Pharmacology Antineoplastic Drugs

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DRUGS THAT ARE CELL CYCLE-SPECIFIC
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ANTIMETABOLITES CAMPTHOTHECINES MISCELLANEOUS VINCA ALKALOIDS PODOPHYLLOTOXINS TAXANES
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ANTIMETABOLITES
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5-Fluorouracil (5-FU)
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5-Fluorouracil (5-FU) Use
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• Solid tumors • GI tumors • Palliative management of various tumor
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5-Fluorouracil (5-FU) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Antimetabolite interrupts DNA and RNA synthesis during S phase which leads to cell death. Pharmacokinetics: • Crosses BBB
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5-Fluorouracil (5-FU) Contraindications
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• Patients with poor nutritional status • Depressed bone marrow function • Serious infections • Caution in breast feeding mothers, Pregnancy category D • Pyrimidinemia (enzyme deficiency)
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5-Fluorouracil (5-FU) Adverse Effects
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Common: • Alopecia • Photosensitivity • Increased pigmentation Serious: • Myelosuppression: anemia, leucopenia, thrombocytopenia • Nadir= maximum cytotoxic effect is exerted on bone marrow, causing the lowest blood cell count. • Cardiotoxicity can occur during first 72 hours: angina, palpitations, sweating and or syncope, MI. • Neuro: headache, disorientation, nystagmus, photophobia and blurred vision • GI: nausea, vomiting, anorexia and diarrhea. Gi ulceration can lead to death.
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5-Fluorouracil (5-FU) Nursing Interventions
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• Baseline CBC, monitor CBC before administration of med. • Assess patien’s skin, nail and hair. • Teach client about skin sensitivity to the sun and how to decrease exposure. • Discontinue drug if stomatitis, leucopenia, thrombocytopenia, intractable vomiting, diarrhea, or bleeding occur. • Teach clients if loose stools exceed normal pattern by more than three movements, or if stools are dark or with visible blood to notify provider. • Teach to brush with a soft toothbrush, use sodium bicarbonate and water for rinse. • Do not use aspirin or OTC containing aspirin. • Teach clients s/s of infection, monitor temp, check for bleeding. • Teach client to eat bland, cool, soft foods.
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CAMPTHOTHECINES
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Topoisomerase-I Inhibitors -topotecan hydrochloride (Hycamtin)
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Topoisomerase-I Inhibitors -topotecan hydrochloride (Hycamtin) Use
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• Metastatic ovarian cancer after failure of initial treatment. • Small-cell lung cancer • ALL
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Topoisomerase-I Inhibitors -topotecan hydrochloride (Hycamtin) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Inhibits topoisomerase-K an enzyme responsible for rpair of the cell. The drug leads to damage that the cell is unable to repair efficiently Pharmacokinetics: • Administered IV • Crosses BBB
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Topoisomerase-I Inhibitors -topotecan hydrochloride (Hycamtin) Contraindications
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• Mylosuppressive • Poor Bone Marrow Function: neutropenia, thrombocytopenia • Pregnancy Cat. D
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Topoisomerase-I Inhibitors -topotecan hydrochloride (Hycamtin) Adverse Effects
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Common: • Alopecia, fever and flu-like symptoms • Nausea and vomiting • Fatigue Serious: • Myelosuppression: neutropenia
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Topoisomerase-I Inhibitors -topotecan hydrochloride (Hycamtin) Nursing Interventions
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• Protect unopened vials of drug from light. • Monitor WBC counts prior to administration. • If nadir is especially low, hematopoietic growth factors may be given. If needed growth factor should be administered 24 hours after the last dose of topotecan. • Advise patients in ways to lessen fatigue. • Eat small frequent meal and utilize antiemetics to decrease N/V. • Teach s/s of infection and bleeding
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MISCELLANEOUS
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Hydroxyurea (Hydrea)
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Hydroxyurea (Hydrea) Use
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• Acute lymphoblastic leukemia • Chronic myelogenous leukemia • Essecntial thrombocytopenia, • Polycythemia Vera • Hyperleukocytosis
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Hydroxyurea (Hydrea) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Inhibits robonucleotid reductase which causes inhibition of DNA without inhibiting RNA or protein synthesis. Pharmacokinetics: • Only given PO
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Hydroxyurea (Hydrea) Contraindications
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• Severe anemia • Severely depressed bone marrow (WBC less than 1500) • Caution in patients with decreased renal function • Pregnancy category D
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Hydroxyurea (Hydrea) Adverse Effects
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Common: • Nausea and vomiting, stomatitis and diarrhea or constipation Serious: • Myelosuppression: Leukopenia, anemia, thrombocytopenia • Vasculitis
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Hydroxyurea (Hydrea) Nursing Interventions
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• Monitor CBC • Dose modification may be seen in clients who are receiving or have received radiation or chemotherapy • If difficulty swallowing may empty capsule into glass of water, mis and drink immediately. Careful handling of capsule, contents should not come in contact with skin. • Teach patient s/s o finfection, anemia, when to contact provider.
