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Pharmacology > Deja Ch 3 Chemo > Flashcards

Deja Ch 3 Chemo Flashcards

1
Q

According to the log-kill hypothesis, does the cytotoxic action of anticancer drugs follow first-order or second-order kinetics?

A

First-order kinetics

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2
Q

With first-order kinetics, is it a fixed amount or fixed percentage of tumor cells that are killed by cancer chemotherapeutic agents?

A

Fixed percentage

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3
Q

If a chemotherapy treatment leads to a 4 log-kill reduction, then how many tumor cells would remain if there were 1010 tumor cells to begin with?

A

10^6 (or 10^10/10^4)

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4
Q

give brief summary of G0 phase

A

cells are not actively dividing (resting state)

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5
Q

give brief summary of G1 phase

A

Enzymes and proteins required for DNA replication are synthesized.

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6
Q

give brief summary of S phase

A

Replication of DNA

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7
Q

give brief summary of G2 phase

A

Enzymes and proteins required for mitosis are synthesized.

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8
Q

give brief summary of M phase

A

Mitosis occurs.

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9
Q

The ratio of proliferating (malignant) cells to nonprolifcrating (G0) cells is also known as what?

A

Growth fraction

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10
Q

Are tumor cells more susceptible to cancer chemotherapeutic agents when they are actively dividing or when they are dormant?

A

Actively dividing. Thus, tumor cells which are dormant may not be sufficiently susceptible to the effects of cancer chemotherapeutic agents.

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11
Q

What is the definition of a cell-cycle specific (CCS) cancer chemotherapeutic agent?

A

An agent that kills actively dividing cells (cells currently going through the cell cycle)

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12
Q

Give examples of normal/nonmalignant cells in the body that normally are undergoing rapid proliferation:

A

Bone marrow cells; GI mucosal cells; hair cells. Thus, the common side effects of chemotherapy include myelosuppression, GI disturbances, and alopecia.

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13
Q

P-glycoprotein is an ATP-dependent membrane (efflux) transporter that is responsible for what?

A

Pumping drugs out of cells (responsible for multidrug resistance of chemotherapeutic agents)

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14
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Cardiotoxicity; dilated cardiomyopathy

A

Doxorubicin

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15
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Pulmonary fibrosis; pneumonitis

A

Bleomycin

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16
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Stomatitis; esophagitis

A

Methotrexate; 5-fluorouracil; dactinomycin

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17
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Hemorrhagic cystitis

A

Cyclophosphamide; ifosfamide

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18
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Hemorrhagic diathesis; Peripheral neuropathy; neurotoxicity

A

Plicamycin

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19
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Nephrotoxicity

A

Vincristine

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20
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Allergic reactions

A

Cisplatin

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21
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Hepatotoxicity

A

Etoposide; L-asparaginase

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22
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Pancreatitis

A

6-Mercaptopurine; busulfan; Cyclophosphamide

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23
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Cutaneous toxicity (hand-foot syndrome)

A

L-Asparaginase; 5-Fluorouracil

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24
Q

Give examples of cancer chemotherapeutic agents that are commonly associated with each of the following adverse effects: Disulfiram-type reactions

A

Procarbazine

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25
Q

What is the name of the antidote that binds to and inactivates the toxic metabolites responsible for cisplatin-induced nephrotoxicity?

A

Amifostine

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26
Q

What is the name of the cyclophosphamide and ifosfamide urotoxic metabolite that is responsible for causing hemorrhagic cystitis?

A

Acrolein

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27
Q

What is the name of the antidote that binds to and inactivates acrolein, thereby preventing hemorrhagic cystitis in patients receiving cyclophosphamide or ifosfamide chemotherapy?

A

Mesna

28
Q

Which iron chelating agent is used to decrease the incidence and severity of doxorubicin-induced cardiomyopathy in patients with metastatic breast cancer who have received a lifetime cumulative doxorubicin dose (300 mg/m^2)?

A

Dexrazoxane

29
Q

Give examples of antimetabolite cancer chemotherapeutic agents:

A

Methotrexate; 5-fluorouracil; cytarabine; fludarabine; 6-thioguanine; 6-mercaptopurine

30
Q

Are the antimetabolite cancer chemotherapeutic agents CCS?

A

Yes (S phase)

31
Q

What is the mechanism of action of methotrexate?

A

Inhibits dihydrofolate reductase (DHFR)

32
Q

What reaction does DHFR catalyze?

A

Conversion of folic acid to tetrahydrofolic acid (active form)

33
Q

What drug is used as a “rescue medication” in patients taking methotrexate?

A

Leucovorin, which acts as an active form of folic acid (replenishing the folate pool) that has bypassed the inhibited DHFR and is more readily taken up by normal cells than by malignant cells

34
Q

What are the adverse effects of methotrexate?

