Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Heme/Lymph - Exam 1 > Intro to Antineoplastic Agents - SRS > Flashcards

Intro to Antineoplastic Agents - SRS Flashcards

1
Q

What are the three super categories of classic antineoplastic drugs?

A
  1. Alkylating Agents
  2. Natural Products
  3. Antimetabolites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 6 subcategories of alkylating agents?

A
  1. Nitrogen Mustards
  2. Methylhydrazine derivative
  3. Alkyl sulfonate
  4. Nitrosoureas
  5. Triazenes
  6. Platinum Coordination complexes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 6 sub categories of natural product antineoplastics?

A
  1. Vinca alkaloids
  2. Taxanes
  3. Epipodophyllotoxins
  4. Camptothecins
  5. Antibiotics
  6. Enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the three subcategories of antimetabolite antineoplastic drugs?

A
  1. Folic acid analogues
  2. pyrimidine analogs
  3. purine analogs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the nitrogen mustard antineoplastics on our drug list?

5 with 2 BOLD

A
  1. •Chlorambucil
  2. •Cyclophosphamide
  3. •Ifosfamide
  4. •Mechlorethamine
  5. •Melphalan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the one (non-nbold) methlhydrazine derivative on the drug list?

A

Procarbazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the alkyl sulfonate antineoplastic drug that is on our drug list?

1 BOLD

A

Busulfan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the three nitrosoureas on our drug list?

None bold

A
  1. •Bendamustine
  2. •Carmustine
  3. •Streptozocin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the two (non-bold) triazenes?

A
  1. •Dacarbazine
  2. •Temozolomide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the three platinum coordination complexes on our drug list?

(ONE BOLD)

A
  1. •Carboplatin
  2. •Cisplatin
  3. •Oxaliplatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the three vinca alkaloids on the drug list? (2 bold)

A
  1. •Vinblastine
  2. •Vincristine
  3. •Vinorelbine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two taxanes? (one bold)

A
  1. •Docetaxel
  2. •Paclitaxel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the two Epipodophyllotoxins on our drug list?

A
  1. •Etoposide
  2. •Teniposide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the two camptothecins on our list? (no bold)

A
  1. •Irinotecan
  2. •Topotecan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the seven antibiotics for neoplasms on our drug list?

(Two BOLD)

A
  1. •Bleomycin
  2. •Dactinomycin (actinomycin D)
  3. •Daunorubicin
  4. •Doxorubicin
  5. •Mitomycin C
  6. •Mitoxantrone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the two enzyme drugs on our list? (one bold)

A
  1. •L-Asparaginase
  2. •Pegaspargase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the two folic acid analogs? (one bold)

A
  1. Methotrexate (MTX)
  2. Pemetrexed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the 6 pyrimidine analogs on our list? (one BOLD)

A
  1. 5-aza-cytidine
  2. Capecitabine
  3. Cytarabine (cytosine arabinoside)
  4. Deoxy-5-aza-cytidine
  5. Fluorouracil (5-fluorouracil; 5-FU)
  6. Gemcitabine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 5 purine analogs? (one bold)

A
  1. Clofarabine
  2. Fludarabine
  3. Mercaptopurine (6-MP)
  4. Nelarabine
  5. Pentostatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is “primary induction therapy”?

A
  • The main treatment that provides the best possible outcome
  • Also called first-line therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is neoadjuvant therapy?

Give an example

A
  • Treatment given BEFORE primary induction therapy in order to improve outcome
  • E.g., Chemo or radiation to shrink a tumor before surgery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is adjuvant therapy?

A

•Additional therapy given CONCOMITANTLY or AFTER primary induction therapy in order to reduce the probability of relapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What occurs in G1?

A

Synthesis of components needed for DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What occurs in S phase?

A

Synthesis of DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What occurs in G2?

A

Synthesis of components needed for mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens in M phase?

A

Mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What happens in G0?

A

Resting phase of cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Where are the four cell cycle checkpoints?

A
  1. G1 to S
  2. End of S
  3. G2 to M
  4. End of M
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Why is the cell cycle stuff important for this topic?

A

Many antineoplastics are either cell cycle specific or cell cycle non-specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the 7 categories of drugs that are cell cycle specific?

