Ch.29: Anti-Cancer Agents (Milner) Flashcards

1
Q

agents that can affect DNA are called:

A

mutagenic

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2
Q

indications for chemotherapy

A

1) systemic neoplasia sensitive to chemo (i.e. lymphoma)
2) palliative for gross metastatic dz
3) adjuvant to eradication of micrometastatic dz (i.e. osteosarcoma, hemangiosarcoma)
4) radio-sensitization

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3
Q

4 cell types that can be targeted

A

round cells
epithelial cells
mesenchymal cells
hematopoietic cells

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4
Q

Which cell type is MOST and LEAST susceptible to chemo at a given dose?

A

MOST: hematopoietic
LEAST: mesenchymal

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5
Q

what do “phase specific” drugs target

A

specific phases in the cell cycle

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6
Q

How does the drug methotrexate work

A

affects pyrine and pyrimidine synthesis by having an affect on folate synthesis within the cell (folate needed for DNA synthesis)

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7
Q

5 Phase non-specific drugs

A

1) alkylating drugs
2) nitrosoureas
3) antitumor abx
4) procarbazine
5) platinum derivatives

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8
Q

3 Phase specific drugs that target DNA synthesis*

A

cytosine arabinoside
hydroxyurea
methotrexate

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9
Q

4 Phase specific drugs that target mitosis*

A

vincristine
vinblastine
paclitaxel
docetaxel

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10
Q

Classifications of chemo drugs

A
alkylating agents*
antimetabolites
tumor antibiotics
vinca alkaloids
platinum derived
hormones
targeted therapy
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11
Q

biggest group of anti-cancer drugs

A

alkylating agents

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12
Q

antimetabolite drugs Mech. of action (MOA)?

A

S phase specific drugs that affect DNA production

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13
Q

Hormone drugs MOA?

A

can induce apoptosis and exert effect on lymphocytes

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14
Q

name one thing that normal cells can usually repair but cancer cells can’t?

A

intra-strand cross-linking

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15
Q

Where are pro-drugs activated?*

A

in the liver via cytochrome P450

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16
Q

Is chlorambucil a pro-drug?

A

NO

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17
Q

Is cyclophosphamide a pro-drug?**

A

YES

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18
Q

How does targeted therapy work?

A

create a specific cocktail of drugs to target a specific kind of cancer

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19
Q

alkylating agents MOA

A

cause intra and inter-strand DNA cross-linking –> prevent replication/ protein synthesis

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20
Q

alkylating agents cell cycle specific/non-spec.?

A

non-specific

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21
Q

Is there cross-resistance among alkylating agents?

A

Yes

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22
Q

Name 4 alkylating agents

A

cyclophosphamide
chlorambucil
lomustine
procarbazine

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23
Q

tissue type most sensitive to chemo drug***

A

bone marrow. Therefore, MYELOSUPPRESSION is the most common side effect of chemotherapy (will by MC question!!)

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24
Q

Where is cyclophosphamide activated/excreted?

A
hepatic activation
renal excretion (<-- reduce dose if p in renal failure!)
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25
Q

Signs of cyclophosphamide toxicity

A

myelosuppression*
GI
sterile hemorrhagic cystitis

transitional cell carcinoma

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26
Q

Acrolein

A

by-product of cyclophosphamide administration. Irritates the bladder lining and can cause cystitis, ulceration, edema, necrosis, etc.
Prevention: do UA to check for blood in urine; stop cyclophosphamide therapy if there is blood

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27
Q

Tx for cyclophosphamide bladder toxicity

A
  • Discontinue chlorambucil and replace with chlorambucil
  • Prednisolone to increase diuresis/inhibit activation of cyclophosphamide
  • Antibiotics
  • MESNA, DMSO

If persistent: N-acetylcysteine

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28
Q

What is SIADHS

A

syndrome of inappropriate ADH secretion

  • results from cyclophosphamide
  • causes PU/PD and electrolyte changes
  • used for many tumor types
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29
Q

excretion of chlorambucil

A

renal

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30
Q

most common uses of chlorambucil

A

-substitute for cytoxan
-chronic lymphocytic leukemia
-feline GI (small cell) lymphoma
(treats low grade forms of cancer)

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31
Q

signs of chlorambucil toxicity

A

mild myelosuppression, GI. Does NOT cause renal toxicity like cyclophosphamide does

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32
Q

Does chlorambucil target rapidly dividing cells well?

A

NO

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33
Q

Which is more irreversible: inter or intra-strand DNA cross-linking?

A

inter

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34
Q

What is the substitute for cyclophosphamide?***

A

chlorambucil

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35
Q

CCNU aka:

A

lomustine

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36
Q

Lomustine has inc/dec. metagenesis compared to cyclophosphamide and chlorambucil? Why?***

A

Increased due to INTER-strand cross-linking.

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37
Q

lomustine class of drug

A

alkylating agent

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38
Q

Chars. of lomustin

A
  • completely absorbed PO
  • INTER-linking
  • highly lipid soluble
  • crosses BBB!
  • “rescue drug” - use when others fail
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39
Q

metabolism/excretion of Lomustin***

A
  • metabolites become active via 1st pass hepatic degradation

- mainly renal excretion, some hepatic via enterohepatic cycle

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40
Q

side effects of lomustin

A

myelosppression
hepatotoxicity**
myelosuppression

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41
Q

what class of drug is procarbazine?

A

alkylating agent

42
Q

signs cisplatin toxicity

A
  • nephrotoxic
  • nausea**
  • fatal pulmonary edema in cats**
43
Q

cisplatin cell cycle specific or non-specific?

A

non-specific

44
Q

cisplatin low/high protein bound?

