Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology > Anti-cancer drugs > Flashcards

Anti-cancer drugs Flashcards

1
Q

List three drugs that are anti-metabolites

A
  • 5-FU:pyrimidine analog, FdUMP blocks thymadilate synthase, decreased DNA and RNA synthesis
  • gemcitabine: pyrimidine analog, inhibits DNA polymerase and dFdCTP is incorporated into DNA and causes strand termination (toxicity not confined to S phase)
  • methotrexate: folic acid analog, inhibits dihydrofolate reductase which is required for biosynthesis of purines- decreased DNA, RNA, protein synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List two drugs that are spindle poisons

A
  • vincristine: disrupts microtubule assembly and mitotic spindle formation, causes arrest in M phase and inhibits cell division
  • paclitaxel: promotes polymerization and assembly of microtubules, makes them highly stable and non-functional, causes arrest in M phase and inhibits cell division
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List two drugs that are topoisomerase inhibitors

A
  • etoposide: forms complex with DNA and topoisomerase II, prevents re-ligation of double strand breaks- progression of cell cycle is stopped. Mainly active in S and G2
  • irinotecan: binds to and stabilizes the DNA- topoisomerase I complex leading to accumulation of single strand breaks that ultimately lead to double strand breaks and cell death. S-phase specific
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List three general classes of drugs that are considered cell cycle specific

A
  • antimetabolites (5-FU, gemcitabine, methotrexate)
  • topoisomerase inhibitors (etoposide, irinotecan)
  • spindle poisons (vincristine, paclitaxel)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List 6 general classes of anti-cancer drugs

A
  1. DNA damaging drugs
  2. Anti-metabolites
  3. Anti-mitotics (spindle poisons)
  4. Topoisomerase inhibitors
  5. Hormonal agents
  6. Target specific agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

List three categories of drugs that are considered DNA damaging drugs

A
  • alkylating agents (cyclophosphamide, temozolomide)
  • platinum compounds (carboplatin)
  • anti-tumor antibiotics (bleomycin, doxorubicin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List the general effects of DNA damaging drugs

A

Cause DNA cross linking, abnormal base pairing, single or double strand breaks

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

List three categories of drugs that are considered target specific drugs

A
  • monoclonal antibodies (bevacizumab, cetuximab, rituximab, trastuzumab)
  • mTOR inhibitors (temsirolimus)
  • tyrosine kinase inhibitors (erlotinib, imatinib, sumitinab)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List two alkylating agents

A

cyclophosphamide, temozolomide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

List two anti-tumor antibiotics

A

Bleomycin, doxorubicin

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

List four monoclonal antibodies used to treat cancer

A

bevacizumab, cetuximab, retuximab, trastuzumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List three tyrosine kinase inhibitors

A

erlotinib, imatinib, sumitinib

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

Cyclophosphamide is a _______ alkylating agent and can form DNA-DNA and DNA-DNA protein cross links, while temozolomide is a __________ alkylating agent that methylates guanine residues

A

Bifunctional; monofunctional

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

The hemorrhagic cystitis seen in cyclophosphamide use is attributed to the formation of the ___________ metabolite

A

acrolein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

_________ is an alkylating agent that is often used to treat cancers in the brain because it has good _________ permeability

A

temozolomide, blood-brain barrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

When a patient is being treated with cyclophosphamide, they should also receive ______ to help degrade the toxic ________ metabolite and reduce the risk of hemorrhagic cystitis

A

MESNA, acrolein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Name the nitrogenous functional group responsible for the mechanism of action of alkylating agents

A

Nitrogen mustard

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Carboplatin functions when the _______ moiety is displaced by water molecules in the process of ________ to produce a highly reactive molecule that interacts with nucleophilic sites to form interstrand and intrastrand DNA cross links

A

oxylate; aquation

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

Because a major side effect of carboplatin is severe nausea and vomiting, it is recommended to treat with ___________ drugs such as D2 antagonists, 5-HT3 antagonists, or cannabis

A

antiemetic agents

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

______________ is the dose limiting toxicity in carboplatin use

A

myelosuppression

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

Carboplatin causes (more/less) neurotoxicity, ototoxicity, and nephrotoxicity than cisplatin

