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Hematology-Oncology Exam 2 > Anti-Cancer Agents: Part 1 > Flashcards

Anti-Cancer Agents: Part 1 Flashcards

1
Q

What are the 2 categories of major anti-neoplastic drugs?

A
  1. Cell cycle specific

2. Cell cycle nonspecific

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2
Q

Antimetabolites, taxanes, vinca alkaloids, epipodophyllotoxins, and antitumor antibiotics are examples of what?

A

Cell Cycle- Specific Anti-Neoplastic Drugs (Target cell & Give it in appropriate phase)

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3
Q

Aklyating agenst, anthracyclines, platinum analogs, camptothecins, and antitumor antibiotics are examples of what?

A

Cell Cycle NonSpecific (doesn’t matter when given)

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4
Q

What are some drugs that are S-Phase Specific?

A

Cyotsine, arabinoside, hydroxyurea (Anti-metabolites)

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5
Q

What are some drugs that are S-Phase Specific, but self limiting?

A

6-mercaptopurine and methotrexatre

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6
Q

What is the G2 phase also known as?

A

Pre-mitotic interval

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7
Q

What drugs are M-phase specific?

A

Vinca Alkaloids: Vincristine, Vinblastine, Paclitacel

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8
Q

What are some drugs that are phase-nonspecific?

A

Alkylating drugs, nitrosoureas, antitumor antibiotics, procarbazine, cis-platinum, dacerbazine

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9
Q

What is the principle of selective toxicity?

A

To destroy neoplastic cells via selective killing versus normal cells

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10
Q

What can selective toxicity be described in terms of?

A

Chemotherapeutic Index (CTI)

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11
Q

What is CTI?

A

Toxicity to CA cells (lethal dose)/Toxicity to normal cells

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12
Q

What is toxicity measured by?

A

LD50

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13
Q

What is LD50?

A

Lethal dose for 50% cell population

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14
Q

Do conventional cytotoxic drugs have a lot of success with selective toxicity?

A

No

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15
Q

What is a common AE of conventional cytotoxic drugs?

A

Myelosuppression

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16
Q

What can Low WBC counts (leukopenia) contribute to?

A 
INFECTION
Fever
Sore throat
Cough or shortness of breath
Nasal congestion
Burning during urination
Shaking chills
Redness, swelling and warmth at the site of an injury
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17
Q

What can low RBC counts (anemia) cause?

A 
Fatigue
Irritability
Dizziness
Shortness of breath
Headaches
An increase in heart rate/breathing
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18
Q

What can you give to a patient to help speed up the recovery of reduced WBCs?

A

G-CSF or GM-CSF

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19
Q

What is Nadir in terms of WBC and when does it occur?

A

The lowest WBC after chemo- occurs 7-14 days post-therapy

-Chemo for brain tumors can have a delayed nadir

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20
Q

What is the life span of a WBC and what is the implication of this?

A

Few hours-days… these have to be made new more often so the chemo effects on WBC are more pronounced

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21
Q

What is the lifespan of a RBC?

A

120 days

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22
Q

What is a major AE of conventional cytotoxic drugs?

A

Thrombocytopenia and neutropenia

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23
Q

What can low platelet counts cause?

A 
Bruise easily
Bleed longer than usual after minor cuts or scrapes
Have bleeding gums or nose bleeds
Develop large bruises (echymyoses) and multiple small bruises (petechiae)
Serious internal bleeding
Hair loss (alopecia)
Appetite loss
Weight loss
Impact on sexuality
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24
Q

What is the general threshold of platelet count where you would have to decrease dose of chemo drugs?

