3 - Antineoplastic Drugs Flashcards
What are the 3 steps of carcinogenesis?
- Tranformation
- Proliferation
- Metastasis
What’s the challenge in dose-limiting toxicities?
To give an adequate dose to kill cancer cells without killing too many healthy cells
What’s the mechanism of action for chemotherapy?
- Interfere with cell proliferation
- Relative selectivity against cancer cells
What is p53?
- Transcription factor that regulates the cell cycle
- Functions as a tumor suppressor
- Cancers that express p53 are highly responsive to chemo (leukemias, lymphomas, testicular cancer)
What are the benefits of using combination chemotherapy?
- Some regimens offer synergistic benefits
- Typically use intermittent dosing
- Reduces emergence of drug resistance
What are some examples of cancers that require combination chemotherapy?
- Hodgkin’s disease
- Testicular cancer
- Breast cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Lung cancer
- Cancer of the head and neck
What is the current emphasis on cancer chemotherapy on?
The use of drug combination therapy
How can drugs be broken down by the cell cycle they affect?
- Cell-cycle specific - drug affects one phase
- Cell-cycle non-specific - drug affects any/all phases
What are some important characteristics of chemotherapy drugs?
- Not safe
- Lack of specificity - affects normally proliferating cells (bone marrow, skin, intestinal mucosa)
- Signs of toxicity appear in those areas
What are the alkylating agents mechanism of action?
Transfer alkyl groups to important cell constituents
What are some examples of Alkylating Agents?
- cyclophosphamide (Cytoxan) - multiple cancers, bone marrow transplants
- ifosfamide (Ifex) - nitrogen mustard - multiple cnacers
- procarbazine (Matulane) - Hodgkin’s disease
What do Antimetabolites do?
- Serve as fraudulent substrates for biochemical interactions
- S Phase specific
What are the different classes of Antimetabolites?
- Folic acid antagonists
- Purine antagonists
- Pyrimidine antagonists
What are the characteristics of Folic Acid Antagonists and whats the common preparation?
- Inhibits DNA synthesis
- Cell-cycle specific = S phase
- **methotrexate **(Rheumatrex, Trexall)
What are the characteristics of Purine Antagonists and what’s the common preparation?
- Inhibits enzymes that convert hypoxanthine ribonucleotide to adenine and xanthine ribonucleotide
- Cell-cycle specific = S phase
- mercaptopurine (Purinethol)
What are the characteristics of Pyrimidine Antagonists and what are the common preparations?
- Inhibit pyrimidine synthesis
-
fluorouracil (Adrucil) “5-FU” - many cancers
- Interferes with DNA synthesis
-
cytarabine (Cytosar-U) “Ara-C” - blood cancers
- Cell cycle specific = S phase
What are the common preps of Platinum complexes?
-
carboplatin (Paraplatin)
- small-cell lung cancer, ovarian cancer
-
cisplatin (Platinol)
- bladder, testicular, ovarian cancers
What are the toxicities associated with platinum-derived compounds?
- Myelosuppression
- Nephrotoxicity
- Neurotoxicity
- Ototoxicity
- Nausea/vomiting
What type of alkyloids are derived from the periwinkle plants?
Vinca Alkyloids
How do Vinca Alkyloids act? What are the common preps?
- Inhibit mitotic division
- M and S Phases (cell-cycle specific)
- vinblastine (Valban)
- vincristine (Oncovin)
Where to hormonal agents act?
Hormones interrupt cells in the G phase - reduction in the amount of circulating hormones
What are the different types of hormonal agents?
- Estrogens - prostate/mammary CA
- Androgens - mammary CA postmenopausal
- Progestins - renal and endometrial CA
-
Glucocorticoids - hematologic, lymphomas
- Prednisone
What type of drug is tamoxifen and what does it do?
- Anti-estrogen, breast CA treatment/prevention
- G0 & G1 phases
- tamoxifen (Nolvadex)
What do antibiotics do in the chemotherapy drugs?
- bind with DNA to inhibit cell division
- Attack cells in different phases:
- non-cell cycle specific
- cell cycle specific
- Most effective for solid mass tumors
What are the selected agents of antibiotics preparations?
-
bleomycin (Blenoxane)
- G2, M
-
doxorubicin (Adriamycin)
- S phase, Kaposi’s sarcoma
- daunorubicin citrate (DaunoXome) = HIV-associated Kaposi’s sarcoma
How do other antibiotic agents work?
- Inhibit DNA and RNA synthesis
What are the indications for thalidomide (Thalomid)?
- Multiple myeloma
- Crohn’s
- AIDS-related aphthous lesions
- Classic model drug for teratogensis
What are the systemic effects of chemotherapy?
- Suppression of bone marrow
- GI disturbances
- Dermatological reactions
- Hepatotoxicity
- Nephrotoxicity
- Neurotoxicity
- Immune deficiencies
- Infertility
