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Pharmacology > Neoplastic Drugs > Flashcards

Neoplastic Drugs Flashcards

1
Q

What is the action site of antimetabolite neoplastic drugs?

A

DNA synthesis

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2
Q

What is the action site of alkylating neoplastic agents?

A

DNA

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3
Q

What is the action site of spindle poisons?

A

Mitosis

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4
Q

Most normal cells are in the ___ phase of the cell cycle.

A

Go

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5
Q

Most neoplastic cells are in the ___ phase of the cell cycle.

A

Go

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6
Q

What is the Goldie-Coleman hypothesis?

A

1 in 10,000 tumor cells are resistant

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7
Q

What are 3 angiogenic factors influencing tumor success?

A
  1. Tumor vessels are disorganized and leaky, so there is poor penetration of the drug
  2. Tumor centers are necrotic and hypoxemic, so there is little blood supply to allow delivery of the drug
  3. Acidic environment promotes cell migration and degradation of ECM
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8
Q

What are 3 reasons for using drugs in combination?

A
  1. Maximize tumorcidal effects
  2. Decrease drug resistance
  3. Minimize toxicities
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9
Q

When using drugs in combination, what are 3 big factors?

A
  1. Do not want to overlap toxicities
  2. Use the maximum tolerated dose
  3. Want different mechanisms of action
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10
Q

To which cell cycle phase is Vincristine specific?

A

M phase

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11
Q

What is the MOA of Vincristine?

A

Binds tubulin and interferes with microtubule disassociation

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12
Q

Where is Vincristine metabolized?

A

Liver

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13
Q

How is Vincristine excreted?

A

Via bile

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14
Q

What are the adverse effects associated with Vincristine?

A
  1. Myelosuppression
  2. GI toxicity
  3. Tissue damage
  4. Neurotoxicity
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15
Q

Which patients are at an increased risk for adverse effects associated with Vincristine?

A

MDR-1 mutant dogs

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16
Q

In homozygous MDR-1 mutant dogs, you would reduce the Vincristine dose by ____%.

A

50%

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17
Q

In heterozygous MDR-1 mutant dogs, you would reduce the Vincristine dose by ____%.

A

25%

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18
Q

What are 3 uses for Vincristine?

A
  1. Lymphoma
  2. Transmissible venereal tumors
  3. Immune-mediated diseases
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19
Q

To which cell cycle phase are alkylating agents specific?

A

None - they are cell cycle phase NON-SPECIFIC

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20
Q

What is the only tumor that is completely cured with chemotherapy?

A

Transmissible venereal tumor

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21
Q

What is cyclophosphamide?

A

An alkylating agent

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22
Q

What is the MOA of cyclophosphamide?

A

Binds exposed hydroxyl, sulfhydryl, or amine groups on DNA or RNA, causing crosslinking

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23
Q

Explain the conversion of cyclophosphamide into its alkylating metabolites.

A

Cyclophosphamide –> 4-OH-cyclophosphamide –> aldophosphamide –> acrolein + phosphoramide mustard

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24
Q

How is cyclophosphamide primarily excreted?

A

Renal system

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25
Q

What are 4 adverse effects associated with cyclophosphamide?

A
  1. GI effects - anorexia, nausea
  2. Bone marrow effects - neutropenia
  3. Hemorrhagic cystitis
  4. Transitional cell carcinoma
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26
Q

What product of cyclophosphamide causes the hemorrhagic cystitis?

A

Acrolein

27
Q

How can the hemorrhagic cystitis associated with cyclophosphamide be prevented?

A
  1. Provide access to water
  2. Give in the AM with diuretic
  3. Walk often
  4. Prednisone
28
Q

What are the uses for cyclophosphamide?

A
  1. Lymphoma
  2. Lymphoid leukemia
  3. Carcinomas
  4. Sarcomas
29
Q

Topoisomerase II inhibitors are derived from soil species ____.

