Chemotherapy

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Author:
xinchen3
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195708
Filename:
Chemotherapy
Updated:
2013-01-27 21:19:13
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Chemo
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Chemo
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  1. Alkylators - MoA
    • form covalent bonds with cellular structures (proteins, DNA, RNA)
    • N7 position guanine on DNA
    • more toxic in cells with DNA repair deficient
    • cell cycle NON-specific
  2. Alkylators - Adverse Effects
    • BM suppression
    • Vesicant
    • Hemorrhagic cystitis
    • Secondary malignancy
  3. Alkylators - Resistance
    • MDR protein increase
    • Intracellular thiol increase
    • Enzymatic inhibition increase
    • DNA repair mechanism increase
  4. Nitrogen mustard
    • Alkylator
    • extreme vesicant
  5. Chlorambucil
    • Alkylator
    • used for slow progressive malignancies
  6. Melphalan
    Alkylator
  7. Cyclophosphamide
    • Alkylator
    • cause Hemorrhagic cystitis (give MESNA)
  8. Ifosfamide
    • Alkylator
    • cause Hemorrhagic cystitis (give MESNA)
  9. Nitrosourea
    • Alkylator
    • cross BBB (fat soluble)
    • prolonged BM suppression
  10. Busulfan
    • Alkylator
    • old CML drugs (replaced Gleevac)
    • significant pulmonary toxicity (interstitial fibrosis)
  11. Dacarbazine
    • Alkylator
    • Use: metastatic melanoma
  12. Procarbazine
    • Alkylator
    • antabuse/disulfiram effect (avoid alcohol)
  13. Temozolamide
    • Alkylator
    • cross BBB
    • Use: Glioma
  14. What is MESNA used for?
    (Mercapto Ethane Sulfonate sodium)
    • prevent hemorrhagic cystitis caused by alkylators that has a toxic intermediate (Acrolein)
    • - Ifosfamide & Cyclophosphamide
  15. Anti-Metabolites - MoA
    • resembles normal molecules but inhibits normal cellular process
    • cell cycle specific
  16. Methotrexate - MoA
    (anti-metabolite)
    • inhibits Dihydrofolate reductase (DHFR)
    • multiple cancer use
    • intrathecal use for brain tumor (stays in CSF by BBB)
    • 3rd spacing effect
  17. Methotrexate - Adverse Effects
    (anti-metabolites)
    • BM suppression
    • skin rash
    • mucositis
    • Hepatotoxicity
    • Pulmonary toxicity
    • (just think of organs that replicates really fast)
  18. Methotrexate - Resistance
    (anti-metabolites)
    • increase DHFR
    • decrease DHFR affinity
    • decrease uptake into cell
    • decrease polyglutamate (needed to trap MTX in cell)
  19. Pemetrexed
    Ralititrexed
    anti-folate
  20. what do you use to control Methotrexate toxicity
    • Folate resucue (Leucovorin)
    • when MTX killed all the rapidly dividing cells, we then use Leucovorin to help and safe all the normal cells from further damage
  21. 5-Fluorouracil (anti-pyrimidines)
    Capecitabine (pro-drug of 5-FU)
    • MoA:
    • - inhibits Thymidylate synthetase
    • - incorporated into RNA (5F-dUMP)
    • - activity enhanced by folinic acid
    • AE: BM suppression, Mucositis, Sun sensitivity
    • Resistance:
    • - decrease PRPP - allopurinol (activates 5-FU)
    • - increase Thymidylate synthetase activity
    • - reduce drug sensitivity
  22. Capecitabine - Adverse effect
    Hand/foot syndrome
  23. Cytosine arabinoside (ara-C)
    • MoA: pyrimidine analogue - incorporates into DNA
    • AE: BM suppression, mucositis, Neurotoxicity (cerebellar dysfunction)
    • Resistance:
    • Inc. cytidine deaminase (inactivator)
    • dec. deoxycytidine kinase (activator)
    • dec. affinity
  24. Gemcitabine
    MoA: cytosine analogue
  25. 6-mercaptopurine (6-MP)
    6-thioguanine (6-TG)
