In autoimmune diseases, different mechanisms have involvement in choosing methotrexate as a drug of choice. This mechanism is utilized in the treatment of cancer because of its cytotoxic effect. Methotrexate-polyglutamate further inhibits the de novo purine synthesis of both purine and thymidylate synthase, thereby inhibiting DNA synthesis. Tetrahydrofolate is necessary for the synthesis of the nucleotides of both DNA and RNA. Both the methotrexate and the methotrexate-polyglutamate inhibit the enzyme dihydrofolate reductase, which catalyzes the conversion of dihydrofolate into tetrahydrofolate, the active form of folic acid. Methotrexate is taken up into the cell by carriers called the human reduced folate carriers (SLC19A1), and it forms methotrexate-polyglutamate. In cancer, methotrexate acts as an antifolate antimetabolite. Methotrexate has a distinct mechanism of action regarding its use in chemotherapy and immunosuppression in autoimmune diseases. Methotrexate is used in off-lain cases of mycosis fungoides, dermatomyositis, pityriasis rubra pilaris, eczema, sarcoidosis, Non- Hodgkin's lymphoma (advanced stage), and non-metastatic osteosarcoma. The medication has the same effects as cyclosporin for patients with graft-versus-host disease. Also, methotrexate can be combined with anti-TNF agents and has shown effective in managing patients with ulcerative colitis, lymphoma (non-Hodgkin's type), carcinoma of the breast, small-cell carcinoma of the lung, epidermal tumors of the head and neck, and carcinoma of the ovary. The medication is also effective in patients with organ transplantation because of its anti-inflammatory and immunomodulatory activity. However, drug safety and efficacy have not been established in patients with blood dyscrasia, and it is not recommended in pregnant women. The medication is also safe and effective for patients with psoriasis, systemic lupus erythematosus, inflammatory bowel disease, vasculitis, and many other connective tissue diseases. In today's world, methotrexate is one of the major chemotherapeutic choices for various types of cancers.
Aminopterin was originally considered the parent compound for the methotrexate was first used successfully to treat childhood leukemia.
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Gubner first suggested methotrexate use in rheumatoid arthritis after performing a double blinded-placebo controlled clinical trial of methotrexate in patients with rheumatoid arthritis.
Methotrexate is an FDA-approved folic acid antagonist indicated for the treatment of rheumatoid arthritis because of its high potency and efficacy in such patients it can also be useful in patients with juvenile idiopathic arthritis.
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This activity will highlight the mechanism of action, adverse event profile, and other key factors (uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional healthcare team in managing patients with cancer and auto-immune conditions. This activity describes the indications, action, and contraindications for Methotrexate as a valuable agent in treating a wide variety of neoplastic diseases. Methotrexate (MTX) is an anti-metabolite most commonly used in chemotherapy and immunosuppressant in auto-immune diseases.
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