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Flashcards in Hem Onc Drugs Deck (73):
1

Methotrexate (MTX) mech:

Folic acid analog that inhibits dihydrofolate reductase, which leads to dTMP -> decreased DNA and decreased protein synthesis

2

Methotrexate Clinical use:

Cancers: Leukemias, Lymphomas, Choriocarcinoma, Sarcomas. Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD

3

Methotrexate Toxicity:

Myelosuppression, which is reverible with leucovorin (folinic acid) 'rescue'. Macrovesicular fatty change in liver. Mucositis. Teratogen

4

5-FU Mech:

Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase which leads to a decrease in dTMP,, leading to decrease DNA and protein synthesis

5

5-FU Clinical Use:

Colon cancer, pancreatic cancer, basal cell carcinoma (topical)

6

5-FU Toxicity:

Myelosuppression, which is not reversible with leucovorin. OD: rescue with uridine. Photosensitivity.

7

Cytarabine mech:

pyrimidine analog that inhibits DNA polymerase

8

Cytarabine Clinical Use:

Leukemias, Lymphomas

9

Cytarabine Toxicity:

Leukopenia, thrombocytopenia, megaloblastic anemia, CYTarabine causes panCYTopenia

10

Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) mech:

purine (thiol) analogs lead to decreased de novo purine synthesis. Activated by HGPRT

11

Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) Clinical Use:

Preventing organ rejection, RA, SLE (azathioprine). Leukemia, IBD (6-MP, 6TG).

12

Azathioprine, 6-mercaptopurine, 6-thioguanine (6-TG) Toxocity:

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

13

The antimetabolites inlcude

MTX, 5-FU, Cytarabine, Azathioprine/6-MP

14

What are the antitumor antibiotics?

Dactinomycin, Doxorubicin (Adriamycin), Daunorubicin, Bleomycin

15

Dactinomycin (Actinomycin D) mech:

intercalates in DNA

16

Dactiomycin (Actinomycin D) use:

Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Used for childhood rumors (children act out)

17

Dactinomycin (Actinomycin D) Toxicity:

Myelosuppression

18

Doxorubicin (Adriamycin), Daunorubicin mech:

Generate free radicals. Intercalate in DNA which leads to breaks in DNA and decrease in replication.

19

Doxorubicin (Adriamycin), Daunorubicin use:

Solid tumors, Leukemias, Lymphomas

20

Doxorubicin (Adriamycin), Daunorubicin Toxicity:

Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Toxic to tissues following extravasation. Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity

21

Bleomycin mech:

Induces free radical formation, which causes breaks in DNA strands.

22

Bleomycin use:

Testicular cancer, Hodgkin lymphoma

23

Bleomycin Toxicity:

Pulmonary fibrosis, skin changes, mucositis. Minimal myelosuppression.

24

What are the alkylating agents?

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

25

Cyclophosphamide, ifosfamide mech:

Covalently X-linked (interstrand) DNA at guanine N-7. Require bioactivation by liver.

26

Cyclophosphamide, ifosfamide use:

Solid tumors, leukemia, lymphomas, and some brain cancers

27

Cyclophosphamide, ifosfamide toxicity:

Myelosuppression; hemorrhagic cystitis, partially prevented with mesna (thio group of mesna binds toxic metabolites)

28

Nitrosoureas (carmustine, lomustine, semustine, streptozocin) mech:

Require bioactivation. Cross blood-brain barrier to CNS. Cross-Links DNA

29

Nitrosoureas (carmustine, lomustine, semustine, streptozocin) clinical use:

brain tumors (including glioblastoma multiforme)

30

Nitrosoureas (carmustine, lomustine, semustine, streptozocin) toxicity:

CNS toxicity (convulsions, dizziness, ataxia)

31

Busulfan mech:

Cross-links DNA

32

Busulfan clinical use:

CML. Also used to ablate patient's bone marrow before bone marrow transplantation

33

Bustulfan toxicity:

Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation.

34

What are the microtubule inhibitors?

Vincristine/Vinblastine & paclitaxel and other taxols.

