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34 Cards in this Set
- Front
- Back
Name the 3 main classes of Antimetabolites.
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Pyrimidine analogues
Folate antagonists Purine analogues |
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What are the 3 main Pyrimidine analogue agents?
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Fluorouracil (5-FU)
Gemcitabine Cytarabine |
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What are the 2 main Folate antagonists?
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Methotrexate
Pemetrexed |
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What are the 3 main Purine analogues?
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Mercaptopurine
Thioguanine Fludarabine |
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What phase do antimetabolites specifically inhibit?
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S phase
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What are the 3 main toxicities associated with antimetabolites?
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Myelosuppression
GI distrubances Dermatological disturbances Hepatic Pulmonary Dermatologic |
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What is 5-FU indicated for?
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GI cancer
Breast cancer Head/neck cancer |
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What is 5-FU's MOA?
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Pyrimidine analog resembling uracil - falsely incorportes into DNA to inhibit synthesis and replication
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What are 5-FU's two active metabolites?
What is the inactive metabolite and how is it converted to this? |
5-FUTP - inhibits DNA synthesis
5-FUMP - inhibits thymidylate synthetase - DNA synthesis Inactive form via enzyme DPD |
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What is Leucovorin? What is its significance in anti-cancer therapy?
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It is reduced folate
Co-administration with Flurouracil enhances the activity of fluorouracil. This occurs because Leucovorin stabilizes the binding of 5-dUMP (active metabolite) to thymidylate synthetase. This however is also associated with greater toxicity |
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What is Capecitabine?
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The prodrug of 5-FU
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What is the mechanism of resistance for 5-FU?
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Increase Thymidylate synthetase
Decreased activation to active metabolite |
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What is Gemcitabine and what are its 3 indications?
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Pyrimidine analog
Pancreatic cancer Lung cancer Bladder cancer Inserts as false pyrimidine - blocks DNA synthesis |
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What metabolite of Gemcitabine is the actual inhibitor of DNA synthesis?
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Gemcitabine triphosphate
***5-FU is given as an infusion Gemcitabine is given as a bolus |
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What is Cytarabine indicated for?
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Acute Leukemia
Lymphoma Also inserts falsely as a pyrimidine and blocks DNA synthesis |
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What is the actual metabolite of Cytarabine that exhibits anti-DNA synthesis effect?
What enzyme converts Cytarabine to this active form? |
Cytarabine triphosphate
Nucleoside diphosphate kinase |
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What is the main mechanism of resistance associated with Cytarabine?
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Increased levels of Cytidine deaminase and Deoxycytidylate deaminase - two enzymes that convert Cytarabine to inactive forms.
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What toxicity is unique to Cytarabine amongst the anti-metabolite class?
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Central nervous system toxicities
Ocular toxicity |
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What is the mechanism of resistance involved with Cytarabine?
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Increased DNA Polymerase
Increase Inactivation by cytidine deaminase |
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What are the two folate antagonist agents?
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Methotrexate
Pemetrexed |
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What is Methotrexate indicated for?
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Acute Leukemia
Lymphoma Breast Cancer CNS Malignancies |
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What is the MOA of these agents?
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Mimic folate
Binds to/inhibits Dihydrofolate Reductase Decreases the production of reduced folate (tetrahydrofolate) needed for DNA synthesis Also inhibits thymidylate synthetase |
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What toxicity is unique to this agent?
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Acute Renal Failure
CNS toxicity |
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Why is Leucovorin administered after Methotrexate?
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A Leucovorin Rescue occurs that rescues normal cells from death and reduces toxicity
Cancer cells lack the transport carrier system to utilize leucovorin rescue |
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What is Pemetrexed indicated for?
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Lung cancer
Bladder cancer |
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What is given with Pemetrexed to reduce bone marrow suppression?
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Folic acid and Vitamin B12
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What is the mechanism of resistance for folate antagonists?
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Increased synthesis of dihydrofolate reductase
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What are the two main Purine analog agents?
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Fludarabine
Mercaptopurine |
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What is the indication of Fludarabine?
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Hematologic malignancies
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What is the MOA of Fludarabine?
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Inhibits DNA polymerase alpha
Inhibits ribonucleotide reductase Inhibits DNA primase Falsely incorporates itself into DNA Also is metabolized to triphosphate active form |
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What clinical pearl is important for Fludarabine?
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Fludarabine inhibits T-cells an dincreases the risk of opportunistic infection. Anti-infectives given prophylactically
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What is the main indication of Mercaptopurine?
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ALL - used a lot in children with this disease
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What is the active form of 6-Mercaptopurine?
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Azathioprine --> 6 - MP --> 6 -thioguanine nucleotides (triphosphate form) --> incorporated into DNA/RNA
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What is the drug-drug interaction with Mercaptopurine
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Xanthine Oxidase Inhibitors - Allopurinol
Xanthine Oxidase metabolized mercaptopurine. If inhibited, MC levels rise |