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MITOTIC INHIBITORS
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VINCA ALKALOIDS PODOPHYLLOTOXINS TAXANES
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VINCA ALKALOIDS
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Vincristine (Oncovan)
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Vincristine (Oncovan) Use
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• Acute lymphoblastic leukemia • Hodgkin’s • Non-Hodgkin’s lymphomas • Breast cancer • Wilm’s tumor
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Vincristine (Oncovan) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Mitotic inhibition which arrests cell division in the metaphase stage of mitosis. Pharmacokinetics: • IV administration • Poor BBB crossing
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Vincristine (Oncovan) Contraindications
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• May increase neurotoxicity in clients with underlying disorders. • Contraindicated in patients with demyelinating form of Charcot Marie-Tooth syndrome. • May need lower dosages in clients with liver impairment. • IV routes only, can be fatal intrathecally • Vesicant solution increased monitoring of IV required. Central line administration best.
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Vincristine (Oncovan) Adverse Effects
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Common: • Vesicant solution results in extravasation Serious: • Loss of deep tendon reflexes • Motor, sensory and autonomic neuropathies. • Constipation which can be warning sign of paralytic ileus.
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Vincristine (Oncovan) Nursing Interventions
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• Caution clients that motor and sensory deficits can cause safety hazards • Drug is light sensitive, protect from light. • Assess bowel pattern due to risk of ileus • Teach patients strategies for taking care of hair and skin (hair will regrow in a few months) • Teach patients to report pain, redness, swelling or blistering at the infusion site. • Monitor infusion, watch for extravasation and be familiar with treatment (hyaluronidase locally at site) • Conduct neurologic exam prior to each infusion to monitor for changes • Report in changes to oncologist
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PODOPHYLLOTOXINS
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Etoposide (VP-16)
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Etoposide (VP-16) Use
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• Refractory testicular tumors • Small-cell lung cancer • Hodgkins and non-Hodgkin’s lymphomas • ALL, • Breast cancer
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Etoposide (VP-16) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Inhibits a DNA enzyme (topoisomerase II) this action inhibits DNA so cells do not enter mitosis and prophase. Pharmacokinetics: • Usually IV, though oral form also available
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Etoposide (VP-16) Contraindications
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• Hypersensitivity • Never given IV push or rapid IV administration (may result in hypotension) • Infuse over 30-60 minutes • Monitor PT if patient taking warfarin also.
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Etoposide (VP-16) Adverse Effects
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Common: • Irritation at infusion site, apply warmth. • Hypotension related to rapid infusion. Serious: • Hypersensitivity or anaphylaxis: hypotension, chills, fevers facial flushing, bronchospasm and tachycardia. • Myelosuppression • Liver toxicity • Radiation recall in clients who have received radiation
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Etoposide (VP-16) Nursing Interventions
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• Monitor WBC prior to administration • Observe client for hypotension or s/s of anaphylaxis • Give by slow infusion • Apply warm compresses to site, if irritation • Monitor hepatic and renal function before and during therapy • If oral form used also use antiemetics and take on a full stomach • Metallic taste can be dealt with by sucking on hard candies.
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TAXANES
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Paclitaxel (Taxol)
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Paclitaxel (Taxol) Use
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• Ovarian- given if failure of first line treatment • Breast Cancer (Given if cancer has progressed or relapse) • Second line treatment for AIDS related Kaposi sarcoma.