A
  1. Antimetabolites
  2. Antitumor antibiotic - Bleomycin
  3. Taxanes
  4. Vinca alkaloids
  5. topoisomerase I inhibitors
  6. Topoisomerase II inhibitors
  7. enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What phase of the cell cycle do antimetabolits work on?

A

S phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What phase of the cell cycle does bleomycin work on?

A

S-G2 phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What cell cycle phase do taxanes work on?

A

M phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What cell cycle phase do vinca alkaloids work on?

A

M phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What phase do topoisomerase I inhibitors work on?

A

S-G2 phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What cell cycle phase do Topoisomerase II inhibitors work on?

A

S-G2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the 4 categories of cell cycle nonspecific agents?

A
  1. Alkylating agents
  2. anthracyclines
  3. antitumor antibiotics (except bleomycin)
  4. platinum analogs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is “growth fraction”?

A

Ratio of proliferating cells to resting cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is growth fraction a determinant of?

A

Responsiveness to chemotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are 4 examples of cells with high growth fractions?

A
  1. •Bone marrow
  2. •GI tract
  3. •Hair follicles
  4. •Sperm-forming cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the smallest detectible tumor mass and cell count?

A

1 gram

One billion cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

How does Burkitt lymphoma respond to chemotherapy?

A

Burkitt lymphoma is an example of a high growth fraction neaplasm, and is thus cureable by chemotherapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

How does colorectal carcinoma, a low growth fraction neoplasm, respond to chemotherapy?

A

Poorly, as is typical of low growth fraction neoplasms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

How can the growth fraction of solid tumors be increaseD?

A

Reduction of the tumor burden by surgery or radiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What percent of cells does a three-log kill eliminate?

A

99.9%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Efficacy vs toxicity must be carefully considered in antineoplastic therapy. What are five example of factors to consider?

A
  • Renal and hepatic function
  • Bone marrow reserve
  • General performance status
  • Concurrent medical problems
  • Patient willingness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Describe what is meant by “primary resistance”.

What is this thought to be due to?

A
  • An absence of response on the first drug exposure
  • Thought to be due to genomic instability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Acquired resistance develops in response to exposure to a given antineoplastic agent. Often highly specific to a single drug, or class of drugs, and is usually due to an increased expression of one or more genes

What are four examples of single agent resistance pathways?

A
  1. •decreased drug transport into cells
  2. •reduced drug affinity due to mutations or alterations of the drug target
  3. •increased expression of an enzyme that causes drug inactivation
  4. •increased expression of DNA repair enzymes for drugs that damage DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the important example of a method by which multidrug resistance occurs?

What gene is associated with this?

A

•The P-glycoprotein is an ATP-dependent efflux pump that actively pumps antineoplastic agents out of cells

-(MDR1 gene)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What are five drugs that are especially prone to ATP-dependent transport resistance?

A
  1. anthracyclines
  2. vinca alkaloids
  3. etoposide
  4. paclitaxel
  5. dactinomycin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the major limiting factor in tx of cancer with chemo?

A

Lack of specificity, hits cells we would prefer they not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What are the major tissue sites of chemo toxicity?

Give examples

A
  • Rapidly proliferating normal tissues (tissues with high growth fractions) are the major sites of toxicity
  • bone marrow, gastrointestinal tract, hair follicles, buccal mucosa, sperm forming cells
53
Q

Many antineoplastics are themselves mutagenic and can give rise to secondary neoplasms years after therapy. What is an example of this?

A

Alkylating agents have been shown to cause AML and ALL

54
Q

What are five common adverse effects that occur during therapy with nearly all classic antineoplastic agents?

A
  • Vomiting
  • Fatigue
  • Stomatitis
  • Alopecia
  • Nausea
55
Q

What are three other common adverse effects of the classic antineoplastic agents?

A
  • Myelosuppression – can lead to impaired wound healing and predisposition to infection
  • Low sperm counts and azoospermia
  • Depressed development of children exposed to antineoplastic agents
56
Q

In chemotherapy it is important to take steps that limit adverse effects. One way to do this by selecting a route of administration that limits toxicity.

What are some pharmacological agents for reducing toxicity?

