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Methotrexate

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About

Methotrexate is a treatment for Crohn's Disease that results in impaired DNA synthesis and IL-1 inhibition. It is an antometabolitic drug, specifically an antifolate. This means that it inhibits the metabolism of Folate. Common side effects such as diarrhea, nausea, or vomiting, can be reduced with folic acid supplementation. It is available as a shot given in the muscle or under the skin and in an oral form. In a multicenter trial using weekly intramuscular or subcutaneous injections, clinical Remission was maintained during a 16-week trial and half of the patients continued to show sustained responses at one year.[1]

This drug is used to treat cancers and a variety of auto-immune diseases including Inflammatory Bowel Disease, Rheumatoid Arthritis and Ankylosing Spondylitis. It is also used as an abortifacient in early stages of pregnancy.

How it Works

Methotrexate has a similar chemical composition to folic acid and this allows it to bind with an enzyme known as dihydrofolate reductase, inhibiting it. Dihydrofolate reductase works to convert a chemical called dihydrofolic acid to tetrahydrofolic acid, which is important in the synthesis of amino acids (proteins) and nucleic acids (DNA and RNA) within cells.

When cells are reproducing, there is a stage, known as the synthesis phase (S phase) where the DNA is synthesized or replicated. If the DNA cannot be synthesized properly, the cell halts its replication cycle. This means that cells which rapidly divide, such as those that make up the intestinal mucosa are particularly affected, slowing their reproduction.

Side Effects

  • Nausea
  • Dizziness
  • Fatigue
  • Hair loss
  • Increased susceptibility to infection
  • Chills and fever
  • Dermatitis

Risks

As with most medications, there are risks associated with Methotrexate. It can increase the potential for liver damage and as such, regular blood tests monitoring liver function are important. Methotrexate can also increase the risk of developing lymphoma.

Methotrexate may increase requirements for choline which is an essential nutrient. Choline deficiency can lead to fatty liver or liver damage. If your liver function tests ever come back abnormal, you may want to discuss choline supplementation with your doctor or dietician.[2]

Other Options

Pfizer received approval for its new drug Xeljanz. Xeljanz is approved for Rheumatoid Arthritis patients who are not responding to Methotrexate or who are unable to take Methotrexate. It is thought that Xeljanz will be a major competitor for Biologics if approval is also received for Crohn's Disease, Psoriasis and Ulcerative Colitis.

References


Popular Threads Discussing Methotrexate



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09-21-2010, 02:35 PM   #1
Shellybum
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Join Date: Sep 2010
Location: Newport, United Kingdom

Thanks for the info on meds, really informative for people like me, new to the disease and it's medication, effects, side effects etc
09-21-2010, 04:01 PM   #2
seaofdreams
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Join Date: Aug 2009
Location: Brisbane, Queensland, Australia
I've been on Methotrexate for two week now and I thought it would give me a good excuse to learn more about it (:
I'm hoping to add some more info as I learn more about the drug.
__________________
~ Nicci

"Never feel guilty for being sick and try to stop comparing yourself and your life to others. You're doing the best you can under the circumstances you have and you're doing great."

Diagnosed with Crohn's in August 2009
Medication: 20mg Methotrexate injection weekly
Supplements: Folic Acid|Vitamin D|B12|Iron Complex|Magnesium Complex|Calcium|
09-21-2010, 05:12 PM   #3
beth
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Join Date: Mar 2009
Location: United Kingdom
Hmmm, the How it Works section I'm not 100% sure about. I know the wikipedia entry has a similar passage, but the way it was described to me by the consultant and my GP, is the significant modus operandi is to limit the immune systems ability to respond to the perceived threat - i.e. it cannot rapidly replicate the 'soldiers' as quickly, and therefore slows the inflammatory process.

The page should also describe the use of Folic Acid. IIRC it is used to "rescue" the body periodically from the other (side) effects, which is where I think the mucosal lining is pertinent. But it's late here and I'm struggling to think! Anyone able to fill in more detail?
09-21-2010, 05:34 PM   #4
seaofdreams
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Join Date: Aug 2009
Location: Brisbane, Queensland, Australia
There's a lot more to be included, it's nowhere near a complete guide, I've been adding to it when I've got a few minutes here and there at work.

Last edited by seaofdreams; 09-21-2010 at 06:33 PM.
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