A

LESS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Bleomycin is a ______ agent and causes accumulation of cells in the ______ phase of the cell cycle

A

cell cycle specific; G2

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

Mechanism of action of belomycin

A

Binds to DNA, generates oxygen free radicals from O2 to cause oxidative damage to the deoxyribose moieties of nucleotides; opens the deoxyribose ring resulting in single- and double-strand DNA breaks

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

Dose limiting toxicity of bleomycin

A

Slowly progressing pulmonary toxicity

–> do ongoing pulmonary function tests during treatment

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

Drugs like carboplatin, bleomycin, etoposide are excreted by the _______ so dose should be decreased of ______ tests are below normal ranges

A

kidneys; CrCL

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

Bleomycin is dosed as a mixture of two ________- chelating peptides that is used in the treatment of various carcinomas (including testicular, head, neck, penis, cervix, vulva as well as Hodgkins and non-Hodgkins lymphoma)

A

copper

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

Bleomycin and doxorubicin are both anti-tumor _______

A

antibiotics

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

Doxorubicin is one of the most active single anticancer agents and is a standard component of therapy for many cancers. It has a three fold mechanism of action. Describe its three main anti-tumor effects

A
  1. Intercalates between DNA base pairs, causing the helix to change shape, thereby inhibiting DNA and RNA polymerases
  2. Stabilizes the DNA-topoisomerase II enzyme complex, inhibits topoisomerase II re-ligation activity, leading to double-strand DNA breaks and apoptosis
  3. Forms superoxide anion and hydroxyl radicals that damage cell components; stimulated by Fe
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Deficiency in this enzyme enhances 5-FU toxicity because it is the enzyme that degrades 5-FU in the liver, intestinal mucosa, and tumor cells

A

dihydropyrimidein dehydrogenase

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

5-FU is a ___________ analog that is metabolized to FdUMP which blocks _____________, the enzyme required for the conversion of dUMP to TMP

A

pyrimidine, thymidylate synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Addition of _______, a folic acid derivative, enhances the toxicity of 5-FU

A

leucovorin

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

5-FU is a CCS drug; its effects are limited to the ____ phase of the cell cycle

A

S phase

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

List the main effect of 5-FU

A

decreased DNA and RNA synthesis due to blockage of thymidylate synthase and incorporation of FdUTP into DNA/RNA

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

List some side effects that are UNIQUE to 5-FU

A

Derm: hand-foot syndrome

ocular irritation and excessive lacrimation

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

Gemcitabine is a ________ analog that is metabolized to nucleotide analogs that inhibit __________

A

pyrimidine; DNA polymerase

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

List the main effect of Gemcitabine

A

dFdCTB is incorporated into DNA to cause strand termination and inhibits replication and repair of DNA, decreased DNA and RNA synthesis

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

Gemcitabine is a potent _________ and should not be used with radiotherapy except in certain clinical trials

A

radiosensitizer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Methotrexate is a ________ analog that is a high affinity active site inhibitor of ________, the enzyme required for biosynthesis of dTTP and purines

A

folic acid; dihydrofolate reductase

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

Methotrexate is also converted to MTX-polyglutamates which accumulate and inhibit ____________ as well as some other enzymes

A

thymidylate synthase

40
Q

Methotrexate is eliminated primarily by renal excretion. Because excretion exceeds GFR, we can conclude that there is ______________ of methotrexate

A

active tubular secretion

41
Q

Mention some UNIQUE side effects of methotrexate

A

Derm- toxic epidermal necrolysis, SJS, exfoliative dermatitis

42
Q

Explain why NSAIDs may enhance methotrexate toxicity

A

NSAIDs appear to reduce tubular secretion of methotrexate- thus enhanced toxicity`

43
Q

Vincristine binds to tubulin and __________ microtubule assembly and mitotic spindle formation, leading to inhibition of cell division. There is arrest in the ______ phase of the cell cycle

A

disrupts; M phase

44
Q

__________ administration of vincristine is uniformly fatal

A

Intrathecal or cisternal

45
Q

What is the dose-limiting adverse effect of vincristine?

