Drugs to Know: 1.

Inflammatory Process - NSAIDS - COX 2 Inhibitors - Leukotrien Inhibitors COX 1 PG12: Gastric mucosal integrity Gastric Irritation- instruct to take with meal and full glass of water PGE2: Bronchodilation, renal function by dilating renal arterioles trigger asthma attack, decrease GFR and Na Retention Contraindicated with CHF and Renal insufficiency (BUN & Creatinine elevated) TXA2: Platelet function risk for bleeding monitor for bleeding & assess if patient is taking anticoagulants - *More side effects! COX 2 PGE2 & PGF2a: Inflammation anti-inflammatory effect- monitor for efficacy, therapeutic Nonselective COX Inhibitors Acetic Acid Propionic Acid

Fenamate

Salicylate

Naphthylalkanone Oxicam

Diclofenac Etodolac Indomethacin Sulinclac Tolmetin

Fenoprofen Flurbiprofen Ibuprofen Ketoprofen Naproxen Oxaprozin

Meclofenamate Aspirin Meclofenamic Diflunisal acid

Nabumetone

Piroxicam Meloxicam

Choline magnesium trisalicylate Salsalate

Selective COX-2 Inhibitors Celecoxib Rofecoxib *Lesser side effects Dont take if at risk for blood clots! Risks for clotting-HA, stroke, etc. Aspirin - Salicylate NSAID o Antipyretic o Analgesic o Anti-inflammatory o Prophylaxis of diseases due to platelet aggregation - Thromboxane A2 stimulates blood platelet aggregation, essential to the role of platelets in blood clotting. - *The effect of aspirin is long lived because platelets lack a nucleus and do not make new enzyme - At risk for bleeding - 81 mg everyday = anti-platelet - Surgery: hold 7-10 days; Emergency: platelet transfusion Side Effects: same as other Non-Selective COX inhibitors Toxic Effects: Ototoxic, Hepatotoxic, Nephrotoxic, Reyes Syndrome: high fever, vomiting, liver dysfunction, unresponsiveness, delirium, convulsions, coma, possible death, common in children. Acid-Base Imbalance: fluids, bicarbonate, electrolytes, hemodialysis

COX Cox 1 Cox 2 Cox 3

Function Organ pain, platelet function, stomach protection Inducible: inflammation, pain, fever

Inhibitor NSAIDs including aspirin NSAIDs, COX 2 inhibitors including celebrex Acetaminophen & some NSAIDs

Pain pathways, not inflammation pathways Tylenol: only pain not inflammation. Max 24 hours is 4 grams

Pregnancy & NSAIDs: Category C- drugs that have not been studied in pregnant humans but that do appear to cause harm to the fetus in animal studies. May still be given to a pregnant woman if her healthcare provider believes that the benefits outweigh the risks to her unborn childAvoid taking NSAIDs at all during the 3rd trimester. Prolongation of gestation and inhibitor of labor. Risk for Patent Ductus Arteriousus 2. Immunosuppressants Corticosteroid Adverse Effects: - All commonly occur because high doses used for immunosuppression: o Cushings Syndrome Hyperglycemia (Gluconeogenesis) Weight gain (Na & H2O retention) Abnormal fats distribution Hypertension Hypokalemia o Gastric Ulcer o Euphoric personality changes o Osteoporosis Inhibition of osteoblastic activity, decreased calcium absorption, increased urinary calcium excretion o Cataracts Calcineurin Inhibitors : interleukin 2 production blockers Cyclosporine (Sandimmune) Tracolimus (Prograft) Adverse Effects: Adverse Effects: - Nephrotoxicity - Nephrotoxicity - Hepatotoxicity - Increased risk of lymphoma - Hirsutism - Hypersensitivity - Neurotoxicity - GI complaints - Lymphoma - Hypertention - Anaphylaxis Drug Interactions: Drug Interactions: - Induction and inhibition of - Agents that inhibit CYP3A (an hepatic cytochrom: P450 isozyme of cytochrome P450) - Nephrotoxic drugs - Grapefruit juice - Grapefruit juice (inhibits - NSAIDs p450)

