Pharmacology 3620 Lecture Notes - Lecture 12: Cytochrome P450, Dihydrofolate Reductase, Immunosuppression
24 Oct 2016
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Feel free to email me (oneclass512475@gmail. com) if you have any questions or don"t understand something! Describe how antimetabolite drugs work, their uses and limitations. Name examples of alkylating agents used for cancer chemotherapy. Define the basic mechanisms of action of alkylating agents. Antimetabolites are cell-cycle specific because they usually work on rapidly dividing cells and focus on dna synthesis disruption (i. e. mainly s-phase) They are widely used to treat many different tumours. In our bodies, folate is usually converted into fh4 (tetra-hydrofolate) by dhfr to allow the synthesis of thymidine. Methotrexate inhibits dhfr by causing thymidine depletion which interferes with cell division. During synthesis of dna, if there is a lack of thymidine, the cell will undergo apoptosis. Thymidine synthesis can be continued by leucovorin rescue, which can replace fh4 to continue thymidine synthesis and bypass the mechanism of methotrexate: leucovorin is more effectively taken up by normal cells than by tumour cells.
