B3.042 - Antineoplastic Drugs Flashcards
1
Q
what are purine analogs
A
6-mercaptopurine, 6 - thioguanine
2
Q
what is the base of cis platin
A
platinum
3
Q
what diseases are associated with diminished or no UGT1A1
A
crigler najjar
gilbert
hyperbilirubinemia
4
Q
how is bortezomib given
A
IV half life of 5.5 hours
5
Q
AEs of tamoxifen
A
nausea hot flushes vaginal bleeding
6
Q
what are adverse effects of cyclophosphamide
A
nausea and vomiting
bone marrow depression
alopecia
sterile hemorrhagic cystitis
7
Q
primary use of mechlorethamine
A
hodgkins disease
8
Q
if theres no hprt how does that affect purine analogs
A
the drugs wont work
9
Q
bevacizumab is single drug therapy for what
A
glioblstoma
10
Q
what is secondary resistance
A
tumor cells develop resistance during therapy
11
Q
how is myelosuppression treated
A
GM-CSF or platelet transfusions
12
Q
what do aromatase inhibitors
A
block conversions of androgens to estrogens
13
Q
what is neoadjuvant chemo
A
chemo before surgery or radiation
14
Q
when are hydrocortisone and prednisone used
A
leukemias and lymphomas
15
Q
what does Bcr Abl do
A
kinase that drives cell proliferation in CML
16
Q
what is adjuvant chemo
A
chemo following surgery or radiation
17
Q
how is etoposide admiinistered
A
oral and IV
18
Q
how are taxanes administered
A
IV
19
Q
DNA damage requires what, to die
A
P53
20
Q
what are AEs of hydrocortisone and prednisone
A
fluid retention
immunosuppression
diabetes
21
Q
what is Interferon alpha used for
A
alters gene expression, antiviral and immunomodulatory
used against hematologic malignancies, metastatic melanoma, renal cell carcinoma
22
Q
what does UGT1A1 deficiency cause with irinotecan
A
hematological toxicity
23
Q
what are AEs of taxanes
A
acute hypersensitivity, nausea
delated bone marrow suppression, some neuropathy
24
Q
how do secondary malignancies arise
A
carcinogens act by covalently modifying nuclear DNA leading to altered structure and function, so do alkylating agents
25
what is bortezomib
inhibits 26s proteosome
26
what is mechlorethamine
a nigrogen mustard, first alkylating agent
27
what is acrolein
side product of metabolism of cyclophosphamide
28
how do taxanes differ from vincas
they affect microtubules but by stabilization, you build the spindles but cant contract (prevent depolarization)
29
what is imatinib
TKI
30
most alkylating agents are bifunctional meaning what
they bite DNA twice
31
how is SN-38 inactvated
glucuronidation by UGT1A1
32
what do you give when you give 5-FU and why
folinic acid to ensure folic acid will bind to it, required that all 3 are there to enhance its efficacy
33
what are AEs of mechlorethamine
acute - nausea, vomiting
| Delayed - decreased blood counts, moderate iwth most doses
34
what does alkaline phosphatase do
chops off phosphatases blocking active form of drug (triphosphate form)
35
what are AEs of imatinab
myelosuppressive
edema and fluid retention
hepatotoxicirty
36
how is methotrexate excreted
urine
37
what is bevacizumab
inhibitor of angiogenesis
38
what are the taxane drugs
paclitaxel
| docetaxel
39
What are general delayed effects of chemotherapy
myelosuppression
| usully leukopenia and thronbocytopenia
40
what is etoposide
topoisomerase inhibitor
41
what drugs target M phase
microtubule poisons
42
if no TMPT is there genetically then
theres no way to clear purine synthesis
43
what does gemcitabine do
cytosine analogue, inhibits polymerase and chain terminator
44
what is the signature adverse effect of athracyclines
cardiotoxicity, fuction of cumulative dose
45
resistance to methotrexate causes what
decreased drug accumulation, amplified DHFR, altered DHFR
46
how is cis platin administered and cleared
IV, cleared in urine
47
what is the administration and half life of sirolimus
oral
| 60 years
48
what is tamoxifen
ER antagonist in breast
| ER agonist in edometrium
49
about what percentage of cancers can be cured using multi modality therapy?
50%
50
Antitumor antibiotics are produced by what
microbes
51
are alkylating agents cidal or static
static but work better in dividing cells
52
what are AEs of gefitinib
fever
| dyspnea
53
what does nivolumabd do
Human Mab against PD-1
54
adverse effects of anthracyclines
bone marrow suppression
GI
sever alopecia
55
how is gefitinib administered
orally
56
how is tamoxifen given
orally
57
what is sirolimus
inhibits mTORC1 downstream component of PI3K signaling pathway that drives proliferation
58
what makes imatinib and dasatinib so specific
it blocks Bcr Abl which is only in tumor cells
59
what are two current targets of immune checkpoint inhibitors
CTLA-4
| PD-1/Ligand
60
How is selective toxicity achieved?
