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STEP1 2015 > Cancer drugs > Flashcards

Cancer drugs Flashcards

1
Q

Methotrexate- mechanism

A

dihydrofolate reductase inhibitor

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2
Q

Methotrexate- uses

A

Cancer- ALL, AML, breast cancer

Uterine pathology- ectopic pregnancy, abortion, choriocarcinoma, hydatiform mole

Immunosuppression: RA, psoriasis

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3
Q

Methotrexate- toxicity

A

bone marrow suppression- reversible with leucovorin (folin acid analog)

pulmonic fibrosis (methotrexate lung)

hepatotoxicity

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4
Q

5-Fluorouracil-mechanism

A

pyrimidine analog bioactivated to 5F-dUMP, which complexes covalently with folic acid. This complex inhibits thymidylate synthase, which then inhibits DNA synthesis.

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5
Q

5FU uses

A

colon cancer
topical use for actinic keratosis
pancreatic cancer
basal cell carcinoma

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6
Q

5FU side effects

A

Myelosuppression, not reversible with leucovorin

Uridine is a possible rescue agent

photosensitivity

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7
Q

Azathioprine, which is bioactivated to 6MP

MOA

A

purine analog, inhibits PRPP imidotransferase

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8
Q

6MP (azathioprine) uses

A

prevents organ rejection, RA, IBD, SLE

use to wean patients off steroids in chronic disease

use to treat steroid- refractory chronic disease

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9
Q

6MP (azathioprine) toxicity

A

myelosuppression
hepatotoxicity

increased toxicity with allopurinol or febuxostat which are also metabolized by xanthine oxidase enzyme

6TG is metabolized by a different enzyme, so it can be combined with azathioprine

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10
Q

cyclophosphamide/ ifosfamide MOA

A

bioactivated by the liver, then acts as an alkylating agent, cross- links DNA at guanine N7

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11
Q

cyclophosphamide uses

A

cancer: solid tumors, leukemia, lymphomas
immunosuppresant: lupus nephritis, polyarteritis nodosa

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12
Q

ifosfamide uses

A

testicular cancer. Ifosfamide is not used for testicular cancer

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13
Q

cyclofosfamide/ifosfamide toxicity

A

both drugs can lead to myelosuppression.
These alkylating agents form a toxic metabolic Acrolein, which can induce hepatotoxicity. For this reason, administer cyclofosfamide/ifosfamide with Mesna, which binds the Acrolein up and makes cyclophosphamide/ifosfamide safer

Both drugs are also associated with increased rates of transitional cell bladder cancer

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14
Q

Nitrosoureas: MOA

A

bioactivated alkylating agent that cross- links DNA in the CNS

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15
Q

Nitrosoureas- uses

A

brain tumors (including glioblastoma multiforme)

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16
Q

nitrosoureas- toxicity

A

CNS toxicity (convulsions, dizziness, ataxia)

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17
Q

Busulfan- MOA, uses, toxicity

A

alkylating agent that cross- links DNA

used for CML, ablation of bone marrow before bone marrow transplantation

toxicity: PULMONARY FIBROSIS
hyperpigmentation

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18
Q

Doxorubicin, daunorubicin: MOA, uses, toxicity

What drug is used to prevent toxicity?

A
  1. intercalates into DNA so that it can’t unwind
  2. generates free radicals

used to treat lymphoma, leukemia, solid tumors

toxicity: cardiotoxicity (dilated cardiomyopathy)
myelosuppression
alopecia

note: heart muscle relatively deficient in SOD

Dexrazoxane is an iron chelating agent that is used to prevent cardiotoxicity

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19
Q

Dactinomycin

A 
intercalates DNA, 
used for children's tumors
-Wilm's tumor
-Ewing sarcoma
-Rhabdomyosarcoma
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20
Q

generates free radicals and intercalates DNA

A

Daunorubicin/doxorubicin

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21
Q

inhibits dihydrofolate reductase

A

Methotrexate

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22
Q

inhibits thymidylate synthase

A

5-FU

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23
Q

inhibits PRPP amidotransferase

A

6MP

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24
Q

inhibits DNA polymerase

A

Cytarabine (pyrimidine analog)

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25
Q

Give dexrazoxane with … for…

A

dexrazoxan with daunorubicin/doxorubicin

for cardiotocity

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26
Q

Give leucovorin with … for…

A

leucovorin with methotrexate for myelosuppression rescue

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27
Q

give mesna with… for…

A

cyclophosphamide and ifosfamide for toxic acrolein metabolite, which causes hemorrhagic cystitis

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28
Q

give uridine with… for…

A

uridine is a rescue agent for 5FU myelosuppression

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29
Q

Bleomycin

A

generates free radicals leading to DNA damage.
use for testicular cancer (along with etoposide and cisplatin), Hodgkin lymphoma
toxicity: pulmonary fibrosis

lance can’t take bleomycin because he races

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30
Q

pulmonary fibrosis

A

methotrexate (antimetabolite) lung
busulfan alkylating agent
bleomycin antitumor antibiotic

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31
Q

folic acid analog that inhbits dihydrofolate reductase

A

methotrexate

32
Q

pyrimidine analog that inhibits thymidylate synthase

A

5-FU

33
Q

how does the body metabolize 6MP?

A

xanthine oxidase

34
Q

which cancer drug is often used in rheumatoid diseases and ectopic pregnancy?

A

methotrexate

35
Q

alkylates DNA, toxicity includes pulmonary fibrosis

A

Busulfan

36
Q

fragments DNA, toxicity includes pulmonary fibrosis

A

bleomycin

37
Q

blocks purine synthesis, metabolized by xanthine oxidase

A

azathioprine (6MP)

38
Q

nitrogen mustard, alkylates DNA

A

nitrosoureas

39
Q

folic acid analog that inhibits dihydrofolate reductase

A

methotrexate

40
Q

intercalates DNA, produces oxygen free radicals, cardiotoxic

A

doxorubicin, daunorubicin

41
Q

DNA alkylating agents used in brain cancer

A

nitrosoureas

42
Q

applied topically for actinic keratoses and basal cell cancers

A

topical 5FU

43
Q

treatment for childhood tumors (Ewing sarcoma, Wilms tumor, rhabdomyosarcoma)

A

dactinomycin

44
Q

side effect of hemorrhagic cystitis

A

cyclophosphamide and ifosfamide

45
Q

cisplatin, carboplatin, oxaliplatin

A

cross-link DNA
GU treatments include ovarian cancer, bladder, cancer, testicular cancer, lung carcinoma

toxicity includes nephrotoxicity, ototoxicity

prevent nephrotoxicity with amifostine (free radical scavenger), and
chloride (saline) diuresis

46
Q

Etoposide, teniposide

A

etoposide inhibits topoismerase II, enhancing DNA degradation by super-coiling

use for solid tumors (particularly testicular and small cell lung cancer), prostate cancer
leukemias, lymphomas

toxicity includes myelosuppression

47
Q

testicular cancer regimen

Eradicate Ball Cancer

A

etoposide, bleomycin (or ifosfamide), cisplatin

48
Q

irinotecan and topotecan

A

these inhibit topoisomerase I
irinotecan is used for metastatic colon cancer

topotecan is used for small cell lung cancer, ovarian cancer, cervical cancer

49
Q

Vincristine

A

blocks polymerization of microtubules

used to treat hodgkin lymphoma, Wilms tumor, Ewing sarcoma, choriocarcinoma

side effects:
neurotoxicity
peripheral neuritis

50
Q

Vinblastine

A

blocks mictotubule polymerization

indications are also similar to vincristine
WT, choriocarcinoma, Ewing sarcoma, Hodgkin lymphoma

toxicity:
myelosuppression

Vinblastine blasts bone marrow

51
Q

Paclitaxel

A

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

used for ovarian and breast carcinomas

toxicity: hypersensitivity

52
Q

drugs that work on microtubules

A 
vincristine
vinblastine
paclitaxel
mebendazole
albendazole
griseofulvin
colchicine
53
Q

hydroxyurea

A

inhibits ribonucleotide reductase, thereby inhibiting DNA synthesis (S-phase specific)

used for melanoma, CML, sickle cell disease (increased HbF)

toxicity: severe myelosuppression, GI upset

54
Q

Prednisone

A

triggers apoptosis in lymphoid tumors like CLL and Hodgkin lymphoma

55
Q

BAM CUSHINGOID

A

buffalo hump
amenorrhea
moon facies

crazy
ulcers
skin changes
htn
infection
necrotic femoral head
glaucoma
osteoporosis
immunosuppression
diabetes
56
Q

Selective estrogen receptor modulators (SERMs)

Tamoxifen

A

ER antagonist at breast
ER agonist in bone
ER partial agonist in endometrium

use for ER+ breast cancer
prevent cancer in patients with BRCA mutation

tox: increased risk of endometrial carcinoma via overstimulation of endometrial tissue

in women with endometrial cancer, tamoxifen can be used for treatment

57
Q

Raloxifene SERM

A

used to treat osteoporosis
ER antagonist
- breast
-endometrium

ER agonist
-bone

58
Q

Trastuxumab

A

monoclonal antibody against HER2 receptor (TKR), which helps to kill cancers that overexpress HER2.

Useful only for HER-2+ breast cancer and gastric cancer (tras2zumab)

Cardiotoxicity- HER2 Heartceptin hurts the heart

59
Q

inhibits microtubule formation

A

vincristine

60
Q

inhibits microtubule disassembly

A

paclitaxel

61
Q

inhibits ribunucleutide reductase

A

hydroxyurea

62
Q

inhibits topoisomerase II

A

etoposide

63
Q

inhibits topoisomerase I

A

topotecan

64
Q

Cardiotoxicity

A

trastuzumab (herceptin)

65
Q

hypersensitivity reactions

A

paclitaxel

66
Q

increased risk of endometrial cancer

A

tamoxifen

67
Q

nephrotoxicity and ototoxicity

A

cisplatin

68
Q

peripheral neuropathy

A

vincristine

69
Q

Rituximab

A 
antibody against CD20
used for 
lymphomas, leukemias
RA
vasculitis
pemphigus vulgaris
ITP

tox: increases risk of progressive multifiocal leukencephalopathy

70
Q

Bevacizumab

A

monoclonal antibody against VEGF, inhibits angiogenesis

cancers need new blood vessels or they will die

treat metastatic colon cancer
metastatic cervical cancer
certain types of lung cancer
metastatic renal cell carcinoma

side effects: impaired wound healing, severe hemorrhage (hemoptysis, GI bleeding, epistaxis)

71
Q

Imatinib

A

enzyme inhibitor
targets BCR-Abl TKR, produced by t(9;22) Philadelphia chromosome

CML
ALL
AML

72
Q

cross-links DNA, nephrotoxic, ototoxic

A

cisplatin
carboplatin
oxaliplatin

73
Q

prevents tubulin disassm

A

Paclitaxel

74
Q

inhibits ribonucleotide reductase

A

hydroxyurea

75
Q

inhibitor of the mutated tyrosine kinase produced by the Philadelphia chromozome

A

imatinib

76
Q

monoclonal antibody against HER2

A

trastuzumab

77
Q

SERM that does not increase the risk of endometrial cancer

A

raloxifene

STEP1 2015 (30 decks)

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