Antimetabolites Flashcards
What phase does antimetabolites target?
S Phase
What do the Uridine analogs do?
inhibits thymidine synthesis from Uracil
What role does Leucovorin play?
can increase the effectiveness of 5-fluorouracil
can rescue from toxicity of methotrexate; reverses toxic effects of DHFR inhibition
What is the mechanism of action of 5-Fluorouracil
-Uracil analog
-covalent inhibitor
-cannot make thymine as forms a Ternary complex
What is the mechanism of action of Cytarabine?
-aka Ara-C, cytosine arabinoside
-cytosine analog; inhibits DNA synthesis
-also Gemcitabine is a cytosine analog
What role does Tetrahydrouridine play?
increases the effectiveness of Cytarabine via inhibiton of cytidine deaminase
What is the dose-limiting toxicity of Cytarabine?
neurotoxicity
What are the Purine analogs?
6-Mercaptopurine
-thio analog of adenine & blocks synthesis of purine nucleotides
What drug interaction occurs with 6-Mercaptopurine?
TPMT can inactivate the drug in 10% of patients
-allopurinol can affect metabolism of drug and increase toxcity of 6-Mercaptopurine
-6-Thioguanine can avoid this interaction
What is the mechanism of action of antifolates?
inhibits DHFR (enzyme that creates active form of folate tetrahydrofolate); inhibition of thymidine monophosphate (TMP) synthesis
What medications are antifolates?
methotrexate
-pralatrexate, pemetrexed
What rescues a 5-Fluorouracil overdose?
Thymidine
