Pharm Chapter 46: Antineoplastic Drugs Part 2
Pharmacology Overview
-Antineoplastics are drugs that are used to treat malignancies and are classified as cell cycle-specific drugs, cell cycle-non-specific drugs, miscellaneous antineoplastics, and hormonal drugs. -Cell cycle-specific drugs kill cancer cells during specific phases of the cell growth cycle, whereas the cell cycle-nonspecific drugs kill cancer cells during any phase of the growth cycle. -There are currently two broad classes of cell cycle-nonspecific cancer drugs: (1) alkylating drugs and (2) cytotoxic antibiotics.
Nursing Implications
-For patients receiving alkylating drugs, bone marrow suppression (carboplatin), pulmonary fibrosis (busulfan), nephrotoxicity and/or neurotoxicity (more with cisplatin than carboplatin), and hemorrhagic cystitis (cyclophosphamide) may occur. -One of the major adverse effects associated with the use of cytotoxic antibiotics is pulmonary fibrosis; therefore, medical testing (e.g., radiographs, computed tomographic scans, magnetic resonance imaging scans, arterial blood gas levels, and partial pressures of CO2 and O2) may be ordered. -In patients with documented cardiac disease or a history of thoracic irradiation, administer dactinomycin, daunorubicin, and doxorubicin with extreme caution due to cardiovascular toxicity. -With the use of androgens, obtain a thorough gynecologic history of the female patient with attention to any menstrual issues because of the adverse effect of menstrual irregularities. -Bicalutamide, flutamide, and nilutamide are antiandrogens and require thorough assessment of any cardiac diseases due to the potential for peripheral edema, which could exacerbate any pre-existing cardiac disorder. -With use of gonadotropin-releasing hormone agonists, such as leuprolide and goserelin, assess contraceptive history, because patients must use a nonhormonal contraceptive. -For patients taking antiadrenal drugs (e.g., mitotane), inquire about any gastrointestinal (GI) disturbances because of the common adverse effects of nausea and vomiting. -With use of bevacizumab, an angiogenesis inhibitor, assess cardiovascular, central nervous system, GI tract, and renal functioning; and assess metabolism level due to adverse effects of hypotension or hypertension, headache, pain, dizziness, nausea, vomiting, diarrhea, and nephrotoxicity. -With alkylating drugs, the patient will more than likely experience problems related to bone marrow suppression, such as anemia, leukopenia, and thrombocytopenia. -Most nursing interventions are focused on preventing infection, conserving energy, preventing bleeding and injury, and reducing nausea. -One very important component of nursing care with alkylating drugs and their parenteral administration is monitoring the IV site/infusion continually for infiltration. Checking the patency of central venous access devices is also important because the majority of chemotherapy drugs are given via this route. -Extravasation of strong vesicants (e.g., doxorubicin) may lead to severe tissue injury with complications such as permanent damage to muscles, tendons, and ligaments, and possible loss of limb. -Some of the complications that are potential emergencies include infections, infusion reactions and allergy, stomatitis with severe ulceration, bleeding, metabolic aberrations, severe diarrhea, renal failure, liver failure, and cardiotoxicity, including dysrhythmia or heart failure.
The nurse should question a prescription of hydroxyurea (Hydrea) for a client with which laboratory test result? A. Hemoglobin of 15 g/dL B. Platelet count of 8000/mm3 C. Serum creatinine of 1.0 mg/dL D. White blood cell (WBC) count of 8000/mm3
B. Platelet count of 8000/mm3 Hydroxyurea causes bone marrow suppression, which is evidenced by a decrease in red blood cells, WBCs, and platelets. A platelet count of 8000/mm3 compared with a normal platelet count range of 150,000 to 400,000/mm3 is significantly lower than normal. All of the other options are within normal limits.
What is considered a major dose-limiting adverse effect of doxorubicin (Adriamycin)? A. Hepatoxicity B. Nephrotoxicity C. Cardiomyopathy D. Hemorrhagic cystitis
C. Cardiomyopathy Clients receiving doxorubicin need to be monitored for cardiac toxicity. There is a lifetime limited dose that clients are allowed to receive to minimize the occurrence of cardiomyopathy.
The nurse is discussing the use of alkylating drugs with a client. What is the best way for the nurse to describe the action of alkylating drugs on cancer cells? A. They interact within the cell through intercalation. B. They stop the meiosis of cell division and reproduction. C. They alter the chemical structure of the deoxyribonucleic acid (DNA). D. They specifically change the messenger ribonucleic acid sequence.
