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20. antineoplastic and immunosuppressive drugs


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20. antineoplastic and immunosuppressive drugs

  1. 1. Chapter 20 Antineoplastic and Immunosuppressive Drugs Copyright © 2011 Delmar, Cengage Learning
  2. 2. Basic Terminology <ul><li>Anticancer drugs stop the cancerous activity of malignant cells </li></ul><ul><ul><li>Also called antineoplastic agents and chemotherapeutic agents </li></ul></ul><ul><li>Characteristics of malignant cells include rapid cell division and growth, different rates of cellular drug uptake, and increased cellular response to selected anticancer drugs </li></ul><ul><li>Some factors present in malignant cells are also found in normal cells </li></ul><ul><ul><li>Rapid cell division and growth occur in cells of the GI tract, bone marrow, reproductive organs, and hair follicles </li></ul></ul><ul><li>Neoplasms are cancer cells that can spread from the site of origin to other areas of the body that are favorable for cell growth </li></ul>Copyright © 2011 Delmar, Cengage Learning
  3. 3. Cell Cycle Phases <ul><li>The five phases of the cell cycle: </li></ul><ul><ul><li>G 1 : enzymes needed for DNA synthesis are produced </li></ul></ul><ul><ul><li>S: DNA synthesis and replication </li></ul></ul><ul><ul><li>G 2 : RNA and protein synthesis </li></ul></ul><ul><ul><li>M: mitosis phase </li></ul></ul><ul><ul><li>G 0 : resting phase </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  4. 4. Definitions Related to Antineoplastic Agents <ul><li>Growth fraction: percentage of cancer cells that are actively dividing </li></ul><ul><ul><li>A high growth fraction occurs when cells are dividing rapidly </li></ul></ul><ul><ul><li>When tumors age and enlarge, their growth fraction decreases </li></ul></ul><ul><li>Doubling time: time required for the number of cancer cells to double </li></ul><ul><ul><li>When tumors age and enlarge, their doubling time increases </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  5. 5. Administering Antineoplastic Agents <ul><li>Antineoplastic agents are often administered in various protocols known as combination therapy </li></ul><ul><li>Calculation of antineoplastic drug doses is based on body surface area in square meters </li></ul><ul><li>When administering antineoplastic agents, great care must be taken; refer to Table 20-2 in your textbook </li></ul><ul><li>When administering antineoplastic agents IV, infuse unmedicated IV solution before and after administration of the drug to ensure that antineoplastic drug residues do not remain on the equipment </li></ul>Copyright © 2011 Delmar, Cengage Learning
  6. 6. Administering Antineoplastic Agents <ul><li>Pulse Dosing </li></ul><ul><ul><li>A method of delivering some types of chemotherapeutic agents that produces escalating levels of drugs early in the dose followed by a dose free interval </li></ul></ul><ul><ul><li>Offers therapeutic advantages such as reduced dose frequency and greater compliance </li></ul></ul><ul><ul><li>Is the preferred way to administer some chemotherapeutic agents </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  7. 7. Guidelines for Handling Antineoplastic Agents <ul><li>OSHA recommends antineoplastics be prepared under a vertical laminar flow hood </li></ul><ul><ul><li>The vertical laminar flow hood provides both product and operator protection by filtering incoming and exhaust air through a high efficiency air filter </li></ul></ul><ul><li>Use latex gloves to protect the skin </li></ul><ul><li>Good hand-washing before and after drug preparation </li></ul>Copyright © 2011 Delmar, Cengage Learning
  8. 8. Guidelines for Handling Antineoplastic Agents <ul><li>Prevent contact of Antineoplastic agents with skin </li></ul><ul><li>Goggles or a air filtration mask are recommended to protect eyes and mouth </li></ul><ul><li>Wipe all external surfaces of bottles and syringes with alcohol </li></ul><ul><li>Maintain record of all exposures during preparation, administration, clean-up, and spills </li></ul>Copyright © 2011 Delmar, Cengage Learning
  9. 9. Antineoplastic Agents <ul><li>Cell-cycle nonspecific (CCNS): </li></ul><ul><ul><li>Alkylating agents cross-link DNA to inhibits its replication </li></ul></ul><ul><ul><ul><li>Examples include cyclophosphamide, cisplatin, chlorambucil, melphalan, and carboplatin </li></ul></ul></ul><ul><ul><li>Antitumor antibiotics inhibit DNA, RNA, and protein synthesis </li></ul></ul><ul><ul><ul><li>Examples include doxorubicin, dactinomycin, and mitoxantrone </li></ul></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  10. 10. Antineoplastic Agents <ul><li>Cell-cycle nonspecific (CCNS) (cont.): </li></ul><ul><ul><li>Steroid drugs have anti-inflammatory effects, suppress bone marrow cells, reduce edema, and suppress tumor growth </li></ul></ul><ul><ul><ul><li>Examples include corticosteroids, estrogens, progestins, and androgens </li></ul></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  11. 11. Antineoplastic Agents <ul><li>Cell-cycle specific (CCS): </li></ul><ul><ul><li>Antimetabolites affect the S phase involving DNA synthesis </li></ul></ul><ul><ul><ul><li>Examples include methotrexate, 5-fluorouracil, cytarabine, and azathioprine </li></ul></ul></ul><ul><ul><li>Alkaloids stop cancer cell division </li></ul></ul><ul><ul><ul><li>Examples include vincristine and vinblastine </li></ul></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  12. 12. Antineoplastic Agents <ul><li>Biologic response modifiers (BRMs): used to enhance the body’s immune system; used in conjunction with antineoplastic protocols </li></ul><ul><ul><li>Interferons are a group of proteins that have antitumor and antiviral effects; used to treat tumors and viral infections in cats </li></ul></ul><ul><ul><ul><li>There are three types of interferon: alpha, beta, and gamma </li></ul></ul></ul><ul><ul><li>Colony stimulating factors (CSFs) stimulate the growth, maturation, and differentiation of bone marrow stem cells; have been used to treat neutropenia in dogs and cats </li></ul></ul><ul><ul><ul><li>An example is filgrastim </li></ul></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  13. 13. Antineoplastic Agents <ul><li>Biologic response modifiers (BRMs) (cont.): </li></ul><ul><ul><li>Interleukins are a group of chemicals that play various roles in the immune system and promote the replication of antigen-specific T cells </li></ul></ul><ul><ul><li>Acemannan is a potent stimulator of macrophage activity and is used to treat fibrosarcomas and mast cells in dogs and cats </li></ul></ul><ul><ul><li>Monoclonal antibodies have cytotoxic effects on tumor cells and are used in conjunction with other antineoplastic agents </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  14. 14. Antineoplastic Agents <ul><li>Immunosuppressive drugs work by interfering with one of the stages of the cell cycle or by affecting cell messengers </li></ul><ul><ul><li>Cyclosporine inhibits the proliferation of T-lymphocytes; used for managing KCS in dogs and immune-mediated skin disorders </li></ul></ul><ul><ul><li>Azathioprine affects cells in the S phase of the cell cycle and also inhibits T- and B-lymphocytes; used mainly in dogs for immune-mediated disease </li></ul></ul><ul><ul><li>Cyclophosphamide interferes with DNA and RNA replication, disrupting nucleic acid function; has been used for immune-mediated diseases </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  15. 15. Antineoplastic Agents <ul><li>Enzymes </li></ul><ul><ul><li>L-asparaginase is an example of an enzyme used in the treatment of cancer </li></ul></ul><ul><ul><li>L-asparaginase works by hydrolyzing asparagines into aspartic acid and ammonia </li></ul></ul><ul><ul><li>Cancer cells need an exogenous source of asparagine for survival; normal cell can synthesize asparagine </li></ul></ul><ul><ul><li>Side effects of L-asparaginase include pain at the injection site, hypotension, and diarrhea </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  16. 16. Antineoplastic Agents <ul><li>Enzyme Inhibitors </li></ul><ul><ul><li>Offer another approach to treating tumor cells by controlling their growth </li></ul></ul><ul><ul><li>Toceranib is a tyrosine kinase inhibitor used to treat mast cell tumors in dogs </li></ul></ul><ul><ul><li>Is an oral tablet tablet used to manage adverse reactions such as </li></ul></ul><ul><ul><ul><li>neutropenia, diarrhea, anorexia, lethargy, vomiting </li></ul></ul></ul><ul><ul><li>Hands should be washed when handling tablets </li></ul></ul><ul><ul><li>Gloves should be worn when cleaning up body fluids from dogs on Toceranib </li></ul></ul>Copyright © 2011 Delmar, Cengage Learning
  17. 17. Adverse Reactions to Antineoplastic Agents <ul><li>Antineoplastic agents can cause adverse reactions in rapidly dividing normal cells </li></ul><ul><li>Some of these adverse reactions are listed in Table 20-3 of your textbook </li></ul>Copyright © 2011 Delmar, Cengage Learning