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Fall 2018 Pharm Exam 3 > Oncology > Flashcards

Oncology Flashcards

1
Q

susceptibility and growth cycle

A

The fraction of tumor cells that are in the replicative cycle influences their susceptibility to most cancer chemotherapeutic agents
Rapidly dividing cells are generally more sensitive
Slowly proliferating cells less sensitive
Nonproliferating cells usually survive

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2
Q

cell cycle specificty

A

Normal cells and tumor cells go through growth cycles
Cell-cycle specific - chemotherapeutic agents that are effective only against replicating cells
Cell-cycle nonspecific - useful against tumors that have low percentage of replicating cells (still have more toxicity in cycling cells)

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3
Q

growth rate

A

Initially rapid in most solid tumors
Decreases as tumor size increases
Unavailability of nutrients and oxygen due to inadequate vascularization and lack of blood circulation
Surgery or radiation can reduce burden promoting remaining tumor cells into proliferation, increasing susceptibility to chemo agents

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4
Q

treatment protocols

A

combination chemotherapy is more successful than single-drug treatment in most cancers

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5
Q

Generally interfere with the availability of normal purine or pyrimidine nucleotide precursors
Inhibiting their synthesis
Competing with them in DNA or RNA synthesis

A

antimetabolites

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6
Q

MTX

A
  • structurally related to folic acid
  • MTX inhibits dihydrofolate reductase (DHFR) which converts folic acid to its active form
  • poor CNS penetrations
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7
Q

6-Mercaptopurine (6-MP) MOA

A

Nucleotide formation
Penetrates target cells and is converted to 6-thioinosinic acid (TIMP)
Inhibits first step of purine-ring biosynthesis
Blocks formation of AMP and xanthinuric acid
TIMP converted to thioguanine monophosphate (TGMP) which after phosphorylation can be incorporated into RNA and DNA
Results in nonfunctional RNA and DNA
-does not cross BBB

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8
Q

ADR of 6-MP

A

1/3 of patients report hepatotoxicity in the form of jaundice

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9
Q

6-Thioguanine (6-TG)

A

Converted intracellularly to TGMP

MOA similar to 6-MP

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10
Q

Fludarabine

A

Purine nucleotide analog

Decreases synthesis in S phase and affects function

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11
Q

ADR of fludarabine

A

High doses, progressive encephalopathy, blindness and death

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12
Q

cladribine

A 
Purine analog
Similar reactions to fludarabine
Hinders elongation and repair of DNA
Potent inhibitor of ribonucleotide reductase
-distributes through CSF
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13
Q

5-Fluorouracil (5-FU)

A

Pyrimidine analog
Deprives cell of thymidine decreasing DNA synthesis
Administered with leucovorin to increase effectiveness
-crosses BBB

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14
Q

ADR 5-FU

A

“hand-foot syndrome” – erythematous desquamation of the palms and soles

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15
Q

Capecitabine

A

Undergoes enzymatic reactions after being absorbed that results in 5-FU

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16
Q

how to tx a 5-FU or capecitabine OD

A

Uridine Triacetate

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17
Q

floxuridine

A

Analog of 5-FU

Catabolized in the liver to 5-FU

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18
Q

Cytarabine (ara-C)

A

Pyrimidine antagonist

-does not cross BBB

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19
Q

gemcitabine

A

Analog of deoxycytidine

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20
Q

trifluridine and tipiracil

A

thymidine-based nucleoside analog
incorporated into DNA, interferes with DNA synthesis and inhibits cell proliferation
Tipiracil -Thymidine phosphorylase inhibitor
Inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase

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21
Q

dactinomycin

A

Intercalates into the minor groove of the double helix forming a dactinomycin-DNA complex
Interferes primarily with DNA-dependent RNA polymerase
At high doses will hinder DNA synthesis
Causes single-strand breaks
-does not penetrate CNS

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22
Q

doxarubicin/daunorubicin

A

Free radicals induce membrane lipid peroxidation, DNA strand scission and direct oxidation of purine or pyrimidine bases, thiols and amines
-does not penetrate CNS

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23
Q

ADRS of doxarubicin

A

cardiotoxic

stomatitis

24
Q

bleomycin

A

Mixture of different copper-chelating glycopeptides that cause scission of DNA by oxidation