A

Streptomyces

30
Q

For which cell cycle phase are Topoisomerase II inhibitors specific?

A

S phase

31
Q

What is Doxorubicin?

A

Topoisomerase II inhibitor

32
Q

What is the MOA of Doxorubicin?

A

Intercalates between bases in DNA, resulting in inter and intra-strand breaks

33
Q

What are the adverse effects associated with Doxorubicin?

A
  1. Anaphylaxis
  2. Myelosuppression
  3. GI signs - vomiting, anorexia, hemorrhagic gastroenteritis
  4. Cardiotoxicity
34
Q

How would you treat cardiotoxicity associated with Doxorubicin use?

A

Dexrazoxane

35
Q

How would you prevent cardiotoxicity associated with Doxorubicin?

A
  1. Administer slowly
  2. Screen patients prior (ECG)
  3. Not exceed 180-240 mg/m^2
36
Q

What is Dexrazoxane?

A

Iron chelator

37
Q

True or False: cardiotoxicity associated with Doxorubicin is seen more in cats than in dogs.

A

FALSE - seldom seen in cats

38
Q

What are the uses of Doxorubicin?

A
  1. Lymphoma
  2. Carcinomas
  3. Sarcomas
  4. Myeloproliferative diseases
39
Q

What is the equation for body surface area in m^2?

A

(K x BW(kg)^2/3) / 10^4

K (dogs) = 10.1

K (cats) = 10.0

40
Q

Describe the MOA of L-asparaginase.

A

Hydrolyzes free L-asparagine –> depletes extracellular L-asparagine –> deprives malignant lymphocytes of L-asparagine –> apoptosis

41
Q

In which cell cycle phase does L-asparaginase act?

A

G1 phase

42
Q

When would you use L-asparaginase?

A

Lymphoma when neutropenia

43
Q

Neoadjuvant

A

Shrink large tumors

44
Q

Adjuvant

A

Kill cells after surgery

45
Q

What is the toxicity unique to vincristine?

A

Neurotoxicity

46
Q

What is the toxicity unique to doxorubicin?

A

Cardiotoxicity

47
Q

What is the toxicity unique to cyclophosphamide?

A

Hemorrhagic cystitis

48
Q

What is the rate of complication rate associated with chemotherapeutic drugs?

A

15%

49
Q

What is the percentage of chemo patients that require hospitalitzation?

A

<5%

50
Q

What is the percentage of chemo patients that will die from therapy?

A

1%

51
Q

Which 4 normal cell types are most affected by chemo drugs?

A
  1. Bone marrow immature cells
  2. GI cells
  3. Hair follicles
  4. Gametes
52
Q

Neutrophils are in the bone marrow for ___ - ___ days.

A

4-6 days

53
Q

Neutrophils are in circulation for ___ - ___ hours.

A

4-8 hours

54
Q

The half life of a RBC is ____ days.

A

120 days

55
Q

Hyporrhexia and lethargy are most likely associated with chemo toxicity in ___ - ___ hours after admn.

A

24-36 hours

56
Q

Vomiting usually occurs within ___ - ___ hours after chemo.

A

24-48 hours

57
Q

GI mucosal cells are replaced every ___ - ___ days.

A

3-5 days

58
Q

Diarrhea can develop within ___ - ___ days of chemo administration.

A

5-7 days

59
Q

Which chemo drug is most problematic with alopecia?

A

Doxorubicin

60
Q

What are the uses of cisplatin?

A
  1. SCC
  2. Osteosarcoma
  3. Carcinomas
61
Q

What 2 drugs should NEVER be given to cats?

A
  1. Cisplatin

2. 5-FU

62
Q

What does Cisplatin cause in the cat?

A
  1. Pulmonary vasculitis

2. Pulmonary edema

63
Q

What is 5-FU?

A

An antimetabolite

64
Q

What is Cisplatin?

A

A platinum containing alkylating agent

Pharmacology (21 decks)

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