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STEP 1 > Oncology Drugs > Flashcards

Oncology Drugs Flashcards

1
Q

Name the antimetabolites

A

Azathioprine, 6-mercaptopurine, 6-thioguanine, cladribine, cytarabine, 5-fluorouracil, methotrexate

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2
Q

Mechanism of azathioprine, 6-MP and 6-TG

A

purine (thiol) analogs –> decreased de novo purine synthesis
activated by HGPRT
azathioprine is prodrug to 6-MP

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3
Q

Use of azathioprine, 6-MP and 6-TG

A 
preventing organ rejection
RA
IBD
SLE
to wean pts off steroids and to tx steroid-refractory chronic disease
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4
Q

Toxicity of azathioprine, 6-MP and 6-TG

A

MYELOSUPPRESSION

GI, liver

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5
Q

Metabolism of azathioprine and 6-MP

A

metabolized via xanthine oxidase

increased toxicity if used with allopurinol or febuxostat (used to treat gout)

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6
Q

Mechanism of cladribine

A

purine analog –> multiple mechanism (e.g. inhibition of DNA polymerase, DNA strand breaks)

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7
Q

Use of cladribine

A

hairy cell leukemia

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8
Q

Toxicity of cladribine

A

myelosuppression, nephrotoxicity, and neurotoxicity

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9
Q

Mechanism of cytarabine

A

pyrimidine analong –> inhibition of DNA polymerase

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10
Q

Use of cytarabine

A

leukemias (AML), lymphomas

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11
Q

Toxicity of cytarabine

A

leukopenia, thrombocytopenia, megaloblastic anemia

CYTarabine causes panCYTopenia

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12
Q

Mechanism of 5-fluorouracil

A

pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes with folic acid
complex inhibits thymidylate synthase –> decreased dTMP –> decreased DNA synthesis

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13
Q

Use of 5-FU

A

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

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14
Q

Toxicity of 5-FU

A

myelosuppression, which is NOT reversible with leucovorin (folinic acid)

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15
Q

Mechanism of methotrexate

A

folic acid analog that competitively inhibits dihydrofolate reductase –> decreased dTMP –> decreased DNA synthesis

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16
Q

Use of methotrexate

A

cancers: leukemia (ALL), lymphoma, choriocarcinoma, sarcomas

Non-neoplastic: ectopic pregnancy, medical abortion (with misoprostol), RA, psoriasis, IBD, vasculitis

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17
Q

Toxicity of methotrexate

A

myelosuppression (reversible with leucovorin)
hepatotoxicity
mucostitis (e.g. mout ulcers)
pulmonary fibrosis

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18
Q

Name the antitumor antibiotics

A

bleomycin, dactinomycin, doxorubicin, daunorubicin

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19
Q

Mechanism of bleomycin

A

induces free radical formation –> breaks in DNA strands

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20
Q

Use of bleomycin

A

testicular cancer, Hodgkin lymphoma

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21
Q

Toxicity of bleomycin

A

pulmonary fibrosis
skin hyperpigmentation
mucositis

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22
Q

Mechanism of dactinomycin (actinomycin D)

A

intercalates in DNA

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23
Q

Use of dactinomycin

A

Wilms tumor
Ewing sarcoma
Rhabdomyosarcoma

CHILDHOOD TUMORS - Kids ACT out

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24
Q

Toxicity of dactinomycin

A

myelosuppression

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25
Q

Mechanism of doxorubicin/daunorubicin

A

generate free radicals

intercalate in DNA –> breaks in DNA –> decreased replication

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26
Q

Use of doxorubicin/daunorubicin

A

solid tumors
leukemias
lymphomas

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27
Q

Toxicity of doxorubicin/daunorubicin

A

CARDIOTOXICITY (dilated cardiomyopathy)
myelosuppression
alopecia
toxic to tissues following extravasation

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28
Q

Agent given with doxorubicin/daunorubicin to prevent cardiotoxicity

A

Dexrazoxane - iron chelating agent

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29
Q

Name the alkylating agents

A

busulfan, cyclophosphamide, ifosfamide, nitrosureas (carmustine, lomustine, semustine, streptozocin)

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30
Q

Mechanism of busulfan

A

cross-links DNA

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31
Q

Use of busulfan

A

CML

used to ablate bone marrow before transplant

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32
Q

Toxicity of busulfan

A

SEVERE MYELOSUPPRESSION
pulmonary fibrosis
hyperpigmentation

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33
Q

Mechanism of cyclophosphamide/ifosfamide

A

cross-link DNA at guanine N-7

require bioactivation by liver

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34
Q

Use of cyclophosphamide/ifosfamide

A

solid tumors
leukemia
lymphoma

35
Q

Toxicity of cyclophosphamide/ifosfamide

A 
myelosuppression
HEMORRHAGIC CYSTITIS (partially prevented with MESNA and hydration)
36
Q

Mechanism of nitrosureas

A

require bioactivation
cross BBB –> CNS
cross link DNA

37
Q

Use of nitrosureas

A

brain tumors (including glioblastoma multiforme)

38
Q

Toxicity of nitrosureas

A

CNS toxicirty (convulsions, dizziness, ataxia)

39
Q

Name the microtubule inhibitors

A

paclitaxel (other taxols), vincristine, vinblastine

40
Q

Mechanism of paclitaxel/taxols

A

hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur)

41
Q

Use of paclitaxel/taxol

A

ovarian and breast carcinomas

42
Q

Toxicity of paclitaxel/taxol

A

myelosuppression
alopecia
hypersensitivity

43
Q

Mechanism of vincristine/vinblastine

A

vinea alkaloids that bind beta-tubulin and inhibit its polymerization into MTs –> prevent mitotic spindle formation (M-phase arrest)

44
Q

Use of vincristine/vinblastine

A

solid tumors
leukemias
Hodgkin (vinblastine) lymphoma
Non-Hodgkin (vincristine) lymphoma

45
Q

Toxicity of vincristine

A

neurotoxicity (areflexia, peripheral neuritis)

paralytic ileus

46
Q

Toxicity of vinblastine

A

bone marrow supression

47
Q

Mechanism of cisplatin/carboplatin

A

cross-link DNA

48
Q

Use of cisplatin/carboplatin

A

testicular
bladder
ovary
lung carcinomas

49
Q

Toxicity of cisplatin/carboplatin

A

nephrotoxicity, ototoxicity

50
Q

How can prevent nephrotoxicity of cisplatin/carboplatin

A

use with amifostine (free radical scavenger) and chloride (saline) diuresis

51
Q

Mechanism of etoposide/teniposide

A

etoposide inhibits topoisomerase II –> increased DNA degradation

52
Q

Use of etoposide/teniposide

A

solid tumors (testicular and small cell lung)
leukemia
lmyphoma

53
Q

Toxicity of etoposide/teniposide

A

myelosuppression, GI upset, alopecia

54
Q

Mechanism of irinotecan, topotecan

A

inhibit topoisomerase I and prevent DNA unwinding and replication

55
Q

Use of irinotecan, topotecan

A 
colon cancer (irinotecan)
ovarian and small cell lung (topotecan)
56
Q

Toxicity of irinotecan, topotecan

A

severe myelosuppression

diarrhea

57
Q

Mechanism of hydroxyurea

A

inhibits ribonucleotide reductase –> decreased DNA synthesis (S-phase specific)

58
Q

Use of hydroxyurea

A

melanoma, CML, sickle cell disease (increase HbF)

59
Q

Toxicity of hydroxyurea

A

severe myelosupression

GI upset

60
Q

Mechanism of prednisone/prednisolone

A

various; bind intracytoplasmic receptor; alter gene transcription

61
Q

Use of prednisone/prednisolone

A

CLL
non-Hodgkin lymphoma (part of combo)
immunosuppressants (autoimmune diseases)

62
Q

Toxicity of prednisone/prednisolone

A

Cushing like symptoms

63
Q

Mechanism of bevacizumab

A

monoclonal antibody against VEGF inhibiting angiogenesis

64
Q

Use of bevacizumab

A

colon cancer and renal cell carcinoma

age related macular degeneration

65
Q

Toxicity of bevacizumab

A

hemorrhage
blood clots
impaired wound healing

66
Q

Mechanism of erlotinib

A

EGFR tyrosine kinase inhibitor

67
Q

Use of erlotinib

A

non small cell lung carcinoma (adenocarcinoma if EGF positive)

68
Q

Toxicity of erlotinib

A

rash

69
Q

Mechanism of imatinib

A

tyrosine kinase inhibitor of BCR-ABL (philadelphia chromosome fusion gene) and c-kit (GI stromal tumors)

70
Q

Use of imatinib

A

CML, GI stromal tumors

71
Q

Toxicity of imatinib

A

fluid retention

72
Q

Mechanism of rituximab

A

Ab against CD20 on B cells

73
Q

Use of rituximab

A

Non-Hodgkin lymphoma
CLL
IBD
RA

74
Q

Toxicity of rituximab

A

increased risk of progressive multifocal leukoencephalopathy (PML) from JC virus

75
Q

Mechanism of tamoxifen/raloxifene

A

selective estrogen receptor modulators

  • antagonists in breast and agonists in bone
  • block binding of estrogen to ER + cells in breast
76
Q

Use of tamoxifen/raloxifene

A

breast cancer treatment (tamoxifen only) and prevention

osteoporosis for raloxifene

77
Q

Toxicity of tamoxifen

A

partial agonist in endometrium –> increased risk of endometrial hyperplasia and cancer
increased risk for hot flashes

78
Q

Toxicity of raloxifene

A

no increase in endometrial cancer because antagonist in endometrial tissue

79
Q

Mechanism of trastuzumab

A

Ab against Her-2, a tyrosine kinase receptor (through interrupted cellular signaling and antibody-dependent cytotoxicity)

80
Q

Use of trastuzumab

A

HER2 + breast cancer and gastric cancer

81
Q

Toxicity of trastuzumab

A

cardiotoxicity

82
Q

Mechanism of vemurafenib

A

small molecule inhibitor of BRAF oncogene + melanoma

83
Q

Use of vemurafenib

A

metastatic melanoma

STEP 1 (26 decks)

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