Chemotherapy IV Anti-Metabolites Flashcards
Methotrexate MOA
Methotrexate enters the cell via a specific folate carrier protein and MTX binds reversibly to DHFR leading to a buildup of DHF and deficiency of THF - used in purine synthesis.
Methotrexate dose must be reduced in _____________.
Renal insufficiency
Cytarabine MOA
It is converted to a triphosphate and the ARA-CTP triphosphate is the main cytotoxic metabolites and is incorporated into DNA and inhibits template function and chain elongation.
What is cytarabine mainly used to treat?
Acute Myelogenous Leukemia
5-fluorouracil MOA
Production of FdUMP which inhibits thymidylate synthetase. Tetrahydrofolate + FdUMP binds tightly to thymidylate synthetase and decreases the production of thymine nucleotides.
6-Mercaptopurine MOA
6-thioinosinic acid inhibits enzymes of de novo purine nucleotide synthesis.
What phase of the cell cycle are the antimetabolites specific for?
S-Phase
What endogenous substance can rescue the cell from the toxic effects of methotrexate?
THF
What happens when methotrexate is polyglutamated?
Its half life is increased and cells can no longer be rescued
Methotrexate SE
- Myelosuppression
- GI symptoms
What is the level of protein binding of methotrexate?
High
What can be given with methotrexate in order to use high dose methotrexate treatment?
Leucovorin
Can cells with polyglutamated methotrexate be rescued?
No
Pemetrexed MOA
Inhibition of thymidylate synthase
Pemetrexed SE
- Rash
- Stomatitis
- Diarrhea
- Hand Foot Syndrome
