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Foundations 9 > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

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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?

Study These Flashcards
A

Direct (binds to ERE)

Indirect (binds to other TFs)

24
Q

Anastrozole mech

Study These Flashcards
A

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

25
Why give tamoxifen before anastrozole
Tamoxifen acts much more quickly
26
Aromatase enzyme type
P450
27
Tamoxifen side effects
Hot flashes, nausea and vomiting, hair loss, atrophy of vaginal lining...risk of endometrial cancer
28
Anastrozole side effects
Few and no risk of endometrial cancer
29
Metabolism of tamoxifen and anastrozole
Tamox is given orally and has half life of 7-14 days | Anastrozole given orally
30
TAC therapy
Docetaxel (like paclitaxel), doxorubicin, and cyclophosphamide
31
Methotrexate mech and other uses
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
5-FU mech
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
Side effects of methotrexate and 5-FU
Typical
34
Methotrexate metabolism
Interactions with drugs that bind plasma proteins like salicylate, sulfonamides, and phenytoin
35
What happens if you combine methotrexate and sulfonamide
Could see new round of immune suppression/infection
36
5-FU metabolism
Degraded by dihydropyrimidine dehydrogenase...should screen for this beforehand
37
CTZs
Chemoreceptor trigger zones and the vomiting/emesis centers in medulla of the brain
38
Vomiting center rich in which receptors?
Histamine, 5-HT3, dopamine, and cholinergic receptors
39
Ondansetron uses, mech, kinetics, side effects
Anti-emetic for chemotherapy Antagonist for serotonin 5-HT3 receptor Effects persist for a long time...metabolized by p450 pathway Well tolerated
40
1.5 of breast cancer paitents have elevated
HER-2/neu or high EGFR
41
Trastuzumab mech
Targets HER-2/neu
42
Cetuximab mech
Blocks EGFR
43
Erlotinib
Blocks intracellular function of EGFR...binds to active site
44
Trastuzumab screening that must be done
HER2 positivity
45
Lung cancer first and second options
Cisplatin/etoposide | Paclitaxel
46
Lung cancer if high levels of EGFR
Cetuximab - 2-4 months
47
Mutations that make lung cancer tx more effective
Domain 7 mutation means better response to erlotinib | Asian women and appalachia
48
Erlotinib side effects
Diarrhea and rash
49
GI cancer primary drug
5-FU
50
Second drug for GI cancer and mech
Bevacizumab - monoclonal AB to VEGF
51
Why do tumor cells need VEGF
WHen they grow, eventually get hypoxic and need angiogenesis
52
Bevacizumab side effects
Blocks angiogenesis in places where it is needed | Don't use 28 days after surgery
53
Melanoma chemotherapy
Cisplatin or flurouracil cream
54
Melanoma targeted therapy
Many have B-raf kinase mutations which activates downstream signaling...targeted by inhibitor vemurafenib
55
Melanoma immune therapy
Ipilimumab blocks CTLA-4
56
Brain cancer primary therapy
Carmustine
57
Marmustine action, side effects, admin
Alkylation of DNA on O6 guanine Nausea, bone marrow toxic, renal toxocity IV and short lived

Foundations 9 (6 decks)

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