Antineoplastics Flashcards
1
Q
During what phase of the cell cycle are antimetabolites most effective?
A
S-phase
2
Q
What event can increase the resistance to methotrexate?
A
gene duplications of DHFR
decreased affinity of DHFR for methotrexate
3
Q
What drug is a prodrug 5FU? Why is this drug used?
A
capectibane
increased oral availability
4
Q
What enzyme ACTIVATES cytarabine?
A
Deoxycytidine Kinase
5
Q
What enzyme does cytarabine inhibit?
A
DNA polymerase
6
Q
What cancer is most commonly treated with cytarabine?
A
AML
7
Q
What enzyme does ara-C inhibit?
A
DNA polymerase
8
Q
What drug causes cerebellar syndrome? Why?
A
cytarabine
cytadine deaminase levels are low in CNS
9
Q
What enzyme inactivates cytarabine?
A
cytidine deaminase
10
Q
What are the two enzymatic mechanisms by which resistance to cytarabine develops?
A
loss of deoxycytidine kinase
increase cytidine deaminase
11
Q
What is gemcitabine an analogue of?
A
Difluorodeoxycytidine
12
Q
What enzyme activates gemcitabine?
A
Deoxycytidine Kinase
13
Q
What enzyme does deoxycytidine kinase inactivate?
A
Ribonucleotide Reductase
14
Q
What are the two mechanisms by which tumor cells can increase resistance to gemcitabine?
A
decreased expression of deoxycytidine kinase
increase expression of deoxycytidine
15
Q
What enzyme activates 6-MP and 6-TG?
A
HGPRTase
16
Q
What is 6-MP converted to?
A
thio-IMP
17
Q
What is 6-TG converted to?
A
thio-GMP
18
Q
What can thio-IMP be converted into?
A
thio-GMP
19
Q
What two products does IMP get converted into?
A
AMP and GMP
20
Q
What can thio-GMP be converted into?
A
thio-dGTP
21
Q
What is the main side effect of 6-MP and 6-TG?
A
myelosuppression
22
Q
How do cells become resistant to 6-MP and 6-TG?
A
mutations in HGPRTase
23
Q
Is fludarabine a purine or pyrimidine analogue?
A
purine
24
Q
What enzyme activates fludarabine?
A
Deoxycytidine kinase
25
What two enzymes does fludarabine inhibit?
DNA polymerase and RNR
26
What cancer is most often treated with fludarabine?
CLL
27
What is the mechanism by which fludarabine resistance can develop?
decreased activity of deoxycytidine kinase
28
Is cladribine a purine or pyrimidine analogue?
purine
29
What enzyme activates cladrabine?
deoxycytidine kinase
30
What enzyme is inhibited by cladrabine ?
RNR
31
What disease is most often treated with cladrabine?
hairy cell leukemia
32
What are the two mechanisms by which a cell can become resistance to cladribine?
decreased activity of deoxycytidine kinase
increased expression of RNR
33
What is the most common site for alkylating agents to function?
Guanine N7
34
What disease often presents after treatment with an alkylating agent?
leukemia
35
What type of drug is Mechlorethamine?
alkylating agent
36
What type of drug is cyclophosphamide?
alkylating agent
37
What is the main side effect of cyclophosphamide?
hemorrhagic cystitis
38
What drug is used to treat the side effects of cyclophosphamide? What is the MOA of this drug?
Mesna
scavenges acroleid
39
What is the MOA of carmustine? What type of drug family does carmustine fall into?
alkylating agent
nitrosurea
40
What type of cancer is most often treated with carmustine?
brain tumors
41
What are the three non-classical alkylating agents ?
carboplatin
cisplatin
oxaliplatin
42
What are the three main adverse effects of cisplatin?
nephrotoxicity
peripheral neuropathy
ototoxicity
43
What is the main difference between cisplatin and carboplatin?
carboplatin does not cause nephrotoxicity or neuropathy
44
What is used to mitigate the deleterious effects of cisplatin?
co-administration with IV saline
45
What is the MOA of vinblastine?
prevents formation of microtubules
46
What is the MOA of vincristine?
prevents formation of microtubules
47
What is the main side effect of cytarabine?
pancytopenia
48
What is the main side effect of Carboplatin?
myelosuppression
49
What is the main side effect of vinblastine?
myelosuppression (BLASTs bone marrow)
50
What is the main side effect of vincristine?
neurotoxicity
51
What subunit of microtubules does paclitaxel bind? What does this prevent?
β-tubulin
disassembly of microtubules
52
What are the two main side effects of paclitaxel?
PERIPHERAL NEUROPATHY and myelosuppression
53
What drug is used to ameliorate the myelosuppressive side effects of paclitaxel? What is the MOA of this drug?
