Chemotherapy

Question 1

What are some of the difficulties with chemotherapy drugs?

Answer 1

• 99.9% killed but 0.1% left still contains a lot of cells
• no immune back up
• PK not well known with animals
• small therapeutic window (small margin of safety)
• dose based on SA not BW (correlated with metabolic weight), hard to measure
• can develope resistance (multidrug protocol)

Question 2

What is the hardest part for clients to deal with and why is it important for them to understand?

Answer 2

adverse events are severe and very demanding, often clients dont want to deal with
think quality vs quantity of life

Question 3

What are the three classes of Chemo drugs?

Answer 3

cycle non-specific: kills at all phases
cycle specific: spare resting cells (G0)
Phase specific: only specific phases

Question 4

What is MOA of alkylating agents (nitrogen mustards) used for chemo?

Answer 4

binding of DNA bases, cross linking dsDNA = abnormal pairing and misreading, no replication = cell death

Cell cycle non-specific

toxic to rapidly growing cells

Question 5

What are two alkylating agents drugs (nitrogen mustards)?

Answer 5

cyclophosphamide (procytox)

chlorambucil (leukeran)

Question 6

What is cyclophosphamide used for, AE, and important things to know?

Answer 6

used for: carcinomas, sarcomas, feline lymphoproliferative diseases, mammary carcinomas, lymphoma

AE: bone marrow toxicity (leukopenia, thrombocytopenia, cat marrow suppression), vomiting, diarrhea
hemorrhagic cycstitis (minimize with furosemide), alopecia

Its a prodrug: need hepatic function

Question 7

What is the use of Chlorambucil (leukeran)?

Answer 7

similar to cyclophosphamide
less potent (decreased myelosuppresion, vomitting
expensive (cats and dogs)
used for immunosuppresive for cats after predisone

Question 8

What is the MOA of alkylating agents (nitrosoureas)?

Answer 8

also cross link DNA

Question 9

What is one used nitrosourea? its use and AE?

Answer 9

CCNU (lomustine)

• great oral F
  use: crosses BBB (brain tumors), lymphoma and mast cell tumours

AE: leukopenia, thrombocytopenia

Question 10

What is a nitrosourea used for insulinomas?

Answer 10

streoptozocin (Zanosar)
- toxic to pancreatic B-cells
AE: tubular necrosis (use only with IV diruesis), type 1 diabetes, vomiting in dogs

Question 11

What is the mechanism of action of platinum based chemotherapy drugs?

Answer 11

binds to DNA bases cross linking around the platinum ion rather than alkyl group, therefor inhibiting DNA synthesis

Question 12

What are two platinum based drugs?

Answer 12

Cisplatin (platinol)

Carboplatin (paraplatin)

Question 13

What is the USE and AE of Cisplatin?

Answer 13

USE: solid tumors (osetosarcoma, carcinoma, mast cell tumors, skin tumors in horses (sarcoids)
- multimodal with surgery or amputation

AE: nephrotoxicity, fatal pulmonary edema in cats, vomiting and diarrhea

Question 14

Which animal should not be given cisplatin for chemotherapy?

Answer 14

Cats

- fatal pulmonary edema

Question 15

What is the comparison of carboplatin to cisplatin?

Answer 15

less nephrotoxic than cisplatin
carboplatin causes thrombocytopenia
safe for cats

Question 16

What is a conjunctive therapy used for osteosarcoma that is not a chemo drug?

Answer 16

Bisphosphonates

Drug: pamidronate

Question 17

What are the MOA and AE of pamidronate?

Answer 17

• inhibits osteoclasts (decreases bone resorption)
• must treat hypercalcemia of malignancy

AE: renal excretion - nephropathy

Question 18

What is the MOA of anti-metabolites (cellular enzyme inhibitors)?

Answer 18

inhibit nucleic acid synthesis by binding to cellular enzymes responsible for Purine or Pyrimidine synthesis

Question 19

What drug is a cellular enzyme inhibitor?

