Hem & Onc - Pharm (Groups of Cancer Drugs) Flashcards Preview

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Flashcards in Hem & Onc - Pharm (Groups of Cancer Drugs) Deck (56):
1

What are the phases of the cell cycle and the major event occurring in each? Which cancer drugs act at each phase?

G1 - Synthesis of components needed for DNA synthesis = NO DRUGS ACT HERE; S - DNA Synthesis = ANTIMETABOLITES & ETOPOSIDE act here; G2 - Synthesis of components needed for mitosis = ETOPOSIDE & BLEOMYCIN act here; M - Mitosis = VINCA ALKALOIDS & TAXOLS act here (Note: G0 [rest] & Differentiation exit out of the cycle)

2

Which drug acts at multiple phases in the cell cycle? What are the phases in which it acts?

Etoposide; S & G2

3

What are the steps leading up to neoplastic cell division, starting at nucleotide synthesis and ending with cellular division? What are the important drugs that act at each step?

(1) Nucleotide synthesis - METHOTREXATE/5-FU & 6-MP (2) DNA - ALKYLATING AGENTS/CISPLATIN, DACTINOMYCIN/DOXORUBICIN, & ETOPOSIDE (3) RNA - NONE (4) Protein - NONE (5) Cellular Division - VINCA ALKALOIDS & PACLITAXEL

4

On what general process do methotrexate and 5-FU act? More specifically, what is their effect?

Nucleotide synthesis; Decrease thymidine synthesis

5

On what general process does 6-MP act? More specifically, what is its effect?

Nucleotide synthesis; Decrease purine synthesis

6

On what general process do Alkylating agents & Cisplatin act? More specifically, what is their effect?

DNA (Synthesis); Cross-link DNA

7

On what general process do Dactinomycin and Doxorubicin act? More specifically, what is their effect?

DNA (Synthesis); DNA intercalators

8

On what general process does Etoposide act? More specifically, what is its effect?

DNA (Synthesis); Inhibits topoisomerase II

9

On what general process do Vinca alkaloids act? More specifically, what is their effect?

Cellular division; Inhibit microtubule formation

10

On what general process does Paclitaxel act? More specifically, what is its effect?

Cellular division; Inhibits microtubule disassembly

11

What are 4 examples of antimetabolites? In what phase of the cell cycle do all of these cancer drugs act?

(1) Methotrexate (MTX) (2) 5-fluorouracil (5-FU) (3) Cytarabine (arabinofuranosyl cytidine) (4) Azathioprine/6-mercaptopurine (6-MP)/6-thioguanine (6-TG); S-phase

12

What is MTX? What is its mechanism?

Methotrexate; Folic acid analog that inhibits dihydrofolate reductase --> decreased dTMP --> decreased DNA and decreased Protein synthesis

13

What are the 4 cancers for which methotrexate is clinically used? What 5 other non-neoplastic clinical uses does methotrexate have?

CANCERS: (1) Leukemias (2) Lymphomas (3) Choriocarcinoma (4) Sarcomas; NON-NEOPLASTIC: (1) Abortion (2) Ectopic pregnancy (3) Rheumatoid arthritis (4) Psoriasis (5) IBD

14

What are the 4 toxicities/side effects associated with methotrexate?

(1) Myelosuppression (which is rversible with leucovorin [folinic acid] "rescue") (2) Macrovesicular fatty change in liver (3) Mucositis (4) Teratogenic

15

What is 5-FU? What is its mechanism?

5-fluorouracil; Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase --> Decreased dTMP --> Decreased DNA & Decreased protein synthesis

16

What are the 3 cancers for which 5-FU is clinically used?

(1) Colon cancer (2) Pancreatic cancer (3) Basal cell carcinoma (topical)

17

What are the 2 toxicities/side effects associated with 5-FU?

(1) Myelosuppression (which is not reversible with leucovorin; instead, overdose rescue with uridine) (2) Photosensitivity

18

What is the major toxicity/side effect shared by both MTX and 5-FU? How is it handled in each case?

MYELOSUPPRESION; w/ MTX - reversible with leucovorin (folinic acid) "rescue... w/ 5-FU - not reversible with leucovorin, but instead overdose rescue with uridine

19

What is another name for Cytarabine? What is its mechanism?

Arabinofuranosyl cytidine; Pyrimidine anlog --> inhibition of DNA polymerase

20

What are the 2 cancers for which Cytarabine is clinically used?

(1) Leukemias (2) Lymphomas

21

What are the 3 toxicities/side effects associated with Cytarabine?

(1) Leukopenia (2) Thrombocytopenia (3) Megaloblastic anemia; Think: "CYTarabine causes panCYTopenia."

22

What other drugs share the same mechanism as Azathioprine? What is this mechanism? What activates them to take this action?

6-Mercatopurine (6-MP) & 6-Thioguanine (6-TG); Purine (thiol) analogis --> Decrease de novo purine synthesis; HGPRT

23

What 3 conditions are prevented with use of Azathioprine?

Preventing organ rejection, RA, SLE (azathioprine)

24

Where are the 3 toxicities/side effects associated with Azathioprine, 6-MP, and 6-TG?

(1) Bone marrow (2) GI (3) Liver

25

Which drugs are metabolized by xanthine oxidase? Given this fact, what increases toxicity of this drug, and why?

Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have increased toxicity with allopurinol, which inhibits their metabolism

26

What are the antitumor antibiotics?

(1) Dactinomycin (actinomycin D) (2) Doxorubicin (Adriamycin, daunorubicin) (3) Bleomycin

27

What is the brand name for Dactinomycin? What is its mechanism?

Actinomycin D; Intercalates in DNA

28

For what 3 cancers is dactinomycin used clinically? In general, how is dactinomycin used clinically?

(1) Wilms' tumor (2) Erwing's sarcoma (3) Rhadomyosarcoma; Used for children tumors (Think: "children ACT out")

29

What is/are the toxcity(-ies) associated with Dactinomycin?

Myelosuppression

30

What is the brand name for Doxorubicin? What is another drug that shares the same mechanism? What is their mechanism?

Adriamycin; Daunorubicin; Generate free radicals. Noncovalently intercate in DNA --> breaks in DNA --> Decreased replication

31

For what 3 cancers are doxorubicin/daunorubicin used clinically?

(1) Solid tumors (2) Leukemias (3) Lymphomas

32

What is/are the toxcity(-ies) associated with Doxorubicin/daunorubicin?

(1) Cardiotoxicity (dilated cardiomyopathy) (2) Myelosuppression (3) Alopecia (4) Toxic to tissues following extravasation

33

What is used to prevent cardiotoxicity as a result of doxorubicin/daunorubicin, and what kind of agent is this?

Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity

34

What is the mechanism of bleomycin?

Induces free radical formation, which causes breaks in DNA strands

35

For what 2 cancers is bleomycin clinically used?

(1) Testicular cancer (2) Hodgkin's lymphoma

36

What are 4 toxicities associated with Bleomycin? Which of these is minimal (relative to other antitumor drugs)?

(1) Pulmonary fibrosis (2) Skin changes (3) Mucositis. (4) Minimal myelosuppression

37

What are 3 examples of alkylating agents?

(1) Cyclophosphamide, ifosfamide (2) Nitrosoureas (carmustine, lomustine, semustine, streptozocin) (3) Busulfan

38

What other drug shares the same mechanism as cyclophosphamide? What is their mechanism? What is required for this action to occur?

Ifosfamide; Covalently X-link (interstrand) DNA at guanine N-7; Require bioactivation by liver

39

For what 4 cancers are cyclophosphamide and/or ifosfamide clinically used?

(1) Solid tumors (2) Leukemia (3) Lymphomas (4) Some brain cancers

40

What are 2 toxicities associated with cyclophosphamide and/or ifosfamide?

(1) Myelosuppression (2) Hemorrhagic cystitis (partially prevented with mesna [thiol group of mesna binds toxic metabolite])

41

What prevents hemorrhagic cystitis from cyclophosphamide/ifosfamide usage, and how?

Hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna binds toxic metabolites)

42

What are 4 examples of Nitrosoureas? What is their mechanism? What is required for this action?

(1) Carmustine (2) Lomustine (3) Semustine (4) Streptozocin; Cross blood-brain barrier --> CNS; Cross-links DNA; Require bioactivation

43

For what cancers are Nitrosoureas used clinically?

Brain tumors (including glioblastoma multiforme)

44

What kind of toxicity and/or side effects are associated with Nitrosoureas?

CNS toxicity (convulsions, dizziness, ataxia)

45

What is the mechanism of Busulfan?

Cross-links DNA

46

What are 2 clinical uses for Busulfan?

(1) CML (2) Ablate patient's bone marrow before bone marrow transplantation

47

What are 3 toxicities associated with Busulfan? Which of these occurs in almost all cases?

(1) Severe myelosuppression (in almost all cases) (2) Pulmonary fibrosis (3) Hypersegmentation

48

What are 2 examples of microtubule inhibitors?

(1) Vincristine, vinblastine (2) Paclitaxel, other taxols

49

What drug shares the same mechanism as vincristine? What is their mechanism and ultimate effect?

Vinblastine; Vinca alkaloids that bind to Beta-tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest)

50

For what 3 cancers are vincristine and/or vinblastine used clinically?

(1) Solid tumors (2) Leukemias (3) Lymphomas

51

What toxicities are associated with vincristine versus vinblastine?

VINCRISTINE - Neurotoxicity (areflexia, peripheral neuritis), paralytic ileus; VINBLASTINE - BLAsts bone marrow (suppression)

52

What is the mechanism and ultimate effect of Paclitaxel and other Taxols?

Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (i.e., anaphase cannot occur); Think: "it is TAXing to stay polymerized"

53

For what 2 cancers are Paclitaxel and/or other Taxols clinically used?

(1) Ovarian (2) Breast carcinomas

54

What 3 toxicities are associated with Paclitaxel and/or other Taxols?

(1) Myelosuppression (2) Alopecia (3) Hypersensitivity

55

What are 2 conditions treated by 6-MP? What other drug is used to treat these same conditions?

Leukemia, IBD (6-MP, 6-TG)

56

Draw a diagram showing the relationship between the following: (1) CH2-THF (2) DHF (3) DHF reductase (4) dTMP (5) dUMP (6) F-FU (7) MTX (8) THF (9) Thymidylate synthase.

See p. 403 in First Aid 2014 for diagram at bottom of page