Brainscape's Knowledge GenomeTM

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


See full index

FPP > Antineoplastic Drugs > Flashcards

Antineoplastic Drugs Flashcards

1
Q

What are 5 major classes of antineoplastic drugs?

A 
Alkylating agents
Antimetabolites
Natural products
Hormones
Other
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Alkylating Agents:

  • mechanism
  • What do they effect
  • what are their effect on DNA
A

Alkylating agents have Sn1 formed unstable bonds that are attacked by nucleophiles to form alkyl bonds with DNA, RNA, and protein.

It causes ds breakage, crosslinks DNA, and causes misreading of DNA

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

List three alkylating agents.
What subcatagories of Alkylating agents are they?
What are their specificity for cell cycle/phase? What does this mean?

A

Mechlorethamine (Nitrogen Mustard): cell cycle and phase nonspecific
Carmustine (nitrosourea): cell cycle and phase nonspecific
Cyclophosphamide (Nitrogen Mustard): cell cycle specific, phase nonspecific

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

What are three common side effects of Akylating agents?

What are the specific drugs’ relative severity for these?

A

-GI irritation (N/V/D; damage to mucosa), Hematopoiesis suppression (can indicate effectiveness/nl cell recovery; increases chances of infection), alopecia

  • Mechlorethemine has mild alopecia but serious GI and myelosuppression
  • Cyclophosphamide has relatively milder myelosuppression
  • Carmustine has delayed myelosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is Nadir, and which drug has the nadir that is most immediate post tx in terms of myelosuppression? Which has the least immediate

A

Nadir is the time at which the most myelosuppression occurs.

Mechlorethamine (10 days)
Cyclophosphamide (18 days)
Carmustine (35 days…and not as severe depression)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Mechlorethamine

  • cell cycle specificity?
  • Therapeutic use
  • Mechanism (nonspecific)
  • Administration/CNS involvement?
A
  • Cell cycle/phase nonspecific
  • Hodgkin’s and non-Hodgkin’s lymphoma
  • mechanism: crosslinking to DNA)
  • IV admin/ no CNS involvement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cyclophosphamide

  • cell cycle specificity
  • Administration/CNS involvement?
  • Mechanism
  • Unique side effect? What’s is it caused by?
  • Therapeutic use
A
  • cell cycle specific/ phase nonspecific
  • oral or parenteral admin/No CNS involvement
  • PRODRUG activated by CYP in liver to an intermediate that spontaneously degrades to Phosphamine and acrolein
  • Acrolein causes bladder toxicity
  • Cyclophosphamide is used for many cancers…most widely used agent in the alkylating agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What agent is responsible for bladder toxicity in Cyclophosphamide? How can this be prevented

A

Acrolein post spontaneous degradation of intermediate generated from CYP metabolism
-Use Mesna with Cyclophosphamide to prevent bladder toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Carmustine

  • cell cycle specificity
  • CNS involvement?
  • therapeutic use
A
  • cell cycle and phase nonspecific
  • YES CNS involvement as it crosses BBB very well
  • brain tumors, multiple myeloma, melanoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q 
Antimetabolites
List the 5 drugs
What steps do they block?
What are three general mechanistic strategies of the antimetabolites?
-cell cycle specificity
A

-cytarabine, 5, fluorouracil, hydroxyurea, metotrexate, mercaptopurine,

  • Methotrexate, Cytarabine and 5 fluorouracil blocks DNA syntehsis from deoxynucleotides
  • hydroxyurea blocks deoxyribonucleotide synthesis
  • Mercaptopurine and Methotrexate blocks synthesis of ribonucleoic acids

General mechanisms: analogs of folate, purine, and pyrimidine.

-ALL are S phase specific cell cycle specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Methotrexate

  • mechanism (specific)
  • What is the difference between nl and cancer cell metabolism of methotrexate
  • Side effects (unique)
  • Therapeutic uses
A
  • methotrexate binds to dihydrofolate reductase… dihydrofolate CANNOT be converted to tetrahydrofolate… therefore thymidine kinase cannot convert dUMP to dTMP. thereby blocking DNA synthesis.
  • CA cells canc onvert methotrexate to polyglutamate-Methotrexate, which minds dihydrofolate reductase even more than nl cells
  • GI effects/myelosuppression. tubular necrosis of kidneys, displacement of drugs bound to serum albumin.
  • acute lymphocytic leukemia, choriocarcinoma, osteosarcoma, head/neck CA, lung/breast CA.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Leucovorin

  • What is it/what does it do?
  • what is the difference in metabolism between nl and ca cells of Leucovorin
A

It is a synthetic folatic acid. It is used to replenish folate post large dose of methotrexate.
-nl cells can take in leucovorin much better than CA cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Fluorouracil (5-FU)

