Pharmacology in Nursing Antineoplastic Drugs Part 1 Cancer

Pharmacology in Nursing Antineoplastic Drugs Part 1: Cancer Overview and Cell Cycle– Specific Drugs Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer Cellular transformation Uncontrolled and rapid cellular growth Invasion into surrounding tissue Metastasis to other tissues or organs Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer (cont’d) Cancerous cells do not have: Growth control mechanisms Ø Positive physiologic function Ø Cancer cells either: Grow and invade adjacent tissues, or Ø Break away from original tumor mass and travel by means of blood or lymphatic system to distant sites Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer (cont’d) Primary lesion Ø Original site of growth Metastasis Uncontrolled cell growth Ø Secondary lesion, in a new and remote part of the body Ø Neoplasm (“new tissue”) Ø Mass of new cells; tumor Tumor Benign Ø Malignant (cancer) Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

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Cancer: Tissues of Origin Carcinomas Ø Sarcomas Ø Malignant tumors arise from connective tissue Lymphomas Ø Epithelial tissue throughout the body Cancer within lymphatic tissue leukemias Cancer within bone marrow and blood Ø Hematologic malginancy Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Paraneoplastic Syndromes Various group of symptoms May be the first sign of malignancy Cachexia (most common) Ø Fatigue, fever, weight loss Ø Others Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Etiology of Cancer Age- and sex-related differences Genetic factors Ø Ethnic factors Ø Mutagen – substance that changes DNA molecules Radiation Ø Epstein-Barr – mononucleosis / associated with nasopharyngeal cancer Occupational and environmental carcinogens Ø Specific receptors Oncogenic viruses Ø Cancer of the breast, colon, & stomach – heredity plays a role Ionizing, high energy – potent & penetrate deeply into the body Immunologic factors Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cell Growth Cycle G 0 –resting phase G 1 –postmitotic (gap) phase S –DNA synthesis phase G 2 – second gap - premitotic - phase M –mitosis phase (cell reproduction) Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Chemotherapy Pharmacologic treatment of cancer Antineoplastic drugs Divided into two groups based on where in the cellular life cycle they work Cell cycle nonspecific (CCNS) Ø Cell cycle specific (CCS) Ø Some drugs have characteristics of both Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

