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Pharm 2014 Unit 1 > Cancer 3 > Flashcards

Cancer 3 Flashcards

1
Q

What are names of DNA intercalating agents?

A
  1. Dactinomycin
  2. Daunorubicin, Doxorubicin
  3. Bleomycin
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2
Q

DNA intercalating agents are also called

A

anti-tumor antibiotics, which are derived from various strains of the soil microbe Streptomyces

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3
Q

what is the mech of DNA intercalating agents?

A

bind to DNA through intercalation between specific bases and block synthesis of DNA, RNA, or both, cause DNA strands break, and interfere with cell replication

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4
Q

Dactinomycin is also known as

A

Actinomycin D

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5
Q

what is the mech of Dactinomycin (Actinomycin D)?

A

intercalates between G-C base pairs of DNA, forming stable dactinomycin-DNA complex. The complex interferes with DNA-dependent RNA polymerase causing inhibition of transcription of DNA

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6
Q

what is the main therapeutic uses of Dactinomycin?

A

to treat pediatric umors such as Wilms’ tumor, rhabdomyosarcoma and Ewing’s sracoma

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7
Q

what are antrhacycline antibiotics derived from Streptomyces that have a broad spectrum of clinical usefulness in hematologic and solid tumors?

A

Daunorubicin, Doxorubicin, Epirubicin, and Idarubicin

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8
Q

daunorubicin and idarubicin are mainly used for

A

AML treatment

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9
Q

what are the toxicity of - rubicin drugs?

A

irreversible does-limiting cardiotoxicity (cardiomyopathy)

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10
Q

what is a mixture of two copper-chelating peptides obtained from Streptomyces?

A

bleomycin

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11
Q

what is the mech of bleomycin?

A

in the presence of Fe and O2, it forms free radical and induce

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12
Q

what is the therapeutic usage of bleomycin?

A

testicular tumors (usually in combination with vinblastine or etoposide)

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13
Q

toxicity of bleomycin?

A 
pulmonary toxicity (pulmonary fibrosis)
cutaenous toxicity (hyperpigmentation)
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14
Q

what are the three monoclonal antibodies?

A
  1. Rituximab
  2. Trastuzumab (Herceptin)
  3. Cetuximab
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15
Q

what is useful for treating Non-Hodgkin’s lymphomas?

A

Rituximab

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16
Q

what is a monoclonal antibody that targets the CD20?

A

Rituximab

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17
Q

what are two tyrosine kinase inhibitors?

A
  1. Imatinib (Gleevac)

2. Gefitinib

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18
Q

what is an inhibitor of Abl kinase?

A

Imatinib

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19
Q

Imatinib also inhibits

A

PDGFR and c-kit and effective treating CML

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20
Q

Imatinib is approved for CML, but also approved for

A

gastrointestinal tumor

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21
Q

what are the miscellaneous agents used to treat cancer?

A
  1. Hydroxyurea
  2. Retinoids
  3. Arsenic Trioxide
  4. Thalidomide
  5. Interferons
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22
Q

what is the mech of hydroxyurea?

A

inhibits the enzyme ribonucleoside diphosphate reductase, which catalyze the conversion of ribonucleotides to deoxyribonucleotides (a critical rate limiting step in the biosynthesis of DNA)

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23
Q

what are the two therapeutic usage of hydroxyurea?

A
  1. sickle cell diz

2. myeloproliferative neoplasms polycythemia vera and thrombocythemia

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24
Q

what is all-trans retinoic acid (ATRA) what is useful for treating acute promyelocytic leukemia (APL)?

A

Retinoids

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25
Q

what is used for relapsed APL?

A

arsenic trioxide

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26
Q

what is used for treating multiple myeloma and myelodysplastic syndromes?

A

thalidomide

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27
Q

what is used for treating of hairy-cell leukemia, CML, and AIDS-related Kaposi’s sarcoma?

A

Interferons

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28
Q

what are the hormone therapies for prostate cancer?

A
  1. Leuprolide, Goserelin

2. Flutamide, Bicalutamide

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29
Q

what are gonadotropin-releasing hormone (GnRH) analogs?

A

Leuprolide, Goserelin

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30
Q

what is the mech for leuprolide?

A

GnRH analogs, they bind to GnRH receptor and inhibit the release of FSH and LH

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31
Q

as a result of leuprolide what happens?

A

reduced testicular production of testosterone

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32
Q

what are nonsteroidal androgen-receptor (AR) blockers?

A

flutamide, bicalutamide

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33
Q

what is the mech of AR blocker (flutamide)

A

compete with the natural hormone for binding to the androgen receptor and prevent its translocation to the nucleus

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34
Q

what is complete androgen ablation therapy?

A

it involves combination of GnRH analogs and AR blockers

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35
Q

what is aromatase enzyme?

A

conversion of androstenedione and testosterone to the estrogen, estrone and estradiol.

36
Q

in breast cancer pts, there is increased

A

aromatase activity

37
Q

what is the 1st generation AI?

A

aminoglutathamide

38
Q

paclitaxel can cause what kind of toxicity?

A

peripheral neuropathy

39
Q

what is a 3rd generation AI?