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Paclitaxel (Taxol) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Inhibits microtubular network during interphase and mitosis. This prevents depolymerization which triggers cell death in rapidly dividing cells. • Also prevents transition from G phase to the S phase. Pharmacokinetics: • Can be given IV or intraabdominally through inserted catheter.
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Paclitaxel (Taxol) Contraindications
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• Hypersensitive to drugs formulate in Cremophor EI. • Not used in Children
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Paclitaxel (Taxol) Adverse Effects
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Common: • Nausea, vomiting, alopecia and joint pains. Serious: • Hypersensitivity or anaphylaxis. Occurs in first 20 minutes of infusion or first or second exposure to drug.: hypotension, tachycardia, wheezing and chest pain are s/s • Myelosuppression: severe neutropenia
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Paclitaxel (Taxol) Nursing Interventions
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• Store diluted paclitaxel in glass bottles or plastic bags and administer with polyethylene line administration sets with an in line micron filter. • Monitor patient’s vital signs during first 15 minutes of infusion and continue monitoring the patient for the first hour. Stay with patient because most hypersensitivity reactions in first 20 minutes. • Premedication with diphenhydramine, H2 antagonist 30 minutes before infusion decrease sensitivity • Monitor WBC; teach s/s of infection and ways to decrease risk of infection. • Discuss medications to alleviate adverse effects such as Tylenol or ibuprofen • Explain s/s of peripheral neuropathy and potential on patient’s activities. • Explain importance of oral hygiene. • Watch for fluid retention.
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DRUGS THAT ARE CELL CYCLE-NONSPECIFIC
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ALKYLATING AGENTS NITROSUREAS ANTITUMORANTIBIOTICS HORMONES AND HORMONE ANTAGONISTS
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ALKYLATING AGENTS
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Cyclophosphamide (Cytoxan)
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Cyclophosphamide (Cytoxan) Use
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• Hodgkins and non-Hodgkins lymphoma • Acute and chronic leukemias • Solid tumors
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Cyclophosphamide (Cytoxan) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Transfers alkyl groups to nuclear DNA leading to eventual cell death. • Becomes cytotoxic through hydroxylation during metabolism. Pharmacokinetics: • Oral and IV administration
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Cyclophosphamide (Cytoxan) Contraindications
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• Compromised bone marrow function • Hypersensitivity • Modifications may be necessary in treatment of clients with hepatic or renal dysfunction
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Cyclophosphamide (Cytoxan) Adverse Effects
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Common: • Leukopenia • Hemorrhagic cystitis: hematuria, pain, burning on urination. • SIADDH • Cardiomyopathy, CHF • Secondary malignancies Serious: • Leukopenia • SIADH • Cardiomyopathy, CHF • Secondary malignancies
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Cyclophosphamide (Cytoxan) Nursing Interventions
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• Ensure adequate renal function prior to administration • Monitor CBC • Tell patient to drink at least 2L per day and empty bladder frequently to decrease incidence of cystitis • In high dose therapy uroprotective agent mesna may be used. • Monitor urine output. • Review s/s of hypersensitivity reaction • Tell patient to notify provider of decreased urine output, burning with urination, t of 100.3F or greater, excessive vomiting or diarrhea • Black stools • Teach patient how to use antiemetic therapy for nausea/vomiting • If oral form taken, encourage patient to take in early morning on empty stomach. Drink 2L per day minimum of fluid, and empty bladder every 2 hours. • Discuss sperm and egg donation with client considering having children.
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NITROSUREAS
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Carmustine (BCNU)
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Carmustine (BCNU) Use
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• Palliative therapy of brain tumors, multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma. • Preparative regimen for stem cell transplants in lymphoma patients.