A

high

45
Q

excretion of cisplatin

A

renal

46
Q

primary uses of cisplatin

A

osteosarcoma

squamous cell carcinoma

47
Q

carboplatin specific or non-specific?

A

non-specific

48
Q

excretion of carboplatin

A

renal

49
Q

signs of carboplatin toxicity

A

myelosuppression

may affect platelets

50
Q

can you use carboplatin in cats?

A

yes

51
Q

advantages of carboplatin

A

fewer GI effects, can use in cats

52
Q

antimetabolites are cell phase specific/non-spec.?***

A

S phase specific

53
Q

chemical composition of antimetabolites

A

purine or pyrimidine analogues

54
Q

Antimetabolite MOA

A

insert into DNA to make it non-functional

55
Q

Name 2 antimetabolite drugs

A

methotrexate

cytosine arabinoside

56
Q

methotrexate MOA

A

Is a dihydrofolate reductase antagonist. (stops folate synthesis in the body

57
Q

Does methotrexate cross BBB?

A

yes

58
Q

signs of methotrexate toxicity

A

myelosuppression
GI
(reversible with leucovorin)

59
Q

uses of methotrexate

A

lymphoma

CNS tumors

60
Q

when is 5-Fluorouracil contraindicated?**

A

in cats (SEIZURES)

61
Q

cytosine arabinoside is removed from circulation by:

A

kidneys

62
Q

cytosine arabinoside metabolized by:

A

liver

63
Q

how is cytosine arabinoside ideally administered?

A

by continous infusion

64
Q

Does cytosine arabinoside cross BBB?

A

Yes

65
Q

most common uses of cytosine arabinoside

A

renal lymphoma
lymphoma rescue
CNS tumors

66
Q

antibiotics are cell cycle phase specific/non-specific

A

non-specific

67
Q

antibiotics usually have a trade-off between efficacy and toxicity

A

:)

68
Q

MOA of anthracyclines

A

free radical damage, inhibition of topoisomerase II (which unwinds DNA)

69
Q

where is doxorubicin metabolized/excreted?

A

metabolized: liver
excreted: kidney

70
Q

side effects of doxorubicin***

A
may turn urine orange/red
anaphylaxis***
vesicant***
cardiotoxicity***
*Do NOT want it to leak out of vein!
71
Q

Protective agent you can give with doxorubicin

A

Dexrezoxane

72
Q

where is mitoxantrone metabolized

A

liver

73
Q

Signs of mitoxantrone toxicity

A

myelosuppression

GI

74
Q

most common uses of mitoxantrone

A

LSA rescue
transitional cell carcinoma
thymomas

75
Q

disadvantages of mitoxantrone

A
  • very expensive*

- turns urine blue-green

76
Q

how is actinomycin D excreted?

A

urine, feces

77
Q

signs of actinomycin D toxicity

A

myelosuppression

GI

78
Q

Does Actinomycin D cross BBB?

A

No

79
Q

most common uses of Actinomycin D

A

lymphoma rescue

non-cardiotoxic substitute for Doxorubicin

80
Q

Name 2 plant alkaloids

A

vincristin

vinblastine

81
Q

plant alkaloids are cell cycle phase specific/non-specific?**

A

M phase (mitosis) specific

82
Q

do plant alkaloids have cross resistance?*

A

no

83
Q

plant alkaloid MOA

A

prevents assembly

84
Q

how are vincristine and vinblastine excreted?

A

Liver (biliary)

85
Q

signs of vincristine toxicity

A
  • vesicant
  • myelosuppression
  • peripheral neuropathy
86
Q

primary uses of vincristine

A

lymphoma
transmissible venereal tumor
thrombocytopenia

87
Q

What are the 2 main drugs that act as vesicants if they get out of vein?

A

vincristine and doxorubicin

88
Q

CHOP protocol includes which drugs

A

Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

89
Q

signs of vinblastine toxicity

A

vesicant

myelosuppression

90
Q

primary uses of vinblastine

A

mast cell tumor

substitute for vincristine

91
Q

prednisone (hormone) MOA

A
  • bind to cytoplasmic receptors & inhibit DNA synthesis

- lympholytic

92
Q

signs of prednisone toxicity

A

PU/PD
polyphagia
panting
GI ulceration

93
Q

primary uses of hormones (i.e. prednisone)

A

lymphoma
mast cell tumor
insulinoma
intracranial neoplasia

94
Q

major caution with hormones (i.e. pred)

A

DO NOT USE WITH NSAIDS

95
Q

signs of L-asparaginase toxicity**

A

anaphylaxis*
potentiate vincristine-induced myelosuppression (not myelosuppressive alone)*
pancreatitis

96
Q

1ary used of L-asparaginase

A

lymphoma

97
Q

Name 2 Targeted Therapy Receptor-Kinase Inhibitors

A

Toceranib

Masitinib

98
Q

Toceranib and Masitinib MOA

A

Target RT-Kinases KIT, PDGF.
**Toceranib also targets VEGF

Many cancers have intuitively activated CKIT, which is blocked by these drugs

99
Q

Toceranib/masitinib side effects

A

related to effect on KIT: myelosuppression, GI, skin, renal

100
Q

1aryuse of Toceranib/masitinib

A

mast cell tumor

101
Q

Which anti-cancer drugs have urinary (renal) excretion?

A
actinomycin D
carboplatin
cisplatin
cyclophosphamide
Minimally: doxorubicin, vincristine, vinblastine
102
Q

Which anti-cancer drugs have biliary (hepatic) excretion?

A

actinomycin D
cisplatin
doxorubicin
vincristine/vinblastine