Oh, also have the patient rest and recover.

A
  • Hematopoietic agents for neutropenia, thrombocytopenia, and anemia
  • Serotonin receptor antagonist (ondansetron) and other drugs for emetogenic effects
  • Bisphosphonates to delay skeletal complications
57
Q

Which nitrogen mustard is the most widely used alkylatin agent and one of the most emetogenic agents?

A

Cyclophosphamide

58
Q

What is the MOA for alkylating agents?

A

Form covalent linkages with DNA

59
Q

Cyclophosphamide is a prodrug that is degraded to 4-hydroxycyclophosphamide and aldophosphamide. Aldophosphamide is further degraded to a toxic metabolite.

What is this metabolite and what is it known for causing?

A

•Acrolein: causes hemorrhagic cystitis

60
Q

What is used as prophylaxis for the acrolein induced cystitis?

A

Mesna - inactivates acrolein

61
Q

Systemic toxicities d/t alkylating agents are dose related. What can happen at the site of injection?

A

Direct vesicant effects and tissue damage. (Oral admin is the ticket)

62
Q

Many alkylating agents produce acute toxicity, such as nausea and vomiting within 30-60 minutes. This can be pretreated with serotonin antagonists.

What are some examples of delayed toxicities from alkylating agents.

A
  1. bone marrow suppression with leukopenia
  2. thrombocytopenia
  3. nephrotoxicity
  4. alopecia
  5. mucosal ulceration
  6. intestinal denudation
63
Q

What is one specific delayed toxicity for cyclophosphamide?

A

Hemorrhagic cystitis

64
Q

What are two delayed toxicities specific to cisplatin?

A

renal tubular damage

ototoxicity

65
Q

What is a specific delayed toxicity associated with busulfan?

A

Pulmonary Fibrosis

66
Q

What are the three major types of antimetabolites? What is one bolded drug from each category?

A

1.Folic acid analogs (methotrexate)

2.Pyrimidine analogs (5-Fluorouracil)

3.Purine analogs (6-mercaptopurine)

67
Q

What is the MOA for the antimetabolites?

A

Structural analogs to compounds necessary for cell proliferation that block or subvert pathways that are involved in or lead to cell replication.

68
Q

So, based on their MOA, what part of the cell cycle do the antimetabolites work at?

A

S

69
Q

What is the specific MOA of methotrexate?

A

Inhibits dihydrofolate reductase (DHFR)

70
Q

What are three indications for use of methotrexate?

Describe the dosing as high or low for each.

A
  • Cancer - High dose
  • Rheumatoid arthritis - Low dose
  • Psoriasis - Low dose
71
Q

In the event of an accidentaly methotrexate overdose, how would you treat the patient?

A

Leucovorin - allows reduced folate to bypass the DHFR

72
Q

What is the prototype pyrimidine structural analog?

A

5-Fluorouracil

73
Q

5-FU is a prodrug, what are the active components, and what do they do? 3

A
  1. FdUMP - covalently binds thymidylate synthetase and blocks de novo synthesis of thymidylate.
  2. FdUTP - incorporated into DNA
  3. FUTP - incorporated into RNA
74
Q

What is the purine structural analog?

A

•6-Mercaptopurine (6-MP)

75
Q

What are the MOA of 6-Mercaptopurine (6-MP)?

A
  • Inhibition of several enzymes of de novo purine nucleotide synthesis
  • Incorporates into DNA and RNA
76
Q

Biotransformation of 6-MP includes metabolism to the inactive metabolite 6-thiouric acid by xanthine oxidase via first pass effect.

What medication must we use caution with when considering using 6-MP?

How does this change the dosing for oral and IV 6-MP?

A
  • Allopurinol - commonly used to prevent hyperuricemia d/t tumor cell lysis, will result in increased levels of 6-MP, since it is a xanthine oxidase inhibitor.
  • Must reduce the oral 6-MP dose by 50 - 75% when taking with allopurinol.
  • IV dosing is unaffected since not subject to first pass metabolism. (xanthine oxidase is in the liver)
77
Q

The antimetabolite drugs have relatively little acute toxicity after initial dose, and are cell cycle specific, working on the S-phase.

What are the three common routes of administration?

