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Chemo Exam 4 Pharm Flashcards

1
Q

What is Herceptin

A

It is a Her2 specific antibody for Tx of Breast Cancer

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2
Q

What occurs in the G phases of the Cell Cycle

A

RNA and Prot Synthesis

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3
Q

What occurs in the S phase of the Cell Cycle

A

DNA duplication

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4
Q

What are the Cycle-Specific Agents?

A
  1. Alkylating Agents 2. Cytotoxic Abx 3. Platinum Derivatives
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5
Q

What ist he MOA of Alkylating Agents?

A

They form covalent bonds w/ DNA that denature it and impee DNA transcription and translation

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6
Q

What base is the main molecular target of the Alkylating agents?

A

Guanine

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7
Q

What are the Nitrogen Mustards

A

Cyclophsophamide, Ifosfamide+mesna, Chlorambucil, Mechlorethamine

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8
Q

How do nitrogen mustards work?

A

They intercalate into double DNA strands and crosslink DNA

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9
Q

What is a contraindication of cyclophosphamide?

A

It is activated by CYP450 oxidases so it cannot be used in liver deficient pts

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10
Q

What is a major toxicity of cyclophosphamide and how can it be overcome?

A

Hemorrhagic cystites due to acrolein (metabolite), can help if drink lots of H2O to pee it off

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11
Q

What is Mechlorethamine used for?

A

Tx Hodgkin’s Disease

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12
Q

What alkylating agents can go through the BBB?

A

Nitroso-ureas

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13
Q

What is a major toxicity of Doxorubicine?

A

Cummulative cardiotoxicity leading to arrhythmias and HF

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14
Q

What is Cisplatin?

A

Water-soluble planar coordination complex w/ 2 Cl- and 2 NH3 groups

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15
Q

MOA of Cisplatin?

A

Interstrand and Intrastrand Cross-linking; Causes H-bond breaking b/w guanine and cytosine

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16
Q

What are good uses of Cisplatin?

A

Testicular and ovarian cancers

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17
Q

What are the S-Phase Specific Agents?

A
  1. Antimetabolites 2. Etoposide 3. Hydroxyurea
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18
Q

What is the MOA of S-phase Specific Agents?

A

Block metabolic PW involved in DNA Synthesis

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19
Q

What enzyme does Methotrexate Inhibit?

A

Dihydrofolate reductase and also Thymidylate synthase

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20
Q

What is MOA of 5-FU

A

Incorporated into mRNA and inhibits Thymidilate synthetase activity to inhibit DNA synthesis

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21
Q

What is the MOA of Etoposide?

A

Induces stable DNA double strand breaks by inhibiting topoisomerase II activity

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22
Q

What phase of the cell cycle does Etoposide inhibit?

A

S-G2 Transition

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23
Q

What is the MOA of M phase Specific Agents?

A

Poisons of the mitotic spindle

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24
Q

What are the M phase Specific Agents?