C. They alter the chemical structure of the deoxyribonucleic acid (DNA). The alkylating drugs work by preventing cancer cells from reproducing. Specifically, they alter the chemical structure of the cells' DNA, which is essential to the reproduction of any cell. This stops the cancer from reproducing or spreading. Cytotoxic antibiotics interact with DNA through a process called intercalation, in which the drug molecule is inserted between the two strands of a DNA molecule, ultimately blocking DNA synthesis.
Alkylating Drugs
-The alkylating drugs commonly used in clinical practice in the United States today fall into three categories: (1) classic alkylators (the nitrogen mustards); (2) nitrosoureas, which have a different chemical structure than the nitrogen mustards but also work by alkylation; and (3) miscellaneous alkylators, which also have a different chemical structure than the nitrogen mustards but are known to work at least partially by alkylation. -Classic alkylators (nitrogen mustards) include chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, nitrosoureas, carmustine, lomustine, and streptozocin. -Miscellaneous alkylators include altretamine, busulfan, carboplatin, cisplatin, dacarbazine, oxaliplatin, procarbazine, temozolomide, and thiotepa. -The alkylating drugs work by preventing cancer cells from reproducing, altering the chemical structure of the cells' deoxyribonucleic acid (DNA). -Alkylating drugs can be characterized by the number of alkylation reactions in which they can participate. Bifunctional alkylating drugs have two reactive alkyl groups that are able to alkylate two sites on the DNA molecule. Polyfunctional alkylating drugs can participate in several alkylation reactions. -The most commonly used alkylating drugs today are effective against a wide spectrum of malignancies, including both solid and hematologic tumors. -The adverse effects of these drugs are important because of their severity, but they can often be prevented or minimized by prophylactic measures. For instance, nephrotoxicity from cisplatin can often be prevented by adequately hydrating the patient with IV fluids. -The most important rule for preventing such drug interactions is to avoid administering an alkylating drug with any other drug capable of causing similar toxicities.
Cytotoxic Antibiotics
-The cytotoxic antibiotics consist of natural substances produced by the mold Streptomyces as well as semisynthetic substances in which chemical changes are made in the natural molecule. -Cytotoxic antibiotics have bone marrow suppression as a common toxicity. The one exception is bleomycin, which instead causes pulmonary toxicity (pulmonary fibrosis and pneumonitis). -Other severe toxicities associated with the use of cytotoxic antibiotics are heart failure (daunorubicin) and, in rare cases, acute left ventricular failure (doxorubicin). -The available cytotoxic antibiotics are categorized according to the specific subclass—anthracyclines or other cytotoxic antibiotics—to which they belong. -Anthracyclines include daunorubicin, doxorubicin, epirubicin, idarubicin, and valrubicin. -Other cytotoxic antibiotics include bleomycin (which is actually a cell cycle-specific drug), dactinomycin, mitomycin, mitoxantrone, and plicamycin. -Cytotoxic antibiotics are used to treat a variety of solid tumors and some hematologic malignancies as well. -As with all antineoplastic drugs, cytotoxic antibiotics have the undesirable effects of hair loss, nausea and vomiting, and myelosuppression. -They all tend to produce increased toxicities when used in combination with other chemotherapeutic drugs or with radiation therapy. -Medication errors have occurred because one "rubicin" has been mistaken for another. It is important to refer to these drugs by both trade and generic names rather than as a "rubicin."
Miscellaneous Antineoplastics
-The miscellaneous antineoplastic drugs, because of their unique structure and mechanism of action, cannot be classified into the previously described categories. -Drugs currently in the miscellaneous category include bevacizumab, everolimus, hydroxyurea (which is actually cell cycle specific), ipilimumab, imatinib, mitotane, ofatumumab, pazopanib, romidepsin, sorafenib, sunitinib, hormonal drugs, and radioactive and related antineoplastic drugs. -Hormonal drugs, both agonists and antagonists, and female and male hormones, are used to treat a variety of malignancies. -Hormonal drugs are used in the treatment of a variety of neoplasms; the rationale is that sex hormones act to accelerate the growth of some common types of malignant tumors, especially certain types of breast and prostate cancer. Therapy may involve administration of hormones with opposing effects (i.e., male versus female hormones) or drugs that block the body's sex hormone receptors, most commonly as palliative and adjuvant therapy. For certain types of cancer, they may be used as drugs of first choice. -Porfimer sodium is used to treat esophageal or bronchial tumors that are present on the surface mucosa. The medication is given intravenously, and administration is followed by one or more sessions of laser light therapy to the esophageal or bronchial mucosa for direct tumor lysis and manual débridement. -Radiopharmaceuticals are used to treat a variety of cancers or symptoms caused by cancers. -Five commonly used radioisotopes are: (1) chromic phosphate P 32 (for cancer-induced peritoneal or pleural effusions), (2) samarium SM 153 lexidronam (for bone cancer pain), (3) sodium iodide I-131 (for thyroid cancer and hyperthyroidism), (4) sodium phosphate P 32 (for leukemias and palliative treatment of bone metastases), and (5) strontium Sr 89 chloride (for bone cancer pain). -Bevacizumab (Avastin) was the first antineoplastic drug in a new category—angiogenesis inhibitors. Angiogenesis is the creation of new blood vessels that supply oxygen and other blood nutrients to growing tissues. Angiogenesis that occurs within a malignant tumor mass promotes continued tumor growth. Inhibiting this process offers a promising new mechanism for antineoplastic drug action. -Certinib (Zykadia) is a new tyrosine kinase inhibitor indicated for ALK-positive lung cancer that is unresponsive to other therapies. It was approved under accelerated approval by the U.S. Food and Drug Administration and is considered "breakthrough" therapy. -Sipuleucel-T (Provenge) is a new form of treatment of prostate cancer. It is not a chemotherapeutic agent, rather it is an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic hormone-resistant prostate cancer.
