Ans. Methotrexate is used as immunosuppressant drug (in rheumatoid arthritis, psoriasis and other autoimmune disorders) in low doses.
While in high doses methotrexate is used as anti-cancer drug.
It is one of the most commonly used anticancer drug. Methotrexate is useful in choriocarcinoma, non-Hodgkin lymphoma, Breast, bladder, head and neck cancers, childhood acute lymphoblastic leukaemia (ALL) etc.
Methotrexate is folic acid analogue (structurally resembles folic acid). It inhibits dihydrofolate reductase enzyme (DHFRase), due to which conversion of dihydro folic acid (DHFA) to tetrahydro folic acid (THFA) is prevented.
This Tetrahydro folic acid is essential coenzyme, required for purine and thymidylate synthesis which are necessary components for DNA and RNA synthesis and cell division.
When methotrexate is given in higher doses, it acts on rapidly dividing cells including cancer cells and host cells. The action on rapidly diving host cell (like bone marrow) are responsible for its side effects.
Major adverse effect of methotrexate are bone marrow suppression, thrombocytopenia, mucosytosis, diarrhoea, alopecia.
Folinic acid/leucovorin is a form of folate that can be readily utilized by the body and it prevents the normal cells form methotrexate adverse effect (they can perform their normal function in presence of methotrexate). While cancer cells having higher need of folate then normal cells, does not protected to same extent.
So adding Folinic acid/leucovorin is useful while cancer treatment because-
- Rescue from Methotrexate Toxicity (reduced side effects)
- Shortening of Recovery time from chemotherapy
- It is possible to give higher doses of Methotrexate during cancer treatment as normal cells are less affected (increased therapeutic index)