Introduction to Clinical Pharmacology Chapter 50- Antineoplastic Drugs

Cell Cycle Strategy of antineoplastic drug therapy is to affect cells that rapidly divide and reproduce-delays spread of cancer to other sites

How Does Chemotherapy Work? There are 5 phases in the cell cycle, designated by letters and numbers: G0 = Resting stage G1 = RNA and protein synthesis S = DNA synthesis G2 = Construction of mitotic apparatus M = Mitosis

The Cell Cycle G0 phase (resting stage): Cells have not yet started to divide. Cells spend much of their lives in this phase. Depending on the type of cell, it can last for a few hours to a few years. When the cell is signaled to reproduce, it moves into the G1 phase. G1 phase: During this phase, the cell starts making more proteins to get ready to divide. This phase lasts about 18 to 30 hours. S phase: In the S phase, the chromosomes containing the genetic code (DNA) are copied so that both of the new cells formed will have the right amount of DNA. This phase lasts about 18 to 20 hours. G2 phase: The G2 phase is just before the cell starts splitting into two cells. It lasts from 2 to 10 hours.

The Cell Cycle M phase (mitosis): In this phase, which lasts only 30 to 60 minutes, the cell actually splits into 2 new cells. This cell cycle is important to cancer doctors (oncologists) because many chemotherapy drugs work only on actively reproducing cells (not on cells in the resting phase, G0). Some of these drugs specifically attack cells in a particular phase of the cell cycle (the M or S phases, for example). Understanding how these drugs function helps oncologists predict which drugs are likely to work well together. Doctors can also effectively plan how often doses of each drug should be given based on the timing of the cell phases. American Cancer Society-2006

Herbal Alert Green tea Antioxidant Patients with insomnia and ulcers should use green tea with caution

Cell Cycle Specific Drugs: Actions and Uses Plant Alkaloids: Vinca alkaloids: Interfere with amino acid production in S phase and formation of microtubules in M phase Taxanes: Interfere in M-phase with microtubules

Cell Cycle Specific Drugs: Actions and Uses (cont’d) Antimetabolites: Interfere with synthesis of RNA and DNA, make it impossible for cancerous cell to divide into two daughter cells Drugs are used to treat: Leukemia, lymphoma, solid tumors, autoimmune diseases

Cell Cycle Nonspecific Drugs: Actions and Uses Alkylating agents: Change cell to more alkaline environment, which in turn damages the cell Nitrosureas are unique in that they can cross the blood-brain barrier and therefore used to tx brain tumors EX: Busulfex-CML; Cytoxan-Hodgkin’s, leukemia, multiple myleoma; Mustargen-Hodgkin’s disease, leukemia Antineoplastic antibiotics: Interfere with DNA and RNA synthesis, delaying or inhibiting cell division ; Adriamycin-acute leukemia, Wilm’s tumor; Idamycin-leukemia; Mutamycin-adenocarcinoma of stomach, pancreas; Mithracin-malignant testicular tumors

Cell Cycle Nonspecific Drugs: Actions and Uses Miscellaneous antineoplastic drugs: Number of drugs are used for antineoplastic actions, do not belong to any one category EX:Oncaspar- ALL;Platinol/cisplatin-metastatic testicular tumors, bladder cancer, ovarian tumors Antimetabolites-EX:Leustatin-hairy cell leukemia; Adrucil-carcinoma of breast, stomach, pancreas, colon; Fludara-CLL Hormones-EX: Teslac-breast cancer;Depo-Provera- endometrial or renal cancer;Megace—breast or endometrial cancer;Nolvadex/tamoxifen**-breast cancer;Zoladex, Lupron (Gonadotropin-Releasing Hormones) Mitotic Inhibitors-EX:Taxol-ovarian cancer;Velban;Oncovin, Vincasar**-acute leukemia

Cell Cycle Nonspecific Drugs: Adverse Reactions Nausea and vomiting from highly emetic drugs or potential of IV extravasation of irritating solutions Adverse reactions common to antineoplastic drugs: Bone marrow suppression;-anemia, leukopenia, thrombocytopenia , Stomatitis; Diarrhea; Hair loss Leukopenia and thrombocytopenia may cause cycles of chemotherapy to be delayed until blood cell counts can be raised Damage gonads causing fertility problems

Adverse Reactions Intensity increases with higher doses Bone marrow suppression, n/v, stomatitis, diarrhea, alopecia Toxic Hyperuricemia (increase fluids)

