Cancer Pharmacology Flashcards

1
Q

Activation of oncogenes overrides what part of cell cycle?

Inactivation of tumor suppressor genes overrides?

A

1) G1 arrest

2) G2 arrest

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2
Q

What anticancer drugs have cell cycle effects on the S-phase?

A

1) Methotrexate
2) 5-fluorouracil
3) 6-mercaptopurine
4) Topotecan

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3
Q

What anticancer drugs have cell cycle effects on the S-G2 phase?

A

Etoposide

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4
Q

What anticancer drugs have cell cycle effects on the G2-M phase?

A

Bleomycin

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5
Q

What anticancer drugs have cell cycle effects on the M phase?

A

1) Paclitaxel
2) Vinblastine
3) Vincristine

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6
Q

What type of chemotherapy is done in order to reduce the size of the primary tumor before surgical resection?

A

Neoadjuvant chemo

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7
Q

What type of chemotherapy is done after surgical resection in order to prevent relapse?

A

Adjuvant chemo

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8
Q

What is growth fraction?

A

Ratio of proliferating cells to G0 cells

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9
Q

As a general rule, antineoplastic agents are more effective on cells with what type of growth fraction?

A

High growth fraction

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10
Q

Why can solid tumors be more difficult to treat with chemotherapeutic agents?

A

Because their growth fraction decreases over time

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11
Q

Antineoplastic therapy follows what order of kinetics?

What does this mean?

A

1) First-order kinetics

2) Given dose of drug destroys constant fraction of cells

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12
Q

Why do we use high-dose intermittent chemotherapy?

A

Allows recovery of normal, healthy tissues

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13
Q

Primary/inherent resistance to anti-cancer drugs in the natural products category can be due to high baseline expression of what?

A

p-Glycoprotein

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14
Q

What do bone marrow, GI tract, hair follicles, oral mucosa and sperm forming cells all have in common in terms of cancer therapy?

A

They are are the major sites of toxicity due to being rapidly proliferating tissues (tissues with high growth fractions)

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15
Q

What pharmacologic agents help decrease adverse effects such as neutropenia, thrombocytopenia, and anemia?

What is used to decrease emetogenic effects?

What is used to delay skeletal complications?

A

1) Hematopoietic agents
2) Serotonin receptor antagonist (ondansetron)
3) Bisphosphonates

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16
Q

What nitrogen mustard is the most widely used alkylating agent and one of the most emetogenic agents?

A

Cyclophosphamide

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17
Q

What is the MOA for alkylating agents?

A

Form covalent linkages with DNA

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18
Q

Because Cyclophosphamide is a pro-drug, what must activate it?

A

CYP2B

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19
Q

What is an adverse effect of cyclophosphamide?

What metabolite of CP causes it?

What can be given to inactivate the metabolite and is used for prophylaxis?

A

1) Hemorrhagic cystitis
2) Acrolein
3) Mesna

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20
Q

What are adverse effects of Cisplatin?

A

1) Renal tubular damage

2) Ototoxicity

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21
Q

What are the adverse effects of Busulfan?

A

Pulmonary fibrosis

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22
Q

Antimetabolites block or subvert pathways that are involved in, or lead to?

A

Cell replication (nucleotide and nucleic acid synthesis)

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23
Q

What is the MOA for methotrexate?

A

It inhibits dihydrofolate reductase and leads to reduction in dTMP

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24
Q

Methotrexate is an analog to what compound?

