Neoplastic Drugs Flashcards
What is the action site of antimetabolite neoplastic drugs?
DNA synthesis
What is the action site of alkylating neoplastic agents?
DNA
What is the action site of spindle poisons?
Mitosis
Most normal cells are in the ___ phase of the cell cycle.
Go
Most neoplastic cells are in the ___ phase of the cell cycle.
Go
What is the Goldie-Coleman hypothesis?
1 in 10,000 tumor cells are resistant
What are 3 angiogenic factors influencing tumor success?
- Tumor vessels are disorganized and leaky, so there is poor penetration of the drug
- Tumor centers are necrotic and hypoxemic, so there is little blood supply to allow delivery of the drug
- Acidic environment promotes cell migration and degradation of ECM
What are 3 reasons for using drugs in combination?
- Maximize tumorcidal effects
- Decrease drug resistance
- Minimize toxicities
When using drugs in combination, what are 3 big factors?
- Do not want to overlap toxicities
- Use the maximum tolerated dose
- Want different mechanisms of action
To which cell cycle phase is Vincristine specific?
M phase
What is the MOA of Vincristine?
Binds tubulin and interferes with microtubule disassociation
Where is Vincristine metabolized?
Liver
How is Vincristine excreted?
Via bile
What are the adverse effects associated with Vincristine?
- Myelosuppression
- GI toxicity
- Tissue damage
- Neurotoxicity
Which patients are at an increased risk for adverse effects associated with Vincristine?
MDR-1 mutant dogs
In homozygous MDR-1 mutant dogs, you would reduce the Vincristine dose by ____%.
50%
In heterozygous MDR-1 mutant dogs, you would reduce the Vincristine dose by ____%.
25%
What are 3 uses for Vincristine?
- Lymphoma
- Transmissible venereal tumors
- Immune-mediated diseases
To which cell cycle phase are alkylating agents specific?
None - they are cell cycle phase NON-SPECIFIC
What is the only tumor that is completely cured with chemotherapy?
Transmissible venereal tumor
What is cyclophosphamide?
An alkylating agent
What is the MOA of cyclophosphamide?
Binds exposed hydroxyl, sulfhydryl, or amine groups on DNA or RNA, causing crosslinking
Explain the conversion of cyclophosphamide into its alkylating metabolites.
Cyclophosphamide –> 4-OH-cyclophosphamide –> aldophosphamide –> acrolein + phosphoramide mustard
How is cyclophosphamide primarily excreted?
Renal system
What are 4 adverse effects associated with cyclophosphamide?
- GI effects - anorexia, nausea
- Bone marrow effects - neutropenia
- Hemorrhagic cystitis
- Transitional cell carcinoma
What product of cyclophosphamide causes the hemorrhagic cystitis?
Acrolein
How can the hemorrhagic cystitis associated with cyclophosphamide be prevented?
- Provide access to water
- Give in the AM with diuretic
- Walk often
- Prednisone
What are the uses for cyclophosphamide?
- Lymphoma
- Lymphoid leukemia
- Carcinomas
- Sarcomas
Topoisomerase II inhibitors are derived from soil species ____.
Streptomyces
For which cell cycle phase are Topoisomerase II inhibitors specific?
S phase
What is Doxorubicin?
Topoisomerase II inhibitor
What is the MOA of Doxorubicin?
Intercalates between bases in DNA, resulting in inter and intra-strand breaks
What are the adverse effects associated with Doxorubicin?
- Anaphylaxis
- Myelosuppression
- GI signs - vomiting, anorexia, hemorrhagic gastroenteritis
- Cardiotoxicity
How would you treat cardiotoxicity associated with Doxorubicin use?
Dexrazoxane
How would you prevent cardiotoxicity associated with Doxorubicin?
- Administer slowly
- Screen patients prior (ECG)
- Not exceed 180-240 mg/m^2
What is Dexrazoxane?
Iron chelator
True or False: cardiotoxicity associated with Doxorubicin is seen more in cats than in dogs.
FALSE - seldom seen in cats
What are the uses of Doxorubicin?
- Lymphoma
- Carcinomas
- Sarcomas
- Myeloproliferative diseases
What is the equation for body surface area in m^2?
(K x BW(kg)^2/3) / 10^4
K (dogs) = 10.1
K (cats) = 10.0
Describe the MOA of L-asparaginase.
Hydrolyzes free L-asparagine –> depletes extracellular L-asparagine –> deprives malignant lymphocytes of L-asparagine –> apoptosis
In which cell cycle phase does L-asparaginase act?
G1 phase
When would you use L-asparaginase?
Lymphoma when neutropenia
Neoadjuvant
Shrink large tumors
Adjuvant
Kill cells after surgery
What is the toxicity unique to vincristine?
Neurotoxicity
What is the toxicity unique to doxorubicin?
Cardiotoxicity
What is the toxicity unique to cyclophosphamide?
Hemorrhagic cystitis
What is the rate of complication rate associated with chemotherapeutic drugs?
15%
What is the percentage of chemo patients that require hospitalitzation?
<5%
What is the percentage of chemo patients that will die from therapy?
1%
Which 4 normal cell types are most affected by chemo drugs?
- Bone marrow immature cells
- GI cells
- Hair follicles
- Gametes
Neutrophils are in the bone marrow for ___ - ___ days.
4-6 days
Neutrophils are in circulation for ___ - ___ hours.
4-8 hours
The half life of a RBC is ____ days.
120 days
Hyporrhexia and lethargy are most likely associated with chemo toxicity in ___ - ___ hours after admn.
24-36 hours
Vomiting usually occurs within ___ - ___ hours after chemo.
24-48 hours
GI mucosal cells are replaced every ___ - ___ days.
3-5 days
Diarrhea can develop within ___ - ___ days of chemo administration.
5-7 days
Which chemo drug is most problematic with alopecia?
Doxorubicin
What are the uses of cisplatin?
- SCC
- Osteosarcoma
- Carcinomas
What 2 drugs should NEVER be given to cats?
- Cisplatin
2. 5-FU
What does Cisplatin cause in the cat?
- Pulmonary vasculitis
2. Pulmonary edema
What is 5-FU?
An antimetabolite
What is Cisplatin?
A platinum containing alkylating agent
