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Focus on PHARMACOLOGY ESSENTIALS FOR HEALTH PROFESSIONALS CHAPTER 16 Antineoplastic Agents Cancer • Second most common cause of death in United States – Most common types: breast, prostate, lung, colorectal – Characterized by uncontrolled cellular division, hyperplasia, local tissue invasion, and metastasis – Two types of tumor: benign and malignant Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Naming Benign and Malignant Tumors • Benign tumors: names are created by adding –oma to name of cell type – Adenoma: benign tumor of glandular origin • Malignant: names often contain word carcinoma – Adenocarcinoma: malignant cancer of glandular origin Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Benign Tumors • Benign: cells resemble cells from which they developed – Slow growing – Seldom metastasize; rarely recur once removed Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Malignant Tumors • Malignant: atypical appearance – Proliferate rapidly; become more and more atypical – Invade and destroy surrounding tissues – Induce formation of new blood vessels (angiogenesis) to supply tumor with blood Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Malignant Cancer Terms • Sarcoma: malignant growth of muscle or connective tissue • Carcinoma in situ: cancer limited to epithelial cells where it begins Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini 7 Warning Signs of Cancer Change in bowel or bladder habits Sore that does not heal Unusual bleeding or discharge Thickening or lump in breast or elsewhere • Indigestion or difficulty swallowing • Obvious change in wart or mole • Nagging cough or hoarseness • • • • Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Topic of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Neoplasms • Arise from four tissue types – Epithelial – Connective – Muscle – Nerve Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Oncogenes • Develop from normal genes: protooncogenes – Protooncogenes are present in all cells and regulate normal cell function, including cell cycle. – Genetic alteration of the protooncogene may activate oncogenes. – Alteration caused by carcinogenic agents. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Tumor Suppressor Genes • Normally function to regulate and inhibit inappropriate cellular growth and proliferation Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Cell Cycle • G0: Resting, dormant stage • G1: Cell makes proteins to prepare for division (18–30 hours) • S: DNA synthesis occurs (18–20 hours) • G2: Occurs just before cell splits (2–10 hours) • M: Mitosis (30–60 minutes) Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Figure 16-1 The four steps of the cell cycle. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Chemotherapy • Use of chemical agents to interact with cancer cells to stop or control growth – Primary: used alone to cure – Palliative: used to ease disease’s effects – Adjuvant: used before or after radiation or surgery – Neoadjuvant: given in preoperative setting to reduce tissue damage, decrease tumor size, or destroy micro metastases Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Chemotherapy Agents • Characterized by mechanism of action or origin • Many agents target rapidly proliferating cells at selective or multiple sites of cell cycle. – Agents with selective activity: cell cycle phase-specific • Agents may target cellular synthesis of DNA, RNA, and proteins. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Five Primary Cancer Therapies • Surgery: treatment of choice for many solid tumors; local treatment • Radiation therapy: local treatment • Chemotherapy: systemic treatment • Immunotherapy: stimulates host’s immune system • Hormonal therapy: systemic treatment Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Response to Treatment • Cure: free of disease • Complete response: disappearance of cancer with no evidence of new disease for at least 1 month after treatment • Partial response: 50% or greater decrease in tumor size or other cancer markers; no evidence of disease for at least 1 month Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Response to Treatment • Stable disease: no change in tumor size • Progression of disease Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Chemotherapy Routes of Administration • Oral: becoming more popular because of ease of use • Intramuscular • Subcutaneous • Intravenous Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alkylating Agents: Uses • Greatest value in treating slow-growing cancers • Cell cycle phase–nonspecific: act directly on DNA causing cross-linking of DNA strands, abnormal base pairing, or strand breaks • Five types: nitrogen mustards, ethyleneimines, alkyl sulfonates, nitrosoureas, temozolomide Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alkylating Agents: Adverse Effects • Dose-limiting toxicity to bone marrow and intestinal mucosa • Common: alopecia, toxicity to reproductive system • Serious: pulmonary fibrosis and venoocclusive liver disease, renal failure, central neurotoxicity Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alkylating Agents: Contraindications • Do not use in pregnancy (teratogenic). • May interact with antidepressants, other anticancer medication, warfarin, vaccines, aspirin, and vitamins Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Procarbazine Interactions • Procarbazine can produce an acute disulfiram-like reaction (flushing, headache, acute vomiting, and chest or abdominal pain) if combined with alcohol. • Taking procarbazine with tyraminecontaining foods (aged cheese, chocolate, wine, etc.) can cause lifethreatening elevation of blood pressure. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alkylating Agents: Patient Information • Teach patients about symptoms and signs of bone-marrow depression. • Advise patients to avoid contact with people who have colds or other infections. • Reassure patients that hair will regrow after treatment. