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chemo drugs Flashcards

1
Q

advantages of combination therapy

A
  • suppresses development of resistance
  • increased killing of cells
  • decreased toxicity
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2
Q

cyclophosphamide MOA and uses

A

alkylating agent; converted by CYP to phosphoramide mustard
alkylates N-7 guanine causing cross-linking and DNA strand breakage
use: NHL, breast ca, ovarian ca, neuroblastoma

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3
Q

cyclophosphamide ADR

A

hemorrhagic cystitis d/t acrolein

rare: SIADH, pulmonary toxicity

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4
Q

prevention of cyclophosphamide hemorrhagic cystitis

A

MESNA - a sulfhydryl donor that neutralizes acrolein

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5
Q

cisplatin MOA and uses

A

alkylating agent

use: testicular carcinoma, bladder ca, lung ca, ovarian ca

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6
Q

cisplatin ADR

A

nephrotoxicity, ototoxicity, peripheral neuritis, n/v (worst drug)

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7
Q

prevention of cisplatin nephrotoxicity

A

amifostine

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8
Q

carboplatin

A

alkylating like cisplatin but fewer ADRs

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9
Q

procarbazine MOA and use

A

alkylating agent, forms H2O2 causing DNA damage

use: Hodgkin’s disease

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10
Q

procarbazine ADR

A

disulfiram-like reaction, leukemia

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11
Q

thiotepa

A

alkylating agent used in ovarian ca

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12
Q

busulfan

A

alkylating agent used in CML; can cause pulmonary fibrosis

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13
Q

nitrosoureas

A

alkylating agents used in CSF and brain tumors d/t lipid solubility

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14
Q

carmustine

A

a nitrosourea (alkylating agent for CNS)

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15
Q

lomustine

A

a nitrosourea (alkylating agent for CNS)

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16
Q

streptozocin

A

alkylating agent used in insulin-secreting islet cell tumors

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17
Q

mechlorethamine

A

alkylating agent; a prodrug
used in Hodgkin’s disease
ADR: extravasation during IV infusion -> irritation

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18
Q

chlorambucil

A

alkylating agent
DOC for CLL
*least toxic of nitrogen mustards b/c slow acting

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19
Q

cell-cycle specificity of alkylating agents

A

nonspecific

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20
Q

mechanisms of resistance against alkylating agents

A
  • increased repair mechanisms
  • increased expression of Pgp and MDR (efflux) or decreased permeability
  • “trapping” by chemical production
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21
Q

cell-cycle specificity of anti-metabolites

A

S phase specific

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22
Q

methotrexate MOA

A

antimetabolite

folic acid analog inhibiting DHFR, preventing THF synthesis (dec thymidylate, purine, serine, methionine synthesis)

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23
Q

MTX resistance mechanisms

A
  • decreased transport into cell
  • altered DHFR
  • decreased polyglutamate formation
  • increased levels of DHFR
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24
Q