A

Oral

IV

Intrathecal

78
Q

When would you want to do an intrathecal administration of methotrexate?

A

When there is invasion of the CNS by neoplasm

79
Q

In addition to diarrhea, nausea, and vomiting, what are 5 more ADR’s caused by the antimetabolites?

A
  1. Immunosuppression
  2. thrombocytopenia
  3. leukopenia
  4. hepatotoxicity
80
Q

What are the prototype vinca alkaloids?

A

Vinblastine and Vincristine

81
Q

What are two general ADRs of the vinca alkaloids?

A

Alopecia

myelosuppression

82
Q

Vincristine has some additional ADRs beyond the alopecia and myelosuppression of the vinca alkaloids. What are these?

4

A

​Neurotoxicity

  1. numbness and tingling of the extremities
  2. loss of DTRs
  3. motor weakness
  4. autonomic dysfunction
83
Q

As mentioned previously the vinca alkaloids are associated with myelosuppression. Which one of the two prototypes is this more common with?

A

Vinblastine more than vincristine

84
Q

What is the mechanism of action for the vinca alkaloids?

A

Bind to •β-tubulin and inhibit microtubule assembly

85
Q

Are vinka alkaloids cell cycle specific?

A

Yes. They inhibit mitosis (M phase)

86
Q

What is the MOA for taxanes?

A

Bind to β-tubulin and stabilize microtubule assembly

87
Q

Based on their MOA, are taxanes cell cycle specific?

A

Yes, they work on the M-phase

88
Q

What ADRs are associated with paclitaxel? 2

A
  1. Hypersensitivity reactions in hands and toes
  2. Change in taste
89
Q

What is the MOA of the camptothecins?

A

Inhibition of type I topoisomerase

90
Q

What does type I topoisomerase do?

A

cuts one strand of dsDNA, relaxes the strand and reanneals it.

91
Q

What does Topoisomerase II do?

A

Cuts BOTH strands of dsDNA simultaneously to wind and unwinds DNA supercoils.

92
Q

What are two inhibitors of type II topoisomerase?

A

Epidophyllotoxins - etoposide

Anthracycline antibiotics - doxorubicin

93
Q

Are the topoisomerase inhibitors cell cycle specific?

A

Yes, except for anthracyclines which are CCNA.

They are primarily S phase, but also G1 and G2

94
Q

What are the four major antineoplastic antibiotics?

2 BOLD

A
  1. anthracyclines - doxorubicin
  2. Bleomycin
  3. dactinomycin
  4. mitomycin
95
Q

What are the main effects of the antitumor antibiotics?

A

mainly on DNA

96
Q

All the antineoplastic antibiotics are products of various species of what bacterial genus?

A

streptomyces

97
Q

What are the MOA of doxorubicin?

A
  1. Inhibit topoisomerase II
  2. Intercalate DNA
  3. Oxygen free radicals cause single and double strand DNA breaks
98
Q

Based on the MOA of doxorubicin, is it cell cycle specific?

A

Cell cycle nonspecific - but cycling cells are more susceptible.

99
Q

What ADRs are associated with doxorubicin?

A
  1. significant cardiotoxicity d/t free radical production
  2. cumulative cardiac dmg leads to arrhythmias and heart failure
100
Q

What is the MOA of bleomycin?

A

Free radical production leading to single and double stranded DNA breaks

101
Q

Is bleomycin cell cycle specific?

A

yes - G2 arrest

102
Q

What are the ADRs associated with Bleomycin?

A
  1. minimal myelosuppression
  2. significant pulmonary toxicity (usually presents as pneumonitis with cough, dyspnea and dry inspiratory crackles.
103
Q

What is the prototype antineoplastic enzyme drug?

A

L-aspariginase

104
Q

What is the MOA for L-asparaginase?

A

hydrolyzes circulating L-asparagine into aspartic acid and ammonia, effectively inhibiting protein synthesis

105
Q

So, cells can synthesize their own amino acids, why then is L-asparaginase useful?

A

Acute lymphoblastic leukemia (ALL) cells lack the enzyme asparagine synthetase and thus require an exogenous source of L-asparagine.

106
Q

Is L-asparaginase cell cycle specific?

