metotreksas

Metotreksas, known in English as methotrexate (MTX), is a folate analogue antimetabolite used to treat several cancers as well as inflammatory and autoimmune diseases. It inhibits key enzymes in folate metabolism, most notably dihydrofolate reductase, reducing the synthesis of DNA, RNA, and proteins. At low doses, MTX also exerts anti-inflammatory effects in part by promoting the release of adenosine.

Pharmacokinetics and administration: MTX can be given orally, intramuscularly, subcutaneously, or intravenously depending on the indication. It is variably absorbed from the gut; after cellular uptake, polyglutamated forms accumulate and prolong activity. It is mainly cleared by the kidneys, and its half-life is influenced by renal function. High-dose MTX often requires leucovorin (folinic acid) rescue to mitigate toxicity; lower-dose regimens do not.

Indications: Common cancer indications include acute lymphoblastic leukemia, osteosarcoma, and certain lymphomas. In autoimmune diseases, MTX is used for rheumatoid arthritis, psoriasis, psoriatic arthritis, and sometimes inflammatory bowel disease, among others.

Adverse effects and safety: Major risks include myelosuppression, mucositis, hepatotoxicity, nephrotoxicity, and pulmonary toxicity. It is teratogenic and contraindicated in pregnancy. Other effects can include fatigue, nausea, alopecia, and increased infection risk. Toxicity can be increased by alcohol use and by certain drugs such as NSAIDs, some antibiotics, and proton pump inhibitors.

Monitoring and contraindications: Before and during treatment, clinicians monitor blood counts, liver and kidney function, and pregnancy status in women of childbearing potential. Absolute contraindications include pregnancy, significant liver disease, alcoholism, severe renal impairment, active infections, and certain blood dyscrasias. Folinic acid rescue is used with high-dose regimens; folic acid supplementation is often used with low-dose regimens to reduce toxicity while preserving efficacy in autoimmune uses.