Filgrastim
acts as G-CSF
54
What drug has the identical MOA of paclitaxel?
Docetaxel
55
Paclitaxel and docetaxel requires the pretreatment with what two drugs? Why?
Dexamethosone or anti-histamine
prevent hypersensitivity
56
Topoisomerase I is inhibited by what two drugs? What phase of the cell cycle do these two drugs work?
irinotecan and topotecan
S-phase
57
What enzyme does etoposide inhibit?
topoisomerase II
58
What are the three MOAs of doxorubicin?
intercalates DNA
inhibit DNA polymerase
inhibits topoisomerase II
59
What is the main adverse effect of doxorubicin?
cardiomyopathy
60
What drug functions similar to doxorubicin but has a lower liklihood of developing cardiomyopathy?
Epirubicin
61
Iron and copper can be chelated by what drug?
Bleomycin
62
What is the MOA of bleomycin?
causes single and double stranded DNA breaks
63
What is the main side effect of bleomycin?
pulmonary fibrosis
64
What type of cancer would prednisone be useful for? Why?
lymphocytic leukemias
causes apoptosis of lymphocytes
65
What cancer is dexamethasone used to treat?
multiple myeloma
66
Other than endometrial issues, what can tamoxifen cause?
thromboembolism
67
How does a cell develop a resistance to tamoxifen?
decreased affintity for the estrogen receptor
68
What is the MOA of anastrazole? What patient group?
aromatase inhibitor
post-menopausal women
69
What specific type of cancer is anastrazole used to treat?
estrogen sensitive breast cancer
70
What two drugs are androgen receptor antagonists?
Flutamide and bicalutamide
71
What specific type of cancer are flutamide and bicalutamide used to treat?
prostate
72
What two drugs affect GnRH release? Are they agonists or antagonists?
Leuprolide and Goserelin
Agonists
73
Leuprolide and Goserelin are used to decrease the secretion of what? How do they do this?
LH and FSH
desensitizing GnRH receptors
74
What is the GnRH antagonist?
Degarelix
75
What is another name for trastuzumab?
Herceptin
76
What family does HER2/Neu belong?
EGFR
77
What is the main side effect of trastuzumab?
cardiotoxicity
78
What type of antibody is Cetuximab? What does Cetuximab target? What cancer?
monoclonal
EGFR
colorectal
79
How does resistance to cetuximab develop?
mutations in Ras signaling
80
What three proteins can imatinib inhibit?
BCR-ABL
c-Kit
PDGF
81
How does resistance against imatinib develop?
point mutations in ABL
82
What receptor is inhibited by Erlotinib? What is the MOA of erlotinib?
EGFR inhibitor
prevent ATP from binding
83
What rxn does asparaginase catalyze?
asparagine into aspartate
84
What cancer is most often treated with asparaginase?
ALL
85
What is the primary side effect of asparaginase?
allergic rxn
86
What is the MOA of bortezomib? The txn of what gene can be inhibited by Bortezomib?
inhibitor of proteasome
NFKB
87
What is the mechanism by which bortezomib can inhibit neoplasia?
inhibition of apoptosis during hypoxic conditions
88
What specific important protein can Bortezemib inhibit the activity of ?
p53
89
What is the most common side effect of bortezemib?
peripheral neuropathy
90
Temsirolimus is an analogue of what drug? What complex is inhibited? What does this lead to?
rapamycin
mTOR
apoptosis
91
What cancer is temsirolimus currently in approval for treatment of?
renal cell carcinoma
92
What are the two specific toxicities of methotrexate?
interstitial pneumonitis
nephrotoxic
93
Cytarabine is an incredibly important drug in treating what cancer?
AML
94
When cell cycle phase is cytarabine most effective ?
S-phase
95
What is the primary mode of resistance in AML?
loss of deoxycytidine kinase activity
96
What enzyme does gemcitabine inhibit?
ribonucleotide reductase
97
What is the main treatment of ALL?
6-MU/Azathioprine
98
What organ is acrolein most toxic to?
bladder
99
What is the important functional group of mesna?
sulfhydryl
100
What molecule can a cell produce in order to increase resistance to an alkylating agent?
glutathione
101
What enzyme can cells increase to provide resistance against alkylting agents? What is the MOA of this enzyme?
MGMT
quickly removes alkyl group from DNA
102
What transporter is used to get platinum containing drugs into the cell?
copper transporter
103
What is a shared toxicity between cisplatin and carboplatin?
anaphylaxis reactions
104
What cancer is procarbazine used to treat?
Hodgkin's lymphoma
105
What three cancers can dacarbazine treat?