A

Anastrozole

40
Q

what are selective estrogen-receptor downregulator?

A

pure anti-estrogens (they are devoid of estrogen agonist activity)

41
Q

what is the name of SERDs drug?

A

Fulvestrant

42
Q

what is Fulvestrant?

A

the 1st FDA approved SERDs, it binds to ER with much higher affinity (more than 100 fold) than tamoxifen

43
Q

how is Fulvestrant diff from tamoxifen?

A

tamoxifen stabilizes or even increase ER expression, fulvestrant reduces the number of ER molecules in cells

44
Q

what is therapeutic uses of Fulvestrant?

A

approved for postmenopausal women with ER-positive metastatic breast cancer

45
Q

dactinomycin is also known as

A

Actinomycine

46
Q

the main therapetuic uses of Dactinoomycin is

A

Wilm’s tumor, Ewing’s sarcoma in children

47
Q

what are anthracyclines?

A

daunorubicin, doxorubicin, epirubicin, idarubicin

48
Q

mech of action of anthracyclines (doxorubicin)?

A

intercalate between DNA base pairs, donate electrons to make superoxide

49
Q

sarcomas treatment?

A

Doxorubicine

50
Q

what is important about the side effect of anthracycline?

A

dose-limiting cardiotoxicity,

51
Q

Dexrazoxone is an

A

iron-chelating agent that blocks the fomration of free radical

52
Q

bleomycin is

A

a mixture of two peptides obtained from Streptomyces, G2 phase specific

53
Q

therapeutic usage of bleomycin?

A
  1. squamous cell caricnomas, ABVD
54
Q

toxicity of bleomycin?

A
  1. minimally myelosuppressive

2. dose-related pulmonary toxicity (pulmonary fibrosis)

55
Q

microtubule inhibitos

A

vinca alkaloids, taxanes

56
Q

mech of vinca?

A

prevent polymerization of tubulin into microtubules

57
Q

what is the therapeutic usage of vinca alkaloids?

A

Vinblastine –> ABVD

Vincristine –> MOPP, used with glucocorticoids in the treatment of childhood ALL

58
Q

what is the resistance mech of vinca?

A

P-glycoprotein, mutation in tubulin

59
Q

what are taxanes?

A

paclitaxel, docetaxel

60
Q

where are taxanes from?

A

alkaloids dervied from the ye tress

61
Q

the mech of taxanes?

A

prevent the depolymerization of microtubules

62
Q

docetaxel is useful against

A

hormone refractory prostate cancer

63
Q

what are the toxicity of taxanes?

A

perepheral neuropathy

64
Q

topoisomerase inhibitors?

A
  1. epipodophyllotoxins: etoposide, teniposide (top II)

2. camptothecin analgos: irinotecan, topotecan (top I)

65
Q

epidophyllotoxins

A

inhibit topoisomerase II –> apoptosis

66
Q

camptothecin analogs

A

inhibitn topoisomerase I –> apoptosis

67
Q

hormone therapy is suefull in

A

lymphomas and leukemia, breast, prostate

68
Q

glucocorticoids (prednisone, dexamethasone) are used for

A

lymphomas and leukemia

69
Q

prednisone is used for

A

ALL, both Hodkin and non-Hodgkin

70
Q

breast cancer is usually

A

estrogen dependent, so it can be suppressed by estrogen antagonist

71
Q

SERMs

A

selective estrogen receptor modulators: Tamoxifen

72
Q

tamoxifen is

A

a weak agonist in endometrium –> increase risk for endometrial cancer and thromboembolism

73
Q

SERDs

A

selective estrogen-receptor downregulators: Fulvestrant

74
Q

SERD, Fulvestrant

A

bins to ER with a much higher affinity (more than 100 fold) than tamoxifen

75
Q

hydroxyurea inhibit

A

ribonucleotide reductase, for sickle cells

76
Q

all trans-retinoic acid is for

A

APL = AML M3 –> promotes differentiation of promyelocyte

77
Q

inteferone alpha

A

hairy cell leukemia, Kaposi’s sarcoma

78
Q

Gefitinib

A

EGFR inhibitor

79
Q

Cetuximab is a

A

mAb against ErbB1 for treatment of metastatic colon cancer

80
Q

multi-drug resistance

A

P-glycoprotines –> drug efflux

81
Q

what is verapamil?

A

Ca2+ channel antagonist, which inhibits these drug transporters

82
Q

P-glyoprotein forms

A

a central channel for the ATP dependent pumping of drugs from the cell

83
Q

what are the 3 toxicities of cisplatin?

A
  1. nephrotoxicity
  2. ototoxicity
  3. peripheral neuropathy
84
Q

what are the 3 toxicities of methotrexate?

A
  1. renal toxicity
  2. hepatotoxicity
  3. bone marrow toxicity
85
Q

toxicity of paclitaxel?

A

perepheral neuropathy

86
Q

toxicity of vincristine?

A

neurotoxicity (peripheral neuropahty)

87
Q

resistance to which anticancer drug is associated with decreased expression of hypoxanthine-guanine phosphoribosyl transferase (HGPRT)?

A

6-MP

Pharm 2014 Unit 1 (13 decks)

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