1. unique target present on pathogen and not host
2. target structurally different in pathogen than host
3. target more essential in pathogen than in host
61
what cardiac effects do anthracyclines cause
arrhythmias, cardiomyopathy, CHF
62
what does dexrazoxane do
given with anthracyclines offers protection from free radicals causing cardiotoxicity
63
what are AEs of Nivolumab
rash, fatigue, dyspnea
64
what does cremophor do
helps taxanes efficacy, cause a lot of AEs
65
What are the two anthracycline antitumor antibiotics
Doxorubicine daunorubicin
66
how is mechlorethamine administered
IV only
67
What are the types of cell cycle non specific drugs
Alkylating agents
| Antitumor antibiotics
68
how are hydrocortisone and presdnisone administered
orally
69
how doe satezolimumab work
blocks interaction of PD-L1 with PD-1 promote T cell antitumor response
70
how do alkylating agents block access to DNA
crosslinking
71
what are general characteristics of tumor cells
1. excessive/inappropriate growth
2. diminished apoptosis
3. loss of differentiation
4. invasive
5. metastatic
72
does trastuzamab cross the blood brain barrier
no
73
how do antimetabolites work
enter normal met pathway and blocks that pathway
74
how does bevacizumab work
humanized Ab against VEGF-A
75
what does bevacizumab do
decreases vascularization and increases capillary permeability
76
what is a secondary malignancy
malignancy due to drug for cancer
77
Is toxicity to pathogen v host relative or absolute?
Relative
78
what drugs are S cell specific
antimetabolites
79
how do taxanes work
block progress through mitosis
80
what are adverse effects of alkylating agents
targets bone marrow, GI tract, spermatogenesiis
81
what is ipilimumab
human Mab against CTLA-4
82
what does gefitinib do
inhibits EGF-R TK
83
Cure requires what
"total kill"
84
what is bortezomib approved to treat
multiple myeloma mantle cell lymphoma
85
What norma cell populations have high proliferative potentila
Bone marrow
Epithelial cells
immune system
hair follicles
86
how is atezolimumab given
IV q21 days
87
what are AEs of vinblastin
nasea vomiting
bone marrow depression
alopecia
88
what do hydrocortisone and prednisone do
suppress proliferation of immune cells
89
how are antitumor antibiotics given
IV
90
what is trastuzumab used for
breast cancer
| monocllonal antibody agaisnt HER2neu oncogene product
91
what does cytarabine do
cytosine analogue, chain terminator
92
how does imatinab work
blocks grwoth factor signaling in chronic myelogenous leukemia
also blocks kit kinase in GI stromal tumors
93
what is the t1/2 of mechlorethamine
several minutes
94
what are AEs of interferon alpha
fever chills anorexia weakness
95
how is sterile hemorrhagic cystitis pervented
give lots of fluids and/or give Mensa
96
what are general acute adverse effects of chemotherapy and how is it treated
Nausea and vomiting treated with antiemetics
97
what are AEs of aromatase inhibitors
mild nausea, headaceh, fatigue, hot flushes
98
acute adverse effects of cis platin
severe nausea, vomiting
| renal toxicity
99
how many cancer cells is incompatible with like
10x12
100
how is trastuzumab administered and what are AEs
IV
hypersensitivity
cardiomyopathy
101
how are purine analogs cleared
TPMT chops methyl group and makes them not useful as dugs
102
what are AEs of bortezomib
thormbocyopenia
fatigue
peripheral neuropathy
103
What is hand and foot syndrome
neuropathy in hands and feet
104
what is folinic acid rescue
high dose given of methotrexate and then given folinic acid is supplied to save normal cells
105
what are antiemetics
5-HT3 antagonists
| Phenothiazines
106
how is vinca administered/excreted
IV, biliary
107
how are purine analogs administered
orally
108
what is cis platin
bifucntional platinating agent
109
what is hprt
enzyme that adds sugar back onto purine to make a nucleoside, only functional when drugs are in active form
110
what are adverse effects of sirolimus
rash
mucositis
anemia
fatigue
111
what are the cell cycle specific drug types
Antimetabolites
Topoisomerase inhibitors
microtubule poisons
112
which is more toxic pyrimidine or purine analogs
pyrimidine
113
what is the rule to preventing drug resistance
combination chemo
114
what drug has antifolate effects and what does that mean
Methotrexate, bone marrow and GI get affected
115
how do purine analogs work
block DNA and RNA synthesis
116
how does 6-TG work
incorporated into RNA and DNA altering fucntion
117
what are AEs of vincristine
less toxic to bone marrow, no nausea and vomiting
| peripheral neuropathy so used in limited duration
118
chronic use of methotrexate can cause what AE
hepatotoxicity
119
why can cyclophosphamide be given orally?