Sirolimus (Rapamune) Adverse Effects: - Raises levels of cholesterol and triglycerides - Thrombocytopenia - Severe complications in the liver and lung - Nephrotoxic (increases incidence when combined with cyclosporine) Drug Interactions: - Hepatic metabolism by CYP450A4 - High fat foods, Grapefruit Juice

Cytotoxic Agents T-Cells & B-Cells Proliferation Blockers 1) Azathioprine (Imuran) 2) Cyclophosphamide (Cytoxan, Neosar) 3) Mycophenolate mofetil (CellCept, Myfortic) 4) Leflunomide (Arvara) 5) Methotrexate (Rhumatrex, Trexall) Adverse Effects: - Bone Marrow Suppression-Pancytopenia - GI disturbance (ANV) - Hepatotoxicity - Nephrotoxicity - Respiratory Function - Increase risk for secondary neoplasia - Cyclophosphamide Hemorrhagic Cystitis Bioactive Immunosuppressants Anti-thymocyte antibodies 1) OKT3 (Muromonab-CD3) a. Monoclonal antibody to CD3 on T cell i. Actions & Uses 1. Blocks all T cell function 2. Inhibits cytotoxic T killer cell function 3. Opsonizes circulating T lymphocytes and enhances their removal a. Depletes T cells prior to bone marrow transplant b. Used to prevent or reverse acute graft rejection 4. Problem with Muromunab antibody is the formation of anti-OKT3 antibodies which limit its action a. Only given by IV infusion for 7-14 days 2) Antilymphocyte Globulin 3) Antithymocyte Globulin-Rabbit - Used to treat acute rejection transplant - Mechanisms o Removal of T cells from circulation o Decrease cytokine induced reactions - Adverse Effects o Hypersensitivity reactions may occur with nonhuman antibodies resulting in: Chills Fever Thrombocytopenia Erythema Pruritis

IL-2 Receptor Antibodies Basilixmab (Simulect) & Daclizumab (Zenapax) - Monoclonal antibody against human IL-2 receptor alpha subunit of activated T cell - Blocks activation and inhibits clonal expansion of T cells - Used to induce immunosuppression and to prolong organ transplants in combination with other immunosuppressants Nursing Implications - Thorough assessment should be performed before administering these agents. o Renal, liver, cardiovascular & respiratory function o Baseline CBC o Clients need to be told that lifelong therapy with immunosuppressants is indicated with organ transplantation & some autoimmune disorders Priority Nursing Diagnosis - Risk for infection o Hand washing o Mask o Use of strict aseptic technique in caring for IV lines, urinary catheter & wound care o Assess frequently for infection Observe the oral cavity often for white patches on the tongue, mucous membranes, and oral pharynx Monitor VS with O2 sat every 4 hours Report fever, tachypnea, tachycardia, hypotension, restlessness, change in O2 saturation o Neutropenic Precaution: Reverse isolation-positive pressure (air out) No fresh flowers or raw foods (peppers) Limiting visitors esp. with infection, colds or flu o Clients taking immunosuppressants should be encouraged to take measures to reduce the risk of infection Avoiding crowds Avoiding people with colds or other infection o Clients should be told to report any fever, sore throat, chills, joint pain, fatigue, or other signs of a severe infection immediately Cytotoxic Agents o Azathioprine (Imuran), Cyclophosphamide (Cytoxan), Cyclosporine (Sandimmune), Mycophenolate mofetil (CellCept) Bone Marrow Suppression Risk for infection Anemia o Blood transfusion o Administer Procrit as ordered o Supplemental oxygen Platelet <75,000