A

Neurotoxicity- paresthesias distributed in stocking and glove formation, cranial nerve damage, paralysis, ANS dysfunction

46
Q

Unlike many other chemotherapeutic agents,the adverse effect _________ reverses even without cessation of therapy

A

alopecia

47
Q

Like vincristine, paclitaxel is a spindle poison. Explain how its mechanism of action is different from that of vincristine

A

Paclitaxel actually promotes polymerization and assembly of microtubules and works by making them highly stable and thus nonfunctional. Cell cycle arrests in M phase

48
Q

What is responsible for hypersensitivity reactions seen with paclitaxel?

A

The vehicle it is administered in- 50% EtOH and 50% castor oil

49
Q

Treatment with these drugs before starting paclitaxel can reduce the risk of hypersensitivity reaction

A

H1 antagonist (ex diphenhydramine), H2 antagonist (ex ranitidine) and a glucocorticoid

50
Q

Doses of paclitaxel must be reduced if patients have dysfunction or metastasis to the ______

A

liver (metabolism by CYP2C8 and CYP3A4)

51
Q

A major precaution for paclitaxel use is ____ abnormalities, which can be asymptomatic.

A

ECG abnormalities/ bradycardia.

52
Q

Describe the mechanism of action of etoposide

A

Forms stable complex with DNA and prevents re-ligation of double-strand breaks induced by topoisomerase II; strand breaks accumulate and progression in the cell cycle is stopped; cell undergoes apoptosis

53
Q

Etoposide is a CCS drug; it is mainly active in ________ phases

A

S and G2

54
Q

Explain why hepatic function is closely associated with etoposide toxicity

A

etoposide is highly bound to serum albumin

55
Q

What is the dose limiting toxicity of etoposide?

A

leukopenia

56
Q

What cancers are treated with etoposide?

A

lung and testicular cancers, also lymphomas, nonlymphocytic leukemia, Kaposi sarcoma

57
Q

Explain the mechanism of action of irinotecan

A

Binds to and stabilizes the normally transient DNA-topoisomerase I cleavable complex, leading to the accumulation of single-stranded DNA breaks; collision of a DNA replication fork with this opened strand of DNA causes an irreversible double-strand DNA break, ultimately leading to cell death

58
Q

Irinotecan is active in what phase of the cell cycle?

A

S phase

59
Q

Irinotecan is metabolized by CYPs that are induced by ___________ drugs, so people taking these drugs may have accelerated metabolism (decreased effect) of irinotecan

A

anti-seizure

60
Q

Individuals homozygous for the UGT1A1*28 allele are at increased risk of _________ when taking irinotecan

A

Neutropenia

61
Q

One side effect specific to irinotecan is ____________ caused by inhibition of AChE. This is usually short lived and does respond to atropine

A

cholinergic syndrome

62
Q

Bevacizumab is a humanized monoclonal antibody that was the first anti-__________ agent to show efficacy in cancer patients

A

angiogenesis

63
Q

Bevacizumab is an inhibitor of _________ by binding to its receptor and blocking receptor-ligand interaction

A

VEGF

64
Q

Therapy with bevacizumab should be suspended when there is >2g of ________ per 24 hour collection period

A

proteinuria

65
Q

This monocolonal antibody is a human- mouse fusion IgG directed against EGF receptor

A

cetuximab

66
Q

This monocolonal antibody is a human-mouse fusion IgG directed against CD20, a B-lymphocyte antigen

A

rituximab

67
Q

Rituximab is used mostly in treatment of refractory __________

A

B cell non-Hodgkin lymphoma

68
Q

Rituximab binds to _____, a B lymphocyte antigen

A

CD20

69
Q

Cetuximab binds to ________ to inhibit signaling

A

EGF-R

70
Q

When _______ is administered, patients should be monitored for an hour after infusion to watch for signs of anaphylaxis

A

cetuximab

71
Q

All patients receiving _______ should take diphenhydramine, acetaminophen, and corticosteroids as premedication prior to infusions

A

rituximab

72
Q

Both rituximab and cetuximab can cause infusion reactions to mouse proteins, including what effects?

