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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
ara-C TOX
leukopenia thrombocytopenia megaloblastic anemia
26
cladrabine MOA
purine analog that is resistant to degradation by adenosine deaminase - can reach high intracellular concs and cause DNA strand breaks
27
cladrabine USE
hairy cell leukemia - complete remission
28
antitumor antibiotics
dactinomycin doxorubicin, daunorubicin bleomycin etoposide, teniposide
29
dactinomycin (actinomycin D) MOA
intercalates in DNA
30
dactinomycin USE
Wilms tumor Ewings sarcoma rhabdomyosarcoma (childhood tumors)
31
dactinomycin TOX
myelosuppression
32
doxorubicin (adriamycin) and daunorubicin MOA
generate FREE RADICALS that noncovalently intercalate in DNA DNA breaks = decreased replication
33
doxorubicin (adriamycin) and daunorubicin USE
Hodgkin lymphomas myeloma sarcoma solid tumor (breast, ovary, lung)
34
doxorubicin (adriamycin) and daunorubicin TOX
dose-related DILATED CARDIOMYOPATHY. myelosuppression. alopecia.
35
what prevents cardiotoxicity with doxorubicin (adriamycin) and daunorubicin?
dexrazoxane - iron chelating agent
36
bleomycin MOA
induce FREE RADICAL formation which causes breaks in DNA strands
37
bleomycin USE
testicular cancer | Hodgkin lymphoma
38
bleomycin TOX
PULMONARY FIBROSIS skin changes (flagellate skin discoloration) minimal myelosuppression
39
etoposide (VP-16) and teniposide MOA
inhibit topoisomerase II to increase DNA degrad
40
etoposide (VP-16) and teniposide USE
small cell carcinoma of lung prostate cancer testicular carcinoma
41
etoposide (VP-16) and teniposide TOX
myelosuppression GI irritation alopecia
42
alkylating agents
cyclophosphamide, ifosfamide nitrosureas busulfan
43
cyclophosphamide, ifosfamide MOA
covalently X-link (inter strand) DNA at guanine N-7 requires bioactivation by liver (P450)
44
cyclophosphamide, ifosfamide USE
non-Hodgkin lymphoma breast, ovarian carcinoma immunosuppressants
45
cyclophosphamide, ifosfamide TOX
myelosuppression | HEMORRHAGIC CYSTITIS
46
what partially prevents cyclophosphamide, ifosfamide tox?
mesna - thiol group binds toxic metabolite, acrolein
47
nitrosureas
carmustine lomustine semustine streptozocin
48
nitrosurea MOA
require bioactivation. | can cross BBB into CNS.
49
nitrosurea USE
BRAIN TUMOR including glioblastoma multiforme
50
nitrosurea TOX
CNS toxicity - dizziness, ataxia
51
busulfan MOA
alkylates DNA
52
busulfan USE
CML also used to ablate BM before BM transplant
53
busulfan TOX
PULMONARY FIBROSIS | hyperpigmentation
54
which chemo drug can cross BBB and thus, treat brain tumor?
nitrosureas
55
microtubule inhibitors
vincristine, vinblastine | paclitaxel, other taxols
56
vincristine, vinblastine MOA
alkaloids that bind beta-tubulin in M-PHASE and block polymerization of microtubules so mitotic spindle cannot form
57
vincristine, vinblastine USE
Hodgkin lymphoma Wilms tumor choriocarcinoma ALL
58
vincristine TOX
NEUROTOXICITY - areflexia, peripheral neuritis paralytic ileus. myelosuppression.
59
paclitaxel, other taxols MOA
hyperstabilize polymerized microtubules in M-PHASE so that mitotic spindle cannot break down and ANAPHASE CANNOT OCCUR
60
paclitaxel, other taxols USE
breast, ovarian carcinomas
61
paclitaxel, other taxols TOX
myelosuppression. | hypersensitivity.
62
cisplatin, carboplatin MOA
contains platinum. | cross-links DNA.
63
cisplatin, carboplatin USE
testicular, bladder, ovary, lung carcinomas
64
cisplatin, carboplatin TOX
NEPHROTOXICITY AND ACOUSTIC NERVE DAMAGE
65
how can platinum drug nephrotoxicity be prevented?
amifostine - free radical scavenger | PLUS chloride diuresis
66
hydroxyurea MOA
inhibit ribonucleotide reductase - decrease DNA synthesis (S PHASE)
67
hydroxyurea USE
melanoma CML sickle cell disease (increase HbF)
68
hydroxyurea TOX
myelosuppression. | GI upset.
69
prednisone MOA
trigger apoptosis. | may even work on nondividing cells.
70
prednisone USE
CLL Hodgkin lymphoma* immunosuppressant for AI d/o *part of MOPP regimen
71
prednisone TOX
``` Cushing-like syndrome immunosuppression cataracts acne osteoporosis HTN peptic ulcers hyperglycemia psychosis ```
72
tamoxifen, raloxifene MOA
SERMs - block binding of estrogen to ER+ cells. receptor antagonists in BREAST, agonists in BONE.
73
tamoxifen, raloxifene USE
breast cancer | *also useful for preventing osteoporosis
74
tamoxifen TOX
may increase risk of endometrial carcinoma via partial agonist effects. also cause hot flashes.
75
raloxifene TOX
NO INCREASE in endometrial carcinoma bc it is an endometrial antagonist
76
trastuzumab (Herceptin) MOA
monoclonal Ab against HER2 (erb B2), a tyrosine kinase helps kill breast cancer cells that overexpress HER2, possibly through Ab-dependent cytotoxicity
77
trastuzumab USE
metastatic breast cancer
78
trastuzumab TOX
cardiotoxicity
79
imatinib (Gleevec) MOA
inhibit Ph chromo bcr-abl tyrosine kinase
80
imatinib USE
CML | GI stromal tumors
81
imatinib TOX
fluid retention
82
rituximab MOA
monoclonal Ab against CD20 on most B cell neoplasms
83
rituximab USE
``` non-Hodgkin lymphoma rheumatoid arthritis (plus MTX) ```
84
ondansetron
``` 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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