Antineoplastics #2

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mp
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215175
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Antineoplastics #2
Updated:
2013-04-22 19:19:33
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Med Chem III Antineoplastics
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Antineoplastics #2
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  1. Anti-metabolites
    • Purine Analogs -- Mercaptopurine
    • Folic Acid Analogs -- Methotrexate
    • Pyrimidine Analogs -- 5FU
  2. Purine Analogs
    • some are prodrugs
    • inhibit synthesis (S-Phase)
    • disrupt nucleic acid fx -- analog incorporates into DNA
  3. methotrexate -- Trexall
    • folic acid antagonist
    • inhibits dihydrofolate reductase and thymidylate synthase
    • bone marrow depression
  4. Leucovorin rescue and carboxypeptidase G2 -- Voraxaze
    reverses the effects of methotrexate
  5. pemetrexed -- Alimta
    • inhibits dihydrofolate reductase, thymidylate synthase, glycinamide ribonucleotide formyltransferase
    • advantage -- converted to polyglutamate form (can't back diffuse out)
    • pts must take B12 and folic acid to prevent toxicity
  6. pralatrexate -- Folotyn
    • complete inhibition of dihydrofolate reductase and polyglutamylation
    • Teratogenic
    • pts must take B12 and folic acid
  7. levoleucovorin -- Fusilev
    • (rescue therapy) antidote to drugs decreasing folic acid levels
    • reduces anemia in pts tx'd with dapsone
  8. Pyrimidine Analogs
    • All are prodrugs!
    • Inhibit synthesis
    • disrupt nucleic acid fx
  9. Pyrimidine Analogs -- drugs
    • 5-FU
    • Floxuridine
    • Cytarabine -- Cytosar-U
    • Gemcitabine -- Gemzar
    • Capecitabine -- Xeloda
    • Azacitidine -- Vidaza
  10. 5-FU
    • prevents DNA synthesis, suicide substrate at thymidylate synthase
    • extreme care to avoid extravasation
    • leucovorin can increase effects -- use lower doses of 5-FU
  11. floxuridine
    prodrug of 5-FU
  12. citarabine -- Cytosar-U
    inhibits DNA polymerase
  13. decitabine -- Dacogen
    • phosphorylated and incorporated into DNA and inhibits DNA methyltransferase
    • analog of natural nucleoside 2' -- deoxycytidine
  14. Purine Analogs -- drugs
    • Thioguanine -- 6-TG
    • Mercaptopurine -- Purinethol
    • Cladribine -- Leustatin
    • Fludarabine -- Fludara
    • Pentostatin -- Nipent
    • Clofarabine -- Clolar
    • Nelarabine -- Arranon
  15. Thioguanine -- 6TG
    incorrect DNA synthesis
  16. Mercaptopurine -- Purinethol
    • incorrect DNA synthesis
    • prodrug
    • interacts with 20+ enzymes
    • genotyping is recommended
  17. cladribine -- Leustatin
    inhibits DNA synthesis
  18. fludarabine -- Fludara
    stops DNA synthesis
  19. pentostatin -- Nipent
    • potent trasition state analog inhibitor leading to inhibition of ribonucleotide reductase
    • natural product
  20. clofarabine -- Clolar
    • inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools
    • no drug-drug interaction
  21. Nelarabine -- Arranon
    prodrug demethylated by adenosine deaminase and converted to triphosphate and incorporated into DNA leading to cell death

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