Methotrexate: Effects, Uses & Risks

Methotrexate is used as a drug for chemotherapy in various malignant tumor diseases. It is a cytostatic drug that prevents the rapid cell division of cancer cells. The drug is also used successfully not only in cancer therapy but also as a basic therapeutic agent for chronic inflammatory processes.

What is methotrexate?

Methotrexate is used as a drug for chemotherapy in various malignant tumor diseases. Methotrexate is also known as amethopterin. As a cytostatic drug, methotrexate is a cytotoxin that stops the natural division rate of body cells, also known as mitosis. For this reason, the drug is used primarily in tumor diseases of the hematopoietic system with a high rate of division. As with all cytostatic drugs, healthy body cells are also affected to a certain extent during use, which can result in unpleasant side effects for the patient. There are different classes of cytostatic drugs for tumor therapy and for the treatment of chronic inflammation. Methotrexate belongs to the so-called folic acid antagonists, which means that the active substance inhibits the enzyme dihydrofolate reductase; this important enzyme is, however, absolutely necessary for cell division. Chemically, methotrexate is very similar to folic acid and is therefore recognized by the organism like folic acid and introduced into the cell metabolism. Folic acid is urgently needed for the formation of DNA and RNA in the cell nucleus, but this formation can no longer be carried out by introducing methotrexate instead of folic acid.

Pharmacologic action

The pharmacologic effect of methotrexate, in short MTX, extends to all organs and organ systems because of its systemic use. In addition to the desired pharmacologic effect on rapidly dividing tumor cells, the active ingredient is invariably introduced into the metabolism of healthy cells as a false folic acid, which also limits their division rate and thus causes dysfunction and side effects. However, in addition to inhibiting the enzyme responsible for the introduction of folic acid into cell metabolism, MTX also inhibits other enzymes. The most important of these is the enzyme thymidilate synthase. This endogenous protein building block catalyzes the metabolic steps of pyrimidine synthesis, which is also required for the unhindered build-up of genetic material in the cell nucleus, i.e. DNA and RNA. Methotrexate thus acts as a chemotherapeutic agent at several interfaces so that tumor cells can be stopped in their rate of division. The active substance is excreted mainly via the kidneys and ultimately the patient’s urine. Healthy kidneys are considerably stressed by this excretion process with the active substance methotrexate during chemotherapy. Therefore, constant monitoring of kidney values, especially creatinine, is very important during chemotherapy with MTX. As soon as the values indicate that renal function is impaired, the therapy must be discontinued as a precautionary measure to prevent terminal renal failure, which may be life-threatening for the patient.

Medical application and use

Methotrexate, MTX, is a cytostatic drug and thus known primarily as a chemotherapeutic agent in cancer medicine. There, very high, systemically effective doses of the drug, which is available by prescription, are administered. The mechanism of action for combating malignant tumor cells is based on the ability of methotrexate to strongly curb the proliferation rate of malignant cells. However, methotrexate is not only a chemotherapeutic agent, but also an immunosuppressant. The cellular and humoral body defense is strongly reduced under the administration of methotrexate, the affected patients are therefore particularly susceptible to infections during a therapy cycle. Good therapeutic successes can also be achieved with the active substance methotrexate in the treatment of psoriasis and chronic rheumatic diseases. For example, methotrexate is considered helpful in the treatment of chronic rheumatoid arthritis. MTX is used as a basic therapeutic agent in this type of chronic inflammatory rheumatism. In addition, there are other autoimmune diseases for which MTX promises good therapeutic success. These include multiple sclerosis, Crohn’s disease and lupus erythematosus.Unlike tumor therapy, however, MTX is used in all of these diseases only at a very low dosage, which is why the side effects are significantly lower than in cancer therapy.

Risks and side effects

Methotrexate is a potent cytotoxin that may be used strictly for specific indications only under medical supervision. Because of the direct intervention in cell metabolism, the side effects are often very pronounced, especially in the therapy of malignant tumor diseases. Patients often suffer from general fatigue during therapy, as well as fatigue and headaches. Among the most frequent side effects are disorders of the gastrointestinal tract, which is due to the fact that the active substance methotrexate is also responsible for the undesirable destruction of epithelial cells of the sensitive mucous membranes in the stomach and small intestine. It is therefore not uncommon for nausea, vomiting or inflammation of the mucous membranes to occur. In high-dose therapy, these side effects cannot be prevented, at least temporarily. In addition, due to the side effect of myelosuppression, insufficient blood cells are produced in the bone marrow, which is why anemia can occur. The greatest risk in a therapy with MTX is pre-damaged kidneys, which can completely or partially stop their service and thus lead to a patient’s need for dialysis. Absolute contraindications to the administration of methotrexate are pregnancy, lactation, known renal insufficiency, or immunodeficiency of any cause.