When providing education to a client undergoing antineoplastic drug therapy, the nurse instructs the client to immediately notify the health care provider for which signs and symptoms? (Select all that apply.) A. Blood in urine B. Bleeding gums C. Swollen tongue D. Difficulty sleeping E. New and persistent cough F. Nausea on the day of treatment
A. Blood in urine B. Bleeding gums C. Swollen tongue E. New and persistent cough The client must contact the health care provider immediately if any of the listed signs or symptoms occur: · Fever or chills with a temperature higher than 100.5° F (38.1° C) · New sores or white patches in the mouth or throat · Swollen tongue with or without cracks and bleeding · Bleeding gums · Dry, burning, "scratchy," or "swollen" throat · A cough that is new and persistent · Changes in bladder function or patterns · Blood in the urine · Changes in gastrointestinal or bowel patterns, including "heartburn" or nausea, vomiting, constipation, or diarrhea lasting longer than 2 or 3 days
When a client is receiving cisplatin (Platinol), the nurse will monitor the client for which possible severe adverse effects? (Select all that apply.) A. Ototoxicity B. Nephrotoxicity C. Pulmonary toxicity D. Nausea and vomiting E. Peripheral neuropathy
A. Ototoxicity B. Nephrotoxicity D. Nausea and vomiting E. Peripheral neuropathy Cisplatin is known to be ototoxic, nephrotoxic, neurotoxic, and emetogenic.
Which are known severe adverse effects of alkylating agents? (Select all that apply.) A. Ototoxicity B. Neurotoxicity C. Cardiotoxicity D. Nephrotoxicity E. Bone marrow suppression
A. Ototoxicity B. Neurotoxicity D. Nephrotoxicity E. Bone marrow suppression Alkylating drugs are capable of causing pulmonary fibrosis, nephrotoxicity, neurotoxicity, bone marrow suppression, peripheral neuropathy, ototoxicity, and hemorrhagic cystitis. The adverse effects of these drugs are important because of their severity, but they can often be prevented or minimized by prophylactic measures. Cardiotoxicity is not listed as an adverse effect for this class of drugs.
What are the possible severe adverse effects specific to the cytotoxic antibiotics? A. Pneumonitis B. Liver toxicity C. Neurotoxicity D. Nephrotoxicity E. Cardiovascular toxicity
A. Pneumonitis B. Liver toxicity D. Nephrotoxicity E. Cardiovascular toxicity As with all of the antineoplastic drugs, cytotoxic antibiotics have the undesirable effects of hair loss, nausea and vomiting, and myelosuppression. Severe adverse effects specific to the cytotoxic antibiotics include pulmonary fibrosis, pneumonitis, liver toxicity, heart failure, cardiovascular toxicity, tissue damage in the event of extravasation, kidney toxicity, and lung toxicity. This class of drugs is not known for neurotoxicity.
When a client is receiving tamoxifen (Soltamox), the nurse will suspect which type of cancer? A. Lung B. Renal C. Colon D. Breast
D. Breast Tamoxifen is a selective estrogen receptor modulator drug useful in treating malignancies that require estrogen for growth, such as breast cancer.
When a client is receiving cyclophosphamide (Cytoxan), the nurse should advise the client to drink plenty of fluids to prevent which condition? A. Neutropenia B. Renal failure C. Liver dysfunction D. Hemorrhagic cystitis
D. Hemorrhagic cystitis Clients receiving cyclophosphamide should drink at least 2 to 3 L of fluid before, during, and after administration to prevent hemorrhagic cystitis