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antimetabolites: Uses • Cell cycle phase–specific: replace natural substances such as DNA molecules that are required for cell metabolism and protein synthesis • Treat myelocytic leukemia, lymphocytic leukemia, non-Hodgkin’s lymphoma, metastatic breast and colorectal cancer, keratoses, basal cell carcinomas, meningeal leukemia, head and neck cancers Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antimetabolites: Adverse Effects • Common: anorexia, nausea and vomiting, headache, hearing loss, sleep disorders, depression, bone-marrow depression, dyspnea, epistaxis, edema, GI disturbances, alopecia, myelosuppression, hyperuricemia • Serious: hepatotoxicity, severe leukopenia, bone marrow aplasia, thrombocytopenia Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antimetabolites: Contraindications • Avoid in first trimester of pregnancy; in lactating women; and in patients with acute infectious diseases, severe bonemarrow depression, and renal dysfunction • Interact with allopurinol, warfarin, and drugs used to treat ulcerative colitis Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antimetabolites: Patient Information • Advise patients that these drugs may cause bone-marrow suppression and damage to GI lining. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Green Tea: Antioxidant • Studies suggest green tea may reduce the incidence of a variety of cancers, including those of the colon, pancreas, and stomach. • Green tea contains high levels of polyphenols, which have antioxidant and chemopreventive properties. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 (continued) Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 (continued) Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 (continued) Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 (continued) Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 (continued) Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 16-1 (continued) Common Agents Used in the Treatment of Cancer Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Mitotic Inhibitors: Uses • More effective in S- and M-phases of cell cycle • Inhibit DNA and RNA synthesis • Used to treat breast, bladder, ovarian, testicular, and lung cancers; leukemias; and lymphomas Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Mitotic Inhibitors: Adverse Effects • Common: nausea and vomiting, diarrhea, alopecia, dizziness, weakness, headache, depression, stomatitis, anemia, hyperpigmentation of nails, tongue, or oral mucosa Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Mitotic Inhibitors: Contraindications • Do not use in severe cardiac disease, hypocalcemia, bleeding disorders, myelosuppression, or pregnancy. • Interact with phenytoin, erythromycin, and itraconazole Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Mitotic Inhibitors: Patient Information • Tell patients that severe bone-marrow depression and GI damage may occur. • Tell them to avoid coffee, spicy foods, fruits, and raw vegetables if diarrhea occurs. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Toxicity in Elderly Patients • Older adults are at higher risk for adverse effects of antineoplastic agents. • Lower dosages are administered. • Creatinine clearance is used to monitor renal function in elderly patients. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Hormonal Therapy: Uses • Act by blocking hormone production or action • Highly selective • Treat acute lymphocytic leukemia and reproductive tract cancers Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Hormonal Therapy: Adverse Effects • GI disturbances • Impaired fertility • Menstrual irregularities Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Hormonal Therapy: Contraindications • Most hormones are contraindicated during pregnancy. • Interactions occur with tamoxifen, alcohol, St. John’s wort, zinc, magnesium, vitamin B, and thyroid supplements. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Hormonal Therapy: Patient Information • Warn patients that these agents are contraindicated in pregnancy and that strict contraception should be used during and for 3–4 months after treatment. • Some sources advise both men and women to avoid conceiving for 2 years after treatment. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Infertility • Instruct patients that infertility may occur with antineoplastic agents and may not be reversible. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antitumor Antibiotics: Uses • Work by inhibiting DNA and RNA synthesis • Treat breast, ovary, testicular, cervical, head, neck, penis, and bone cancers; Wilms’ tumor, choriocarcinoma, solid tumors, monocytic leukemia, lymphoblastic and myeloblastic leukemias, and lymphomas Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antitumor Antibiotics: Adverse Effects • Common: bone-marrow suppression, stomatitis, GI upset, alopecia, pulmonary fibrosis • Serious: renal impairment (mitomycin) Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antitumor Antibiotics: Contraindications • Should not be used in patients with heart, kidney, and liver disease • Some agents interact with digoxin, aspirin, heparin, warfarin, or NSAIDs. • Some agents cause toxicity when used together. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antitumor Antibiotics: Patient Information • Advise patients about signs and symptoms of bone-marrow depression. • Instruct patients to report cardiac abnormalities. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Interferon alfa-2b (Intron A): Uses • Work by targeting and purifying specific proteins • Treats kidney cancers, lymphoma, and melanoma Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Interferon alfa-2b: Adverse Effects • Common: nausea and vomiting, weight gain, fluid retention • Serious: kidney, liver, lung, and nerve damage Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Interferon alfa-2b: Contraindications • Safe use during pregnancy, lactation, or in children younger than 18 is not established. • Use cautiously in severe, preexisting cardiac, renal, or hepatic disease, pulmonary disease, diabetes mellitus, or those prone to ketoacidosis. • Interacts with theophylline and zidovudine Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Interferon alfa-2b: Patient Information • Teach patients how to reconstitute and administer these agents. • Warn patients not to change brands. • Advise woman not to breast feed. • Instruct patients to expect adverse effects and to report severe adverse effects. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Interferon Administration • All changes in interferon administration must be directed by a physician. • Instruct patients to not change administration times or doses of these drugs. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini