Anti-neoplastic pharmacology

Question 1

When is treatment best given?

Answer 1

Early - when tumour/metastasis are small

Sigmoid growth - large tumours less response to Tx

Question 2

What should be considered for anti-neoplastic therapy?

Answer 2

Tumour growth kinetics (grow fastest when small)
Naturally resistant populations
Factors influencing drug penetration of tumour
Patient signalment etc

Question 3

How can we overcome chemotherapy resistance?

Answer 3

Multidrug chemotherapy - broaden range of cells sensitive to Tx
High dose - reduces number of resistant cells (give maximum tolerated dose)

Question 4

If treatments are ideally spaced, how should normal tissue grow and tumour tissue grow?

Answer 4

Normal tissue growth should remain constant (normal rate)

Tumour tissue growth decreases

Question 5

What happens if treatments are too close together?

Answer 5

Toxicity causes normal cells to die as well as tumour tissues

Question 6

What happens if treatments are too far apart?

Answer 6

Tumour tissue continues to grow

Question 7

Some chemotherapies are genotoxic. What does this mean?

Answer 7

Kills DNA

Question 8

What are the 2 ways chemotherapies prevent tumour cell replication?

Answer 8

Damage DNA - non-cell cycle specific

Inhibit DNA replication - cell cycle specific

Question 9

In untargeted chemotherapy, rapidly dividing cells are most affected. What are these 3 tissues?

Answer 9

BAG
Bone marrow - WBCs and RBCs
Alopecia - hair loss
GI - can allow infections and sepsis

Question 10

What factors affect response to chemotherapy and side effects?

Answer 10

ADME
Metabolism - 
Administration
Distribution - ability to reach target site
Excretion

Question 11

Chemotherapy drugs include alkylators. How do they cause tumour cell death? Are they cell cycle specific or not?

Answer 11

Insert alkyl group into DNA
Alters transcription and replication
If not repaired - apoptosis
Non-specific

Question 12

Give an example of an alkylator

Answer 12

Lomustine

Question 13

How do anti-tumour antibiotics work? Are they cell cycle specific or non-specific?

Answer 13

Cause DNA damage

Non-specific

Question 14

Give an example of an anti-tumour antibiotic?

Answer 14

Doxorubicin

Question 15

How do platinizing agents work as chemotherapy drugs? Are they cell cycle specific or non-specific? Give an example

Answer 15

Platinum inserted into DNA 
Alters transcription and replication 
If not repaired - apoptosis
Non-specific
Carboplatin

Question 16

How do vinca-alkaloids work as chemotherapy drugs? Are they cell cycle specific? Give an example

Answer 16

Prevent spindle form during mitosis
Cell cycle specific
Vinblastine

Question 17

How do antimetabolites work as chemotherapy drugs? Are they cell cycle specific or non-specific?

Answer 17

Interact with DNA production pathways

Specific

Question 18

What is metronomic chemotherapy?

Answer 18

Repeated administration of chemotherapy drug, at low dose without drug free periods

Question 19

L’asapraginase is an enzyme used as a biotherapy for which type of cancer? How does this cause cell death?

Answer 19

Lymphoma

Lymphomas dependent on asparagine

Question 20

Give examples of a glucocorticoid that can be used as a biotherapy drug for tumours

Answer 20

Prednisolone

Question 21

How can NSAIDs be used as a biotherapy drug for tumours? Give an example of a drug

Answer 21

Some tumours COX-2 dependent

Meloxicam, piroxicam

Question 22

How do tyrosine kinase inhibitors work as biotherapy for cancer? Give an example

Answer 22

Competitive inhibitors for receptor tyrosine kinase
block ATP binding site
Mastinib

Question 23

Immunotherapy can be used to treat cancer. What are the 2 broad approaches?

Answer 23

Active immunotherapy - stimulate immune system against tumour (active cytotoxic T cells)
Passive immunotherapy - use monoclonal antibodies to target immune response at tumour (in development)

Question 24

Give an example of a non-specific immune stimulator

Answer 24

Iquimod

Question 25

Anticancer therapeutic vaccinations can be given as part of immunotherapy for tumours. Give an example of a cancer this is effective against

Answer 25

Melanoma

Question 26

What is the most common canine skin tumour?

Answer 26

Mast cell tumour | Mast cells in connective tissue, release histamine among other things

Question 27

What controls growth of normal mast cells? Why is mast cell cancer common?

Answer 27

KIT TK receptor | Mutations in this receptor common

Question 28

Which dog breeds are sensitive to vinca alkaloids?

Answer 28

Whippet Collie Westie

Question 29

List 2 chemotherapy drugs that act in a cell cycle specific manner

Answer 29

Vinca-alkaloids | Antimetabolites

Question 30

List 3 chemotherapy drugs that act in a non-cell cycle specific manner

Answer 30

Alkylators Anti-tumour antibiotics Platinating agents

Question 31

Is L'asparaginase more effective to treat lymphomas in cats or dogs?

Answer 31

Dogs