A
  1. Vinca alkaloids 2. Taxanes 3. Epothilones
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25
What 2 M-phase specific cmpds inhibit Microtubule growth and tubulin polymerization?
Vincristine and Vinblastine
26
What is an expected toxicity of Vincristine?
Peripheral Neurotoxicity
27
What is the MOA of Taxanes?
Stabilize MTs in their polymerized state
28
What are the 3 benefits of Epothilones over Taxanes?
1. Easier to synthetically modify 2. Poor substrate for P-glycoprotein 3. High affinity for beta-tubulin isoforms
29
What is the MOA of Arsenic Trioxide?
Induces degredation of PML-RARalpha in APML; and Downregulates Bcr-Abl in CML
30
What is the ending for the Tyr Kinase inhibitors?
Inib
31
What is the MOA of Rapamycin?
It inhibits the mTOR pw
32
What is Tamoxifen?
It is a selective estrogen receptor modulator
33
What is the MOA of Tamoxifen?
Competitive Estrogen Receptor Antagonist
34
What are the Most Common distressing early toxic effects of Chemo
Nausea and Vomiting
35
What is the major problem w/ chemotherapy?
Cell subpopulations can be compartmentalized into dividing cells, temporarily nondividing cells, and permanently nondividing cells
36
Define Cure
Absence of disease resurgence during normal life expectancy
37
What are some barriers to chemo?
1. Hypoxic Cells 2. Drug Resistance 3. Low growth fraction 4. Advanced Tumor 5. Immunoincompetence
38
What is the log kill hypothesis?
A given dose kills a constant proportion of cell population and not number of cells. This means can never get to zero with chemo alone
39
What can Alkylating agents do at high doses?
Kill cells in G0 phase; any drug that can kill in G0 will be highly toxic to bone marrow and immune system
40
What are the indications for Cyclophosphamide?
Broad spectrum
41
What is Mesna?
It is a sulfhydryl reagent w/ uroprotective effects
42
What is the drug of choice for Chronic lymphocytic leukemia?
Chlorambucil
43
What is the MOA of Nitroso-Ureas?
They breakdown to form alkylating and carbamoylating compounds that bind to lysine residues and inactivate DNA repair enzymes
44
What is the MOA of Doxorubicine
Stabilizeds Topoisomerase II so the DNA swivels and seizes up resulting in a DNA break
45
What is important about the dosing of the Cytotocix Abx?
They have cumulative toxicity so one must consider total toxic dose
46
What is the MOA of Bleomycin?
Metal chlating glycopeptide Abx that degrades DNA causing chain fragmentation and release of free bases
47
Where is Bleomycin most effective?
G2 and M phases but also can act in G0
48
What is the major toxicity w/ Bleomycin?
Pulmonary fibrosis (don't use in pts w/ pulmonary insufficiency)
49
What are the major toxicities of Cisplatin?
Nephrotoxic and GI distress
50
What drug has a dose schedule based on the circadian rhythm?
Oxaliplatin
51
How does methotrexate cause cell death?
It ultimately inhibits thymidylate synthesis
52
What is Capecitabine?
It is a prodrug for 5-FU and is converted to active by thymidine phosphorylase
53
What is the single agent in pts w/ breast cancer resistant to conventional therapy?
Capecitabine
54
What cells quickly localize vinca alkaloids?
WBCs and plts
55
What drug was 1 of the most important breakthroughs in chemo tx for breast cancer
Taxanes
56
What are the indications for using taxanes?
Breast and ovarian cancers
57
What is the most important toxicity of taxanes?
Peripheral neuropathy
58
When is DNA Methyl transferase inhibitors the first line of defense?
Pts. w/ AML who are not candidates for intesnsive chemotherapy
59
What are 2 problems w/ Tamoxifen?
Rapid resistance and Endometrial cancers
60
What is Raloxifene?
It is an aromatase inhibitor to block steroid synthesis
61
What is anastrozole?
It is an aromatase inhibitor to block steroid synthesis
62
What are 2 risks of aromatase inhibitors?
Inc. bone turnover and Ultimately resistance
63
What part of the brain mediates emesis?
The Chemoreceptor Trigger Zone of the medulla
64
How is promethazine used to tx emesis resulting from chemo?
It blocks dopamine receptors in the CTZ
65
What is the function of ondansetron and tropisetron?
They antagonize serotonin receptors in the CTZ
66
What is the major side effect of cycle nonspecific drugs?
Hematologic toxicity of the primitive pluripotent stem cell lines
67
What is radiation recall rxn?
When a drug causes an inflammatory rxn in tissue previously exposed to radiotherapy
68
What medication has mandatory premedication for all pts?
Taxol b/c need to prevent hypersensitivity rxns
69
What is a newer way to try to limit toxicity for specific organ?
Target specific tumors by formulating drugs combined w/ a liposomal carrier
70
What is the major reason for anticancer failure?
Chemoresistance
71
What is the primary goal of combination chemo?
Employ different modes of action to diminish resistance and high grade toxicity
72
How do antisense DNA cancer tx work?
The antisense DNA drug binds to the mRNA and prevents translation

Pharm Exam 4 (3 decks)

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