Anti-cancer drugs Flashcards
(97 cards)
1
Q
List three drugs that are anti-metabolites
A
- 5-FU:pyrimidine analog, FdUMP blocks thymadilate synthase, decreased DNA and RNA synthesis
- gemcitabine: pyrimidine analog, inhibits DNA polymerase and dFdCTP is incorporated into DNA and causes strand termination (toxicity not confined to S phase)
- methotrexate: folic acid analog, inhibits dihydrofolate reductase which is required for biosynthesis of purines- decreased DNA, RNA, protein synthesis
2
Q
List two drugs that are spindle poisons
A
- vincristine: disrupts microtubule assembly and mitotic spindle formation, causes arrest in M phase and inhibits cell division
- paclitaxel: promotes polymerization and assembly of microtubules, makes them highly stable and non-functional, causes arrest in M phase and inhibits cell division
3
Q
List two drugs that are topoisomerase inhibitors
A
- etoposide: forms complex with DNA and topoisomerase II, prevents re-ligation of double strand breaks- progression of cell cycle is stopped. Mainly active in S and G2
- irinotecan: binds to and stabilizes the DNA- topoisomerase I complex leading to accumulation of single strand breaks that ultimately lead to double strand breaks and cell death. S-phase specific
4
Q
List three general classes of drugs that are considered cell cycle specific
A
- antimetabolites (5-FU, gemcitabine, methotrexate)
- topoisomerase inhibitors (etoposide, irinotecan)
- spindle poisons (vincristine, paclitaxel)
5
Q
List 6 general classes of anti-cancer drugs
A
- DNA damaging drugs
- Anti-metabolites
- Anti-mitotics (spindle poisons)
- Topoisomerase inhibitors
- Hormonal agents
- Target specific agents
6
Q
List three categories of drugs that are considered DNA damaging drugs
A
- alkylating agents (cyclophosphamide, temozolomide)
- platinum compounds (carboplatin)
- anti-tumor antibiotics (bleomycin, doxorubicin)
7
Q
List the general effects of DNA damaging drugs
A
Cause DNA cross linking, abnormal base pairing, single or double strand breaks
8
Q
List three categories of drugs that are considered target specific drugs
A
- monoclonal antibodies (bevacizumab, cetuximab, rituximab, trastuzumab)
- mTOR inhibitors (temsirolimus)
- tyrosine kinase inhibitors (erlotinib, imatinib, sumitinab)
9
Q
List two alkylating agents
A
cyclophosphamide, temozolomide
10
Q
List two anti-tumor antibiotics
A
Bleomycin, doxorubicin
11
Q
List four monoclonal antibodies used to treat cancer
A
bevacizumab, cetuximab, retuximab, trastuzumab
12
Q
List three tyrosine kinase inhibitors
A
erlotinib, imatinib, sumitinib
13
Q
Cyclophosphamide is a _______ alkylating agent and can form DNA-DNA and DNA-DNA protein cross links, while temozolomide is a __________ alkylating agent that methylates guanine residues
A
Bifunctional; monofunctional
14
Q
The hemorrhagic cystitis seen in cyclophosphamide use is attributed to the formation of the ___________ metabolite
A
acrolein
15
Q
_________ is an alkylating agent that is often used to treat cancers in the brain because it has good _________ permeability
A
temozolomide, blood-brain barrier
16
Q
When a patient is being treated with cyclophosphamide, they should also receive ______ to help degrade the toxic ________ metabolite and reduce the risk of hemorrhagic cystitis
A
MESNA, acrolein
17
Q
Name the nitrogenous functional group responsible for the mechanism of action of alkylating agents
A
Nitrogen mustard
18
Q
Carboplatin functions when the _______ moiety is displaced by water molecules in the process of ________ to produce a highly reactive molecule that interacts with nucleophilic sites to form interstrand and intrastrand DNA cross links
A
oxylate; aquation
19
Q
Because a major side effect of carboplatin is severe nausea and vomiting, it is recommended to treat with ___________ drugs such as D2 antagonists, 5-HT3 antagonists, or cannabis
A
antiemetic agents
20
Q
______________ is the dose limiting toxicity in carboplatin use
A
myelosuppression
21
Q