Cell Cycle Nonspecific Drugs: Contraindications and Precautions Antineoplastic drugs are contraindicated in patients with: Leukopenia; Thrombocytopenia; Anemia; Serious infections; Renal disease; Hypersensitivity to drug; During pregnancy or lactation Used cautiously in patients with: Renal or hepatic impairment; Active infection; Debilitating illnesses; Those who have completed treatment with other antineoplastic drugs or radiation therapy

Contraindications Leukopenia Thrombocytopenia Platelets <100,000 Anemia Infections Renal disease

Cell Cycle Nonspecific Drugs: Interactions Interactant Drug Effect of Interaction Plant Alkaloids Digoxin Decrease serum level of digoxin Phenytoin Increased risk for seizures Oral anticoagulants Prolonged bleeding

Cell Cycle Nonspecific Drugs: Interactions (cont’d) Interactant Drug Effect of Interaction Alkylating Drugs Aminoglycosides Increased risk for nephrotoxicity and ototoxicity Loop diuretics Increased risk for ototoxicity NSAIDs Methotrexate toxicity

Nursing Process: Assessment Preadministration assessment: Initial assessment: The type and location of the neoplastic lesion Obtain v/s, weight CBC if drug causes bone marrow depression Anxiety or fears the patient may have regarding chemotherapy treatments

Nursing Process: Assessment (cont’d) Ongoing assessment: The patient’s general condition The patient’s individual response to the drug Adverse reactions that may occur Guidelines established by the primary health care provider or hospital Results of periodic laboratory tests and radiographic scans

Nursing Process: Nursing Diagnoses Imbalanced nutrition: Less than body requirements Fatigue Risk for injury Risk for infection Disturbed body image Anxiety Impaired tissue integrity

Nursing Process: Planning Expected outcomes: An optimal response to therapy Support of patient needs related to the management of adverse reactions Understanding of prescribed treatment modalities

Nursing Process: Implementation Promoting an optimal response to therapy ( Protection of the provider: The Occupational Safety and Health Administration (OSHA) guidelines Nurses need to be protected during administration and cleanup from accidental ingestion, inhalation, or absorption of drugs PPE’s!!!!!!!!

Nursing Process: Implementation Promoting an optimal response to therapy (cont’d): Parenteral administration: Give injection into large muscles using Z-track method Sites should be rotated, charted appropriately if the injections are given frequently

Nursing Process: Implementation Monitoring and managing patient needs: Imbalanced nutrition: Less than body requirements Assess nutritional status of patient before and during treatment Provide small, frequent meals to coincide with patient’s tolerance for food to stimulate appetite Stress importance of eating meals high in nutritive value, particularly protein Mouth care q 4 hours, rinse with NS, avoid lemon/glycerin swabs-make stomatitis worse

Nursing Process: Implementation Monitoring and managing patient needs Fatigue, infection and injury: Myelosuppression Monitor patients with thrombocytopenia (platelet count <100,000) for bleeding tendencies and take precautions to prevent bleeding ALERT-report bleeding gums, tarry stools, bloody urine to MD Neutropenia-observe for signs of infection ALERT-report temp >100.4, Sore throat

Nursing Process: Implementation Monitoring and managing patient needs (cont’d): Fatigue, infection and injury: Myelosuppression (cont’d): Apply pressure to injection site for 3 to 5 minutes to prevent bleeding into tissue and formation of hematoma Inform patient to avoid use of electric razors, nail trimmers, dental floss, firm toothbrushes, any sharp objects

Nursing Process: Implementation Monitoring and managing patient needs (cont’d): Disturbed body image: Inform patient that hair loss may occur if hair loss is associated with antineoplastic drug being given Forewarn patient that hair loss may occur suddenly and in large amounts Assist in making plans for purchase of wig or cap to disguise hair loss until hair grows back

Nursing Process: Implementation Monitoring and managing patient needs Impaired tissue integrity (cont’d): Monitor IV site continuously and check for blood return frequently during IV push procedures Keep extravasation kit containing all materials necessary to manage extravasation available, along with extravasation policy and procedure guidelines Avoid the sun, wear protective, loose clothing, monitor for erythema

Nursing Process: Implementation Educating the patient and family: Do not take nonprescription drug unless approved by primary healthcare provider Avoid drinking alcoholic beverages unless approved by PCP Inform physicians, dentists, medical personnel of therapy with this drug Keep all appointments for laboratory tests ordered by the primary health care provider

Nursing Process: Evaluation The therapeutic effect is achieved Adverse reactions are identified, reported and managed Anxiety is reduced The patient verbalizes: An understanding of the dosage regimen; Understanding of treatment modalities; Importance of continued follow-up care; Complying with the prescribed therapeutic regimen