Antineoplastics IV - Fitz Flashcards
What are the common motor symptoms seen in neurotoxicity with Vincristine?
Loss of Reflexes
- Occurs within 2-3 weeks of treatment in 100% of patients
- Used as indication of sufficient dose
What are the common autonomic symptoms seen in neurotoxicity with Vincristine?
Constipation
Paralytic ileus
Orthostatic Hypotension
What are the common sensory symptoms seen in neurotoxicity with Vincristine?
Paresthesias (pins and needles)
If loss of reflexes is followed by severe paresthesias and mild to moderate sensory loss, what does this indicate for Vincristine dosing?
Indication to DECREASE the dose (currently at a toxic level)
Why does treatment with natural product drugs (ie vinca alkaloids and taxanes) lead to multi-drug resistance?
Increased expression of P-glycoprotein
What drugs naturally occurs as cortisol?
Prednisone
Dexamethasone
What is the mechanism of action for Prednisone/Dexamethason?
Interferes with the concentration, distribution and function of leukocytes (increases neutrophils; decreases monocytes, T and B lymphocytes, eosinophils and basophils)
=> results in decreased TNF-a and IL-2 release
Compare the trigger for cell division in cancer cells vs. normal immune system:
Cancer Cells: Unstimulated
Normal Immune System: Specific Antigen
Compare the cell division in cancer cells vs. normal immune system:
Cancer Cells: Random
Normal Immune System: Syncrhonized
Compare the drug administration in chemotherapy vs. immunosuppression:
Chemo: High Dose - Pulse cycles
Immunosuppression: Low Dose - Continuous
When are antibodies and fusion proteins prescribed?
When traditional chemotherapy has failed or when patient factors (especially age) prevent cytotoxic drug use
What is the goal of using antibodies as therapeutic proteins?
Use the immune system to suppress itself by getting it to recognize and kill cells that express a particular antigen
How are cytokines cytotoxic?
They recruit the immune cells to do recognize the tumor cells as foreign and kill them
What drug is known for causing a cytokine storm and what is this?
IL-2
Activation and expansion of lytic lymphocytes causing inflammation, vascular leak syndrome, secondary release of cytokines (TNF and IFN-a)
What is palmar-plantar erythrodysesthesia?
Hand-foot syndrome
What is the number one complication of antineoplastic drugs?
Bone Marrow Suppression = Dose Limiting Complication
What is the role of tyrosine kinases?
Phosphorylate Tyrosine Residues
What are important regulators of intracellular signal transduction pathways responsible for development and multicellular communication?
Tyrosine Kinases
How does Trastuzumab work?
Antibody binds to the HER2 receptor, interfering with signaling and identifying HER2 overexpressing cells as foreign
How does Pertuzumab work?
First antineoplastic Dimerization Inhibitor
Prevents HER2 from dimerizing with other HER receptors
How does Ado-Trastuzumab Emtansine work?
Internalized and undergoes lysosomal degradation to:
Trastuzumab and DM1 (disrupts microtubule network by binding tubulin)
Describe the synergistic cytotoxicity in giving Methotrexate and then L-Asparaginase.
Methotrexate cell killing is dependent upon synthesis of enzymes necessary for DNA synthesis (DNFR and Thymidylate Synthase)
By giving L-Asparaginase (Asparagine -> Aspartate) after MTX, you shut down any remaining DNA synthesis by depriving the ALL cancer cell of Asparagine (cells already lack asparagine synthetase so they can’t convert Aspartate -> Asparagine)
What first generation HDAC inhibitor that is used as a mood stabilizer and an antiepileptic is being explored for cancer treatment?
Valproic Acid
What other diseases are HDAC inhibitors being used for?
Huntington’s Disease
ALS