  • mechanism (Specific)
  • Side effects
  • Therapeutic uses
A
  • 5 FU is incorporated directly into RNA. It is also converted to d5TMP thereby interfering with normal thymidine synthesis (AKA DNA synthesis)
  • delayed myelosuppression; GI effects
  • Wide therapeutic spectrum. Used in colon (and other GI related), and breast CA, and basal cell carcinoma. Also Head, neck, bladder, pancreas, stomac, ovarian CA.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cytarabine (AraC)

  • Mechanism (specific)
  • Side effects (unique)
  • administration (specific strategy/method)
  • Uses
A

-compete with nl cytosine for phosphorylation into CMP, CDP, CTP. Therefore interferes with DNA synthesis n causes chain termination

  • Neurotoxicity; MARKED myleosuppression
  • want to infuse “continuously” (about 2x per day for 5 days) at low doses since it’s phase specific to S phase.
  • great for acute myelocytic leukemia (cells over turn about 18 hours) also for lymphomas, head and neck CA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mercaptopurine

  • mechanism (general)
  • Side effects (unique)
  • Therapeutic uses
A
  • purine analog–> disrupts DNA and RNA synthesis.
  • Side effects: GI and myelosuppression, Jaundice.
  • acute leukemias, chronic granulocytic leukemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What can lead to toxicity with use of mercaptorpurine? How does that work?

  • about how many percent pts are homozygous for this?
  • about how many percent pts are heterozygous for this?
A

polymorphisms in thiopurine methyltransferase gene. If deficient, mercaptopurine will be activated for much longer and cause severe myelosuppression

  • 1% homozygous–>really really bad. DO NOT GIVE
  • 10% heterozygous–>really really bad. probably shouldn’t give.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hydroxyurea

  • Mechanism
  • Where does it inhibit the cell cycle?
  • Therapeutic uses
  • What is it good in conjunction with and why?
  • Side effects
A
  • it binds ribonucleotide reductase, which inhibits conversion of NTP to dNTP… therefore no DNA synthesis
  • It arrests cell in the G1 and S interphase.
  • Used in Granulocytic Leukemia, head and neck CA
  • good in conjunction with radiation, since dNTPs are needed for repair.
  • GI disturbance, and myelosuppression.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Vinca alkaloids

  • Name the two drugs
  • Mechanism
  • cell cycle specificity
A
  • Vinblastine, Vincristine

- binds tubulin and therefore does not for MT and thus cells are arrested in metaphase of mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Vinblastine

  • Side effects
  • Therapeutic uses
A
  • severe myelosuppression
  • epithelial ulceration
  • neurological disturbances
  • bronchospasms
  • N/V

-lymphomas, breast cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Vincristine

  • Side effects
  • Therapeutic uses
A

Less myelosuppression than vinblastine
alopecia, neuromuscular abnormalities
bronchospasms
N/V

-acute lymphocytic leukemia, lymphomas, Wilm’s tumor, neuroblastoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Taxanes

  • Name of drug
  • Mechanism
  • cell cycle specificity
A
  • Paclitaxel
  • stablize microtubules via Beta subunit of tubulin
  • cells are arrested in late G2 phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which phase is most sensitive to radiation?

What drug can be used for radiosensitizing?

A

G2 phase; Paclitaxel

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

Paclitaxel

  • Therapeutic uses
  • Side effects
A
  • Breast and Ovarian Cancer

- Leukopenia, arthralgia/myalgia, peripheral neuropathy, hypersensitivity with Cremaphor EL detergents

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

What combo of drugs is used for Ovarian cancer?

Why is this good?

A
  • Paclitaxel with Cisplatin

- Cisplatin damages DNA and Paclitaxel apparently can intervere with repair.

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

Name the Antibiotic antineoplastic drugs

A

Doxorubicin, Bleomycin

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

Doxorubicin

  • mechanism (Specific)
  • cell cycle specificity
  • therapeutic uses
  • side effects (unique)
A

-1. intercalates DNA, generates ROS via quinone redox, binds DNA/topoisomerase II–>cannot seal ds breaks

  • cell cycle specific, phase NONspecific
  • lymphomas, breast/ovarian, small cell lung
  • Cardiomyopathy dilated; dose-related and cumulative due to H2O2 (dextrazoxane can chelate to Fe and lessen ROS), bone marrow suppression, GI, and alopecia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Bleomycin

-Mechanism

A
  • iron (III) containing glycoproteins bind DNA and causes oxidative damage–> ds and ss strand breaks.
  • specific strand breaks at 5’-GC-3’ 5’-GTAC-3’
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Bleomycin

