotrexate? Wouldn’t MTX lose its efficacy since leucovorin reverses the effects of MTX?

colonelred_  MTX will still work but yes some purine/pyrimidine synthesis can still occur. You often give leucovorin to decrease adverse effects of MTX. +  
welpdedelp  ok I have a question, leucovorin is the same as folic acid...so why give one over the other? +  
lsmarshall  Leucovorin, folinic acid, is a modified version of THF and enter folate metabolism where THF is, after the point where methotrexate takes its effect. I have a pharm. card that says "toxic effects on normal cells may be reduced by administration of folinic acid (a.k.a. leucovorin or citrovorum factor), which is **preferentially taken up by normal cells versus tumor cells**." +2