Cell-cycle specific
Causes cells to accumulate in the G2 phase

25
Q

ADR of bleomycin

A

pulmonary

26
Q

Mechlorethamine

A

Once transported into the cell, forms a reactive intermediate that alkylates a guanine residue in one or both strands of a DNA molecule

27
Q

Cyclophosphamide and Ifosfamid

A

Biotransformed in liver to hydroxylated intermediates which are then broken down to phosphoramide mustard and acrolein
-cross BBB

28
Q

ADRs of cyclophosphamide and ifosfamid

A

Germ cells
Amenorrhea, testicular atrophy, aspermia, sterility
Veno-occlusive disease of the liver ~25% of patients

29
Q

nitrosureas (carmustine, lomustine, streptozocin)

A

Alkylation that inhibits replication and RNA and protein synthesis
Primarily cytotoxic to actively dividing cells
Nondividing can escape if DNA repair occurs
Inhibit key enzymatic processes by carbamoylation of amino acids
-cross BBB

30
Q

Dacarbazine/Temozolomide

A

Undergoes biotransformation through CYP450 to become active – methyltriazenoimidazole carboxamide (MTIC)
-crosses BBB

31
Q

Cell-cycle and phase specific
Block mitosis in metaphase (M phase)
Binds tubulin and prevents formation of microtubules

A

vincristine/vinblastine

32
Q

Active in G2/M phase of the cell cycle

Bind irreversibly to the β- tubulin subunit

A

paclitaxel/docetaxel

33
Q

Estrogen antagonist

A

tamoxifen

34
Q

Inhibits adrenal and extra-adrenal synthesis, aromatase inhibitor

A

Aminoglutethimide

35
Q

Imidazole aromatase inhibitors

A

anastrozole/letrozole

36
Q

Steroidal, irreversible inhibitor of aromatase

A

exemastane

37
Q

Occupy GnRH receptor in pituitary, inhibiting release of FSH and LH

A

leuprolide, goserelin

38
Q

Inhibit growth of prostatic tissue by blocking LH production

A

estrogens

39
Q

Synthetic, nonsteroidal antiandrogens

A

Flutamide, Nilutamide, Bicalutamide

40
Q

Converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase

A

abiraterone actetate

41
Q

Androgen receptor inhibitor

A

enzalutamide

42
Q

Induces complement and antibody dependent , cell-mediated cytotoxicity of B cells
Often used in combo such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)

A

rituximab

43
Q

CD20-directed cytolytic antibody

A

Obinutuzumab

44
Q

Antiangiogenesis agent

A

bevacizumab

45
Q

Believed to target the epidermal growth factor receptor on cancer cells, inhibiting growth

A

cetuximab

46
Q

reversible proteasome inhibitor

preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome

A

ixazomib

47
Q

Binds guanine in DNA forming inter- and intrastrand cross-links
Inhibits DNA replication and RNA synthesis

A

Cisplatin, Carboplatin, Oxaliplatin

does not penetrate CNS

48
Q

mammalian target of rapamycin (mTOR) inhibitor
MTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription

A

everolimus

49
Q

kinsase inh end in

A

nib

50
Q

Target topoisomerase II
Block cells in late S to G2 phase
Irreversible double-strand breaks

A

Etopside and Teniposide

51
Q

Catalyzes deamination of asparagine to aspartic acid and ammonia

A

L-asparaginase

52
Q

hedgehog pathway inhibitor
Hedgehog (Hh) is an intercellular signaling molecule essential for normal embryonic development and plays critical roles in adult tissue maintenance, renewal and regeneration

A

vismodegib

“gib”

53
Q

histone deacetylase (HDAC) inhibitor

A

belinostat

“stat”

54
Q

inhibitor of BCL-2, an antiapoptotic protein

A

venetoclax

55
Q

poly (ADP-ribose) polymerase (PARP) inhibitor

PARP enzymes play a role in DNA repair

A

rucaparib

“parib”

56
Q

a CD19-directed genetically modified autologous T cell immunotherapy

A

Tisagenlecleucel

57
Q

genetically modified oncolytic viral therapy

replicate within tumors and to produce the immune stimulatory protein GM-CSF

A

Talimogene Laherparepvec

Fall 2018 Pharm Exam 3 (3 decks)

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