35

Vincristine/Vinblastine mech:

Vinca alkaloid that bind beta tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest)

36

Vincristine/Vinblastine use:

Solid tumors, leukemias, and lymphomas

37

Vincristine/Vinblastine toxicity:

1) Vincristine - neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. 2) Vinblastine blasts bone marrow (suppression)

38

Paclitaxel, other taxols mech

Hyperstabalize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur). 'It is taxing to stay polymerized'

39

Paclitaxel clinical use

Ovarian and breast carcinomas

40

Paclitaxel toxicity:

Myelosupression, alopecia, hypersensitivity

41

Cisplatin, carboplatin mech:

cross-link DNA

42

Cisplatin, carboplatin use:

Testicular, bladder, ovary, lung carcinoma

43

Cisplatin, carboplatin toxicity:

Nephrotoxicity and acoustic nerve damage. Prevent nephrotoxicity with amifostine (free radial scavenger) and chloride diuresis.

44

Etoposide, teniposide mech:

eTOPOside inhibits TOPOisomerase II which increases DNA degradation.

45

Clinical use of etoposide, teniposide:

Solid tumors (particularily testicular and small cell lung cancer), leukemias, lumphomas.

46

Etopoise, teniposide toxicity:

myelosuppression, GI irritation, alopecia

47

Irinotecan, topotecan mech:

Inhibit topoisomerase I and prevent DNA unwinding and replication

48

Irinotecan, topotecan clinical use:

Colon cancer (irinotecan); ovarian and small cell lug cancers (topotecan)

49

Irinotecan topotecan toxicity:

Severe myelosuppression, diarrhea

50

Hydroxyurea mech:

Inhibits ribonucleotide reductase which leads to decreased DNA Synthesis (S-phase specific)

51

Hydroxyurea use:

Melanoma, CML, sickle cell disease (increased HbF)

52

Hodoxyurea toxicity:

Bone marrow suppression, GI upset

53

Prednisone, prednisolone mech:

may trigger apoptosis. may even work on nondividing cells.

54

prednisone, prednisolone use:

most commonly used glucocorticoid in cancer chemo. used in CLL, non-hodgkin lymphomas (part of combination chemo regimen). Also used as imunosuppressants (i.e autoimmune diseases).

55

Prednisone, prednisolone toxicity:

Cushing-like symptoms; weight gain, central obesity, muscle breakdown ,cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycmia, psychosis

56

Tamoxifen, raloxifene mech

SERMS - receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER + cells

57

Tamoxifen, raloxifene clinical use

breast cancer treatment (tamoxifen only) and prevention. Raloxifene for osteoporosis.

58

Tamoxifen toxicity

partial agonist in endometrium, which increases the risk of endometrial cancer; 'hot flashes'

59

Raloxifene toxicity

no increase in endometrial carcinoma because it is an endometrial antagonist

60

Trastuzumab (herceptin) mech

monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill breast cancer cells that overexpress HER-2, through inhibition of HER2 initiated cellular signaling and antibody dependent cytotoxicity

61

Trastuzumab (herceptin) clinical use:

HER-2 + breast cancer and gastric cancer (tras2zumab)

62

Trastuzumab toxicity:

Cardiotoxicity. "HEARTceptin' damages the heart

63

Imatinib (Gleevac) mech:

Tyrosine Kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)

64

Imatinib use:

CML, GI stromal tumors

65

Imatinib toxicity:

fluid retention

66

Rituximab mech:

monoclonal antibody against CD20, which is found on most B-cell neoplasms

67

Rituximab use:

non-hodgkin lymphoma, rheumatoid arthritis (with MTX); ITP

68

Rituximab toxicity:

increased risk of progressive multifocal leukoencephalopathy

69

Vemurafenib mech:

Small molecule inhibitor to forms of the B-Raf kinase with the V600E mutation

70

Vemurafenib use:

Metastatic melanoma

71

Bevacizumab mech:

monoclonal antibody against VEGF, inhibits angiogenesis

72

Bevacizumab clinical use:

Solid tumors (colorectal cancer, renal cell carcinoma)

73

Bevacizumab toxicity:

Hemorrhage and impaired wound healing