Term
| What are the different classes of anti-metabolites? |
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Definition
- Folic acid analogs
- Pyrimidine analogs
- Purine analogs
**All are S phase specific |
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Term
| How is dTMP/thymidylate made? |
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Definition
dUMP converted to thymidine, phosphorylated using THF. Thymidylate synthase + THF transfers the methyl group.
**Methotrexate blocks DHFR, needed to convert DHF to THF |
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Term
| What is polyglutamated-Methotrexate? |
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Definition
| A form used by the body that inhibits DHFR, thymidylate synthase, and purine synthesis. |
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Term
| How is methotrexate dosed? |
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Definition
- IV
- Myelosuppression, GI, NEPHROtoxic
**Rescue - leucovorin, but decreases efficacy |
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Term
| How does pemextred compare to methotrexate? |
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Definition
More potent inhibitor of purines
Better transport into tumor cells
**Also IV, nephrotoxic |
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Term
| What are purines and pyrimidines? |
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Definition
- Purines: Adenosine and Guanine
- Pyrimidines: Cytosine and thymine |
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Term
| What drugs are pyrimidine (C/T) antagonists? |
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Definition
- 5-FU - blocks thymidylate synthesis. Fluorine stabilizes complex inactivating enzyme. Give w/ leucovorin. IV
- Capecitabine - prodrug of 5-FU. Can give PO, more diarrhea
- Cytarabine - Cytosine, competes for chain termination. IV/IT infusion
- Gemcitabine - fluorine, prevents elongation. IV
**Hand-foot |
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Term
|
Definition
- Rescue for MTX
- Increases efficacy of 5-FU |
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Term
| How does Azacitidine work? |
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Definition
incorporates into DNA and inhibits methyltransferase, causing demethylation in DNA - does not block synthesis
- IV |
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Term
| What drugs are purine analogs? |
|
Definition
- 6-mercaptopurine - PO, guanine analog. HYPERURICEMIA, can use allopurinol but must decr dose 75% due to xanthine oxidase
- Fludarabine - Adenosine analog. Resistant to deamination = long half life. IV, HEMOLYTIC ANEMIA
- Clofarabine - IV, capillary leak/SIRS
- Nelarabine - IV, neurotoxic
- Pentostatin - guanine, 7 member ring. IV |
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Term
| How does hydroxyurea work? |
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Definition
inhibits ribonucleotide reductase to block DNA synthesis
PO |
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