HL, Melanoma, Sarcoma
106
What two cancers can temozolomide treat?
gliablastoma and metastatic melanoma
107
What drug is often co-administered with doxorubicin? What is the MOA of this drug?
Dexrazoxane
to chelate iron
108
What cell cycle phase is interrupted by bleomycin?
G2
109
What is a notable characteristic about bleomycin concerning its administration with other drugs?
minimally myelosuppressive
110
What family of drugs are used to reduce intracranial pressure?
glucocorticoids
111
What is the most common side effect of bevacizumab?
hypertension
112
Which two receptors does Lapatinib inhibit? What is the MOA of this drug?
EGFR and HER-2
inhibits tyrosine kinase activity of HER2 and EGFR
113
Does imatinib inhibit BCR or ABL? By what mechanism?
ABL
competitive inhibitor of ABL ATP binding site
114
What cancer is asparaginase used to treat? Why?
ALL
tumor cells cant produce enough asparagine
115
What cancer is bortezemib used to treat?
refractory multiple myeloma
116
What drug is used in combat the negative effects of methotrexate? What is the MOA of this drug?
Leucovorin
folinic acid
117
Methotrexate causes can kill which two types of cell?
bone marrow and intestinal epithelial
118
How does hemorrhagic cystitis manifest?
blood in urine
119
What is the most severe side effect of carmustine?
myelosuppression
120
What three reasons is carbiplatin used in the place of cisplatin?
decrease ototoxicity
decreased nephropathy
decreased peripheral neuropathy
121
What drug is used to mitigate the effects of paclitaxel? Why?
filgastrim
acts as GCSF
122
What is another side effect of paclitaxel, other than myelosuppression and peripheral neuropathy?
Hypersensitivity rxn
123
What are the two main side effects of irinotecan and topotecan?
myelosuppression and diarrhea
124
Which antineoplastic can chelate iron and copper ?
bleomycin
125
What is the MOA for how Degarelix is used to treat prostate cancer?
decreases FSH and LH secretion from anterior pituitary
126
What drug is trastuzumab often used in combination with?
paclitaxel
127
What type of symptoms do all monoclonal therapies produce?
B-cell symptoms
128
What is the common side effect of avastin?
HTN
129
Which component of BCR-ABL fusion has the kinase activity?
ABL
130
How do cells develop resistance against imatinib?
point mutations in ABL
131
Erlotinib is used to treat which type of cancer?
metastatic non-small cell lung carcinoma
132
Bortezomib is used to treat what cancer?
multiple myeloma
133
Does methotrexate inhibit DNA or RNA or synthesis of both?
both
134
Does methotrexate inhibit purine or pyrimidie or synthesis of both?
both
135
What drug is methotrexate often used in combination with?
Dactinomycin
136
What enzyme does 5-FU inhibit?
thymidylate synthase
137
What is 5-FU metabolized into?
FdUMP
138
Does 5-FU cause damage to DNA or RNA or both?
both
139
Which phase of the cell cycle is cytarabine effective in?
S-phase
140
What is 6-MP converted into?
thio-IMP
141
What is 6-TG converted into?
thio-GMP
142
Thiopurine methyltransferase selectively inhibits which anti-neoplastic? What is the severe effect in individuals who have mutations in this enzyme?
6-MP
life-threatening bone marrow suppression
143
Does thio-IMP inhibit the synthesis or salvage or both of purines?
both
144
During what cell cycles are alkylating agents cytotoxic?
all cell cycles
145
What is the main side effect of all alkylating agents?
myelosuppression
146
What are the two mechanisms of resistance for all alkylating agents?
glutathione
MGMT (methylguanosine-methyl transferase)
147
What nucleophile do non-classical alkylating agents target?
Guanine N7
148
How do non-classical alkylating agents get into the cell?
copper transporter
149
What electrolyte can cisplatin disturb?
magnesium
150
Which two alkylating agent can cause hypersensitivity rxns?
Cisplatin and carboplatin
151
What cancer is treated with procarbazine?
HL
152
What two cancers are treated with dacarbazine?
melanoma and sarcoma
153
What cell cycle phase does paclitaxel arrest cells in?
mitosis
154
Lapitinib is a monoclonal antibody against which two receptors? Which cancer is lapitinab used to treat?
EGFR and HER2
refractory breast
155
What are the two mechanisms by which a cancer may develop resistance to erlotinib?
mutation in EGFR
amplification of MET oncogene
156
Tamoxifen can increase the risk for what cancer?
endometrial
157
Flutamide and bicalutamide prevent what agonist from binding the androgen receptor?
dihydrotestosterone
158
Which anti-neoplastics can cause blister and damage veins?
alkylating agents
159
What is the main use of bevucizimab?
colorectal cancer
