Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming.

Methotrexate (MTX): Methotrexate is a medication used for several conditions, including:

1. Cancer Treatment – Used in chemotherapy for leukemia, lymphoma, breast cancer, lung cancer, and other cancers.

2. Autoimmune Diseases – Treats rheumatoid arthritis, psoriasis, and lupus by suppressing the immune system.

3. Ectopic Pregnancy – Helps stop the growth of a fertilized egg outside the uterus.

It works by slowing down cell growth and reducing immune system activity. However, it has significant side effects, so it’s used under strict medical supervision. Let me know if you need details!

Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions. It has a long duration of action and is generally given to patients once weekly.

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Mechanism of Action (MOA) and Metabolism of Methotrexate

Mechanism of Action (MOA):

Methotrexate primarily works by inhibiting enzymes involved in nucleotide synthesis, which is crucial for DNA replication and cell division. This action impacts rapidly dividing cells, making methotrexate effective in diseases like cancer and autoimmune disorders. Key aspects of its MOA include:

Enzyme Inhibition: Methotrexate inhibits enzymes such as:

• Dihydrofolate Reductase (DHFR): Prevents the formation of tetrahydrofolate, crucial for nucleotide synthesis.
• Thymidylate Synthase and AICART (Aminoimidazole Carboxamide Ribonucleotide Transformylase): Critical for DNA and purine synthesis.
• Amido Phosphoribosyltransferase: Further suppresses nucleotide production.

Impact on Autoimmune Diseases (e.g., Rheumatoid Arthritis):

• Methotrexate is converted to polyglutamate within cells, which strongly inhibits AICART.
• This leads to an accumulation of AICART ribonucleotide, inhibiting adenosine deaminase and increasing extracellular adenosine, a molecule with potent anti-inflammatory effects.

Methotrexate Metabolism:

Methotrexate undergoes conversion and metabolism primarily in tissues and the liver:

Conversion to Methotrexate Polyglutamate:

• Methotrexate is enzymatically transformed by folylpolyglutamate synthase into methotrexate polyglutamate, which enhances its intracellular retention and efficacy.

Role of Gamma-Glutamyl Hydrolase:

• This enzyme hydrolyzes methotrexate polyglutamate back into methotrexate, maintaining a dynamic balance.

Formation of Metabolites:

• A small portion of methotrexate is converted to 7-hydroxymethotrexate, an inactive metabolite.

These metabolic processes ensure methotrexate’s activity and elimination while influencing its therapeutic and toxic effects in various tissues.

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Common Side Effects of Methotrexate

Methotrexate is a widely used medication, but it can cause several side effects. Here are the common ones to be aware of:

• Digestive Issues: Abdominal pain, nausea, vomiting, loss of appetite, diarrhea, and dyspepsia.
• Oral Problems: Mouth ulcers, throat ulcers, and stomatitis (mouth inflammation).
• Blood and Immune System Effects: Decreased white blood cell count, low blood platelets, anemia (low red blood cell count).
• Liver Effects: Increased liver enzyme levels, indicating potential liver stress.
• Skin and Allergic Reactions: Exanthema (rash), erythema (skin redness), and itching.
• Respiratory Issues: Pneumonitis (lung inflammation).
• Neurological and General Effects: Headache, fatigue, and drowsiness.

Available Medicines for Methotrexate

Below is a list of common Methotrexate-based medicines along with manufacturers and price ranges:

1. Folitrax – Ipca Laboratories Ltd: ₹33 to ₹566 (13 variants)
2. Mext – Wallace Pharmaceuticals Pvt Ltd: ₹33 to ₹447 (6 variants)
3. Biotrexate – Biochem Pharmaceutical Industries: ₹49 to ₹1030 (6 variants)
4. Oncotrex – Sun Pharmaceutical Industries Ltd: ₹45 to ₹148 (3 variants)
5. Imutrex – Cipla Ltd: ₹47 to ₹121 (4 variants)
6. Merex – Intas Pharmaceuticals Ltd: ₹601 to ₹2025 (4 variants)
7. Methocel – Celon Laboratories Ltd: ₹35 to ₹904 (5 variants)
8. Mexate – Zydus Cadila: ₹35 to ₹563 (6 variants)
9. Meditrex – Overseas Healthcare Pvt Ltd: ₹55 to ₹339 (7 variants)
10. Remtrex – Alkem Laboratories Ltd: ₹42 to ₹713 (4 variants)

FAQs on Methotrexate

1. Can Methotrexate affect fertility?
Yes, Methotrexate can temporarily affect fertility in both males and females.

• In Males: It may reduce sperm count.
• In Females: It may cause menstrual irregularities.
  These effects are generally reversible after discontinuing the therapy.

2. What precautions should be taken if planning a pregnancy?

• If your husband is taking Methotrexate, avoid pregnancy during the treatment.
• Additionally, wait for at least 3 months after therapy cessation before attempting pregnancy, as the drug can lead to severe fetal abnormalities.

Within metabolic processes, methotrexate functions and is eliminated, impacting therapeutic and toxic properties in diverse tissues. To determine the full extent of methotrexate’s effects, further investigation into these processes is warranted.