Flashcards in Fitz- Antimitotics and Antineoplastics Deck (37):
Compare the mechanism of action among anti-mitotic drugs:
Vinca alkaloids: Prevent extension of spindles
Taxanes: Enhance assembly
Epilone: Enhance spindle assembly
What is the primary advantage of ixabepilone w/ respect to development of resistance?
It is NOT limited by MDR (p-glycoprotein)
What are the mechanisms of resistance for VA and taxanes?
VA- decrease accumulation by increasing p glycoprotein, change tubulin so the drug doesn't bind
What toxicities are associated w/ VA?
cytotoxic- BMS, N/V
vinCristine is related to ______toxicity, so it's more likely to be ___________.
Cns toicity (more lipid soluble--> fatal intrathecally)
vinBlastine is realted to __________, so it's more like to cause
cytotoxic sxs: BMS and N and V
When treating with vincristine, what does a loss of reflexes show? What does parasthesis show?
Loss of reflexes occurs in 100% of pts ands is a sign that you have titrated the drug correctly.
Parasthesis (pins and needles) is a severe side effect and suggests that you should decrease the dose.
What toxicities are associated w/ taxanes?
hypotension and arrythmias
What are the main differences in the use of glucocorticoids for cancer chemotherapy vs. immunosuppression?
Immunosuppression: glucocorticoids are given at a continuous low dose (targets specific antigens and synchronized cell division)
Cancer chemotherapy: glucocorticoids are given at a HIGH dose, pulse (allows normal cells to recover) (cell division is unstimulated and random)
What cytokines have been approved for use in cancer treatment?
How do the MOAs differ for the three cytokines?
IL-2-Induce and expand T cell
INF alpha- decrease FGF and decrease cell division
TNF alpha- causes fibroblast proliferation, increases IL-6 and 8 to activate B and T cells
Which cytokine has a t 1/2 of 13 mins and can cause fatal hypotension and a coma?
It must be given continously or in multiple daily doses
Which cytokine causes BMS and depression?
Which cytokine has a short half life and causes flu-like sxs?
What monoclonal ab targets anti-CD 20 B cells?
What monoclonal ab targets anti-CD 53 B cells?
What monoclonal ab targets IL-2 and diptheria toxin?
What are the common side effects of monoclonal antibodies?
What monoclonal antibodies cause heart or lung toxicity?
What monoclonal antibodies cause tumor lysis syndrome?
What are the vinca alkaloids?
What are taxanes?
What is ixabepilone?
What type of drug resistance is commonly seen with vinca alkaloids?
Increased expression of p glycoprotein
Why is ixabepilone often approved for use in breast cancer pts who have failed anthracycline antibioitc and taxane treatments?
Because it DOES NOT produce MDR
This drug when used for cancer chemo therapy is given in higher doses w/ a "pulse" regimen.
Dexamethasone and prednisone
What immunosuppressive antibioitcs are used to prevent rejection following bone marrow transplants?
What immunosuppressive antibiotics are used as angiogenesis inhibitors?
Immunosuppressive antibiotics play a role in what two pathways?
1. NFAT mediated regulation of IL synthesis
2. mTOR regulation of cell growth and angiogenesis
What are the common characteristics shared by cytokines used for cancer chemotherapy?
Short half lives
NOT cytotoxic by themselves--> recruit immune cells to do the actual killing
How are monoclonal antibodies used as drugs and what do they target?
They can selectively recruit the immune system to destroy cancer cells (specifically ones w/ molecular targets that distinguish cancer cells from normal cells)
They target CDs and surface proteins.
What is the common dose limiting complication of many antineoplastic drugs?
To combat BMS colony stimulating factors have been developed. What do they do?
Sagramostim- gm-csf--> granulocytes, eosinophils, basophils, monocytes
IL-11 and THrobopoietin--> platelets
What protein function inhibitors target a unique aspect of a specific cancer type?
What protein function inhibitors target less specific cancer types and exploit the overexpression of a particular protein?
What drugs target rapidly dividing cells and/or angiogenesis?