    • MoA: inhibit PRPP & HGPRT (purine cycle) => inhibit DNA synthesis
    • Use: Leukemias
    • AE: BMS, mucositis, GI toxicity
    • Resistance: increase XO, decrease affinity
  26. Allopurinol
    • MoA:
    • - inhibits Xanthine Oxidase
    • - inhibits PRPP
    • Use: Gout prophylaxis, enhance cytotoxic effect of purine analogues (6-MP)
  27. Fludarabine
    • MoA: adenosine analogue
    • Use: low grade lymphoma
  28. Cladribine
    • MoA: adenosine analogue
    • Use: Hairy cell leukemia
  29. what is the interaction between Allopurinol with 6-MP and 5-FU
    • increase activity of 6-MP
    • decrease activity of 5-FU
  30. Hydroxyurea
    • MoA: inhibits ribonucleotide reductase (converts RNA to DNA)
    • Use: CML & Sickle cell disease
    • AE: BMS, Diarrhea, N&V
  31. Anthracyclines (-rubicin)
    - Doxorubicin
    - Epirubicin
    - Daunorubicin
    - Idarubicin
    • MoA:
    • - intercalate DNA
    • - inhibit Topoisomerase 2
    • - generates ROS
    • Use: variety of cancers
    • AECardiac toxicity, BMS, alopecia, N&V, Secondary malignancy
    • Resistance: MDR
  32. Anthracenedione
    - Mitoxantrone
    same as anthracyclines, but less active and toxicity
  33. Dactinomycin
    • MoA: intercalate DNA
    • UsePediatric tumor (Wilm's, RB, Neurofibromatosis)
    • AE: BMS, severe vesicant
  34. Mitomycin
    • MoA: alkylator, cause cross linking 
    • AE: TTP
    • Resistance: MDR
  35. Bleomycin
    • MoA: intercalate DNA (G2 only!!!)
    • Use: Testicular ca.
    • AE: Lung toxicity, liver toxicity, anaphylactic reaction, Skin toxicity
    • Resistance: MDR
  36. Vinca alkaloids
    - vincristine, vinblastine, vindesine, vinorelbine
    • MoA: cause MT depolymerization
    • AEPeripheral neuropathy (motor irreversible)
    • Resistance: MDR
  37. Taxanes
    - paclitaxel, docetaxel
    • MoA: prevent MT depolymerization
    • AE: BMS, allergy, myalgia, arthralgia, neuropathy, skin & nail toxicity (use steroids to prevent these effects)
    • Resistance: MDR (except carbazitaxel)
  38. Podophyllotoxin
    - etoposide, teniposide
    • MoA: inhibit topoisomerase-2
    • AE: BMS, hypotension (give large dose)
    • Resistance: MDR
  39. Camptothecin
    - irinotecan, topotecan
    • MoA: inhibit topoisomerase-1
    • AE: BMS, excessive diarrhea, acute cholinergic side effects (use atropine)
    • Resistance: MDR
  40. Platinums
    - cisplatinum(1), carboplatinum(2), oxaliplatinum(3)
    • MoA: alkylator
    • Use: Testicular ca. (cisplatinum)
    • AE: neurotoxicity, nephrotoxicity(1), BMS(2), cold intolerance(3)
    • Resistance: MDR, increase thiol, increase DNA repair
  41. Preventions of Nephrotoxicity in platinums
    • hydration
    • replace K & Mg
    • amifosine - remove cisplatin 
  42. Prevention of neurotoxicity in platinums
    • Ca2+ & Mg2+ replacement
    • Avoid cold
  43. L-Asparaginase
    • MoA: hydrolyses circulating asparagine (tumor cells can't make asparagine)
    • Use: pediatric ALL
  44. Arsenic trioxide
    Use: combination with ATRA in PML
  45. Anti-estrogen therapy
    • Tamoxifen
    • Aromatase inhibitors
    • Progestins
    • LHRH/GnRH
  46. Tamoxifen
    • MoA: block estrogen on cancer cells
    • Use: breast ca.
    • AE:
    • - thromboemolism => retinopathy 
    • - endometrial ca.
    • Resistance:
    • - change in ER 
    • - ER- cell selection
  47. Aromatase inhibitors
    - Anastrozole
    - Letrozole
    - Exemestane
    • MoA: inhibit aromatase (dec. estrogen)
    • only used in menopausal settings
    • Use: Breast ca.
    • AE:
    • - osteoporosis => arthralgias
    • - hot flushes
  48. Progestins
    - Megestrol
    - Medroxyprogesterone
    • MoA: act like progesterone, decrease estrogen receptors
    • Use: breast ca.