A

100,000

-Packaging often times will tell you what it is… usually drug is C/I if it is under 50,000

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25
Which class of drugs resemble normal substrates such as purine/pyrimidine analogs?
Antimetabolites
26
What do antimetabolites do?
Inhibit DNA synthesis...they incorporate into DNA and fool it
27
What are 2 main issues with antimetabolites?
1. BM cell replication is profoundly inhibited | 2. GI toxicity
28
True or False: Antimetabolites are highly cell specific?
TRUE- S phase
29
What is the result of an antimetabolite incorporating into DNA?
It will go through transcription and translation and result in a non-functional protein
30
What does 5-fluorouracil inhibit?
dTMP synthesis by inhibiting thymidylate synthase | No dUMP --> dTMP for DNA to be made
31
What does methotrexate do?
Inhibits dihydrofolate reductase which makes THF from DHF
32
Why inhibiting the production of THF, what does methotrexate ultimately inhibit the production of?
Methylenetetrahydrofolate (MTHF)
33
What is MTHF?
This is a folate compound that is required to make dTMP from dUMP (along with enzyme thymidylate synthase which is inhibted by 5-fluorouracil)
34
What 2 steps involved in DNA synthesis does Hydroxyurea inhibit?
1. UMP to dUMP (via ribonucleotide reductase) 2. CTP to dCTP (via ribonucleotide reductase) -Both of these will result in a lack of DNA synthesis
35
So generally, what is methotrexate?
A folic acid analogue which inhibits dihydrofolate reductase and decreases nucleic acid synthesis
36
Folic acid is required for what?
DNA synthesis
37
What binds strongly to DHFR to inhibit the formation of MTHF, which a folate required for dTMP synthesis?
Methotrexate
38
Cells in what phase of the cell cycle are most sensitive to methotrexate?
S phase
39
What are 2 taxanes?
1. Paclitaxel | 2. Docetaxel
40
What is a risk with both taxanes?
Hypersensitivity
41
What is paclitaxel extracted from?
Bark of Pacific yew
42
What is Docetaxel extracted from?
Bard of English yew
43
How do both taxanes work against cancer?
By interfering with mitosis
44
How do taxanes interfere with mitosis?
Bind to microtubules and inhibit their depolymerization (molecular disassembly into tubulin)
45
What kind of tumors is paclitaxel used for?
Solid tumors
46
What drug blocks a cell's ability to breakdown the mitotic spindle during mitosis (cell division)?
Paclitaxel
47
If the spindle is still in place, what can the cell not do?
Divide into daughter cells
48
What class of drugs block mitosis by keeping the spindle from being formed in the first place?
Vinca Alkaloids
49
How does paclitaxel have to be given and why?
IV- Irritates skin and mucous membranes on contact (avoid necrosis)
50
What are 5 indications for docetaxel?
``` Breast cancer Non-Small Cell lung cancer (NSCLC) Hormone refractory prostate cancer Advanced gastric cancer Squamous cell head and neck cancer ```
51
What is given with docetaxel for hormone refractory prostate cancer?
Prednisone
52
What are 2 general AE of taxanes?
1. Myelosuppression | 2. HS
53
What is a SE specific to Paclitaxel?
Neurotoxicity - Usually reversible - Can reduce dose, but not desirable if trying to cure
54
What is a SE specific to Docetaxel?
Fluid retention
55
How can you prevent fluid retention with docetaxel?
Take prednisone (steroids) night before and in AM
56
What drugs are important in the MOPP regimen?
Vinca alkaloids | -Oncovin (or Vincristine) is the O in MOPP
57
Generally, what 2 things are vinca alkaloids used for?
1. Solid tumors | 2. Leukemias
58
What are the 3 main vinca alkaloids?
1. Vinblastine 2. Vincristine 3. Vindesine
59
Where do vinca alkaloids come from?
Periwinkle plant- Mix of plant synthesized and synthetically synthesized
60
How do vinca alkaloids work?
They bind to tubulin and prevent the cells from making the spindles it needs to be able to move its chromosomes around as it divides
61
What kind of arrest and when is observed with vinca alkaloids?
Colchicine-like arrest in metaphase
62
How are vinca alkaloids given?
IV in sulfate form once a week
63