  • cell cycle specificity
  • therapeutic use
A
  • G2 specific

- germ cell cancers, lymphomas, head/neck, lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Bleomycin

-Side effects

A
  • pulmonary toxicity (dose related cumulative and potentially fatal)
  • hypermigmentation/vesiculation
  • minimal myelosuppression

(bc skin and lungs have LOWEST levelof Bleomycin hydrolase)

30
Q

Etoposide (VP16)

  • mechanism (specific)
  • cellcycle specificity
  • Uses
  • Side Effects
A
  • irreversible binding to DNA-topoII complex… no repair
  • late G2 specific
  • lymphoma, acute leukemia, small cell lung, and testicular
  • Leukopenia, N/V/D, alopecia
31
Q

What are Biological Response Modifiers? (BRM)

2 Examples

A

natural substances that mimic or act upon natural proteins

  • Imatinib
  • Filgrastim
32
Q

Biological Response Modifiers (BRM)

  • potential benefits (2)
  • Limitations (3)
A

-boost host response to cancer, and theoretically safer because it’s similar to endogenous compounds

  • not always effective depending on tumor subtype
  • variable results
  • sometimes very serious side effects
33
Q

Filgrastim

  • What is Filgrastim
  • What is it used for?
  • Side effects
A
  • G-CSF: granulocyte colony stimulating factor
  • It’s to be used to stimulate neutrophil due to chemo induced neutropenia…therefore chemo can continue and to lessen chance of infections
  • bone pain!!! DUHHH, hyperuricemia, leukocytosis
34
Q

mab naming system

What are the 4 parts?

A

Variable naming, TARGET, SOURCE, mab

35
Q

What are the 4 major sources of mabs?

A

O=mouse
U=fully human
Xi=chimeric
Zu=humanized

36
Q

For mAB naming, what are “tu”, “ci”,

A

tu=tumor, ci=cardiovascular

37
Q

Trastuzumab

  • mechanism
  • Use
  • Side effects
A
  • mAb binds against Her2/Neu AKA ERB B2 receptor and stops abnl signalling and cell proliferation.
  • Used for breast cancer (Her2/Neu positive ones)
  • Cardiomyopathy, hypersensitivity, and infusion reactions (fevers chills)
38
Q

Best combo for Her2/Neu positive breast cancer

A

Trastuzumab +Paclitaxel

39
Q

Cisplatin

  • mechanism
  • newly discovered mechanism
A
  • platinum coordinated complexes–>hydrolysis to form cross links to DNA
  • binds thioredoxin reductase to promote apoptosis. Thioredoxin reductase is often overexpressed in cancer cells.
40
Q

Cisplatin

  • Cell cycle specificity
  • therapeutic uses
A

cell cycle specific, phase nonspecific

  • WIDE SPECTRUM
  • Ovarian and Testicular cancer.
  • Also, Head/neck, bladder, small cell lung, colon, and esophagus.
41
Q

Combo for Testicular Cancer

A

bleomycin, Etoposide, cisplatin

42
Q

Cisplatin side effects

A
  • Nephrotoxicity
  • ototoxicity
  • peripheral neuropathy
  • electrolyte disturbances
  • N/V (100%)
  • myelosuppression
43
Q

List the platinum coordinating drugs (3)

-what’s the difference

A

Cisplatin, Oxaliplatin, Carboplatin
Oxaliplatin and carboplatin have narrower spectrum and less nephrotoxicity
-

44
Q

What is the regimen for colorectal cancer?

A

FOLFOX: leucovorin, 5FU, Oxaliplatin

45
Q

Procarbazine

  • Mechanism
  • Use
  • Side effects
A
  • Prodrug: activated by microsomal enzymes (NOT THE CYPS!) and is an atypical alkylating agent. NO cross reaction with the alkylating agents.
  • Hodgkin’s
  • typical stuff like GI, Myelo supp
46
Q

What portion of breast cancer and what percent of breast cancer with estrogen receptors are responsive to hormone therapy?

A

33% of all breast cancers

66% with good estrogen receptor counts

47
Q

Hormone therapy strategies (2)

and what is the consequence of this?

A
  • use opposite hormones (estrogen for prostate ca, use androgen for breast ca, use progestin for endometrial ca)
  • use anti hormone therapy
  • consequence: inhibits growth and puts more cells in G0
48
Q

What are some advantages of hormone therapy?

A

-specific and long lasting. (however resistance can occur)

49
Q

What are some beneficial side effects of hormone therapy?