Carboplatin causes (more/less) neurotoxicity, ototoxicity, and nephrotoxicity than cisplatin
A
LESS
22
Q
Bleomycin is a ______ agent and causes accumulation of cells in the ______ phase of the cell cycle
A
cell cycle specific; G2
23
Q
Mechanism of action of belomycin
A
Binds to DNA, generates oxygen free radicals from O2 to cause oxidative damage to the deoxyribose moieties of nucleotides; opens the deoxyribose ring resulting in single- and double-strand DNA breaks
24
Q
Dose limiting toxicity of bleomycin
A
Slowly progressing pulmonary toxicity
–> do ongoing pulmonary function tests during treatment
25
Drugs like carboplatin, bleomycin, etoposide are excreted by the _______ so dose should be decreased of ______ tests are below normal ranges
kidneys; CrCL
26
Bleomycin is dosed as a mixture of two ________- chelating peptides that is used in the treatment of various carcinomas (including testicular, head, neck, penis, cervix, vulva as well as Hodgkins and non-Hodgkins lymphoma)
copper
27
Bleomycin and doxorubicin are both anti-tumor _______
antibiotics
28
Doxorubicin is one of the most active single anticancer agents and is a standard component of therapy for many cancers. It has a three fold mechanism of action. Describe its three main anti-tumor effects
1. Intercalates between DNA base pairs, causing the helix to change shape, thereby inhibiting DNA and RNA polymerases
2. Stabilizes the DNA-topoisomerase II enzyme complex, inhibits topoisomerase II re-ligation activity, leading to double-strand DNA breaks and apoptosis
3. Forms superoxide anion and hydroxyl radicals that damage cell components; stimulated by Fe
29
Deficiency in this enzyme enhances 5-FU toxicity because it is the enzyme that degrades 5-FU in the liver, intestinal mucosa, and tumor cells
dihydropyrimidein dehydrogenase
30
5-FU is a ___________ analog that is metabolized to FdUMP which blocks _____________, the enzyme required for the conversion of dUMP to TMP
pyrimidine, thymidylate synthase
31
Addition of _______, a folic acid derivative, enhances the toxicity of 5-FU
leucovorin
32
5-FU is a CCS drug; its effects are limited to the ____ phase of the cell cycle
S phase
33
List the main effect of 5-FU
decreased DNA and RNA synthesis due to blockage of thymidylate synthase and incorporation of FdUTP into DNA/RNA
34
List some side effects that are UNIQUE to 5-FU
Derm: hand-foot syndrome
| ocular irritation and excessive lacrimation
35
Gemcitabine is a ________ analog that is metabolized to nucleotide analogs that inhibit __________
pyrimidine; DNA polymerase
36
List the main effect of Gemcitabine
dFdCTB is incorporated into DNA to cause strand termination and inhibits replication and repair of DNA, decreased DNA and RNA synthesis
37
Gemcitabine is a potent _________ and should not be used with radiotherapy except in certain clinical trials
radiosensitizer
38
Methotrexate is a ________ analog that is a high affinity active site inhibitor of ________, the enzyme required for biosynthesis of dTTP and purines
folic acid; dihydrofolate reductase
39
Methotrexate is also converted to MTX-polyglutamates which accumulate and inhibit ____________ as well as some other enzymes
thymidylate synthase
40
Methotrexate is eliminated primarily by renal excretion. Because excretion exceeds GFR, we can conclude that there is ______________ of methotrexate
active tubular secretion
41
Mention some UNIQUE side effects of methotrexate
Derm- toxic epidermal necrolysis, SJS, exfoliative dermatitis
42
Explain why NSAIDs may enhance methotrexate toxicity
NSAIDs appear to reduce tubular secretion of methotrexate- thus enhanced toxicity`
43
Vincristine binds to tubulin and __________ microtubule assembly and mitotic spindle formation, leading to inhibition of cell division. There is arrest in the ______ phase of the cell cycle
disrupts; M phase
44
__________ administration of vincristine is uniformly fatal
Intrathecal or cisternal
45
What is the dose-limiting adverse effect of vincristine?