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Carmustine (BCNU) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Alkylates DNA and RNA, blocking synthesis and repair. Pharmacokinetics: • IV administration
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Carmustine (BCNU) Contraindications
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• Hypersensitivity • Caution in patients with impaired respiratory or bone marrows function. • Skin contamination can cause hyper pigmentation
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Carmustine (BCNU) Adverse Effects
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Common: • Nausea and vomiting • Pain at injection site, flushing of the skin Serious: • Bone marrow suppression: Thrombocytopenia, leucopenia.(This can be a delayed response) • Pulmonary inflammation and fibrosis
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Carmustine (BCNU) Nursing Interventions
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• Warm patients about acute nausea and vomiting treat accordingly with antiemetics • Medication should be in glass container, no plastic. Protect from light • Monitor CBC regularly • Monitor renal and hepatic and pulmonary function tests • Use a large vein or central venous access to minimize pain, • To decrease inflammation or vein and pain, flush with 125ml NS after infusion. • Teach s/s of infection and or bleeding and when to call provider. • Advise patients to avoid taking aspirin or drugs that contain aspirin. – notify provider of dark stools, bloody gums and or bruises.
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ANTITUMORANTIBIOTICS
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Doxorubicin (Adriamycin)
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Doxorubicin (Adriamycin) Use
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• Leukemias • Hodgkin’s and non-Hodgkins lymphomas • Multiple myeloma • Carcinoma of breast, ovary, prostate, stomach, thyroid,
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Doxorubicin (Adriamycin) Pharmacodynamics and Pharmacokinetics
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Pharmacodynamics: • Blocks synthesis of new RNA or DNA through intercalation between base pairs in the DNA. Pharmacokinetics: • May produce reddish colored urine • Liposomes encapsulate the drugs molecule and allow for increased concentration and decreased clearance of the drug.
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Doxorubicin (Adriamycin) Contraindications
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• Severe CHF • Myelosuppression from irradiation or chemotherapy • Doses need to be reduced in clients with hepatic dysfunction
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Doxorubicin (Adriamycin) Adverse Effects
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Common: • Alopecia, nausea and vomiting • Hyper pigmentation of the nail beds and dermal creases. Serious: • Suppression of bone marrow function • Cardiotoxicity • Local effects: radiation recall: redness, blisters, edema, vesicle formation ulcer formation. • Extravasation: can form free radicals which will also delay wound healing
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Doxorubicin (Adriamycin) Nursing Interventions
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• Cardioprotectants such as Zinecard should be used to protect the heart. • Assess cardiac and hematologic status prior to beginning treatment. • Monitor for extravasation, administer vesicants through the side port of a free-flowing IV set to allow for dilution. Blood return checks should be made during administration. If patient complains of discomfort or if there is not blood return, infusion should be stopped. • Give antiemetics prior to administration • Discuss s/s of cardiotoxicity with client & s/s of depressed bone marrow • Caution client against taking aspirin
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HORMONES AND HORMONE ANTAGONISTS
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Anti-estrogen Tamoxifen (Nolvadex)
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Anti-estrogen Tamoxifen (Nolvadex) Use
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• After mastectomy or dissection. • Premenopausal women with metastatic breast cancer, • Alternative to oophorectomy and irradiation. • Approved to prevent breast cancer in high risk women
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Anti-estrogen Tamoxifen (Nolvadex) Pharmacodynamics
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Pharmacodynamics: • Competes with estrogen for binding sites in tissues high in estrogen receptors such as breast tissue. • Deprives estrogen sensitive tumors of estrogen. • May stimulate production of growth factor-beta which inhibits the growth of most breast cancers.
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Anti-estrogen Tamoxifen (Nolvadex) Contraindications
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• Hypersensitivity • Pregnancy and lactation • Monitor clients with myelosuppression • Endometrial changes such as hyperplasia, polyps and endometrial cancer has been reported with long term use.
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Anti-estrogen Tamoxifen (Nolvadex) Adverse Effects
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Common: • Hot flashes- especially with premenopausal women • Visual side effects Serious: • Endometrial cancer • Thromboembolic events
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Anti-estrogen Tamoxifen (Nolvadex) Nursing Interventions
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• Monitor CBC • Teach client how to handle menopausal symptoms by wearing cotton clothing, lowering the thermostat at home, avoiding caffeine and spicy food, exercising regularly. • Teach patient to report changes in visual acuity, caution with driving, and have periodic vision checkups. • Have client report any s/s of hypercalcemia: nausea, vomiting, constipation, malaise, loss of muscle tone. • Teach client need for contraception. • Notify provider of any pain and swelling in legs, ankles. • Teach client about a disease flare, possible s/s: bone and tumor pain. Teach that this indicate tumor is responding to treatment.

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