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Foundations 9 > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

S phase fraction

A

High in proliferating tumor cells

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2
Q

What are processes occurring during S pahse?

A

DNA replication, unwinding of DNA, DNA synthesis with polymerases and primases, need to make nucleotides as well

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3
Q

What happens when S pahse disrupted?

A

Fires off checkpoint that freezes origins of replication

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4
Q

Checkpoints in cancer

A

Typically down regulated to promote growht

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5
Q

What cell cycle are most human cells in ?

A

G0 or G1

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6
Q

All chemotherapies cause

A

Immune suppression, vomiting, and nausea

Also gastirc ulcers, oral pain, hair loss, and psycosis

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7
Q

Why do cancer drugs cause immune suppression?

A

Immune cells rapidly dividing

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8
Q

Cisplatin action, side effects, admin

A

Cross-linking and alkylating DNA
Causes renal toxicity
IV

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9
Q

Hormonal signals and direct DNA damage cell stage

A

G1

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10
Q

NTP cell stage

A

S

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11
Q

Topoisomerase cell stage

A

Late S

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12
Q

Microtubulates cell stage

A

M

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13
Q

Paclitaxel action

A

Promotes polymerization and blocks dissembly…arrests cells in mitosis…only effective against cells in mitosis

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14
Q

Paclitaxel side effects and metabolism

A

Neuropathy-MTs important in neuronal transport

Metabolism - Inactivated by p450 enzymes

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15
Q

Doxorubicin action

A

topoisomerase 2 inhibitor…also intercalates into DNA, binds to cell membranes, and generates free radicals

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16
Q

Doxorubicin side effects

A

Cardiotoxicity and red urine

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17
Q

Doxorubicin metabolism

A

Metabolized by p450 in the liver…elimination is biphasic

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18
Q

Cyclophsphamide action

A

Transfer alkyl groups to DNA, damage and cross-linking it…especially dividing cells

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19
Q

Why would DNA alkylation trigger cell death?

A

Replicaiton fork cannot replicate through it…could also cause mutation or inhibit polymerase

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20
Q

Cyclophosphamide side effects

A

Toxic to bone marrow and used to prevent organ rejection after transplant

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21
Q

Admin and metabolism of cyclophosphamide

A

Most given orally…make sure to be hydrated to prevent bladder damage
Activated by p450 enzymes

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22
Q

Tamoxifen action

A

Inhibitor and partial agonist of estrogen receptor…also high estrogenic activity in the uterus

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23
Q

Why does one drug have opposite effects in different tissues?

A

Direct (binds to ERE)

Indirect (binds to other TFs)

24
Q

Anastrozole mech

A

Inhibitor of aromatase used for estrogen receptor positive breast cancer…binds to heme group

25
Q

Why give tamoxifen before anastrozole

A

Tamoxifen acts much more quickly

26
Q

Aromatase enzyme type

A

P450

27
Q

Tamoxifen side effects

A

Hot flashes, nausea and vomiting, hair loss, atrophy of vaginal lining…risk of endometrial cancer

28
Q

Anastrozole side effects

A

Few and no risk of endometrial cancer

29
Q

Metabolism of tamoxifen and anastrozole

A

Tamox is given orally and has half life of 7-14 days

Anastrozole given orally

30
Q

TAC therapy

A

Docetaxel (like paclitaxel), doxorubicin, and cyclophosphamide

31
Q

Methotrexate mech and other uses

A

Arthitis and psoriasis
Similr to folic acid and inhibits DHFR which blocks formation of tetrahydrofolate…depletes cells of cofactor i synthesis of important things
Methotrexate is polyglutamated in the cell to retain it…varies from person to person

32
Q

5-FU mech

A

Inhibits biosynthesis of pyrimidines…can be incorporated into RNA or DNA…also blocks thymidylate synthase

Must be converted to active form in the cell

33
Q

Side effects of methotrexate and 5-FU

A

Typical

34
Q

Methotrexate metabolism

A

Interactions with drugs that bind plasma proteins like salicylate, sulfonamides, and phenytoin

35
Q

What happens if you combine methotrexate and sulfonamide

A

Could see new round of immune suppression/infection

36
Q

5-FU metabolism

A

Degraded by dihydropyrimidine dehydrogenase…should screen for this beforehand

37
Q

CTZs

A

Chemoreceptor trigger zones and the vomiting/emesis centers in medulla of the brain

38
Q

Vomiting center rich in which receptors?

A

Histamine, 5-HT3, dopamine, and cholinergic receptors

39
Q

Ondansetron uses, mech, kinetics, side effects

A

Anti-emetic for chemotherapy
Antagonist for serotonin 5-HT3 receptor
Effects persist for a long time…metabolized by p450 pathway
Well tolerated

40
Q

1.5 of breast cancer paitents have elevated

A

HER-2/neu or high EGFR

41
Q

Trastuzumab mech

A

Targets HER-2/neu

42
Q

Cetuximab mech

A

Blocks EGFR

43
Q

Erlotinib

A

Blocks intracellular function of EGFR…binds to active site

44
Q

Trastuzumab screening that must be done

A

HER2 positivity

45
Q

Lung cancer first and second options

A

Cisplatin/etoposide

Paclitaxel

46
Q

Lung cancer if high levels of EGFR

A

Cetuximab - 2-4 months

47
Q

Mutations that make lung cancer tx more effective

A

Domain 7 mutation means better response to erlotinib

Asian women and appalachia

48
Q

Erlotinib side effects

A

Diarrhea and rash

49
Q

GI cancer primary drug

A

5-FU

50
Q

Second drug for GI cancer and mech

A

Bevacizumab - monoclonal AB to VEGF

51
Q

Why do tumor cells need VEGF

A

WHen they grow, eventually get hypoxic and need angiogenesis

52
Q

Bevacizumab side effects

A

Blocks angiogenesis in places where it is needed

Don’t use 28 days after surgery

53
Q

Melanoma chemotherapy

A

Cisplatin or flurouracil cream

54
Q

Melanoma targeted therapy

A

Many have B-raf kinase mutations which activates downstream signaling…targeted by inhibitor vemurafenib

55
Q

Melanoma immune therapy

A

Ipilimumab blocks CTLA-4

56
Q

Brain cancer primary therapy

A

Carmustine

57
Q

Marmustine action, side effects, admin

A

Alkylation of DNA on O6 guanine
Nausea, bone marrow toxic, renal toxocity
IV and short lived

Foundations 9 (6 decks)

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