itself it isnt reactive it has to be metabolized to active form
120
what do the microtubule poisons like vinca do and when in the cell cycle
inhibit/reverse tubulin polymerization, disrupt mitotic spindles causing metaphase arrest
121
what is dasatinib
Bcr-Abl inhibitor
122
when is bleomycin active in the cell cycle
G2
123
how does methotrexate work
DHFR substrate and inhibitor
| Blocks production of DNA synthesis
124
all of the antitumor antibiotics are what except bleomycin
CCNS, bleomycin is CCS (G2)
125
what is cyclophosphamide
alkylating agent
126
resistance to purine analogs is caused by what
hprt activity, or increase in alkaline phosphatase
127
how is bevacizumab given and whats half life
IV, 4 weeks
128
what does cis platin do
its an alkylating agent that crosslinks DNA
129
which alkylating agent is relatively non toxic to bone
cis platin
130
how is ipilimumab given
IV usually q21 days x 4
131
how are purine analogs tolerated
well, bone marrow depression only at high doses
132
how does nivolumab work
blocks interaction with PD-1 ligands restore or maintain . T cell antitumor response
133
what are 2 uses of folinic acid in chemo drugs
1. methotrexate used for salvage therapy
| 2. 5-FU used to enhance drug efficacy
134
what are AEs of irinotecan
nausea vomiting diarrhea
| bone marrow suppression nausea dose limiting diarrhea
135
the most effective anticancer drugs do what
activate apoptosis
136
how does 6-MP work
inhibits AMP and GMP synthesis
137
when are CCNS agents most effective
rapidly cycling cells
138
what are adverse effects of bleomycin
hypersensitivity, cutaneous rxns
| pulmonary toxicity, fibrosis
139
concern for alkylating agents inducing second malignancy is inversely proportional to what
age
140
what are AEs of etoposide
nausea, vomiting, alopecia, bone marrow suppression
141
Are all chemo drugs toxic?
yes
142
what are taxanes
microtubule poisons
143
what proteins can export multiple classes of anticancer drugs out of the cell
P glycoprotein Pgp, MDR1
144
what does flutamide do
orally given used to block androgen receptors
145
What do alkylating agents do
covalently bind to/modify biological molecules
| DNA is the key target
146
what does bleomycin do
binds DNA, generates radicals
| causes strand breaks
147
how do antitumor antibiotics work
block access to/function of DNA or RNA
148
TPMT is polymorphic meaning
genotype is needed pre treatment
149
what does 5-FU do
inhibits thymidylate synthase, you can make DNA without thymidine so it causes a thymineless death
150
what are signature delayed adverse effects of chemo other than myelosuppression
GI effects
Alopecia
neuropathies
Hand and foot syndrome
151
how do doxorubicin and daunorubicin work
intercalate DNA and RNA
block topoisomerase II
Inhibit DNA and RNA synthesis and cause strand breaks
generate free radicals
152
If you give alkylating agents and a patients CBC remains normal what does that mean
dose is too low and something needs to be adjusted
153
why are anticancer drugs more effective in replication phase
theres less time to repair
154
what is atezolimumab
human Mab against PD-:1
155
whats the difference between alkylating agents and antitumor antibiotics
AAs interact with DNA and/or RNA but most do not alkylate
156
how are doxorubicin and daunorubicin metabolized
in the liver
157
what is primary resistance
tumor cells initially not sensitive to a given drug
158
alkylating agents must be
reactive, inherent or generated by metabolism
159
resistance mechanisms for alkylating agents
impermeable to drug, pump drug out
alternate targets
increased DNA repair
no apoptosis
160
what do CTLA-4 and PD-1 do
associated with T cell response to antigens
161
what does vinca come from
perriwinkle
162
when does etoposide work
arrests cells in S-G2 stage
163
what are anastrazole and letrozole used for
treatment for ER+ primary and metastatic breast cancer
164
how is methotrexate administered
orally, IV, intrathecally
165
how does irinotecan work
gest converted to SN-38 by esterase, inhibits topoisomerase I
166
what is total kill
must kill all cells with proliferative potential
167
how is cyclophosphamide administered/activated
oral or IV
168
how does ipilimumab work
blocks interaction with B7 enhancing T cell activation
169
what are AEs of ipilimumab
skin and GI tract
| immune inflammatory adverse effects
170
how does etoposide work
causes double strand breaks, DNA degradation
171
what is bleomycin
mixture of glycopeptides used as an antitumor antibiotic
172
what is irinotecan
a topoisomerase inhibitor
173
what are AEs of bevacizumab
risk of blood vessel injury and bleeding
hypertension proteinuria
arterial thromboembolic events