  49. LHRH/GnRH
    - Leuprolide
    - Goserilin
    • MoA: inhibits LH & FSH release
    • Use: Breast ca., Prostate ca.
  50. Anti-androgen therapy
    • Flutamide, Bicalutamide
    • LHRH
    • Abiterone
  51. Flutamide, Bicalutamide
    • MoA: androgen blocker
    • Use: prostate ca.
    • AE:
    • - impotence
    • - andropause
    • - hot flushes
    • Resistance:
    • - change in androgen receptors
    • - receptor neg cell selection
  52. Abiterone
    • MoA: inhibits 17a-hydroxylase; decrease androgen & corticosteroid
    • Use: prostate ca.
  53. Rituxumab
    • MoA: anti-CD20
    • Use: B cell lymphoma
  54. Alemtuzumab
    • MoA: anti-CD52
    • Use: B cell lymphoma
  55. Ipilimumab
    • MoA: anti-CTLA-4
    • Use: metastatic melanoma
  56. Trastuzumab/Herceptin
    • MoA: anti-EGFR
    • Use: Her-2/neu breast cancer
    • AE: cardiac toxicity (reversible), skin rash
    • (avoid usage with Doxorubicin)
  57. Cetuximab
    • MoA: anti-EGFR
    • Use: SCC, wild type k-ras colon cancer
    • AE: skin rash (steroids)
  58. Panitunumab
    • MoA: anti-EGFR
    • Use: wild type k-ras colon cancer
    • AE: skin rash (steroids)
  59. Bevacizumab
    • MoA: anti-VEGF
    • Use: colon cancer
    • AE: cause ineffective wound healing
  60. Interferons
    • MoA: interferes with cell replication
    • AE: flu-like symptoms, Hepatotoxicity, BMS
  61. Interleukins
    • MoA: stimulates cytotoxic T-cell
    • AE: leaky membrane (edema)
  62. TNF-a
    • MoA: stimulate apoptosis
    • AE: inflammatory response
  63. Lapatinib
    • MoA: Her-2 TKI
    • Use: breast ca.
  64. Gefitinib, Erlotinib
    • MoA: non-Her2 TKI
    • Use: lung ca.
  65. Sunitinib
    • MoA: VEGF TKI
    • Use: renal cell ca.
  66. Sorafinib
    • MoA: VEGF TKI
    • Use: Hepatocellular ca.
  67. Imatinib, Nilotinib
    • MoA: Bcr-abl oncogene product
    • Use: CML, GIST
  68. Vemurafenib
    • MoA: R-raf inhibitor, RAS pathway inhibitor
    • Use: metastatic melanoma
  69. Sirolimus, Temsirolimus, Everolimus
    • MoA: M-TOR inhibitor
    • Use: transplant immunosuppression
  70. Bortezomib
    • MoA: proteosome inhibitor
    • Use: MM, mantel cell lymphoma
  71. Thalidomide
    • MoA: inhibit angiogenesis 
    • Use: MM
    • AE: birth defect (no limbs)
  72. Drugs that cause Alopecia
    • Anthracycline
    • Taxanes
    • Alkylating agents
  73. Drugs that cause Nausea & vomiting
    • Platinum
    • Anthracyclines
    • Nitrogen mustard
  74. Drugs that cause Mucositis
    Anti-metabolites
  75. Drugs that cause Extravasation/vesicants
    • Alkylators
    • Naturally occurring products
  76. Drugs that cause Discoloration
    Anti-metabolites
  77. Drugs that cause Hand-Foot syndrome
    Capecitabine
  78. Drugs that cause Acneiform
    • EGFR inhibitors
    • steroids
  79. Drugs that cause Pharyngolaryngeal dysesthesia
    Oxaliplatin
  80. Drugs that cause Cholinergic syndrome
    Irinotecan
  81. Drugs that cause Neurologic toxicity
    • Vinca alkaloids
    • Taxanes
    • Platinum
  82. Drugs that cause Cardiac toxicity
    • Anthracyclines
    • 5-FU
    • cyclophosphamide
  83. Drugs that cause Nephrotoxicity
    • cisplatinum
    • Mitomycin
    • Cyclophosphamide
  84. Drugs that cause Pulmonary toxicity
    • Bleomycin
    • Gemcitabine
    • Busulfan
  85. Drugs that cause Hematologic toxicity
    • Alkylators
    • Anthracyclines
  86. Drugs that cause TTP
    Mitomycin

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