MTX ADR

A

BMS, mucositis, folic acid deficiency

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25
how to correct MTX-induced folic acid deficiency
leucovorin
26
leucovorin uses and MOA
folinic acid analog used to prevent/correct MTX folic acid deficiency and to increase effect of 5-FU in low folate state (reduced folate required for 5-FU MOA)
27
6-MP MOA
antimetabolite activated by HGPRT -> toxic metabolites -> inhibit purine synthesis
28
thioguanine
antimetabolite activated by HGPRT -> toxic metabolites -> inhibit purine synthesis
29
resistance to 6-MP and thioguanine
- decreased HGPRT | - increased alkaline phosphatase activity to inactivate drugs
30
cytarabine MOA
antimetabolite: pyrimidine analog activated to AraCTP by kinases -> inhibit DNA polymerase * most S-phase specific
31
cytarabine ADR
neurotoxicity (cerebellar dysfunction, peripheral neuritis) | hand-foot syndrome
32
hand-foot syndrome cause
leakage of chemo drugs from capillaries in high heat or friction areas (extremities) causes redness, tenderness, peeling, numbness/tingling
33
5-FU MOA
antimetabolite converted to 5-FdUMP, competes with dUMP for thymidylate synthetase, preventing formation of dTMP for DNA synthesis and growth "thymidineless death"
34
5-FU resistance
- decreased activation of 5-FU | - decreased thymidylate synthetase activity
35
5-FU uses
metastases of breast ca, GI ca, hepatoma | carcinoma of ovary, cervix, bladder, prostate, pancreas, oropharynx, colon cancer (+ levamisole)
36
5-FU ADR
nausea, mucositis, diarrhea, hand-foot syndrome, alopecia, hyperpigmentation neurologic deficits, BMS
37
cell cycle specificity of vinca alkaloids
M phase specific
38
vinca alkaloid MOA
prevent assembly of tubulin dimers into microtubules
39
vinca alkaloid resistance
increased efflux (Pgp and MDR)
40
vinca alkaloid ADRs
severe neurotoxicity: paresthesias, loss of reflexes, foot drop, ataxia
41
vinblastine specific ADR
BMS, alopecia, anorexia, n/v/d
42
vinblastine uses
Hodgkin's disease, breast ca, testicular ca
43
vincristine uses
childhood leukemias, childhood tumors (Hodgkin's, Wilm's, neuroblastoma)
44
vincristine specific ADR
peripheral neuritis, paresthesias, weakness | *spares bone marrow
45
cell cycle specificity of topoisomerase inhibitors
late S - early G2 specific
46
uses of etoposide and teniposide
small cell lung ca, prostate ca, testicular ca
47
etoposide and teniposide MOA
topoisomerase 2 inhibitors -> double strand DNA breaks
48
topotecan and irinotecan MOA
topoisomerase 1 inhibitors -> prevents single strand break necessary in supercoiling -> DNA breakage
49
paclitaxel and docetaxel MOA and ADR
taxanes: prevent microtubule disassembly ADR: neutropenia, peripheral neuropathy
50
cell cycle specificity of taxanes
M phase specific
51
doxorubicin and daunorubicin MOA
anthracycline antibiotics: intercalate DNA, inhibit topo2, generate free radicals block DNA and RNA synthesis and cause strand scission
52
anthracycline ADR
cardiac toxicity d/t free radicals: acute (arrhythmia, ECG changes, pericarditis, myocarditis) and chronic (DCM, HF) BMS, alopecia, radiation recall reaction
53
dexrazoxane
inhibits Fe-mediated free radical generation | used to prevent cardiotoxicity from anthracyclines
54
bleomycin MOA
G2 phase specific antibiotic binds DNA and generates free radicals (DNA-bleomycin-Fe(II) -> chromosome aberrations, SSB, DSB) and inhibits DNA synthesis
55
bleomycin use and ADR
use: Hodgkin's disease; sclerosing agent for breast and ovarian cavitary lesions ADR: pulmonary fibrosis
56
L-asparaginase MOA
catalyzes deamination of asparagine into aspartic acid and ammonia, depriving tumor of nutrient *asparagine required for growth and function of cells, but cancer cells have decreased level of asparagine synthetase
57
L-asparaginase use and ADR
use: childhood ALL ADR: acute pancreatitis
58
imatinib
targets BCR-ABL in CML | competitive inhibitor of kinase activity
59
interferon alpha-2a use
HCL, CML, AIDS-related Kaposi sarcoma
60
interferon alpha-2b use
HCL, melanoma, AIDS-related Kaposi sarcoma, follicular lymphoma
61
trastuzumab
anti-Her2 for breast cancer | ADR: cardiotoxicity
62
cetuximab
used in colon and head/neck cancers
63
panitumumab
used in colon cancer
64
bevacizumab
used in colon, lung, brain cancer | ADR: HTN, GI bleeding or perforation, thromboembolic events
65
erlotinib
for lung, pancreas ca | ADR: rash, diarrhea
66
sunitinib/ sorafenib
for renal cell ca | ADR: rash, BMS
67
lapatinib
used post-trastuzumab failure for breast ca | ADR: rash, diarrhea
68
everolimus
used in renal cell ca metastases and with anti-estrogens in breast ca
69
treatment of chemo-induced n/v
ondansetron (5HT3 antagonist)
70
treatment of chemo-induced BMS
filgrastim and sargromastim

Pharm 8 (2 decks)

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