A

Stomatitis; bone marrow suppression (BMS); urticaria; alopecia; nausea; vomiting; diarrhea; nephrotoxicity; hepatotoxicity; pulmonary toxicity; neurotoxicity

35
Q

What is the mechanism of action of 5-fluorouracil?

A

Pyrimidine analog that is converted to active 5-FdUMP which inhibits thymidylate synthetase, thereby decreasing the amount of cellular thymidine and subsequent DNA

36
Q

What is the mechanism of action of cytarabine?

A

Pyrimidine antagonist

37
Q

What is the mechanism of action of both 6-mercaptopurine and 6-thioguanine?

A

Purine antagonists

38
Q

What immunosuppressive drug becomes active only after being converted to 6-mercaptopurine?

A

Azathioprine

39
Q

Because 6-mercaptopurine is metabolized by xanthine oxidase, its serum levels may be significantly increased when given concomitantly with what other medication?

A

Allopurinol (xanthine oxidase inhibitor)

40
Q

What enzyme activates 6-mercaptopurine to its corresponding nucleotide form by adding a ribose phosphate to its structure?

A

Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

41
Q

What are the major adverse effects of 6-mercaptopurine?

A

Nausea; vomiting; diarrhea; hepatotoxicity; BMS

42
Q

Give examples of antitumor antibiotics:

A

Doxorubicin; daunorubicin; dactinomycin; plicamycin; bleomycin; idarubicin

43
Q

Are the antitumor antibiotics cell cycle specific

A

Yes (S-phase)

44
Q

Name three anthracycline antitumor antibiotics:

A
  1. Doxorubicin 2. Daunorubicin 3. Idarubicin
45
Q

What is the mechanism of action of the anthracycline antibiotics?

A

Inhibition of DNA topoisomerase II; formation of free radicals (leading to DNA strand scission); DNA intercalation; inhibition of DNA and RNA synthesis

46
Q

Name three non-anthracycline antitumor antibiotics:

A
  1. Dactinomycin 2. Bleomycin 3. Mitomycin
47
Q

What is the mechanism of action of bleomycin?

A

Complexes with iron and reacts with oxygen which in turn leads to DNA strand scission

48
Q

Which phase of the cell cycle is bleomycin specific for?

A

G2

49
Q

Give examples of anticancer alkylating agents:

A

Cyclophosphamide; ifosfamide; mechlorethamine; nitrosoureas (carmustine, lomustine, streptozotocin); cisplatin; carboplatin

50
Q

Are the anticancer alkylating chemotherapeutic agents cell cycle specific

A

No

51
Q

What is the mechanism of action of anticancer alkylating agents?

A

Covalently bind (alkylation) to DNA leading to cross-linked and dysfunctional DNA strands

52
Q

Give examples of anticancer mitotic inhibitors:

A

Paclitaxel; docetaxel; vincristine; vinblastine; vinorelbine

53
Q

Are the anticancer mitotic inhibitors cell cycle specific?

A

Yes (M phase)

54
Q

What is the mechanism of action of vincristine and vinblastine?

A

They are vinca alkaloids that inhibits the ability of tubulin to polymerize, thereby preventing formation of the microtubule structures needed during mitosis.

55
Q

What adverse effects do vincristine and vinblastine have in common?

A

Nausea; vomiting; diarrhea; alopecia; phlebitis; cellulites

56
Q

Are vincristine and vinblastine vesicants?

A

Yes, they are strong vesicants.

57
Q

Which adverse effect is unique to vincristine?

A

Peripheral neuropathy

58
Q

Which adverse effect is unique to vinblastine?

A

BMS

59
Q

What plant are the vinca alkaloids derived from?

A

Periwinkle plant

60
Q

Which plant is paclitaxel a derivative of?

A

Needles of the Western or Pacific yew tree

61
Q

What is the mechanism of action of paclitaxel?

A

Binds to tubulin and increases polymerization and stabilization of the microtubule structure, thereby preventing depolymerization

62
Q

What are the adverse effects of paclitaxel?

A

Neutropenia; alopecia; hypersensitivity reactions

63
Q

How are hypersensitivity reactions prevented in patients receiving paclitaxel cancer chemotherapy?

A

Pretreatment with diphenhydramine and dexamethasone

64
Q

Give two examples of epipodophyllotoxin cancer chemotherapeutic agents:

A
  1. Etoposide 2. Teniposide
65
Q

What is the mechanism of action of the epipodophyllotoxin cancer chemotherapeutic agents?

A

Inhibition of DNA topoisomerase II

66
Q

Give two examples of cancer chemotherapeutic agents that inhibit DNA topoisomerase I:

A
  1. Topotecan 2. Irinotecan
67
Q

What is the mechanism of action of L-asparaginase?

A

Hydrolyzes asparagine to aspartic acid and ammonia, thereby depriving tumor cells of asparagine required for protein synthesi

Pharmacology (25 decks)

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