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Hem/Onc 2 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the main target of cancer that we try direct drugs agaisnt?

A

The frequent cell cycle

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2
Q

Since cancer cell therapy is still working on human cells (and cells that divide rapidly), what is the general therapeutic window for anti-cancer drugs?

A

Its narrow

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3
Q

What tissues have rapid cell division, which can have problems in anti-cancer drugs?

A

GI tract
Bone marrow
Hair

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4
Q

Which polymerase elongates RNA polymers? DNA?

A

RNA pol elongates RNA polymers

DNA pol elongates DNA

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5
Q

What is the type of repair available for DNA replication errors?

A

Mismatch repair (MMR)

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6
Q

What is the type of repair available for small base modifications and single-strand breaks?

A

Base excision repair (BER)

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7
Q

What is the type of repair available for the removal of bulky adducts?

A

Nucleotide excision repair (NER)

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8
Q

What is the type of repair available for double-stranded breaks?

A

Homologous recombination or nonhomologous end-joining

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9
Q

Which cancer involves mutations in MLH1, PMS2, MSH2, or MSH6 in 70-80% of the cases?

A

Hereditary nonpolyposis colon cancer

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10
Q

Sporatic colorectal cancer involves instability of what?

A

Microsatellites

leading to errors in insertion/deletion of microsatellite repeat sequences

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11
Q

In the inosine monophosphate pathway, which drug inhibits Ribonucleotide reductase, which prevents GMP –> dGMP?

A

Hydroxyurea

also inhibits AMP –> dAMP

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12
Q

In the inosine monophosphate pathway, which drugs inhibits IMPDH, which prevents IMP –> XMP?

A

6-mercaptopurine

Thioguanine

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13
Q

In the inosine monophosphate pathway, which drug inhibits IMP –> Adenylosuccinate?

A

6-mercaptopurine

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14
Q

In the inosine monophosphate pathway, which drugs inhibits dATP –> DNA?

A

Fludarabine

Cladribine

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15
Q

So hydroxyurea inhibits ribonucleotide reductase inhibits the conversion of what 2 things?

A

UMP –> dUMP

CTP –> dCTP

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16
Q

Which drug inhibits the conversion of dCTP –> DNA in the aspartate pathway?

A

Cytarabine

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17
Q

Which drug inhibits the conversion of dUMP –> dTMP in the aspartate pathway by blocking thymidylate synthase?

A

5-FU

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18
Q

Which drug inhibits DHFR in the aspartate pathway, which inhibits the conversion of DHF –> THF?

A

Methotrexate

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19
Q

What is the enzyme that uses an RNA template to synthesize TTAGGG repeates to restore the length on the end of the chromosome?

A

Telomarase

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20
Q

Which does 5-FU form a covalent bond with to inhibit thymidylate synthase?

A

MTHF

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21
Q

What is the orally bioavailable prodrug of 5-FU?

A

Capecitabine

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22
Q

What is Capecitabine a first line treatment for?

A

Colorectal cancer

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23
Q

What is Capecitabine a second line treatment for?

A

Breast cancer

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24
Q

What is the folate analogue that acts like 5-FU, which is believed to induce thymineless cell death?

A

Pemetrexed

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25
Q

Which agents are used to treat epithelial tumors, mesenchymal tumors, carcinomas, and sarcomas?

A

Alkylating agents

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26
Q

Generally, alkylating agents are electrophilic and act on which nucleophilic sites on DNA?

A

N-7 and O-6 of guanine

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27
Q

What are some examples of alkylating agnets?

not an obj, just to review the names in case they show up on the exam

A

cyclophosphamide, mechlorethamine, melphalan, chlorambucil, and thiotepa

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28
Q

What “ring” does DNA alkylating agents cleave to cause an icnreased risk of cancer?

A

guanine imidazole ring –> disruption of DNA molecular structure

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29
Q

What 2 things does alkylating agents create abnormal base-pairing with to cause miscoding and mutation?

A

Alkylated guanine and thymine

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30
Q

Which residue does alkylating agents excise (depurination) do ↑ the risk of cancer?

A

Guanine

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31
Q

What is the drug that is used to treat superficial bladder cancers?

A

Thiotepa

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32
Q

Can thiotepa be administered orally?

A

No

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33
Q

What is the drug that targets hypoxic tumor cells, because it required bioreductive activation, which occurs more readily in low-O2 environments?

A

Mitomycin

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34
Q

What cancer is Dacarbazine used for?

A

Hodgkins disease

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35
Q

Procarbazine is also used for Hodgkins disease, but what route of availability can it be used?

A

Oral

gigg. giggity

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36
Q

What is the enzyme that prevents permanent DNA damage by removing alkyl adducts to the O6 position of guanine before cross-links are formed?

A

MGMT

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37
Q

So if there is and ↑ expression of MGMT in neoplastic cells, what drug classes have a hard time working?

A

Alkylating agents

38
Q

What can be damaged in normal cells from alkylating agents?

A

DNA

39
Q

So which rapidly proliferating tissues are at risk for damage from alkylating agents?

A

Bone marrow
GI
Genitourinary tract epithelium
Hair follicles

40
Q

Which cells does alkylating agents cause damage in, which leads to immunosuppression?

A

Lymphocytes

41
Q

What is the drug that consists of a paltinum atom bound to 2 amines and 2 chlorines in the cis conformation?

A

Cisplatin

cis

42
Q

What does cisplatin do to guanine residues to cause DNA damage?

A

forms intrastrand cross-links between adjacent guanine residues

43
Q

What cancer is cisplatin used to treat?

A

Testicular cancer

44
Q

What si teh dose-limiting toxicity for cisplatin?