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Cancer Drugs: Antineoplastic Medications Cell cycle–nonspecific drugs Ø Cytotoxic in any phase of the cycle More effective against large, slowly growing tumors Alkylating drugs Ø Cytotoxic antibiotics Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer Drugs Antineoplastic Medications (cont’d) Cell cycle–specific drugs Drugs that are cytotoxic during a specific cell-cycle phase More effective against rapidly growing tumors Antimetabolites: folate (methotrexate) , purine (cladribine), and pyrimidine (fluorouracil) analogs Ø Natural products: enzymes, vinca alkaloids, others Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer Drugs: Antineoplastic Medications (cont’d) Miscellaneous cell cycle–specific drugs Miscellaneous antineoplastics (cell cycle specificity unclear) Hormonal agents Radioactive antineoplastics Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Chemotherapy (cont’d) Drugs have a narrow therapeutic index Combination of drugs is usually more effective than single-drug therapy Drug resistance Nearly all drugs cause adverse effects Dose-limiting adverse effects Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Chemotherapy (cont'd) Harmful to all rapidly growing cells Harmful cancer cells Ø Healthy, normal human cells • Hair follicles • GI tract cells • Bone marrow cells Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Chemotherapy Terms Alopecia – hair follicle cells – rapidly dividing cells Emetic potential Myelosuppression Bone marrow suppression (BMS) Ø Bone marrow depression (BMD) Ø Nadir (lowest level of WBCs following tx) Extravasation Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Antimetabolites Folic acid antagonist Ø methotrexate (MTX), others Purine antagonists fludarabine (F-AMP) Ø mercaptopurine (6 -MP) Ø Allopurinol Ø Pyrimidine antagonists fluorouracil (5 -FU) Ø cytarabine (ARA-C), others Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Antimetabolites (cont’d) Folic acid antagonism Interferes with the use of folic acid Ø As a result, DNA is not produced, and the cell dies Ø Purine antagonism Interrupts metabolic pathways of purine nucleotides Ø Results in the interruption of the synthesis of DNA and RNA Ø Pyrimidine antagonism Interrupts metabolic pathways of pyrimidine bases Ø Results in interruption of the synthesis of DNA and RNA Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Antimetabolites: Indications Used in combination with other drugs to treat various types of cancer, such as solid tumors and some hematologic cancers Acute and chronic lymphocytic leukemias Ø Leukemias (several types) Ø Colon, rectal, breast, stomach, lung, pancreatic cancers Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Antimetabolites: Indications (cont’d) Oral and topical forms may be used for lowdose maintenance and palliative cancer therapy Often used in combination chemotherapy regimens Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Antimetabolites: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Many other severe adverse effects Leucovorin rescue may be done to reduce severe bone marrow suppression Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mitotic Inhibitors Natural products obtained from the periwinkle plant Ø Vinca alkaloids Semisynthetic drugs obtained from the mandrake (mayapple) plant Drugs obtained from the yew tree Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mitotic Inhibitors (cont’d) Vinca alkaloids (periwinkle) Ø Epipodophyllotoxin derivatives (mandrake plant) Ø vinblastine, vincristine, vinorelbine etoposide, teniposide Taxanes doxetaxel (European yew tree: needles) Ø paclitaxel (western yew tree: bark) Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mitotic Inhibitors (cont’d) Work in various phases of the cell cycle All work shortly before, or during, mitosis Results in slowing of cell division All classified as CCS drugs Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mitotic Inhibitors: Indications Often used in combination therapies Used to treat a variety of solid tumors and some hematologic malignancies Testicular, small-cell lung, breast, Ø Ovarian Ø non–small-cell lung cancers Ø Kaposi’s sarcoma Ø Acute leukemia Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Mitotic Inhibitors: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Liver, kidney, lung toxicities Convulsions Extravasation Ø Several specific antidotes can be used Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Topoisomerase-1 Inhibitors (Camptothecins) Derived from camptothecin, a substance taken from a Chinese shrub topotecan (Hycamtin) Ø irinotecan (cpt-11, Camptosar) Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Cell cycle–specific drugs Inhibit proper DNA function in the S phase Prevent DNA religation Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Indications Ovarian and colorectal cancer Small-cell lung cancer Other tumors Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Adverse effects Bone marrow suppression (predictable, reversible, noncumulative, manageable) GI effects (nausea, vomiting, diarrhea) Irinotecan causes cholinergic diarrhea (delayed, occurring 2 to 10 days after dosage) Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Antineoplastic Enzymes Synthesized using cultures of bacteria and recombinant DNA technology As a result an enzyme is produced This enzyme is isolated and purified for clinical use asparaginase (Elspar): used to treat acute lymphocytic leukemia Ø pegaspargase (Oncaspar) Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications Assess baseline blood counts before giving any antineoplastic drugs Follow specific administration guidelines for each antineoplastic drug Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Remember that all rapidly dividing cells (both normal and cancer cells) are affected Mucous membranes Ø Hair follicles Ø Bone marrow component Ø Monitor for effects on these tissues or complications Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Monitor for complications Ø GI mucous membranes: stomatitis, altered bowel function with high risk for poor appetite, nausea, vomiting, diarrhea, and inflammation and possible ulcerations of GI mucosa Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Monitor for complications Hair follicles: loss of hair (alopecia) Ø Bone marrow components: dangerously low (life-threatening) blood cell counts Ø Possible stimulation of CTZ (chemoreceptor trigger zone) Ø Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Monitor for adverse effects specific to the type of antineoplastic drug given Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Implement measures to monitor for and prevent infection in patients with neutropenia or leukopenia Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Implement measures to monitor for and prevent bleeding in patients with thrombocytopenia and anemia Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Keep in mind that anemia may result in severe fatigue Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Monitor for stomatitis (oral inflammation and ulcerations) and implement measures to reduce the effects if it occurs Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Anticipate nausea and vomiting and implement measures to reduce these effects Antiemetics often work better if given 30 to 60 minutes before chemotherapy is started Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) Women of childbearing age will need to use a nondrug form of contraception during therapy Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.

Nursing Implications (cont’d) In addition to physical measures, keep in mind the need for emotional support during this time for both the patient and family Monitor for therapeutic responses to antineoplastic therapies and the many possible adverse effects Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc. , an affiliate of Elsevier Inc.