Effect of Methotrexate
Methotrexate is an active ingredient used in the treatment of chronic inflammatory diseases and various types of cancer. Methotrexate has three important effects: it has antineoplastic, immunosuppressive and anti-inflammatory effects. Antineoplastic means that methotrexate is effective against malignant tumors (neoplasia).
Substances that have an antineoplastic effect belong to the group of cytostatic drugs. A cytostatic drug inhibits body cell growth or cell division. A cytostatic drug is used in the chemotherapy of cancer in order to inhibit the growth of the tumor.
Methotrexate is used as a cytostatic drug for the treatment of acute lymphatic and myeloid leukaemia, non-Hodgkin’s lymphomas, osteosarcoma in children and adolescents, and solid tumors (breast, lung, and bladder cancer). Furthermore, Methotrexate has an immunosuppressive effect, which means that it reduces the functions of the body’s own defense system. This effect of Methotrexate is mainly used in the treatment of diseases caused by a malfunction of the immune system or where the immune system is directed against the body’s own cells (autoimmune disease).
Immunosuppressive agents such as Methotrexate are not without side effects and risks, as there is a fundamental limitation of the defense mechanisms, which increases the risk of infection. The risk of cancer is also increased, because immunosuppression also makes it easier for malignant cells to multiply and spread in the organism. Methotrexate, as an immunosuppressive agent, is dosed much lower than in cytostatic therapy and is used in rheumatoid arthritis, severe forms of psoriasis and, more rarely, in Crohn’s disease and multiple sclerosis.
Methotrexate also has an anti-inflammatory effect. It intervenes in the inflammatory process in a biochemical way. Methotrexate has a very similar chemical structure to folic acid (vitamin B9).
Folic acid plays an important role in the production of building blocks for the genetic material (RNA and DNA), which a body cell needs in order to divide and function. Due to its similar structure to folic acid, methotrexate acts as an inhibitor of this endogenous production (biosynthesis) of the DNA building blocks, since it is the “wrong” building block that prevents the “correct” incorporation of folic acid. As a result, a cell does not have enough DNA building blocks at its disposal as are needed for the cell to multiply.Fast growing tissues such as cancer cells, bone marrow, skin and mucosal cells are more sensitive to the effects of Methotrexate than slow growing tissues.
In the case of psoriasis (an area of application for methotrexate), cell growth is greatly increased compared to normal skin, which is why methotrexate can have a good effect against cell growth here. Methotrexate initially acts mainly on fast-growing tissues such as tumor cells, but as a cell growth inhibitor it also acts on healthy cells, which explains the numerous side effects of methotrexate. The most common side effects of therapy with Methotrexate are gastrointestinal disorders such as inflammation of the oral mucosa, diarrhea, nausea and abdominal discomfort.
Especially the intestinal mucosa is affected by Methotrexate, because it is a very strong and fast growing tissue whose cell division is inhibited by Methotrexate. Often a bone marrow depression is also observed, i.e. a suspension of normal blood formation in the bone marrow. Very often an increase in liver enzymes (transaminases) occurs as an undesirable effect, which can cause severe liver damage.
In contrast to gastrointestinal complaints, however, this liver enzyme increase can be prevented by the additional administration of folic acid during methotrexate therapy. Other side effects of treatment with Methotrexate are kidney dysfunction, skin rashes, hair loss, allergic reactions and inflammatory changes in the lungs (pneumonitis). For this reason, regular laboratory checks of kidney and liver function are essential during methotrexate therapy. In case of side effects such as fever, shortness of breath or chesty cough, a doctor should be consulted immediately.