Chemotherapy Flashcards
What are some of the difficulties with chemotherapy drugs?
- 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)
What is the hardest part for clients to deal with and why is it important for them to understand?
adverse events are severe and very demanding, often clients dont want to deal with
think quality vs quantity of life
What are the three classes of Chemo drugs?
cycle non-specific: kills at all phases
cycle specific: spare resting cells (G0)
Phase specific: only specific phases
What is MOA of alkylating agents (nitrogen mustards) used for chemo?
binding of DNA bases, cross linking dsDNA = abnormal pairing and misreading, no replication = cell death
Cell cycle non-specific
toxic to rapidly growing cells
What are two alkylating agents drugs (nitrogen mustards)?
cyclophosphamide (procytox)
chlorambucil (leukeran)
What is cyclophosphamide used for, AE, and important things to know?
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
What is the use of Chlorambucil (leukeran)?
similar to cyclophosphamide
less potent (decreased myelosuppresion, vomitting
expensive (cats and dogs)
used for immunosuppresive for cats after predisone
What is the MOA of alkylating agents (nitrosoureas)?
also cross link DNA
What is one used nitrosourea? its use and AE?
CCNU (lomustine)
- great oral F
use: crosses BBB (brain tumors), lymphoma and mast cell tumours
AE: leukopenia, thrombocytopenia
What is a nitrosourea used for insulinomas?
streoptozocin (Zanosar)
- toxic to pancreatic B-cells
AE: tubular necrosis (use only with IV diruesis), type 1 diabetes, vomiting in dogs
What is the mechanism of action of platinum based chemotherapy drugs?
binds to DNA bases cross linking around the platinum ion rather than alkyl group, therefor inhibiting DNA synthesis
What are two platinum based drugs?
Cisplatin (platinol)
Carboplatin (paraplatin)
What is the USE and AE of Cisplatin?
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
Which animal should not be given cisplatin for chemotherapy?
Cats
- fatal pulmonary edema
What is the comparison of carboplatin to cisplatin?
less nephrotoxic than cisplatin
carboplatin causes thrombocytopenia
safe for cats
What is a conjunctive therapy used for osteosarcoma that is not a chemo drug?
Bisphosphonates
Drug: pamidronate
What are the MOA and AE of pamidronate?
- inhibits osteoclasts (decreases bone resorption)
- must treat hypercalcemia of malignancy
AE: renal excretion - nephropathy
What is the MOA of anti-metabolites (cellular enzyme inhibitors)?
inhibit nucleic acid synthesis by binding to cellular enzymes responsible for Purine or Pyrimidine synthesis
What drug is a cellular enzyme inhibitor?
Fluorouracil (5FU)
What does 5FU do, whats its use and AE?
binds and inactivates thymidylate synthetase, required for aynthesis of thymine
USE: squamous cell carcinoma in horses (topical or IV)
What animal should not be given 5FU and why?
NO for CATS
- neuro and hepatotoxic
What is the only vet approved chemodrug?
Rabacfosadine (tanova)
What is the use and AE of tanova?
used for lymphomas
PK: prodrug converted multiple steps to active form in cells
IV over 30mins
AE: fatal pulmonary fibrosis
What breed of dog should not be administered Tanova?
West Highland White Terrier
What are two enzyme chemotheraphy drugs?
Toceranib (palladia)
L-asparaginase (kidrolase)
What is the MOA and use of Toceranib?
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)
What is the MOA, use and AE of L-asparaginase?
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
What is the mOA of vinca alkaloids used for chemotherapy?
from periwinkle plant
binds tubulin protein, intereferes with microtubules needed for chromosomal migration
What drug is a vinca alkaloid?
Vincristine (oncovin)
What is Vincristine used for and what are the AE?
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
What antibiotic is used for anti-tumour chemo?
Doxorubicin (andriamycin) “red death”
What is the MOA of doxorubicin?
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)
what is Doxorubicin used for? PK?
lymphosarcoma, osteosarcoma, mammary carcinomas and other tumours
administer SLOW IV
plasma concen 20-30h
metabolized by liver (limited bile flow must alter dose)
What are some serious and less serious AE of doxorubicin?
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
What Sx can help with mammary tumours?
Spaying
- b/c they are estrogen responsive
What is a plant derives chemotherapy?
Paclitaxel (taxol)
What is the MOA, use and AE of Paclitaxel?
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)
Why are glucocorticoids used for chemotherapy? what do they do?
palliative care
they lys lymphoid cells decrease inflammation from cancer or chemotherapy decrease AE stimulates appetite and attitude decrease cachexia from TNF
What NSAIDs are used and how do they help?
Piroxicam/meloxicam
- for transitional cell (bladder) carcinoma
deracoxib for osteosarcoma
Does chemotherapy drug resistance happen?
yes
