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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
What are antimetabolite neoplastic drugs?
analogs of natural metabolites in RNA and DNA synthesis compete with normal metabolites for enzymes or get incorporated into DNA/RNA S phase specific
26
What is mech of action methotrexate?
folic acid analog that inhibits dihydrofolate reductase --> less dTMP --> less DNA and protein synthesis
27
What drug is a folate analog?
methotrexate
28
What 3 drugs are a purine analog?
- azathioprine - 6-mercaptopurine [6-MP] - 6-thioguanine [6-TG]
29
What drug is an adenosine analog?
cladrobine
30
What 3 drugs are a pyrimidine analog?
- 5- fluorouracil - gemcitabine - cytarabine
31
What are 4 side effects of methotrexate?
- myelosuppression - macrovesicular fatty change in liver - mucositis - teratogenic
32
Why do you give leucovorin with methotrexate?
leucovorin = folinic acid | rescues the BM from myelosuppression caused by methotrexate
33
What is mech of action 5-fluorouracil [5-FU]?
pyrimidine analog bioactivated to 5F-dUMP | complexes with folic acid and inhibits thymidylate synthase --> less dTMP --> less DNA and protein synthesis
34
What are 2 side effects of 5-FU?
myelosuppression photosensitivity
35
What is treatment for 5-FU overdose?
rescue with uridine
36
What is mech of action of cytarabine?
pyrimidine analog --> inhibits DNA polymerase
37
What are 3 side effects of cytarabine?
leukopenia thrombocytopenia megaloblastic anemia CYTarabine causes panCYTopenia
38
What is mech of action of 6-MP?
purine [thiol] analog --> decreases de novo purine synthesis activated by HGPRT
39
What are 3 organs with side effects of 6-MP?
- bone marrow - GI - liver
40
What two purine analogs have increased toxicity with allopurinol?
- 6MP | - azathoprine
41
Why does 6-MP have increased toxicty wtih allopurinol?
allopurinol inhibits its metabolism
42
What is the mech of action of caldribine?
adenosine analog --> inhibits adenosine deaminase
43
Does methortrexate cross the BBB?
yep!
44
Where is methortrexated excreted?
renally ---> impaired renal excretion wtih ASA, NSAIDS, penicillins
45
What is mech of action of gemcitabine?
pyrimidine analog, inhibits DNA polymerase if incoporated into DNA
46
What happens if you give leucovorin with 5-FU?
potentiates the effect of 5-FU by increasing intracellular THF
47
What happens if you give leucovorin with methotrexate?
decreases toxicity of high dose methotrexate = reverses myelosuppression
48
What is mech of action bleomycin?
induces free radical formation causing breaks in DNA strands
49
What are 3 toxicities of bleomycin?
- pulmonary fibrosis - skin changes - mucositis
50
What is the mech of action of doxorubicin?
generate free radicals | intercalate in DNA + inhibit DNA topoisomerases--> breaks in DNA --> decreased replication
51
What are 3 side effects of doxorubicin?
- cardiotoxicity [dilated cardiomyopathy] | - myelosuppression
52
What can you give pt on doxorubicin to prevent cardiotoxicity?
dexrazocane = Fe chelating agent
53
What is mech of action topotecan and irinotecan?
inhibit topoisomerase I and prevent DNA unwinding and replication
54
What are 2 side effects of irinotecan/topotecan?
- severe myelosuppression | - diarrhea
55
What is mech of action of palclitaxel and other taxols?
hyperstablilize polymerized microtubules in M phase so that mitotic spindle cannot break down --> anaphase can't occur
56
What are 3 side effects of paclitaxel?
- myelosuppression - alopesia - hypersensitivity [neuropathy]
57
What are the 2 vinca alkaloids?
- vincristine | - vinblastine
58
What is mech of action vincristine?
bind B tubulin and inhibit polymerization into microtubules --> prevent mitotic spindle formation and cause M phase arrest
59
What are two major side effect of vincristine?
neurotoxicity [areflexia, peripheral neuritis] | paralytic ileus
60
What is major side effect of vinblastine?
bone marrow suppression = vinBLASTine BLASTS the Bone
61
What are the 4 types of monoclonal antibodies?
- human = umab - murine = momab - chimeric = ximab - humanized = zumab
62
What is mech of action rituximab?
chimeric monoclonal antibody against CD-20 = found on B cell neoplasms
63
What is mech of action trastuzimab?
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
What is a side effect of rituximab?
increased risk of progressive multifocal leukoencephalopathy
65
What is a side effect of trastuzumab?
cardiotoxicity = HEARTceptin damages the HEART
66
What is mech of action of Imatinib?
tyrosine kinase inhibitor of bcr-abl [philadelphia chromosome] and c-Kit [common in GI stromal tumors] inhibits proliferation and induces apoptosis
67
What is a side effect of imatinib?
fluid retention
68
What is mech of action cetuximab?
antibody against EGFR receptor
69
What are 2 clinical uses of cetuximab?
stage 4 colorectal cancer | head and neck cancer
70
What is mech of action bevacizumab?
monoclonal antibody against VEGF | inhibits angiogenesis
71
What are 2 side effects of bevacizumab?
hemorrhage and impaired would healing
72
What drug is a monoclonal antibody against HER2/ERbB2?
trastuzumab [herceptin]
73
What drug is a monoclonal antibody against EGFR?
cetuximab
74
What drug is a monoclonal antibody against VEGF?
bevacizumab
75
What drug is a small molecule against bcr-abl, PDGFR ,and ckit?
imatinib
76
What drug is a small molecule against B-Raf?
vemurafenib
77
What is action of glucocorticoids as treatment for lymphoma?
bind and activated DNA binding transcriptional activator, GR. Cell is reprogrammaged --> in lymphocytes leads to apoptosis
78
What is action of tamoxifen as treatment for breast cancer?
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
What is action of leuprolide in prostate cancer?
long acting LHRH analogue --> blocsk testicular androgen secretion
80
What are two side effects of leuprolide?
- decreased 2ndary sex characteristics | - decreased libido
81
What is effect of giving EPO in cancer patients?
helps with anemia associated wtih chronic disease
82
What is effect of giving G-CSF in cancer patients?
growth factor for granulocyte lineage --> helps neutropenia/infection susceptibility
83
What is effect of giving KGF[FGF7] in cancer patients?
growth factor for epithelial cells --> helps mucositis

Heme (20 decks)

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