Fundamentals of Pharmacology for Veterinary Technicians Chapter 20
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1 Figure 20-1
2 Figure 20-2
3 Figure 20-3A
4 Figure 20-3B
5 Figure 20-4
6 Table 20-1 Antineoplastic Agents Used for Chemotherapy in Animals Drug Type Drug Category Examples Cell-Cycle Effect CCNS Alkylating agents: Cross-link DNA to inhibit its replication busulfan (Myleran, Busulfex ) carboplatin (Paraplatin ) chlorambucil (Leukeran ) cisplatin (Platinol ) cyclophosphamide (Cytoxan, Neosar ) dacarbazine (DTIC-Dome ) lomustine (CeeNu ) mechlorethamine (Mustargen ) melphalan (Alkeran ) thiotepa (Ledertepa, Tespamin ) Work on all phases of the cell cycle, but are more effective in the G 1 and Tend to be used for lymphoproliferative diseases, osteosarcoma, mast cell tumors, and carcinomas Antitumor antibiotics: Inhibit DNA, RNA, and (in some cases) protein synthesis bleomycin (Blenoxane ) dactinomycin, also known as actinomycin D (Cosmegen ) doxorubicin (Adriamycin ) mitoxantrone (Novantrone ) streptozocin (Zanosar ) Work on all phases of the cell cycle, but doxorubicin is more effective at the Tend to be used for lymphoproliferative diseases, sarcomas, and carcinomas Steroid drugs: Action may include antiinflammatory effects, suppression of bone marrow cells, reduction of edema, and suppression of tumor growth androgens (danazol [Danocrine ]) estrogens (ECP, Synovex C ) glucocorticoids (prednisone, dexamethasone) progestins (Component E-C ) Work on all phases of the cell cycle, but more effective at the S and M phases Tend to be used for lymphoproliferative diseases, reproductive cancers, mast cell tumors, and CNS tumors CCS Antimetabolites: Cell-cycle-specific drugs that affect the synthesis) azathioprine (Imuran ): antagonizes purine base metabolism 5-fluorouracil (Adrucil, 5-FU ): pyrimidine base analogs cytarabine (Cytosar-U ): pyrimidine base analog hydroxyurea (Hydrea, Droxia ): inhibits thymidine incorporation into DNA mercaptopurine (Purinethol ): antagonizes purine base metabolism methotrexate (Mexate ): inhibits folic acid synthesis thioguanine (Tabloid ): blocks purine nucleotides Work on S phase of the cell cycle. They either inhibit folic acid, which is needed for the synthesis of proteins and DNA, or by being an analog of pyrimidine or purine (which are bases occurring in DNA and RNA) and incorporating into the DNA/RNA molecule Tend to be used for lymphoproliferative Alkaloids: Chemicals derived from plants; stop cancer cell division (mitosis) vinblastine (Alkaban-AQ, Velbane ) vincristine (Oncovin, Vincasar ) Work on the M phase of the cell cycle, inhibiting mitosis and causing cell death Tend to be used for lymphoproliferative diseases, mast cell tumors, sarcomas, and carcinomas Table 20-1
7 Table 20-2 Guidelines for Handling Antineoplastic Agents Antineoplastics should be handled by trained personnel. Handling of antineoplastic agents by pregnant women is generally contraindicated. OSHA recommends that antineoplastic agents should be prepared under a vertical laminar fl ow hood (Figure 20-3). When pharmaceutical practice calls for the use of aseptic techniques and a sterile environment, a horizontal laminar flow hood is sufficient. However, while this type of unit provides product protection, it may expose the operator and the other room occupants to aerosols generated during drug preparation procedures. A vertical laminar flow hood provides both product and operator protection by fi ltering incoming and exhaust air through a high-efficiency particulate air (HEPA) filter. It is unlikely that the majority of practices will have vertical laminar flow hoods. Preparation of drugs without such equipment is a compromise on safety. In this situation, drugs should be prepared in an area away from people and animals, without doors, windows, or draughts, and the maximum possible personal protection used. This should include gloves, disposable arm sleeves and a gown, goggles, and a mask. Use latex gloves to protect the skin. Gloves made of polyvinyl chloride may be permeable