A

Nephrotoxicity

45
Q

What is the drug is synthesized by Strep, has prominent cytotoxic acitivty by binding DNA and chelated iron (II), leading to the formation of free radicles that cause single and double stranded DNA breaks?

A

Bleomycins

46
Q

What is the major side effect of bleomycin?

A

Pulmonary fibrosis

47
Q

What is the target of camptothecins to cause DNA strand dmg?

A

Topoisomerase I

48
Q

What is the drug that interferes with topoisomerase II?

A

Anthracyclines

49
Q

What is the dangerous toxicity of doxorubicin?

A

Heart failure

50
Q

What is the protein that normally serves as an efflux pump, and can cause resistance to chemo drugs if it’s increased?

A

P-glycoprotein

51
Q

What do vinca alkyloids, vinblastine,a nd vincristine bind to at the + end of microtubules?

A

Beta-tubulin

52
Q

Binding to B-tubulin by the vincas prevents what to happen?

A

Tubulin polymerization –> no microtubule extension

53
Q

What is the dose-limiting toxicity of vinblastine?

A

Myelosuppression

54
Q

Which drugs are inhibitors of microtubule DEpolymerization?

A

Taxanes

paclitaxel, docetaxel

55
Q

Imatinib meselate treats CML, which has shows that tumor cells are dependent on what oncogenes for their survival?

A

BCR-ABL

56
Q

In the RAS cascade, which drugs inhibit the EGFR?

A

Cetruximab

57
Q

In the RAS cascade, what drug directly inhibits RAS?

A

Farnesyltransferase inhibitors

58
Q

In the RAS cascade, what inhibits the Tyr-P points on the receptor?

A

Gefitinib

59
Q

In the RAS cascade, what does Imatinib and Dasatinib inhibit?

A

ABL

60
Q

In the RAS cascade, which drug inhibits RAF?

A

Sorafenib

61
Q

In the RAS cascade, MEK inhibitors block what?

A

MEK

lol

62
Q

So to sum it up, what is the whole RAS cascade from receptor –> Myc/Jun/Fos?

A

EGFR –> Tyr-P –> RAS (activated by ABL and SRC) –> RAF –> MEK –> MAPK –nucleus–> MYC + JUN + FOS –> gene trasncription

63
Q

Which pathway does VEGFR2 signal to promote proliferation of endothelial cells?

A

RAF/MAPK pathway

64
Q

Which pathway does VEGFR2 signal to promote survival of endothelial cells?

A

PI3K/AKT

65
Q

RAS is a middle man by encoding which genes, which if left on or mutated, would allow for uncontrolled growth?

A

GTPases

66
Q

What are the main involvements of SRC, which could lead to excessive cell prolifereation if mutated and icnreased?

A

Survival
Angiogenesis
Proliferation

67
Q

Which “chromosome” is associated with BCR-ABL?

A

Philadelphia chromosome t(9,22)

68
Q

The Philadelphia chromosome t(9,22) is associated with which leukemia?

A

CML

69
Q

PTEN is a tumor suppressor that blocks which pathway?

A

AKT/PKB

70
Q

What is the syndrome where there is only 1 fxnl copy of p53, which leaves u for a big risk for tumors?

A

Li Fraumeni syndrome

71
Q

Erlotinib reversibly binds to the ATP binding site of which receptor?

A

EGFR

72
Q

What cancer is Erlotibib used to treat?

A

Metastatic non-small cell lung cancer

73
Q

What is the other EGFR inhibitors but is used for EGFR expressing colorectal cancers and some head and neck tumors?

A

Cetuximab

74
Q

What is the inhibitor of the bcr-abl tyrosine kinase found in CML leukemic cells?

A

Imatinib mesylate

75
Q

What are the 2 reasons that dasatinib is better than imatinib?

A

Greater efficacy against BCR-ABL

Inhibits the activity of imatinib-resistnat BCR-ABL isoforms

76
Q

FLT3 can be mutated in which leukemia?

A

AML

77
Q

Since FLT3’s can be mutated in AML to produce ligan-independent tyrosine kinases, which drugs can demonstrate anti-leukemia cell activity?

A

FLT3 inhibitors

78
Q

What is required for RAS for its association with the plasma membrane?

A

Farnesylation

79
Q

What 3 cancers demonstrate K-RAS mutations?

A

Non-small cell lung CA
Colorectal CA
Pancreastic carcinoma

80
Q

What does Sorafenib inhibit, which is downstream of RAS?

A

RAF

81
Q

What does rapamycin bind to initially?

A

FKBP12

82
Q

After rapamycin binds to FKBP12, what does the complex bind to, thus inhibiting its activity?

A

mTOR

83
Q

Inhibition of mTOR promotes which processes?

A

Cell cycle inhibition, apoptosis, and angiogenesis inhibiton

84
Q

What is Bevacizumab (IgG1 Ab) directed against?

A

VEGF-A

85
Q

Bevacizumab is used to treat what cancer, since it typically has an overexpression of VEGF?

A

Metastatic renal cell carinoma

86
Q

What are the 3 things that sunitinib inhibt?

A

VEGFR-1
VEGFR-2
PDGFR

87
Q

Sorafenib inhibits everything that sunitinib inhibits, plus what other thing?

A

B-RAF

88
Q

What is the first-line treatmnet for multiple myeloma?

A

Thalidomide and Dexamethasone

just FYI:
(T= the drug that causes limb deformities in feti, and D = cortisol, which determines whether cushings is from a ACTH secreting tumor or not)

89
Q

What are the 2 ways that thalidomide acts against multiple myeloma?

A

Inhibits FGF induced angiogensis

Co-stimulate T cells

90
Q

What is the anti-CD20 IgG monoclonal Ab that enchances chemotherapy effects in B-cell non-Hodgkins lymphoma?

A

Rituximab

Hem/Onc 2 (5 decks)

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