Med Chem

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Med Chem
2013-03-26 17:54:21
Med Chem Antivirals Antineoplastics

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  1. What do antimitotic agents do?
    Inhibit topoisomerase and microtubule formation
  2. How do vinca alkaloids work?
    They prevent the formation of microtubules, which prevents the sister chromatids from pulling apart.  This causes the cell to go into the cell death pathway because there is "too much" DNA present.
  3. How do taxanes work?
    They prevent the deconstruction of microtubules, which leads to the cells becoming clogged up, resulting in the "death pathway".
  4. What is paclitaxel used for?
    Breast and Ovarian cancer
  5. Paclitaxel
  6. What is the MOA for paclitaxel?
    • Targets tubulin
    • Stabilizes the microtubules and inhibits their destruction; leads to the cells 'clogging' and stops the metaphase spindle configuration
  7. Where does paclitaxel come from?
    • Bark of yew trees
    • Now semi-synthetically derived
  8. Docetaxel
  9. What is Docetaxel used for?
    Breast and lung cancer
  10. What is the toxicity for paclitaxel and docetaxel?
    Bone marrow
  11. What is the MOA for docetaxel?
    Same as paclitaxel
  12. Ixabepilone
  13. What is the MOA for ixabepilone?
    • Works very similarly to paclitaxel
    • Apparently more potent than paclitaxel and not as prone to resistance.
    • Nitrogen is able to form a bond with O
  14. Which indications is ixabepilone approved for?
    Advanced breast cancer that is resistant to treatment with an anthracycline and taxanes
  15. Name an epothilone
  16. Eribulin
  17. Where did eribulin come from?
    Sea sponges
  18. What is the clinical use of eribulin?
    Treatment of breast cancer resistant to other therapies
  19. What is the MOA for eribulin?
    • Tubulin binder
    • Triggers apoptosis after prolonged mitotic blockade
  20. Imatinib (Gleevec)
  21. What is the MOA for Imatinib (Gleevec)?
    • Tyrosine kinase inhibitor
    • Blocks phosphorylation events in signaling
  22. What is the toxicity for gleevec?
    • None really
    • Can be taken at home
  23. What is the clinical use for gleevec?
    • Chronic myelogenous leukemia
    • GI stromal tumors
  24. What is the MOA for gefitinib?
    Blocks phosphorylation catalyzed by epidermal growth factor receptor (EGFR) and some other kinases
  25. Gefitinib originally reported no adverse effects.  What is the current AE?
    Pulmonary toxicity
  26. Gefitinib (Iressa)
  27. What is the black box warning for nilotinib?
    QT prolongation
  28. What are the two drug transport resistance mechanisms?
    • P-glycoprotein
    • Membrane transporters
  29. What are the three point mutation and regulation resistance mechanisms?
    • Topoisomerase II
    • Dihydrofolate reductase
    • Thymidylate synthase
  30. What is the point mutation resistance mechanism?
  31. What are the two regulation resistance mechanisms?
    • DNA repair enzymes
    • Nucleoside modification/synthesis
  32. Which drugs are important in P-glycoprotein resistance?
    • Etoposide
    • Doxorubicin
    • Taxol
    • Vincristine
  33. What are the trends of P-glycoprotein resistance drugs?
    • Very waxy
    • Nonpolar molecules
    • ATP required
  34. Where are membrane transport resistance mechanisms important?
    Nucleoside analogs
  35. How do membrane transport mechanisms work?
    • Nucleosides require certain cotransporters
    • Modify expression of these transporters to vary the concentration of drugs
  36. How many different membrane transporters are there?
    At least 6
  37. What is the resistance mechanism for alkylators and how does it work?
    • DNA repair
    • Upregulates in response to alkylators
  38. Cannabinol
  39. Nabilone
  40. Methicillin
  41. What is the MOA for methicillin?
    Inhibits bacterial cell wall synthesis
  42. Tetracycline
  43. What is the MOA for tetracycline?
    • Binds to bacterial ribosomes
    • Inhibit protein synthesis
    • Target 30S subunits are not found in mammalian cells
  44. What is Mylotarg and why is it important?
    • First clinical example of a drug that targets specific cell types
    • Withdrawn in 2010 after reports suggested it had no additional benefit and resulted in patient deaths
  45. Provide an example of bacterial drug inactivation
    Beta-lactamases - penicillinase derivative that attacks the amide group of a beta lactam and inactivates it; chemical modification
  46. Provide an example of point mutation.
    HIV-1 rapid mutation to resist protease inhibitors; occurs on the genome level
  47. Provide an example of regulation resistance
    NF-kappaB (which helps resist apoptosis) that is produced by tumor cells in response to drugs
  48. What were the first alkylating agents?
    Nitrogen mustards
  49. In addition to DNA, alkylating agents might also bind to _____.
  50. Which cell-cycle checkpoint do alkylating agents target?
    No specificity for check points
  51. What is the major target for alkylating agents?
    N7 portion of guanine  (the most nucleophilic nitrogen)
  52. What is a major problem for alkylating agents?
    • DNA damage can quickly be repaired
    • Damage may cause secondary carcinomas
  53. How does a bifunctional alkylating agent work?
    By cross-linking guanosine nucleotides in DNA strands, preventing them from uncoiling and separating
  54. Which is more efficient at initiating cell death, mono or bi- functional alkylating agents?
    • Bifunctional alkylating agents: More effective, cross-link DNA strands
    • Monofunctional: cause single-strand DNA breaks, more easily repaired
  55. Mechlorethamine
  56. What is the MOA of mechlorethamine?
    Cross-links guanine residues; bifunctional
  57. What are the drugs involved in MOPP protocol?
    • Mechlorethamine
    • Oncovin (vincristine)
    • Procarbazine
    • Prednisone
  58. What are the clinical uses for mechlorethamine?
    • Lung carcinoma
    • Chronic lymphoctyic leukemia
    • Hodgkin's lymphoma
  59. What is the toxicity of mechlorethamine?
    Bone marrow suppression
  60. How is mechlorethamine rapidly inactivated?
    By hydrolysis, t1/2 = 15 min
  61. Melphalan
  62. How do you increase the reactivity of a nitrogen in a nitrogen mustard?
    Add a EWG to increase acidity
  63. Chlorambucil
  64. What is the MOA for cyclophosphamide?
    • Prodrug 
    • DNA alkylation
  65. Cyclophosphamide
  66. Acrolein - byproduct of cyclophosphamide metabolism
  67. Ifosfamide
  68. Carmustine (BCNU)
  69. Why is carmustine special?
    It is very non-polar and can cross the BBB
  70. Streptozocin