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Hem/Onc > Chemo drugs 0504 > Flashcards

Chemo drugs 0504 Flashcards

1
Q

antimetabolites

A 
methotrexate
5-fluorouracil
6-mercaptopurine
6-thioguanine
cytarabine
cladribine

*ALL ARE S-PHASE SPECIFIC

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2
Q

methotrexate (MTX) MOA

A

folic acid analog that inhibits dihydrofolate reductase

decrease dTMP
decrease DNA
decrease prot synth

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3
Q

MTX cancer USE

A

leukemia
lymphoma
sarcoma
choriocarcinoma

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4
Q

MTX non-neoplastic USE

A

abortion
ectopic preg
rheumatoid arthritis
psoriasis

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5
Q

MTX TOX

A
  1. myelosuppression
  2. macrovesicular fatty change of liver
  3. mucositis
  4. teratogenic
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6
Q

what reverses MTX myelosuppression?

A

leucovorin (folinic acid) rescue

aka N5 formyl-THF

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7
Q

5-fluorouracil (5FU) MOA

A

pyrimidine analog that is bioactivated to 5F-dUMP, which covalently complexes folic acid.

COMPLEX inhibits thymidylate synthase.

decrease dTMP
decrease DNA
decrease prot synth

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8
Q

5FU USE

A

colon cancer and other solid tumors.

topical for basal cell carcinoma.

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9
Q

which drug works in synergy with MTX?

A

5-fluorouracil

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10
Q

5FU TOX

A
  1. myelosuppression

2. photosensitivity

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11
Q

what reverses 5FU myelosuppression?

A

thymidine

NOT LEUCOVORIN

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12
Q

6-mercaptopurine (6MP) MOA

A

purine (thiol) analog that decreases de novo purine synth

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13
Q

what activates 6MP?

A

HGPRTase

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14
Q

6MP USE

A

leukemia

lymphoma (NOT CLL or Hodgkin)

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15
Q

6MP TOX

A

bone marrow, GI, liver

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16
Q

6MP metabolism

A

metabolized by xanthine oxidase

*increased tox with allopurinol

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17
Q

what increases 6MP tox?

A

allopurinol

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18
Q

6-thioguanine (6TG) MOA

A

purine (thiol) analog that decreases de novo purine synth

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19
Q

what drug has the same MOA as 6TG?

A

6-mercaptopurine

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20
Q

6TG USE

A

acute lymphoid leukemia (ALL)

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21
Q

6TG TOX

A

BM depression, liver.

*can be given with allopurinol

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22
Q

cytarabine (ara-C) MOA

A

pyrimidine analog - inhibits DNA polymerase

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23
Q

which antimetabolites are pyrimidine analogs?

A

5-fluorouracil

cytarabine

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24
Q

ara-C USE

A

AML
ALL
high-grade NON-Hodgkin lymphoma

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25
Q

ara-C TOX

A

leukopenia
thrombocytopenia
megaloblastic anemia

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26
Q

cladrabine MOA

A

purine analog that is resistant to degradation by adenosine deaminase - can reach high intracellular concs and cause DNA strand breaks

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27
Q

cladrabine USE

A

hairy cell leukemia - complete remission

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28
Q

antitumor antibiotics

A

dactinomycin
doxorubicin, daunorubicin
bleomycin
etoposide, teniposide

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29
Q

dactinomycin (actinomycin D) MOA

A

intercalates in DNA

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30
Q

dactinomycin USE

A

Wilms tumor
Ewings sarcoma
rhabdomyosarcoma
(childhood tumors)

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31
Q

dactinomycin TOX

A

myelosuppression

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32
Q

doxorubicin (adriamycin) and daunorubicin MOA

A

generate FREE RADICALS that noncovalently intercalate in DNA

DNA breaks = decreased replication

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33
Q

doxorubicin (adriamycin) and daunorubicin USE

A

Hodgkin lymphomas
myeloma
sarcoma
solid tumor (breast, ovary, lung)

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34
Q

doxorubicin (adriamycin) and daunorubicin TOX

A

dose-related DILATED CARDIOMYOPATHY.
myelosuppression.
alopecia.

35
Q

what prevents cardiotoxicity with doxorubicin (adriamycin) and daunorubicin?

A

dexrazoxane - iron chelating agent

36
Q

bleomycin MOA

A

induce FREE RADICAL formation which causes breaks in DNA strands

37
Q

bleomycin USE

A

testicular cancer

Hodgkin lymphoma

38
Q

bleomycin TOX

A

PULMONARY FIBROSIS
skin changes (flagellate skin discoloration)
minimal myelosuppression

39
Q

etoposide (VP-16) and teniposide MOA

A

inhibit topoisomerase II to increase DNA degrad

40
Q

etoposide (VP-16) and teniposide USE

A

small cell carcinoma of lung
prostate cancer
testicular carcinoma

41
Q

etoposide (VP-16) and teniposide TOX

A

myelosuppression
GI irritation
alopecia

42
Q

alkylating agents

A

cyclophosphamide, ifosfamide
nitrosureas
busulfan

43
Q

cyclophosphamide, ifosfamide MOA

A

covalently X-link (inter strand) DNA at guanine N-7

requires bioactivation by liver (P450)

44
Q

cyclophosphamide, ifosfamide USE

A

non-Hodgkin lymphoma
breast, ovarian carcinoma
immunosuppressants

45
Q

cyclophosphamide, ifosfamide TOX

A

myelosuppression

HEMORRHAGIC CYSTITIS

46
Q

what partially prevents cyclophosphamide, ifosfamide tox?

A

mesna - thiol group binds toxic metabolite, acrolein

47
Q

nitrosureas

A

carmustine
lomustine
semustine
streptozocin

48
Q

nitrosurea MOA

A

require bioactivation.

can cross BBB into CNS.

49
Q

nitrosurea USE

A

BRAIN TUMOR including glioblastoma multiforme

50
Q

nitrosurea TOX

A

CNS toxicity - dizziness, ataxia

51
Q

busulfan MOA

A

alkylates DNA

52
Q

busulfan USE

A

CML

also used to ablate BM before BM transplant

53
Q

busulfan TOX

A

PULMONARY FIBROSIS

hyperpigmentation

54
Q

which chemo drug can cross BBB and thus, treat brain tumor?

A

nitrosureas

55
Q

microtubule inhibitors

A

vincristine, vinblastine

paclitaxel, other taxols

56
Q

vincristine, vinblastine MOA

A

alkaloids that bind beta-tubulin in M-PHASE and block polymerization of microtubules so mitotic spindle cannot form

57
Q

vincristine, vinblastine USE

A

Hodgkin lymphoma
Wilms tumor
choriocarcinoma
ALL

58
Q

vincristine TOX

A

NEUROTOXICITY - areflexia, peripheral neuritis

paralytic ileus.
myelosuppression.

59
Q

paclitaxel, other taxols MOA

A

hyperstabilize polymerized microtubules in M-PHASE so that mitotic spindle cannot break down and ANAPHASE CANNOT OCCUR

60
Q

paclitaxel, other taxols USE

A

breast, ovarian carcinomas

61
Q

paclitaxel, other taxols TOX

A

myelosuppression.

hypersensitivity.

62
Q

cisplatin, carboplatin MOA

A

contains platinum.

cross-links DNA.

63
Q

cisplatin, carboplatin USE

A

testicular, bladder, ovary, lung carcinomas

64
Q

cisplatin, carboplatin TOX

A

NEPHROTOXICITY AND ACOUSTIC NERVE DAMAGE

65
Q

how can platinum drug nephrotoxicity be prevented?

A

amifostine - free radical scavenger

PLUS chloride diuresis

66
Q

hydroxyurea MOA

A

inhibit ribonucleotide reductase - decrease DNA synthesis (S PHASE)

67
Q

hydroxyurea USE

A

melanoma
CML
sickle cell disease (increase HbF)

68
Q

hydroxyurea TOX

A

myelosuppression.

GI upset.

69
Q

prednisone MOA

A

trigger apoptosis.

may even work on nondividing cells.

70
Q

prednisone USE

A

CLL
Hodgkin lymphoma*
immunosuppressant for AI d/o

*part of MOPP regimen

71
Q

prednisone TOX

A 
Cushing-like syndrome
immunosuppression
cataracts
acne
osteoporosis
HTN
peptic ulcers
hyperglycemia
psychosis
72
Q

tamoxifen, raloxifene MOA

A

SERMs - block binding of estrogen to ER+ cells.

receptor antagonists in BREAST, agonists in BONE.

73
Q

tamoxifen, raloxifene USE

A

breast cancer

*also useful for preventing osteoporosis

74
Q

tamoxifen TOX

A

may increase risk of endometrial carcinoma via partial agonist effects. also cause hot flashes.

75
Q

raloxifene TOX

A

NO INCREASE in endometrial carcinoma bc it is an endometrial antagonist

76
Q

trastuzumab (Herceptin) MOA

A

monoclonal Ab against HER2 (erb B2), a tyrosine kinase

helps kill breast cancer cells that overexpress HER2, possibly through Ab-dependent cytotoxicity

77
Q

trastuzumab USE

A

metastatic breast cancer

78
Q

trastuzumab TOX

A

cardiotoxicity

79
Q

imatinib (Gleevec) MOA

A

inhibit Ph chromo bcr-abl tyrosine kinase

80
Q

imatinib USE

A

CML

GI stromal tumors

81
Q

imatinib TOX

A

fluid retention

82
Q

rituximab MOA

A

monoclonal Ab against CD20 on most B cell neoplasms

83
Q

rituximab USE

A 
non-Hodgkin lymphoma
rheumatoid arthritis (plus MTX)
84
Q

ondansetron

A 
inhibits serotonin (5HT-3) receptors. 
treat nausea and vomiting due to chemo.

*receptors are located in presyn terminals of vagus nerve and also centrally in chemoreceptor trigger zone and solitary nucleus/tract

Hem/Onc (9 decks)

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