A

Yes - G1

107
Q

What are the acute ADRs associated with L-asparaginase?

A
  1. Acute hypersensitivty reaction
108
Q

What are the delayed toxicities associated with L-asparaginase?

A
  1. Increased risk of clotting and bleeding
  2. pancreatitis
  3. CNS toxicity
    1. lethargy
    2. confusion
    3. hallucinations
    4. coma
109
Q

What are the categories of miscellaneous antineoplastic agents?

8

A
  1. Substituted Urea
  2. Differentiating agents
  3. Biological response modifiers
  4. Immunomodulators
  5. protein tyrosine kinase inhibitors
  6. mTOR inhibitors
  7. proteosome inhibitors
  8. monoclonal antibodies
110
Q

The BCR-ABL fusion protein results from the t(9:22) translocation and is found in 95% of patients with CML. What is the main drug we use on this?

A

Imatinib (Gleevec)

111
Q

What is the MOA of Imatinib?

A
  1. A small molecule inhibitor of the ABL tyrosine kinase
  2. Can also inhibit the RTKs - PDGFR and c-KIT
112
Q

When mutated, overexpressed, or structurally altered, tyrosine kinases can become potent oncoproteins. Aberrant tyrosine kinase activity can occur in receptor tyrosine kinases or cytoplasmic kinases, and has been identified in many human neoplasms.

What do we use to target the extracellular RTK?

How about the cytoplasmic kinases?

A

Extracellular - mabs

Intracellular - nibs

113
Q

What is the MOA of erlotinib and gefitinib?

A

Inhibit epidermal growth factor receptor (EGFR), an RTK

114
Q

What toxicities are erlotinib and gefitinib known for?

A

Dermatologic toxicities - acneform rash

115
Q

What epidermal growth factor receptor is expressed on 25-30% of breast cancers?

A

HER2/neu

116
Q

What drug do we use to inhibit HER2/neu?

A

Trastuzumab

117
Q

What ADR is associated with Trastuzumab?

What does this mean for us in clinical practice?

A

Cardiovascular complications including decreased LVEF and heart failure.

Must get baseline CV measurements prior to treatment, and monitor heart function periodically through therapy.

118
Q

Bevacizumab is used in tx of colorectal and lung cancers. What is its target and what does it down regulate?

A

VEGF - This antibody is against the ligand rather than the receptor.

Downregulates angiogenesis

119
Q

Cetuximab is used in tx of colorectal, lung, pancreatic and breast cancers. What is its target?

A

EGFR - tyrosine kinase

120
Q

Rituximab is used in tx of non-hogkin’s lymphoma, what is its target antigen? What is that antigens function?

A

CD20 - proliferation and differentiation

121
Q

In acute promyelocytic leukemia granulocytic maturation is inhibited by the t(15;17) translocation which creates the fusion protein PML-RARα. What drug do we use to treat this?

A

Tretinoin (all-trans-retinoic acid ATRA)

122
Q

What is the MOA of Tretinoin?

A
  • binds to the PML-RARα fusion protein and antagonizes the inhibitory effect on the transcription of target genes
  • Within 1-2 days the neoplastic promyelocytes begin to differentiate into neutrophils, which rapidly die
123
Q

What are the ADRs of Tretinoin?

A

•Vitamin A toxicity and retinoic acid syndrome are common adverse effects

124
Q

Biological response modifiers are asgents that stimulate or suppress the immune system to help the body fight cancer. What are the two bio response molecules we discussed?

A

Interferons

Interleukin-2

125
Q

What is the MOA of Interferon?

A

Inhibit cellular growth, alter the state of cellular differentiation, interfere with oncogene expression, alter cell surface antigen expression, increase phagocytic activity of macrophages, augment cytotoxicity of lymphocytes for target cells.

126
Q

ADR’s of interferon?

A

bone marrow depression

neutropenia

anemia

renal toxicity

edema

arrhythmias

flu-like syndrome

127
Q

MOA for Interleukin-2?

A

Increase cytocoxic killing by T cells and NK cells

128
Q

What is the major toxicity associated with IL-2?

A

Capillary leak syndrome

129
Q
A

Heme/Lymph - Exam 1 (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions