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Heme > Lec 18-19 Pharm Anti-Neoplasms > Flashcards

Lec 18-19 Pharm Anti-Neoplasms Flashcards

1
Q

What is induction treatment?

A

treatment to induce complete remission

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2
Q

What is consolidation treatment?

A

treats sub-clinical residual disease with intent of increasing cure rate or survival

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3
Q

What is maintenance therapy for chemo?

A

long term low dose therapy to decrease recurrence/progression rate

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4
Q

What is adjuvant chemo therapy?

A

chemo after primary surgery or radiotherapy to increase survival/cure rate

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5
Q

What is neoadjuvant chemo therapy?

A

chemo before primary surgery or radiotherapy to increase cure rate or survival or decreasing morbidity with primary therapy

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6
Q

What is palliative chemo therapy?

A

chemo to alleviate symptoms with intent of prolongation of life or cure

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7
Q

What is the purpose of combination chemo?

A

allow maximum tumor kill with least side effects

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8
Q

What is the mech of action of alkylating agents?

A

cross link DNA, RNA, or proteins

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9
Q

Do alkylating agents require cell proliferation?

A

yes, require cell proliferation even though not cell cycle specific

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10
Q

What is mech of action of resistance to alkylating agents?

A

resistance via enhanced DNA repair of glutathione conjugation

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11
Q

What are the two nitrogen mustards?

A

cyclophosphamide

ifosfamide

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12
Q

What is mech of action of cyclophosphamide?

A

covalently X link DNA at guanine 7

require bioactivation by liver

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13
Q

What are 2 side effects of cyclophosphamide?

A

myelosuppression

hemorrhagic cystitis [prevent with mesna]

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14
Q

What adjuvant can you give with cyclophsophamide to partially prevent hemorrhagic cystitis?

A

mesna

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15
Q

What are the 4 nitrosoureas?

A
  • carmustine
  • lomustine
  • semustine
  • streptozocin
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16
Q

What is mech of action of nitrosoureas [carmustine, lomustine, semustine, streptozocin]?

A

require bioactivation

cross link DNA

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17
Q

Do nitrosoureas [carmustine, lomustine, semustine, streptozocin] cross the BBB?

A

yep!

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18
Q

What are the side effects of the nitrosoureas [carmustine, lomustine, semustine, streptozocin]?

A

CNS toxicity = convulsions, dizziness, ataxia

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19
Q

What is mech of action busulfan?

A

cross links DNA

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20
Q

What are the 3 side effects of busulfan?

A

severe myelosuppression
pulmonary fibrosis
hyperpigmentation

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21
Q

What is the mech of action of cisplatin?

A

cross links DNA

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22
Q

What are 2 side effects of cisplatin?

A
  • nephrotoxicity

- acoustic nerve damage

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23
Q

What can you give with cisplatin to prevent nephrotoxicity?

A

amifostine and chloride diuresis

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24
Q

What is mech of action of ionizing radiation?

A

induces double stranded DNA breaks

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25
Q

What are antimetabolite neoplastic drugs?

A

analogs of natural metabolites in RNA and DNA synthesis
compete with normal metabolites for enzymes or get incorporated into DNA/RNA

S phase specific

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26
Q

What is mech of action methotrexate?

A

folic acid analog that inhibits dihydrofolate reductase –> less dTMP –> less DNA and protein synthesis

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27
Q

What drug is a folate analog?

A

methotrexate

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28
Q

What 3 drugs are a purine analog?

A
  • azathioprine
  • 6-mercaptopurine [6-MP]
  • 6-thioguanine [6-TG]
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29
Q

What drug is an adenosine analog?

A

cladrobine

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30
Q

What 3 drugs are a pyrimidine analog?

A
  • 5- fluorouracil
  • gemcitabine
  • cytarabine
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31
Q

What are 4 side effects of methotrexate?

A
  • myelosuppression
  • macrovesicular fatty change in liver
  • mucositis
  • teratogenic
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32
Q

Why do you give leucovorin with methotrexate?

A

leucovorin = folinic acid

rescues the BM from myelosuppression caused by methotrexate

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33
Q

What is mech of action 5-fluorouracil [5-FU]?

A

pyrimidine analog bioactivated to 5F-dUMP

complexes with folic acid and inhibits thymidylate synthase –> less dTMP –> less DNA and protein synthesis

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34
Q

What are 2 side effects of 5-FU?

A

myelosuppression photosensitivity

35
Q

What is treatment for 5-FU overdose?

A

rescue with uridine

36
Q

What is mech of action of cytarabine?

A

pyrimidine analog –> inhibits DNA polymerase

37
Q

What are 3 side effects of cytarabine?

A

leukopenia
thrombocytopenia
megaloblastic anemia

CYTarabine causes panCYTopenia

38
Q

What is mech of action of 6-MP?

A

purine [thiol] analog –> decreases de novo purine synthesis

activated by HGPRT

39
Q

What are 3 organs with side effects of 6-MP?

A
  • bone marrow
  • GI
  • liver
40
Q

What two purine analogs have increased toxicity with allopurinol?

A
  • 6MP

- azathoprine

41
Q

Why does 6-MP have increased toxicty wtih allopurinol?

A

allopurinol inhibits its metabolism

42
Q

What is the mech of action of caldribine?

A

adenosine analog –> inhibits adenosine deaminase

43
Q

Does methortrexate cross the BBB?

A

yep!

44
Q

Where is methortrexated excreted?

A

renally —> impaired renal excretion wtih ASA, NSAIDS, penicillins

45
Q

What is mech of action of gemcitabine?

A

pyrimidine analog, inhibits DNA polymerase if incoporated into DNA

46
Q

What happens if you give leucovorin with 5-FU?

A

potentiates the effect of 5-FU by increasing intracellular THF

47
Q

What happens if you give leucovorin with methotrexate?

A

decreases toxicity of high dose methotrexate = reverses myelosuppression

48
Q

What is mech of action bleomycin?

A

induces free radical formation causing breaks in DNA strands

49
Q

What are 3 toxicities of bleomycin?

A
  • pulmonary fibrosis
  • skin changes
  • mucositis
50
Q

What is the mech of action of doxorubicin?

A

generate free radicals

intercalate in DNA + inhibit DNA topoisomerases–> breaks in DNA –> decreased replication

51
Q

What are 3 side effects of doxorubicin?

A
  • cardiotoxicity [dilated cardiomyopathy]

- myelosuppression

52
Q

What can you give pt on doxorubicin to prevent cardiotoxicity?

A

dexrazocane = Fe chelating agent

53
Q

What is mech of action topotecan and irinotecan?

A

inhibit topoisomerase I and prevent DNA unwinding and replication

54
Q

What are 2 side effects of irinotecan/topotecan?

A
  • severe myelosuppression

- diarrhea

55
Q

What is mech of action of palclitaxel and other taxols?

A

hyperstablilize polymerized microtubules in M phase so that mitotic spindle cannot break down –> anaphase can’t occur

56
Q

What are 3 side effects of paclitaxel?

A
  • myelosuppression
  • alopesia
  • hypersensitivity [neuropathy]
57
Q

What are the 2 vinca alkaloids?

A
  • vincristine

- vinblastine

58
Q

What is mech of action vincristine?

A

bind B tubulin and inhibit polymerization into microtubules –> prevent mitotic spindle formation and cause M phase arrest

59
Q

What are two major side effect of vincristine?

A

neurotoxicity [areflexia, peripheral neuritis]

paralytic ileus

60
Q

What is major side effect of vinblastine?

A

bone marrow suppression = vinBLASTine BLASTS the Bone

61
Q

What are the 4 types of monoclonal antibodies?

A
  • human = umab
  • murine = momab
  • chimeric = ximab
  • humanized = zumab
62
Q

What is mech of action rituximab?

A

chimeric monoclonal antibody against CD-20 = found on B cell neoplasms

63
Q

What is mech of action trastuzimab?

A

also called herceptin
monoclonal antibody against HER2 [c-erbB2] a tyrosine kinase receptor

inhibits proliferation of tumor cells, sensitizes cells to chemo, kills cells by recruiting other immune cells

64
Q

What is a side effect of rituximab?

A

increased risk of progressive multifocal leukoencephalopathy

65
Q

What is a side effect of trastuzumab?

A

cardiotoxicity = HEARTceptin damages the HEART

66
Q

What is mech of action of Imatinib?

A

tyrosine kinase inhibitor of bcr-abl [philadelphia chromosome] and c-Kit [common in GI stromal tumors]

inhibits proliferation and induces apoptosis

67
Q

What is a side effect of imatinib?

A

fluid retention

68
Q

What is mech of action cetuximab?

A

antibody against EGFR receptor

69
Q

What are 2 clinical uses of cetuximab?

A

stage 4 colorectal cancer

head and neck cancer

70
Q

What is mech of action bevacizumab?

A

monoclonal antibody against VEGF

inhibits angiogenesis

71
Q

What are 2 side effects of bevacizumab?

A

hemorrhage and impaired would healing

72
Q

What drug is a monoclonal antibody against HER2/ERbB2?

A

trastuzumab [herceptin]

73
Q

What drug is a monoclonal antibody against EGFR?

A

cetuximab

74
Q

What drug is a monoclonal antibody against VEGF?

A

bevacizumab

75
Q

What drug is a small molecule against bcr-abl, PDGFR ,and ckit?

A

imatinib

76
Q

What drug is a small molecule against B-Raf?

A

vemurafenib

77
Q

What is action of glucocorticoids as treatment for lymphoma?

A

bind and activated DNA binding transcriptional activator, GR. Cell is reprogrammaged –> in lymphocytes leads to apoptosis

78
Q

What is action of tamoxifen as treatment for breast cancer?

A

binds to ER and allows ER to bind DNA but blocks gene activation in response to estrogen = used to treat estrogen dependent breast cancers

79
Q

What is action of leuprolide in prostate cancer?

A

long acting LHRH analogue –> blocsk testicular androgen secretion

80
Q

What are two side effects of leuprolide?

A
  • decreased 2ndary sex characteristics

- decreased libido

81
Q

What is effect of giving EPO in cancer patients?

A

helps with anemia associated wtih chronic disease

82
Q

What is effect of giving G-CSF in cancer patients?

A

growth factor for granulocyte lineage –> helps neutropenia/infection susceptibility

83
Q

What is effect of giving KGF[FGF7] in cancer patients?

A

growth factor for epithelial cells –> helps mucositis

Heme (20 decks)

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