Neurotoxicity- paresthesias distributed in stocking and glove formation, cranial nerve damage, paralysis, ANS dysfunction
46
Unlike many other chemotherapeutic agents,the adverse effect _________ reverses even without cessation of therapy
alopecia
47
Like vincristine, paclitaxel is a spindle poison. Explain how its mechanism of action is different from that of vincristine
Paclitaxel actually promotes polymerization and assembly of microtubules and works by making them highly stable and thus nonfunctional. Cell cycle arrests in M phase
48
What is responsible for hypersensitivity reactions seen with paclitaxel?
The vehicle it is administered in- 50% EtOH and 50% castor oil
49
Treatment with these drugs before starting paclitaxel can reduce the risk of hypersensitivity reaction
H1 antagonist (ex diphenhydramine), H2 antagonist (ex ranitidine) and a glucocorticoid
50
Doses of paclitaxel must be reduced if patients have dysfunction or metastasis to the ______
liver (metabolism by CYP2C8 and CYP3A4)
51
A major precaution for paclitaxel use is ____ abnormalities, which can be asymptomatic.
ECG abnormalities/ bradycardia.
52
Describe the mechanism of action of etoposide
Forms stable complex with DNA and prevents re-ligation of double-strand breaks induced by topoisomerase II; strand breaks accumulate and progression in the cell cycle is stopped; cell undergoes apoptosis
53
Etoposide is a CCS drug; it is mainly active in ________ phases
S and G2
54
Explain why hepatic function is closely associated with etoposide toxicity
etoposide is highly bound to serum albumin
55
What is the dose limiting toxicity of etoposide?
leukopenia
56
What cancers are treated with etoposide?
lung and testicular cancers, also lymphomas, nonlymphocytic leukemia, Kaposi sarcoma
57
Explain the mechanism of action of irinotecan
Binds to and stabilizes the normally transient DNA-topoisomerase I cleavable complex, leading to the accumulation of single-stranded DNA breaks; collision of a DNA replication fork with this opened strand of DNA causes an irreversible double-strand DNA break, ultimately leading to cell death
58
Irinotecan is active in what phase of the cell cycle?
S phase
59
Irinotecan is metabolized by CYPs that are induced by ___________ drugs, so people taking these drugs may have accelerated metabolism (decreased effect) of irinotecan
anti-seizure
60
Individuals homozygous for the UGT1A1*28 allele are at increased risk of _________ when taking irinotecan
Neutropenia
61
One side effect specific to irinotecan is ____________ caused by inhibition of AChE. This is usually short lived and does respond to atropine
cholinergic syndrome
62
Bevacizumab is a humanized monoclonal antibody that was the first anti-__________ agent to show efficacy in cancer patients
angiogenesis
63
Bevacizumab is an inhibitor of _________ by binding to its receptor and blocking receptor-ligand interaction
VEGF
64
Therapy with bevacizumab should be suspended when there is >2g of ________ per 24 hour collection period
proteinuria
65
This monocolonal antibody is a human- mouse fusion IgG directed against EGF receptor
cetuximab
66
This monocolonal antibody is a human-mouse fusion IgG directed against CD20, a B-lymphocyte antigen
rituximab
67
Rituximab is used mostly in treatment of refractory __________
B cell non-Hodgkin lymphoma
68
Rituximab binds to _____, a B lymphocyte antigen
CD20
69
Cetuximab binds to ________ to inhibit signaling
EGF-R
70
When _______ is administered, patients should be monitored for an hour after infusion to watch for signs of anaphylaxis
cetuximab
71
All patients receiving _______ should take diphenhydramine, acetaminophen, and corticosteroids as premedication prior to infusions
rituximab
72
Both rituximab and cetuximab can cause infusion reactions to mouse proteins, including what effects?
fever, chills, NV, hypotension, angioedema, bronchospasm
73
Trastuzumab is a fully humanized monoclonal antibody against _______
human epidermal growth factor receptor (Her2)
74
Trastuzumab is used specifically in treatment of what kind of cancers?
