Exam 3: Cancer Flashcards
What are the common toxicites that cancer chemotherapy has on rapidly growing cells?
- Bone marrow destruction
- Stomatitis, dysphasia, diarrhea
- Alopecia
- nephrotoxic
- teratogenic
What are the alkylating agents for cancer chemotherapy?
- Cyclophosphamide
- Cisplatin
- Carmustine
What are the antimetabolites for cancer chemotherapy?
- Methotrexate
- 6 mercaptopurine
- 5 Fluorouracil
What are the antibiotics for cancer chemotherapy?
- Doxorubicin Hydrochloride
- Belomycin Sulfate
What are the plant alkaloids for cancer chemotherapy?
-Vincristine sulfate
Vinblastine Sulfate
-Paclitaxel
What are the tyrosine kinase inhibitors for cancer chemotherapy?
Imatinib
What are the growth factor receptor inhibitors for cancer chemotherapy?
- Erlotinib
- Cetuximab
- Bevacizumab
What are the non-specific cell cycle drugs?
The alkylating agents and doxorubicin
What is the MOA of Alkylating agents?
- Not cell cycle specific
- Alkylate DNA causing miscoding, breakage, and crosslinking
What is the common toxicity associated with alkylating agents?
Vesicant- bulla tend to develop at injection sites
What is Cyclophosphamide used for?
Broad spectrum of uses- breast, ovarian, non-Hodgkins.
-Form
What is the toxicity associated with Cyclophosphamide and how do you combat this?
It forms acrolein which causes hemorrhagic cystitis. This is prevented/treated with MESNA and hydration
What is carmustine used for?
It is able to cross the BBB so used for brain cancer, also Hodgkins and non Hodgkin’s lymphoma
What is cisplatin used for?
-Broad spectrum-testicular, NSC and SC lung cancer, esophageal, ovarian, bladder
What are the side effects of cisplatin and how can this be combated?
- Renal toxicity: reduced with amifostine
- Acoustic nerve damage, permanent. Sodium thiosulfate may be able to reduce this.
What is the MOA of doxorubicin?
Intercalated into DNA and destroys it
What is doxorubicin used for?
-One of the most important anti cancer drugs, widely used for lymphomas, leukemia’s, sarcoma, breast, thyroids, etc.
What is the main toxicity associated with doxorubicin?
Cardiotoxic- generates free radicals which can be toxic. Toxicity is increased by iron so used with iron chelator
What drugs affect the S phase?
The antimetabolites
What drug affects the M phase?
Paclitaxel, vincristine, and vinblastine
What drugs affect G2-M phase?
Bleomycin
What is the MOA of methotrexate?
Inhibits dihydrofolate reductase
What is can be given with methotrexate as a rescue?
Leucovorin to decrease toxicity from folate deficiency.
Given AFTER methotrexate
What are the common side effects of methotrexate?
Mucositis, thrombocytopenia, nephrotoxicity, and diarrhea.
**hepatotoxicity when used long term has an immunosuppressive.
What is the MOA fo Mercaptopurine?
Converted by HGPRT to a ribonucleotide and inhibits DNA and RNA synthesis
How does resistance against 6 mercaptopurine develop?
Levels of HGPRT decrease
What is the important relationship between 6 mercaptopurine and allopurinol?
Azathioprine is metabolized to 6 mercaptopurine which is metabolized by xanthine oxidase. Allopurinol inhibits xanthine oxidase metabolism. If a patient is taking allopurinol, dose of azathioprine must be reduced significantly because it can result in fatal blood dyscrasias
What drug is often given with 6 mercaptopurine and why?
Leukovorin used as a “rescue” to decrease toxicity to other cell types. Given after 6-MP
What is the MOA of 5-fluorouracil?
Inhibits thymidylate synthetase- blocks DNA synthesis
What happens when 5-fluorouracil is given with Leukovorin?
The response to 5-FU is increased. Leukovorin should be given prior to 5-FU administration.
-Leukovorin is converted to 5-MTHF which ultimately ends up enhancing thymidylate synthase inhibition
What are the common adverse side effects with 5-FU?
Oral and GI ulceration
What is the MOA of bleomycin?
Cell cycle specific at G2 and M.
-Binds directly to DNA
What are the adverse effects of Bleomycin?
- Myleosuppresion
- Pulmonary fibrosis
- Hypersensitivty
What is the MOA of Vincristine/Vinblastine?
- binds to tubulin interfering with microtubules leading to cell cycle arrest in metaphase.
- Axonal transport required microtubules so they are neurotoxic!
What are the toxicities associated with vincristine and vinblastine?
Vincristine: Neurotoxicity and low myleosuppresion
Vinblastine:
More myelosuppresion and less nephrotoxicity
What is the MOA of Paclitaxel?
-Binds to beta tubulin and promotes assembly of microtubules and stabilizes their formation by inhibiting depolymerization. They are extremely stable and non-functional.
What are the adverse effects of paclitaxel?
- Myelosuppresion
- anemia
- peripheral neuropathy
What is the MOA of Imatinib?
-Inhibitor of BCR-Abl fusion tyrosine kinase protein (only works if patient has this mutation, so test for it)
What cancer is the BCR-ABL mutation common in?
Chronic myelogenous leukemia
What are the most common side effects seen with Imatinib?
Fluid retention (ankle and periorbital edema), nausea, vomiting, malaise, and lethargy
What is the MOA of cetuximab?
Monoclonal antibody that binds to EGF receptor to inhibit tyrosine kinase activity resulting in growth inhibition and apoptosis
What is the MOA of Erlotinib?
Blocks ATP binding to EGF receptor to inhibiti the tyrosine kinase activity resulting in growth inhibition and apoptosis.
What should you do before prescribing an epidermal growth factor inhibitor?
Test for the EGFR expression and mutations
What is the MOA of Bevacizumab?
- Angiogenesis inhibitor
- Recombinant humanized monoclonal antibody that binds to VEGF and prevents binding to VEGF receptor
What are the risks associated with Bevacizumab?
Bleeding and thromboembolism