to some cytotoxic agents. Wearing two pairs of latex gloves is recommended because all gloves are porous to some degree. Good handwashing before and after handling drugs is essential. Prevent contact of antineoplastic agents with skin or mucous membranes. If this occurs, wash the area immediately with large volumes of water, document the contact, and seek medical assistance. Before drug preparation, don a disposable, nonpermeable surgical gown with closed front and knit cuffs that completely cover the wrists. Goggles (or eye shield) and particulate filtration masks are recommended to avoid ocular and respiratory contact. If reconstituting the drug, vent the vial at the beginning of the procedure. Special vent needles are available and should be used. This lowers the internal pressure in the vial and reduces the risk of spilling or spraying the solution when the needle is withdrawn from the vial. Use leur-lock syringes and IV equipment that have screw-on attachments to prevent spillage of antineoplastic agents. Wipe all external surfaces of syringes and bottles with alcohol. All disposable equipment, gloves, and bottles should be placed in a separate disposable leakproof puncture-resistant plastic bag specifically marked for chemotherapy and collected for incineration. Wear latex gloves when disposing of vomit, urine, or feces from animals receiving antineoplastics. Maintain a record of all exposure during preparation, administration, cleanup, and spills. Table 20-2
8 Table 20-3 General Adverse Reactions to Antineoplastic Agents Adverse Reactions Patient Considerations Bone marrow suppression Low white blood cell counts increase the risk of infection Low platelet counts may result in bleeding Low red blood cell counts leading to anemia may cause lethargy Gastrointestinal effects Anorexia may be attributed to foul taste left in the mouth from antineoplastic agents and/or gastrointestinal upset Gastrointestinal upset and vomiting may be secondary to antineoplastic use Diarrhea may be secondary to antineoplastic use and could lead to dehydration Alopecia Infertility Hair loss varies; the animal should be kept out of the cold and should avoid excessive sunlight Infertility secondary to antineoplastic use may be permanent Cardiotoxicity Damage to the heart from certain antineoplastic drugs such as doxorubicin Nephrotoxicity Kidney failure from certain antineoplastic drugs such as cisplatin may be seen especially in animals receiving pulse dosing of medication Table 20-3
9 Table 20-4 Drugs Covered in This Chapter Category Generic Name Trade Name(s) A lkylating agents busulfan Myleran, Busulfex carboplatin Paraplatin chlorambucil Leukeran c isplatin Platinol cyclophosphamide Cytoxan, Neosar dacarbazine DTIC-Dome lomustine CeeNu mechlorethamine Mustargen melphalan Alkeran t hiotepa Ledertepa, Tespamin Antitumor antibiotics bleomycin Blenoxane dactinomycin (actinomycin D) Cosmegen doxorubicin Adriamycin mitoxantrone Novantrone streptozocin Zanosar Steroid drugs androgens (danazol) Danocrine estrogens ECP, Synovex C (Continued ) Table 20-4
10 Table 20-4 (Continued ) Category Generic Name Trade Name(s) glucocorticoids (prednisone, dexamethasone) generic, Azium progestins Component E-C Antimetabolites azathioprine Imuran 5-fluorouracil Adrucil, 5-FU cytarabine Cytosar-U hydroxyurea Hydrea, Droxia mercaptopurine Purinethol methotrexate Mexate thioguanine Tabloid A lkaloids vinblastine Alkaban-AQ vincristine Oncovin, Vincasar Biologic response modifiers interferon Roferon-A injection, Intron A injection, Alferon N injection, Actimmune injection filgrastim Neupogen sargramostim Leukine interleukin-2 Proleukin acemannan Acemannan Immunostimulant monoclonal antibodies Canine Lymphoma Monoclonal Antibody 231 Immunosuppressives cyclosporine Optimmune Ophthalmic Ointment, Sandimmune, Atopica azathioprine Imuran cyclophosphamide Cytoxan mercaptopurine Purinethol E nzyme L-asparaginase Elspar, Oncaspar, Erwinase Enzyme inhibitor Toceranib Palladia Table 20-4 continued
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