Her2+ breast cancer
75
Describe the mechanisms of trastuzumab
Binds to the external domain of HER2/neu tyrosine kinase receptor to prevent receptor activation by EGF; decreases downstream signals, metastatic potential, and promotes apoptosis
Induces antibody-dependent cellular toxicity
76
Because of potentially fatal CV side effects of trastuzumab, it is recommended that _______ be assessed prior to and throughout treatment
LVEF
77
Temsirolimus binds to ________ and the complex then binds to and inhibits _____. This inhibits progression from ___ to _____ phase of the cell cycle
FKBP; mTOR; G1 to S
78
Temsirolimus is used specifically to treat what kind of cancer?
advanced renal cancer
79
Metabolic effects occur very commonly in treatment with temsirolimus, including:
hyperlipidemia, hypertriglyceridemia, edema
80
Why are there often drug interactions in treatment with temsirolimus, erlotinib, imatinib, and sunitinib?
They are all metabolized by CYP3A4
81
Erlotinib is a tyrosine kinase inhibitor that specifically inhibits ___________
epidermal growth factor receptor
82
Erlotinib is used specifically in the treatment of
non-small cell lung cancer, pancreatic cancer
83
Describe the mechanism of action of erlotinib
Reversible inhibitor of EGFR; binds to ATP binding pocket in the receptor tyrosine kinase domain of the EGFR, prevents autophosphorylation of receptor following EGF binding and receptor dimerization
84
_________ is a tyrosine kinase inhibitor that specifically inhibits the epidermal growth factor receptor
Erlotinib
85
Imatinib is a tyrosine kinase inhibitor that specifically targets _____________ but does have action against other tyrosine receptor kinases
constitutively active BCR-Abl tyrosine kinase receptor created by the "Philadelphia" chromosome 9:22 translocation
86
_______ is a drug that targets the constituently active BCR-Abl tyrosine kinase receptor, which is created by the _________ chromosome translocation
Imatinib; Philadelphia
87
Imatinib should be taken with _________
food and water, to minimize GI effects
88
Sunitinib is a tyrosine kinase inhibitor that targets multiple tyrosine kinases including:
PDGF receptors, VEGF receptors, stem cell factor receptor and others which are involved in tumor growth and metastasis
89
The clinical response to sunitinib is decreased ...
angiogenesis, invasion, and metastasis
90
The clinical response to imatinib is decreased....
cell growth and proliferation
91
The MOPP regime consists of Mechlorethamine, Oncovin® (vincristine), Procarbazine, Prednisone and is standard therapy for _______
Hodgkins disease
92
The ABVD regime is composed of Adriamycin® (doxorubicin), Bleomycin, Vinblastine, Dacarbazine and is used in treatment of _______. It is effective as MOPP but with fewer secondary malignancies
Hodgkins disease
93
The COP regime consists of Cyclophosphamide, Oncovin® (vincristine), Prednisone and is standard treatment for
non-Hodgkins disease
94
The PEB regime consists of Platinol® (cisplatin), Etoposide, Bleomycin and is standard treatment for
testicular cancer
95
the CMF regime consists of Cyclophosphamide, Methotrexate, Fluorouracil, with or without tamoxifen and is standard treatment for
post-op breast cancer
96
Mutation in p53 leads to resistance to anti cancer therapy because there is decreased ________
apoptosis
97
How do cells become resistant to drug accumulation?
Increased efflux via P-glycoprotein (ABCB1)
