3b) The drug methotrexate is commonly given as an antineoplastic chemotherapy dr

Question

3b) The drug methotrexate is commonly given as an antineoplastic chemotherapy drug for the treatment of cancer.

As with most chemotherapy drugs, the effects of methotrexate are not specific for cancer/neoplastic cells, and side effects of the drug are often experienced by patients. These side effects include hair loss and low blood cell counts, both of which are a result of methotrexate’s effect on processes with rapidly dividing cells (e.g. hair follicle division and blood cell production in bone marrow). To alleviate some of the side effects, patients will often be given a dose of folinic acid 24 hours after a dose of methotrexate. Folinic acid is a formyl derivative of tetrahydrofolic acid that can be used by normal cells without the action of dihydrofolate reductase. How does this folinic acid “rescue” act to alleviate/reduce the side effects?

Explanation / Answer

Methotrexate inhibits Dihydrofolate reductase, which converts dihydrofolate to tetrahydrofolate.

This tetrahydrofolate is essential for the de novo synthesis of purine, thymidine, and amino acids. All of these are important in normal as well as cancer cell proliferation. For preventing the formation of tetrahydrofolate, Methotrexate is prescribed.

The folinic acid which is a 5-formyl derivative of tetrahydrofolic acid can be converted to tetrahydrofolate without need and action of dihydrofolate reductase. Thus providing purine, thymidine precursors for normal cells to perform cell survival mechanisms.

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