Answer 19

Fluorouracil (5FU)

Question 20

What does 5FU do, whats its use and AE?

Answer 20

binds and inactivates thymidylate synthetase, required for aynthesis of thymine
USE: squamous cell carcinoma in horses (topical or IV)

Question 21

What animal should not be given 5FU and why?

Answer 21

NO for CATS

- neuro and hepatotoxic

Question 22

What is the only vet approved chemodrug?

Answer 22

Rabacfosadine (tanova)

Question 23

What is the use and AE of tanova?

Answer 23

used for lymphomas
PK: prodrug converted multiple steps to active form in cells
IV over 30mins
AE: fatal pulmonary fibrosis

Question 24

What breed of dog should not be administered Tanova?

Answer 24

West Highland White Terrier

Question 25

What are two enzyme chemotheraphy drugs?

Answer 25

Toceranib (palladia) | L-asparaginase (kidrolase)

Question 26

What is the MOA and use of Toceranib?

Answer 26

inhibits tyrosine kinase (slows down a bunch of growth factors that provide tumour with blood) - not technically chemo USE: cutaneous mast cell sarcoma (with or without lymph involvement)

Question 27

What is the MOA, use and AE of L-asparaginase?

Answer 27

MOA: breaks down asparagine to aspartic acid, interferes with protein synthesis USE: some lymphoma protocols, melanoma and mast cell tumors AE: hypersensitivity reactions, minimal myelosupression - give antihistamine before

Question 28

What is the mOA of vinca alkaloids used for chemotherapy?

Answer 28

from periwinkle plant | binds tubulin protein, intereferes with microtubules needed for chromosomal migration

Question 29

What drug is a vinca alkaloid?

Answer 29

Vincristine (oncovin)

Question 30

What is Vincristine used for and what are the AE?

Answer 30

use: lymphoma protocols, other tumors, immune mediated thrombocytopenia (doesn't allow lysosomes within macrophages to destroy platelets) AE: tissue necrosis (perivascular), peipheral neuropathy, constipation, can cause neutropenia

Question 31

What antibiotic is used for anti-tumour chemo?

Answer 31

Doxorubicin (andriamycin) "red death"

Question 32

What is the MOA of doxorubicin?

Answer 32

kills throughout the cell (mostly S phase) - intercalates between bases of DNA molecules, blocking RNA transcription and protein synthesis - binds to cell membranes and alters ion transport (generates free radicals)

Question 33

what is Doxorubicin used for? PK?

Answer 33

lymphosarcoma, osteosarcoma, mammary carcinomas and other tumours administer SLOW IV plasma concen 20-30h metabolized by liver (limited bile flow must alter dose)

Question 34

What are some serious and less serious AE of doxorubicin?

Answer 34

perivascular necrosis bone marrow supression cardiotoxicity (Fe builds up cardiomyocytes, - Acute: cardiac arrest or ECG changes - chronic: diffuse cardiomyopathy and cong HF alopecia, GI, hypersensitivity from mast cell degranulation

Question 35

What Sx can help with mammary tumours?

Answer 35

Spaying | - b/c they are estrogen responsive

Question 36

What is a plant derives chemotherapy?

Answer 36

Paclitaxel (taxol)

Question 37

What is the MOA, use and AE of Paclitaxel?

Answer 37

From yew tree MOA: polymerizes and renders useless the microtubule (similar to vincristine) USE: many tumours in humans AE: hypersensitivity (serious, pretreat with antihistamine, steroids, H2 blockers), Pgyp substrate (test ABCB1)

Question 38

Why are glucocorticoids used for chemotherapy? what do they do?

Answer 38

palliative care ``` they lys lymphoid cells decrease inflammation from cancer or chemotherapy decrease AE stimulates appetite and attitude decrease cachexia from TNF ```

Question 39

What NSAIDs are used and how do they help?

Answer 39

Piroxicam/meloxicam - for transitional cell (bladder) carcinoma deracoxib for osteosarcoma

Question 40

Does chemotherapy drug resistance happen?

Answer 40

yes