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NBME 24 Answers

nbme24/Block 4/Question#44 (reveal difficulty score)
A 71-year-old woman with non-Hodgkin lymphoma ...
Leucovorin ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
tags: oncology pharm

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 +16  upvote downvote
submitted by โˆ—sajaqua1(607)

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: Folate is listed as Folic Acid, methotrexate interferes with DHFR, and Leucovorin is 5-formyl-THF. There is also further description here:

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.

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 +3  upvote downvote
submitted by โˆ—pfebo(13)

Easier way to approach question. Look at the creatinine value it is elevated, Methotrexate is renally excreted so we can preview an increase in levels due to impaired renal excretion which leads to chemotoxicity. Leucovorin is a common chemoprotectant used to avoid Metotrexate toxicities.

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 +1  upvote downvote
submitted by โˆ—medstruggle(20)

Why do you give IV leucovorin with intrathecal methotrexate? Wouldnโ€™t MTX lose its efficacy since leucovorin reverses the effects of MTX?

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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 why give one over the other? +2
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**." +15
jj375  @welpdedelp I also struggled with that and chose the wrong one, but then I remembered something from biochem that I think is helpful:I think the good thing about leucovorin is that it doesn't need to be activated by dihydrofolate reductase. Methotrexate is directly blocking Dihydrofolate reductase, so folate can't be activated to help, but leucovorin doesnt need the activation, it is turned into Tetrahydrofolate and rescues the cell! +2

 +0  upvote downvote
submitted by โˆ—agurl1000(5)

I just wanted to add a note here. I was confused on why you would give the patient leucovorin with the MTX. The reason is that it "rescues" the normal cells from damage/death, and allows the MTX to attack only the cancer cells.

Also another connection we may need to know is that if leucovorin with 5-FU it makes it more effective/toxic at killing cancer cells!

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