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Veterinary Pharmacology > Anti-Neoplastic Drugs, Pt. 3 > Flashcards

Anti-Neoplastic Drugs, Pt. 3 Flashcards

1
Q

Where do most chemotherapeutic drugs exert their effect?

A

rapidly dividing cancer cells, but can also include normal cells that divide rapidly, like cells that line the GI tract, hair cells, and blood cells

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2
Q

What are the 6 major categories of chemotherapeutic drugs?

A
  1. alkylating agents
  2. antimetabolites
  3. plant alkaloids (mitotic inhibitors)
  4. cytotoxic antibiotics
  5. topoisomerase inhibitors
  6. corticosteroids
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3
Q

What are the 3 classes of chemotherapeutic drugs?

A
  1. cell cycle specific (CCS) - antimetabolites (S), vinca alkaloids and taxanes (M), topoisomerase inhibitors (G1-S, G2-M), anti-tumor antibiotics (G2-M)
  2. cell cycle non-specific (CCNS) - alkylating agents, platinum analogs, antibiotics (anthracyclines)
  3. miscellaneous anticancer agents
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4
Q

Cell cycle specific (CCS) chemotherapeutic drugs:

A
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5
Q

What is the mechanism of action of antimetabolites? Where in the cell cycle do they act?

A

interfere with DNA and RNA biosynthesis by preventing de novo nucleotide production - insert themselves into nucleotides to cause DNA breakage and deletion

S phase

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6
Q

What are the 4 classes of antimetabolites?

A

(CCS)
1. antifolates - Methotrexate
2. pyrimidine analogs - 5-Fluorouracil
3. deoxycytidine analogs - Cytarabine, Gemcitabine
4. purine antagonists - 6-Mercaptopurine, 6-Thioguanine

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7
Q

What 3 cancers are treated with Methotrexate? What is another therapeutic use?

A
  1. lymphoma
  2. carcinoma
  3. sarcoma
    (in dogs and cats)

immunosuppressive

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8
Q

What antimetabolite is not commonly included in combination therapy? Why?

A

Methotrexate - high chance of drug interactions

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9
Q

What 3 cancers are treated with 5-Fluorouracil? What animal is it not used in? Why?

A
  1. carcinoma of the GI tract, mammary gland, and lungs
  2. sarcoids
  3. cutaneous sqamous cell carcinoma
    (in horses and dogs)

CATS - causes fatal neurotoxicity

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10
Q

What 2 cancers are treated with Cytarabine and Gemcitabine? What are 2 other therapeutic effects?

A
  1. lymphoreticular neoplasms
  2. CNS lymphoma
    (in dogs and cats)
  • myeloproliferative disease (can cause myelosuppression)
  • granulomatous men
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11
Q

What antimetabolite has the ability to cross the BBB? How does this affect its therapeutic usage?

A

Cytarabine

can be used to treat neoplasms in the brain

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12
Q

What 3 cancers are treated with 6-Mercaptopurine and 6-Thioguanine?

A
  1. acute lymphocytic leukemia
  2. granulocytic leukemia
  3. lymphosarcoma
    (in dogs and cats)
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13
Q

What is the mechanism of action of the 2 classes of microtubule targeting agents?

A
  1. VINCA ALKALOIDS prevent microtubule assembly
    - Vincristine*
    - Vinblastine
    - Vinorelbine
  2. TAXANES prevent microtubule disassembly
    - Paclitaxel (Taxol)
    - Docetaxel

(M PHASE)

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14
Q

What 3 cancers are treated with Vincristine?

A
  1. lymphoreticular neoplasms
  2. carcinomas, sarcomas
  3. transmissible venereal tumors
    (in dogs and cats)
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15
Q

What 2 cancers are treated with Vinblastine?

A
  1. lymphoma
  2. mast cell tumors
    (in dogs and cats)
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16
Q

What cancer is treated with Vinorelbine?

A

pulmonary carcinoma in dogs and cats

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17
Q

What 2 cancers are being investigated to be treated with Paclitaxel? What is another possible therapeutic use?

A
  1. mammary carcinoma
  2. osteogenic osteosarcoma
    (in dogs)

histiocytosis

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18
Q

How are plant alkaloids administered? What does this entail?

A

IV

it is distributed to all but the CNS

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19
Q

What are the 2 mechanisms of action of anti-tumor antibiotics? What part of the cell cycle do they work on?

A
  1. bind to DNA and cause DNA fragmentation via generation of free radicals
  2. mitotic and topoisomerase II inhibitor

G2-M

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20
Q

What 2 antibiotics are used as anti-tumor drugs? Where do they act?

A
  1. Bleomycin - G2 specific, induces DNA damage
  2. Etoposide - G2-M specific, topoisomerase II inhibitor
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21
Q

How is Bleomycin administered?

A

(anti-tumor antibiotic)

electrochemotherapy - electric pulses open cells allowing for a local invasion of chemotherapy into the cells

22
Q

What is the mechanism of action of alkylating agents?

A

(CCNS)

exert cytotoxic effect via the transfer of their alkyl groups to DNA, thereby causing DNA damage

23
Q

What are the 3 classes of cell cycle non-specific chemotherapy drugs?

A
  1. alkylating agents
  2. platinum analogs
  3. antibiotics (Doxorubicin, Epirubicin, Actinomycin D, Mitoxantrone)
24
Q

What are the 2 most common alkylating site on DNA that alkylating agents act on?

A
  1. number 7 (N-7) position of guanine**
  2. O-6 group of the guanine is alkylated by nitrocoureas
25
Q

What does the alkylation of guanine by alkylating agents result in?

A

abnormal nucleotide sequences, causing…
- miscoding mRNA
- cross-linked DNA that cannot replicate
- DNA strand breakage
- other damage to transcription and translation

26
Q

What are the 2 types of alkylating agents? What 3 drugs do not fit into these categories?

A
  1. TYPICAL nitrogen mustards that target N-7
    - cyclophosphamide (Cytoxan)
    - chlorambucil
    - melphalan
    - mechlorethamine
    - ifosfamide
  2. ATYPICAL nitrosoureas that target O-6
    - lomustine
    - carmustine
    - streptozocin (acts via GLUT2)

Dacarbazine, Procarbazine, Hydroxyurea - affect both N7 and O6

27
Q

How does Cyclophosphamide work?

A

CCNS typical alkylating agent

alkylates DNA at N-7 on guanine, which causes cross-linking of base pairs

28
Q

How does Lomustine work? How does it compare to Cyclophasphamide?

A

CCNS atypical alkylating agent

alkylates DNA at O-6 on guanine, forming a covalent bond and is highly lipid-soluble, making it able to cross the BBB and treat brain tumors

29
Q

Which alkylating nitrogen mustard is a prodrug and not used in cats?

A

Cyclophosphamide - activated in the liver

30
Q

Which alkylating nitrogen mustard is associated with less myelosuppression? How does it cause this?

A

Chlorambucil - well-absorbed, slow-acting

31
Q

Which 3 alkylating nitrosoureas are used for CNS neoplasms/malignancies?

A
  1. Lomustine
  2. Carmustine
  3. Procarbazine
32
Q

Which adverse affect is associated with dogs given Streptozocin?

A

CCNS nitrosoureas

toxicity to β-cells diabetes mellitus

33
Q

Which alkylating nitrosoureas is specifically not used in cats?

A

Dacarbazine

34
Q

What are 5 common CCNS alkylating nitrogen mustards?

A
  1. Cyclophosphamide
  2. Chlorambucil
  3. Melphalan
  4. Mechlorethamine
  5. Ifosamide - investigational
35
Q

What are 6 common CCNS alkylating nitrosoureas?

A
  1. Lomustine (BBB)
  2. Carmustine (BBB)
  3. Streptozocin - investigational
  4. Dacarbazine
  5. Procarbazine (BBB)
  6. Hydroxyurea
36
Q

How do the adverse effects of Hydroxyurea compare in dogs and cats?

A

more myelosuppression in cats compared to dogs

37
Q

What is the mechanism of action of platinum analogs?

A

CCNS - cross-links DNA and prevents replication

38
Q

What 3 platinum analogs are commonly used? What do they do?

A
  1. Cisplatin - inorganic metal inhibits cell division
  2. Carboplatin - 2nd gen; less renal and GI toxicity making it better in combination therapy
  3. Oxaliplatin - 3rd gen; no cross-resistance, neurotoxicity is reversible
39
Q

Which platinum analog is not used in cats? Why?

A

Cisplatin

fatal pulmonary toxicity

40
Q

How does Carboplatin compare to Cisplatin?

A
  • less effective in transitional cell carcinoma
  • more effective in malignant melanomas
  • less emetogenic and nephrotoxic effects
41
Q

What is the mechanism of action of CCNS cytotoxic antibiotics? During what phase are they most active? What are they derived from?

A

inhibits topoisomerase II and free radical-mediated DNA damage, inhibiting DNA and RNA synthesis

S phase

Streptomyces fungus

42
Q

What 4 cytotoxic antibiotics are used as CCNS chemotherapy?

A
  1. Doxorubicin (Adriamycin)
  2. Epirubicin (Dox analog)
  3. Actinomycin D
  4. Mitoxantrone
43
Q

What additional action does Actinomycin D have?

A

(CCNS cytotoxic antibiotic) - blocks RNA polymerase

44
Q

What CCNS cytotoxic antibiotic is commonly used to treat prostate cancer?

A

Mitoxantrone

45
Q

What adverse effect is associated with Doxorubicin usage in dogs?

A

chronic cardiomyopathy

46
Q

How does Epirubicin compare to Doxorubicin?

A
  • both CCNS cytotoxic antibiotics
  • is a Doxorubicin analog
  • less cardiotoxic
47
Q

What is the specific mechanism of action of Mitoxantrone? How does it compare to Doxorubicin?

A

(CCNS cytotoxic antibiotic) - topoisomerase II inhibitor

less myelotoxic, cardiotoxic, GI disturbances, anaphylactoid reactions, and tissue damage

48
Q

What are 3 miscellaneous anticancer agents?

A
  1. glucocorticoids
  2. L-asparaginase
  3. Piroxicam
49
Q

How are glucocorticoids used as anticancer agents?

A

CCNS - more active in the G1 phase and inhibits mitosis of lymphocytes

50
Q

How is L-asparaginase used as an anticancer agent? What unique effect does it have?

A

more active in the G1 phase - inhibits asparagine needed for protein synthesis for tumor growth

no myelosuppression when given alone

51
Q

What kind of drug is Piroxicam? How does it work as an anticancer agent? How does its adverse effects compare in dogs and cats?

A

NSAID - COX-2 inhibitor that blocks tumor angiogenesis to limit blood supply

more GI irritation, bleeding, and nephrotoxicity in cats

52
Q

Chemotherapeutic drugs and their MOA:

Veterinary Pharmacology (35 decks)

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