A

fever, chills, NV, hypotension, angioedema, bronchospasm

73
Q

Trastuzumab is a fully humanized monoclonal antibody against _______

A

human epidermal growth factor receptor (Her2)

74
Q

Trastuzumab is used specifically in treatment of what kind of cancers?

A

Her2+ breast cancer

75
Q

Describe the mechanisms of trastuzumab

A

Binds to the external domain of HER2/neu tyrosine kinase receptor to prevent receptor activation by EGF; decreases downstream signals, metastatic potential, and promotes apoptosis
Induces antibody-dependent cellular toxicity

76
Q

Because of potentially fatal CV side effects of trastuzumab, it is recommended that _______ be assessed prior to and throughout treatment

A

LVEF

77
Q

Temsirolimus binds to ________ and the complex then binds to and inhibits _____. This inhibits progression from ___ to _____ phase of the cell cycle

A

FKBP; mTOR; G1 to S

78
Q

Temsirolimus is used specifically to treat what kind of cancer?

A

advanced renal cancer

79
Q

Metabolic effects occur very commonly in treatment with temsirolimus, including:

A

hyperlipidemia, hypertriglyceridemia, edema

80
Q

Why are there often drug interactions in treatment with temsirolimus, erlotinib, imatinib, and sunitinib?

A

They are all metabolized by CYP3A4

81
Q

Erlotinib is a tyrosine kinase inhibitor that specifically inhibits ___________

A

epidermal growth factor receptor

82
Q

Erlotinib is used specifically in the treatment of

A

non-small cell lung cancer, pancreatic cancer

83
Q

Describe the mechanism of action of erlotinib

A

Reversible inhibitor of EGFR; binds to ATP binding pocket in the receptor tyrosine kinase domain of the EGFR, prevents autophosphorylation of receptor following EGF binding and receptor dimerization

84
Q

_________ is a tyrosine kinase inhibitor that specifically inhibits the epidermal growth factor receptor

A

Erlotinib

85
Q

Imatinib is a tyrosine kinase inhibitor that specifically targets _____________ but does have action against other tyrosine receptor kinases

A

constitutively active BCR-Abl tyrosine kinase receptor created by the “Philadelphia” chromosome 9:22 translocation

86
Q

_______ is a drug that targets the constituently active BCR-Abl tyrosine kinase receptor, which is created by the _________ chromosome translocation

A

Imatinib; Philadelphia

87
Q

Imatinib should be taken with _________

A

food and water, to minimize GI effects

88
Q

Sunitinib is a tyrosine kinase inhibitor that targets multiple tyrosine kinases including:

A

PDGF receptors, VEGF receptors, stem cell factor receptor and others which are involved in tumor growth and metastasis

89
Q

The clinical response to sunitinib is decreased …

A

angiogenesis, invasion, and metastasis

90
Q

The clinical response to imatinib is decreased….

A

cell growth and proliferation

91
Q

The MOPP regime consists of Mechlorethamine, Oncovin® (vincristine), Procarbazine, Prednisone and is standard therapy for _______

A

Hodgkins disease

92
Q

The ABVD regime is composed of Adriamycin® (doxorubicin), Bleomycin, Vinblastine, Dacarbazine and is used in treatment of _______. It is effective as MOPP but with fewer secondary malignancies

A

Hodgkins disease

93
Q

The COP regime consists of Cyclophosphamide, Oncovin® (vincristine), Prednisone and is standard treatment for

A

non-Hodgkins disease

94
Q

The PEB regime consists of Platinol® (cisplatin), Etoposide, Bleomycin and is standard treatment for

A

testicular cancer

95
Q

the CMF regime consists of Cyclophosphamide, Methotrexate, Fluorouracil, with or without tamoxifen and is standard treatment for

A

post-op breast cancer

96
Q

Mutation in p53 leads to resistance to anti cancer therapy because there is decreased ________

A

apoptosis

97
Q

How do cells become resistant to drug accumulation?

A

Increased efflux via P-glycoprotein (ABCB1)

Pharmacology (7 decks)

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