What happens if a vinca alklaoid is given intrathecally?
FATAL- Severe neurotoxicity with not antidote....death in a few weeks to months
64
What is an issue with giving Vinca Alkaloids?
It can cause a lot of tissue irritation if they leak out of the vein
65
True or False: There is a lot of cross resistance between vincristine and vinblastine
FALSE... no cross resistance
66
What is a specific side effect of vincristine?
Neurotoxicity
67
What are specific side effects of vinblastine and vinorelbine?
Myelosuppression
68
What are examples of cytostatic (anti-mitotic) glucosides?
Podophyllotoxin (podofilox) and its derivatives (etoposide and teniposide)
69
What is podophyllotoxin an extract of?
Mayapple
70
What cells does podophyllotoxin affect?
Cells undergoing mitosis (division)
71
What is podophyllotoxin used for?
Not as a chemotherapy agent...it is used in creams (Condylox) and topical solutions for treatment of genital warts (squamous cell carcinomas)
72
What are some reactions to topical applications with podophyllotoxin?
Burning and inflammation
73
What is a specific podophyllotoxin dicussed?
Etoposide (VP-16)
74
Where does etoposide (VP-16) block the cell cycle?
2 places 1. G1 phase 2. Replication of DNA (S-Phase)
75
How is Etoposide (VP-16) given?
IV or orally as liquid capsules
76
What is etoposide used mainly to treat?
Testicular CA which hasn't responses to other treatment
77
What are some SE of etoposide (VP-16)?
Hypotension, alopecia, N/V, Myelosuppression
78
How is Etoposide (VP-16) specifically given to prevent hypotension?
IV over 60 minutes (prolong it to prevent hypotension)
79
What else can Etoposide (VP-16) be used for with cisplatin?
Non-small cell lung CA
80
Which route of administration is more common and effective for Etoposide (VP-16)?
IV
81
Make sure to assess risk for what with chemo drugs?
Potential for nausea...stratify it then give drugs based on that... individualize their treatment and have something PRN for them... feel nauseous... take drug ASAP
82
Where do antitumor antibiotics come from?
Streptomyces species
83
What do antitumor antibiotics interact with?
All interact with DNA and/or RNA, but may also interact with other cellular substituents
84
True or False: Antitumor antibiotics are less phase specific than antimetabolites
TRUE
85
What is the only generalized toxicity with antitumor antibiotics?
Tissue necrosis (why drugs are delivered via a port.. decreases risk)
86
How are antitumor antibiotics administered?
IV
87
What is the one exception to antitumor antibiotics being given IV?
Bleomycin...this can be given IV, IM, SubQ, and intrapleural
88
How is chemo dosed?
Body surface area
89
How is bleomycin dosed?
Units
90
What is a big AE with bleomycin?
Pulmonary fibrosis: Can give O2 via nasal canula, but not that effective because the lungs are all fibrotic and the O2 can even it the deep lung tissue
91
What can enhance toxicity of MTX?
Impaired renal function
92
What can an elevated BUN indicate?
Dehydration
93
What is the efficacy of leucovorin therapy dependent on?>
Early administration when MTX toxicity suspected
94
How is leucovorin given?
IV dose equal to or greater than the dose of MTX
95
Again, what does MTX do?
Binds reversibly with dihydrofolate reductase, preventing the synthesis of pruine and pyrimidine nucleotides
96
Where are toxic effects seen with MTX?
Skin and GI mucosa
97
Why can Leucovorin "rescue" attenuate some of the toxic effects of MTX?
Because it is the metabolically active form of folic acid
98
When can you give Leucovorin?
6-24 hours after MTX infusion (if given at same time, it can nullify affects of MTX)
99
If MTX is administered intra-arterial (regional perfusion) or intrathecal injection, how can leucovorin be given?
IM, IV, or orally concomitantly to offset systemic MTX toxicity without abolishing the local activity of the antineoplastic drug
100
So generally, what does leucovorin do?
Replenish folic acid levels (attenuates some of the toxic effects of MTX...6-24 hours after)

Hematology-Oncology Exam 2 (15 decks)

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