Antineoplastics Flashcards
(71 cards)
1
Q
- antimetabolites
- topoisomerase II inhibitors
- microtubule poisons
- bleomycin
- all drugs are cell cycle ______
A
specific
2
Q
- alkylating agents
- antitumor antibiotics
- topoisomerase I inhibitors
- all drugs are cell cycle _______
A
nonspecific
3
Q
bleomycin causes?
A
pulmonary fibrosis
4
Q
cyclophosphamide adverse effect
A
cystitis
5
Q
anthracyclines (daunorubicin, doxorubicin) adverse effects
A
cardiotoxicity
6
Q
cisplatin adverse effects
A
nephrotoxicity
7
Q
cepaceitabine, pemetrexed effects
A
hand and foot syndrome
8
Q
vincristine, docetaxel, paclitaxel adverse effects
A
neurotoxicity
9
Q
irinotecan adverse effects
A
intestinal toxicity (diarrhea)
10
Q
- tumor cells initially not sensitive to a given drug
- test by in vitro sensitivity by cell conolony assays or genotyping
A
primary resistance
11
Q
- tumor cells develop resistance during drug therapy
- changes in permeability, amplification/alteration of targets, enhanced repair
A
secondary resistance
12
Q
- MDR protein
- can export multiple classes of anti cancer drugs (antimetabolites, antibiotics, alkaloids)
A
p-glycoprotein
13
Q
- impermeable to drug or pump drug out
- alternate targets for drug (glutathione)
- no apoptosis
- mechanism of restistance to what class?
A
alkylating agents
14
Q
- bifunctional nitrogen mustard
- vesicant, caustic to skin and mucus membranes
- IV only (sQ causes necrosis), often in arterial supply to tumor
- half life minutes
- n/v, decreased blood counts w/ recovery in 3-6 wks
- use for Hodgkin’s (part of MOPP)
A
mechlorethamine
15
Q
- oral or IV
- bioactivated by host metabolism (liver)
- adverse: n/v, bone marrow depression, alopecia
- sterile hemorrhagic cystitis
A
cyclophosphamide
16
Q
_____ is the major cause of cyclophosphamide cystitis, protect by forced hydration and Mesna
A
acrolein
17
Q
- activated non enzymatically
- lipid soluble, cross BBB
- Lymphomas and brain tumors
- IV or direct brain implant
- GI, myelosuppression
A
nitrosoureas (carmustine, lomustine, beadamustine)
18
Q
- sugar molecule attached to nitrosourea structure
- malignant pancreatic insulinoma, malignant carcinoid
A
streptozocin
19
Q
alkylating agent used for multiple myeloma and myeloablative therapy?
A
melphalan
20
Q
alkylating agent used for CLL?
A
chlorambucil
21
Q
alkylating agent used for CML? seldom used after imatinib, sulfur mustard not nitrogen
A
busulfan
22
Q
- superficial papillary bladder cancer
- palliative for adenocarcinoma of breast or ovary
- controlling intracavity effusions caused by metastatic tumors
A
thiotepa
23
Q
metastatic islet cell carcinoma of pancreas
A
streptozocin
24
Q
- bifunctional platinating agent, cross links DNA
- blocks DNA synthesis
- IV, cleared in urine
- non toxic to bone marrow
- n/v (use ondansetron)
- renal toxicity, dose limiting
A
cisplatin
25
- causes more myelosuppression than cisplatin, less nausea and renal
- solid tumor treatment
carboplatin
26
- less renal than cisplatin, but neurotoxic
- advanced colorectal cancer
- solid tumors
oxaliplatin
27
- alkylating agent, also causes strand cission
- bioactivated, blocks DNA and RNA synthesis
- standard toxicities: n/v/bone marrow suppression
- strongly leukemogenic and teratogenic
procarbazine
28
- IV, converted to active methylating metabolite MTIC by CYP enzyme
- treat malignant melanoma, hodgkin's
dacarbazine
29
- oral prodrug
- crosses BBB
- anaplastic astrocytoma, glioblastoma multiforme
temozolomide
30
- analogs of normal components that target the cells
- enters normal path then blocks
- folate analogs, purine and pyrimidine analogs
antimetabolites
31
- DHFR inhibitor, depletion of tetrhydrofolate shuts down biosynthetic paths
- greater accumulation in tumor cells
- blocks produciton of bases required for DNA synthesis
methotrexate
32
- oral, IV, intrathecal
- excreted in urine
- high dose followed by rescue with folinic acid
- anti folate effects
- resistance: aplified DHFR, decreased accumulation of polyglutamates
methotrexate
33
- oral, well toelrated, bone marrow depression only at high doses
- bioactivated by salvage path (HGPRT)
- blocks DNA and RNA synthesis, inhibits AMP and GMP, or incorporated into DNA altering function
- used for leukemias and lymphomas
- resistance from decrease in hgprt activity, or increase in alk phos
purine analogs
34
- active metabolite, inactivates thymidylate synthase
- folinic acid required for inactivation of thymidylate synthase
- treat many carcinomas
- bone marrow toxicity, GI
5-flurouracil
35
- cytosine analog, chain terminator
- CCS: active during S phase
- treat AML, ALL, CLL, high grade lymphomas
cytarabine
36
- inhibits tubulin polymerization, disrupts mitotic spindles
- metaphase arrest
- IV admin
- biliary excretion
vinca alkaloids (vincristine, vinblastine)
37
-vinca alkaloid that causes alopecia, bone marrow depression
vinblastine
38
-vinca alkaloid that causes peripheral neuropathy
vincristine
39
- affects microtubules by stabilization
- blocks progression through M phase
- effective in solid tumors
- IV in cremaphor --> hypersensitivity
- acute hypersensitivity, nausea