A

Folic acid

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25
Administration of what drug is used in conjunction with high-dose methotrexate therapy to rescue normal cells? (also antidote for accidental drug overdose)
Leucovorin
26
Fluorouracil (5-FU) is a structural analog to what compound?
Pyrimidine
27
What is the MOA of fluorouracil?
Active compound FdUMP covalently binds thymidylate synthetase and blocks de novo synthesis of thymidylate
28
Mercaptopurine (6-MP) is activated into monophosphate nucleotide 6-thioinosinic acid by what enzyme?
HGPRT
29
Allopurinol, a xanthine oxidase inhibitor, is often used as supportive care in the treatment of acute leukemias to prevent?
Hyperuricemia due to tumor cell lysis
30
Simultaneous administration PO 6-MP with what other drug results in increased levels of 6-MP and increased toxicity?
Allopurinol
31
What is the MOA for the vinca alkaloids, vinblastine and vincristine?
Bind to β-tubulin and inhibit microtubule assembly (depolarization)
32
What are common adverse effects of vinblastine and vincristine?
Alopecia and bone marrow depression
33
Which vinca alkaloids causes myelosuppression to a greater extent?
Vinblastine
34
Which vinca alkaloids causes cumulative neurological toxicities to a greater extent?
Vincristine
35
What is the MOA for taxanes such as paclitaxel?
Bind to β-tubulin and stabilize microtubule formation
36
What are common adverse effects of paclitaxel?
1) Hypersensitivity reactions in hands and toes | 2) Change in taste
37
Paclitaxel and taxanes have been the traditional treatment for?
Breast cancer
38
What is the MOA for topotecan?
Inhibit topoisomerase I which causes DNA damage and leads to cell death
39
What is the MOA for etoposide and doxorubicin?
Inhibit topoisomerase II
40
All of the anticancer antibiotics currently in use are products of various strains of what soil microbe?
Streptomyces
41
What are adverse effects of doxorubicin?
Produce free radicals that cause cardiotoxicity which can lead to dysrhythmias and heart failure
42
What is the MOA of Bleomycin?
Induces single- and double-stranded DNA breaks
43
What are adverse effects of Bleomycin?
Can cause significant pulmonary toxicity and usually presents as pneumonitis with cough, dyspnea, dry inspiratory crackles
44
Asparaginase is used in targeted therapy for?
Acute lymphoblastic leukemia (ALL)
45
What is the MOA for asparaginase?
Hydrolyzes circulating L-asparagine into aspartic acid and ammonia, effectively inhibiting protein synthesis
46
Asparaginase is cell cycle specific to what phase?
G1
47
When mutated, overexpressed, or structurally altered, tyrosine kinases can become potent?
Oncoproteins
48
What drug is used to treat Chronic myelogenous leukemia? What is its MOA?
1) Imatinib | 2) Inhibits ABL tyrosine kinase
49
What is a recombinant fusion protein made up of portions of the extracellular domains of human VEGF receptors (VEGFR) 1 and 2 fused to the Fc portion of the human IgG1 molecule?
Ziv-aflibercept
50
What is the MOA of Ziv-aflibercept?
Inhibition of VEGFR signaling by binding VEGF ligands
51
What inhibits cellular growth, alters the state of cellular differentiation, interferes with oncogene expression, alters cell surface antigen expression, increases phagocytic activity of macrophages, and augments cytotoxicity of lymphocytes for target cells?
Interferon-α2a and -α2b
52
What increases cytotoxic killing by T cells and NK cells?
IL-2
53
What is the major toxicity of IL-2?
Capillary leak syndrome
54
What is the treatment for Non-Hodgkins lymphoma?
Rituximab
55
What is the MOA of rituximab?
Rituximab binds to the CD20 antigen which leads to selective killing of B-cells
56
Dacarbazine and cisplatin are the most active cytotoxic agents used to treat?
Malignant melanoma
57
Drugs that end in -nib act where specifically? Drugs that end in -mabs act where specifically?
1) Intracellular | 2) Extracellular
58
Mucositis is an adverse effect of what drug?
Methotrexate
59
Pulmonary fibrosis is an adverse effect of what drugs?
Bleomycin and busulfan
60
Peripheral neuropathy is an adverse effect of what drug?
Vincristine
61
Ototoxicity is an adverse effect of what drug?
Cisplatin
62
Cardiotoxicity is an adverse effect of what drug?
Doxorubicin
63
Nephrotoxicity is an adverse effect of what drugs?
Cisplatin and cyclophosphamide
64
Hemorrhagic cystitis is an adverse effect of what drugs?
Cyclophosphamide and ifosfamide
65
What is used to treat APML?
Tretinoin
66
What are common adverse effects of tretinoin?
Vitamin A toxicity and retinoic acid syndrome
67
Erlotinib and gefitinib both inhibit the activity of?
EGFR