Adrenalcorticoids
adrogens
progestins

A

Adrenalcorticoids: antiemetic
Androgen: anabolic
Progestins: appetite stimulation

50
Q

Prednisone

  • Mechanism (Specific)
  • uses
  • palliative side effects
A

bind steroid receptors and cause 1. cell arrest in G1. 2. Stopped expression of growth related genes 3. mediates cell lysis

  • Steroid over expressed in lymphoid (leukemias/lymphomas) so they are most susceptible to prednisone
  • also in breast cancer

-antiemetic, increase appetite, antiinflammatory (which is also risky for immunosuppression and infections), myelosuppression isn’t a big issue so good for combo therapy, weight gain

51
Q

Name 2 antiestrogenic drugs

A

Tamoxifen and Letrozole

52
Q

Tamoxifen

  • Mechanism
  • beneficial side effect and why?
  • cellcycle specificity; “static or cidal”
  • uses
A
  • Tamoxifen is a PRODRUG activated by CYP2D6 o endoxifen. This binds to the Estrogen receptor and arrests the cell in G0/G1
  • beneficial b/c also blocks estrogen receptors in bone tissue thereby preventing osteoporosis.
  • ONLY STOPS cell growth…which will pick back up if Tamoxifen is removed. therefore need something else to KILL the cells
  • Used in postmenopausal advanced breast cancer/premenopausal metastatic breast cancer. OR for prophylaxis.
53
Q

Which sub population is likely to experience more complications with tamoxifen?

A

CYP2D6 ultrafast metabolizers due to over activation

54
Q

Tamoxifen

Side effects

A
  • N/V
  • Hot flashes/vaginal bleeding/discharge (menopausal-like sx)
  • fatigue
  • bone/muscle pain
  • MAY INCREASE uterine/endometrial cancer risk.
  • MAY ALSO INCREASE chance of PE
55
Q

Letrozole

  • Mechanism
  • Therapeutic uses
  • Side effects
A
  • irreversibly binds heme group of Aromatase in fat, muscle, and adrenal gland (p450) and inhibits androgen conversion to estrogen–> lessened ER stimulation–>less proliferation
  • post menopausal advanced or metastatic breast cancer (better than tamoxifen or in combo)
  • Bone loss
56
Q

First-line therapy for post-menopausal advanced/metastatic breast cancer?

A

LETROZOLE!!!

More effective and less side effects than Tamoxifen

57
Q

Leuprolide

  • Mechanism
  • Use
  • administration
  • Side effects
A
  • GnRH stimulator –>initially large amount of FSH and LH released and disease flares (prostatic cancer)… then after 2-4 weeks… disease settles as LH and FSH feeds back and desensitized to the large amounts of GnRH.
  • hormone responsive prostatic cancer. Unlabled use (breast and endometrial cancer)
  • monthly subQ injection/implant
  • Hot flashes and impotence
58
Q

What is the first line tx of hormone responsive prostatic cancer?

A

Leuprolide

59
Q

Flutamide

  • Mechanism
  • Use/preferred use method
  • Side effects
A
  • blockage of androgen receptors
  • metatstatic prostate cancer. Use in combo with Leuprolide (gnRH agonist OR as secondline therapy)
  • Gynecomastia, hepatotoxicity, diarrhea.
60
Q

mechanisms of drug resistance

A
  • increased efflux
  • decreased influx
  • DNA damage repair
  • activation of detoxifying systems
  • blocking apoptosis
61
Q

How to overcome resistance

A

combination therapy

62
Q

Multiple drug resistance (MDR)

  • main method
  • which drugs are especially prone to resistance?
A
  • mostly mediated by APT dependent efflux pumps

- vinca alkaloids, taxanes, antibiotics, and etoposide.

63
Q

Strategies to overcome resistance (3)

A
  • increase drug dose
  • increase drug number with multiple mechanisms.
  • recruit cells out of resting phase
64
Q

Combotherapy strategies (4)

A
  • different cell cycle specificities
  • active as single agent
  • overlapping toxicities
  • different mechnisms
65
Q

Example of sequential blockade (2 examples)

A
  • hydroxyurea and cytarabine

- methotrexate and 5FU

66
Q

Example of concurrent inhibition

A

Cytarabine and 5 FU

67
Q

Complementary Inhibition
Definition
Example

A

One drug affects synthesis of the end product; one drug affects function of the end product
-Cytarabine; Doxorubicin
(Synthesis and damage to DNA)

68
Q

Rescue

Example (2)

A

Methotrexate and Leucovorin

Or HPSC transplant post complete deletion

69
Q

Synchronization
Definition
Example

A
  • synchronize cells so they are in one phase, then use drug to kill in specific phase
  • Low doses of 5FU to block S phase, then High dose of Cytarabine to kill in S phase
70
Q

Recruitment
Definition
Example

A

mobilizing slow proliferating or nonproliferating cells to proliferate. Then hit them with cycle specific drugs

-Low doses of carmustine and/or mechlorethamine

FPP (2 decks)

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