- delayed bone marrow suppression, neuropathy
paclitaxel, docetaxel
40
- topoisomerase II inhibitors, double strand breaks, DNa degradation
- induces apoptosis
- oral and IV
- bone marrow suppression, alopecia
etoposide, teniposide
41
etoposide and teniposide arrest cell in _____ stage
S-G2
42
- topoisomerase I inhibitors (ss DNA breaks)
- myelosuppressive
- dose limiting toxicity is severe diarrhea
topotecan, irinotecan
43
______ in combo with 5-FU and leucovorin is first line for metastatic colorectal cancer
irinotecan
44
prodrug metabolized to SN-38, metabolized by UGT1A1 so do genetic testing
irinotecan
45
- block access to/function of DNA or RNA
- all IV
- unique toxicities
- most produced by microbes
antitumor antibiotics
46
- intercalate into DNA
- blocks topoisomerase II, cause strand breaks
- generate free radicals
- IV, hepatic clearance
anthracyclines (dox/daunorubicin)
47
- bone marrow suppression, GI distress, severe alopecia
- signature adverse is cardiotoxicity (arryhtmias, cardiomyopathy, CHF)
- free radicals minimized by dexrazoxance (iron chelator)
anthracyclines (doxo/daunorubicin)
48
- mix of glycopeptides
- binds DNA, generates free radicals --> strand breaks, active in G2
- hypersensitivity, cutaneous rxns
- pulm toxicity, fibrosis
bleomycin
49
- effective against solid tumors
- activation favored by hypoxia, alkylates DNA
- given IV or by bladder instillation
- very toxic: severe bone marrow suppression, GI, renal
mitomycin C (antitumor antibiotic)
50
- intercalates, blocks RNA and DNA synthesis
| - radiation recall: inflammation at sites of prior radiaiton
dactinomycin (actinomycin D)
51
- depletes serum asparagine needed by some tumors
- parenteral
- hypersensitivity
- use in ALL
asparaginase
52
- inhibits ribonucleotide reductase
- oral therapy for leukemias, some head and neck
- mucositis, rash, bone marrow suppression
hydroxyurea
53
- monoclonal antibody, blocks CD20 B cell antigen
- IV, half life 22 days
- for B cell lymphomas, CLL, non hodgkins
- hypogammaglobulinemia, autoimmune disorders
rituximab
54
- suppress proliferation of immune cells (leukocytes, lymphocytes)
- oral
- delayed: fluid retention, immunosuppression, diabetes
prednisone, hydrocortisone
55
- block conversion of androgens to estrogens
| - specific for estrogen production
selective aromatase inhibitors
56
- azole, similar to antifungals
- more effective against peripheral aromatase
- for ER+ primary and metastatic breast cancer
anastrazole, letrozole
57
- steroidal irreversible aromatase inhibitor
- no cross resistance w/ azoles
- fatigue, hot flashes
exemestane
58
- competing ligands for estrogen receptor
| - more effective in post menopausal women
SERMs
59
- ER antagonist in breast, ER agonist in endometrium
- converted by CYP2D6
- chemopreventive for breast cancer
- ER+ primary and metastatic
tamoxifen, toremifine
60
- ER antagonist in breast, ER agonist in bone
- chemoprevention for breast cancer, treatment and prevention of osteoporosis
- hot flashes, vaginal bleeding
raloxifene
61
- use with leuprolide and/or radiation for prostate cancer
| - hot flashes, transient hepatic effects
flutamide, bicalutamide
62
- cytokine produced by WBCs
- parenteral
- alters gene expression, antiviral and immunomodulatory
- used against hematologic malignancies, metastatic melanoma, renal cell carcinoma
- fever and chills, anorexia, weakness
interferon- alpha
63
- monoclonal antibody against Her2neu oncogene (epidermal growth factor)
- receptor amplified in 25% of breast cancers
- IV
- hypersensitivity, cardiomyopathy
trastuzamab (herceptin)
64
- inhibits Bcr-Abl and c-kit (GI stromal tumors) tyrosine kinases
- used in CML
- any hematologic malignancy with Philadelphia chromosome
- myelosuppressive
- edema, fluid retention, hepatotoxic
imatinib (gleevec)
65
- newer receptor tyrosine kinase inhibitors, broad spectrum
| - use in imatinib resistance
dastinib, nilotinib
66
- inhibits bruton's tyrosine kinase, essential for B cell receptor signaling
- oral
- metabolized by CYP3A4
- for mantle cell lymphoma, refractory CLL
- adverse: GI, thrombocytopenia, neutropenia, infections, fatigue
ibrutinib
67
- PI3K inhibitor
- metabolized by aldehyde oxidase and CYP3A4 (Strong inhibitor)
- relapsed CLL and SLL, relapsed follicular B cell lymphoma
- hepatotox, diarrhea, colitis, pneumonitis, intestinal perf
idelalisib
68
- inhibits 26S proteasome, disrupts signal cascades, apoptosis
- multiple myeloma, mantle cell lymphoma
- causes thrombocytopenia, fatigue, peripheral neuropathy
- hypotension upon infusion
bortezimib
69
- monotherapy or w/ anthracycline or arsenic for APL
- binds to RAR-alpha receptor, promotes differentiation
- promotes degradation of PML RAR-alpha fusion protein
- resistance through enhanced clearance (CyP25A1) or loss of expresion of fusion gene
all trans retinoic acid
70
- inhibits thioredoxin reductase, enhancing oxidative stress
- modification and degradation of APL fusion protein
- cytotoxic, promotes differentiation
arsenic trioxide (As2O3)
71
- thalidomide derivative
- CLL, multiple myeloma
- lacks sedative effects and teratogenic of thalidomide
- inhibits rituximab
lenalidomide
