Phenytoin and megaloblastic anemia- HELP....

[mountainman123]

Thanks in advance for your help.
I am reading First Aid 2007 and doing questions from USMLERx and I have come across conflicting answers to the same question. In FA 2007 it says that Phenytoin causes a megaloblastic anemia due to decreased folate absorption. I just took a pharm test on USMLERx and it gave me an answer to this same topic as the megaloblastic anemia being caused by decreased B12, reasoning being that Phenytoin screws with B12. Then the text from First Aid is given at the bottom with the info on Phenytoin and it says there that it is decreased B12, although my hard copy does not. It is from the same page, and everything else is word for word.

I was hoping that someone could help me clear this up as to what the actual cause of megaloblastic anemia is while taking Phenytoin and which First Aid caption is correct so that I can correct/or not in my book.

Thanks......

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[ComstockOSU]

According to Goljan RR pg 129 megaloblastic anemia is caused by a folic acid deficiency. On pg 130 Phenytoin (along with OH, methotrexate, oral contraceptives, trimethoprim, and 5-FU) is listed as a "drug" cause of folate deficiency.

 

[TheEleventhReel]

According to Goljan, Phenytoin inhibits intestinal conjugase, which is responsible for converting polyglutamates (form of folate found in green vegetables) into monoglutamates for absorption. B12 and folate deficiency both cause megaloblastic anemia b/c both are necessary for DNA synthesis. However, Lippincott's Review lists megaloblastic anemia as an adverse reaction for phenytoin "b/c the drug interferes with rxns for which B12 is a cofactor." That's all the detail that I could find in Lippincott's. I tried Katzung's Review and it just listed "anemia" as a side effect but did not specify B12 or folate. Finally, I checked my lecture notes and our professor had phenytoin listed as a cause for folate deficiency but not B12. In summary, I don't think anyone knows.

 

[TheEleventhReel]

P.S. I also checked big Robbins and it lists phenytoin as a cause for folate deficiency but NOT B12 deficiency. I'd go with folate.

 

[lord_jeebus]

This study found an effect on folate but not B12

Here's another

That does not mean that there cannot be an effect on B12 absorption in some people, however. But folate seems more likely.

 

[Hernandez]

This study found an effect on folate but not B12

Here's another

That does not mean that there cannot be an effect on B12 absorption in some people, however. But folate seems more likely.

Keep in mind guys that the liver stores B12 and you can go years before you see any macrocytosis. So folate should be the answer unless they specify that the pt has been on it for years, then it'll be a combination of both.

 

[TheEleventhReel]

Keep in mind guys that the liver stores B12 and you can go years before you see any macrocytosis. So folate should be the answer unless they specify that the pt has been on it for years, then it'll be a combination of both.

Excellent point. We haven't discussed this drug in pharm yet, but I would assume since it's a seizure medication that most ppl are on it for years?

 

[Hernandez]

Excellent point. We haven't discussed this drug in pharm yet, but I would assume since it's a seizure medication that most ppl are on it for years?

for the most part yes. and fyi, you can give both B12 and folate parenterally.

 

[mountainman123]

Thanks so much for your help. I guess that USMLERx is wrong. Maybe it has not been updated to the new 2007 version, which lists the cause as Folate.

 

[Medikit]

From Access Medicine:
Although macrocytosis and megaloblastic anemia usually respond to therapy with folic acid, folic acid should not be administered indiscriminately to patients receiving phenytoin due to its potential detrimental effects on phenytoin efficacy (see Drug Interactions). Some evidence suggests aplastic anemia secondary to phenytoin administration is due to a highly reactive arene oxide metabolite and the inability to detoxify this metabolite.

Don't forget about interference with 25' hydroxylation in the liver causing hypocalcemia via reduced intestinal absorption.