o o o

Bleeding precaution Monitor for abnormal bleeding Avoid ASA &NSAIDs

3. Antihistamines: - Histamine (H1) receptor antagonists bind to H1 receptors - This prevents histamine from binding to its receptor and causing allergic response - Indications o Allergic Rhinitis o Prevention of anaphylaxis o Allergic conjunctivitis o Drug Allergies o Allergic dermatologic conditions o Blood Transfusion First Generation Second Generation Bind to both central and peripheral H1 receptors Bind to peripheral H1 receptor Causes drowsiness Does not cross BBB Possess anticholinergic effects Non-sedating Some are used for motion sickness (30-60 min) - Dipenhydramine - Promethazine Brompheniramine Azlastine Diphenhydramine Cetirizine Chlorpheniramine Desloratidine Dexchlorpheniramine Loratadine Cyproheptadine Fexofenadine Hydroxyzine Clemastine Promethazine Tripolidine Patient Teaching - Contraindicated in pregnancy - 1st generation contraindicated in Glaucoma, peptic ulcer disease, and urinary retention-makes it worse - Do not perform activities that requires attention as antihistamines may cause alcohol - Do not take 1st generation antihistamines during acute asthma, bronchitis, or pneumonia - Do not take more than one antihistamine at a time - Report adverse reactions from the body - Give with food except Loratadine. Cetrizine and Desloratadine may be given with or without food - Monoamine oxidase inhibitors (MAOI) increases duration of action of antihistamines as well as side effects. - Efficacy of Fexofenadine decreases when given with Riampin - Cimetidine, Azole antifungal, & Macrolides increases the effects of loratidine 4. Type 1 Hypersensitivity: Epinephrine: - Place in modified Trendelenburg, start IV with normal saline or LR - Medication of choice for anaphylaxis - SC or IM; 0.01 mg/kg may repeat every 20-30 min prn

Monitor for cardiac arrhythmias! Rapid onset of action, reverses action of Histamine and decreases release from mast cells. o Dilates Bronchioles o Constricts Blood Vessels o Decreases capillary permeability o Stimulates the reformation of tight junction between endothelial cells Side Effects: o Increased pulse rate, pallor, dizziness, chest pain, headache, nausea, vomiting, excitability, anxiety (decreased parasympathetic) neurotransmitter for sympathetic.

Dopamine/Dobutamine: increases blood pressure To further reduce symptoms after lifesaving measures, control: - Antihistamines - Corticosteroids such as Prednisone - Cromolyn Sodium (Intal)-Mast cell stabilizer - Benadryl, Epipen 5. Type 2 Hypersensitivity: - Blood & Saline - Pre-medicate transfusions with Dipenhydramine 6. Type 3 Hypersensitivity: - Mild SLE may be managed with aspirin or other NSAID o Aspirin: prevent thrombosis o Plaqeunil: For skin and arthritic manifestations Reduce frequency of acute episodes - For clients with life threatening symptoms high doses of corticosteroids are given to prevent major organ damage. o Steroids: tapered down as symptoms subside Side Effects: Risk for infection, Mood Swings, Cushings Syndrome, Ulcerogenic, Osteoporosis, Cataracts o Immunosuppresants: may be used alone or in combination with corticosteroids Azathioprine (Imuran) Cyclophosphamide (Cytoxan) Cyclophosphamide (Sandimmune) Mycophenolate (CellCept) Side Effects o Bone Marrow suppression Anemia Administer Procrit as ordered Risk for infection Risk for bleeding *Avoid aspirin & NSAIDs

7. HIV: Opportunistic Infections - PCP o When CD4 count <200, prophylactic RX is started Trimethoprim, sulfamethoxazle-Cotrimoxazole (Bactrim) - TB o Drug interaction between Protease Inhibitors & Rifampin 4 Types of Anti-virals: 1) Reverse Transcriptase Inhibitors (NRT & NNRT): a. Competitive Enzyme Inhibitors i. Zidovudin AZT (Retrovir, Zidobudin) ii. Didanosine (DDI) (Videx) iii. Zalcitabine (DDC) (Hivid) 2) Protease Inhibitors a. Inhibit the viral proteases thus preventing viral maturation i. Saquinavir ii. Ritonavir iii. Intinavir 3) Entry/Fusion Inhibitors a. Interfere with HIV CD4 receptor site binding and entry into cells i. Enfuvirtide (Fuzeon) 4) Nucleoside reverse transcriptase inhibitors- 1st drug a. Zidovudin AZT (Retrovir) first drug approved for HIV b. Aslo used prophylactically for exposures c. Must be taken q4-6 hours round the clock to keep increased blood i. Adverse Effects 1. Bone Marrow toxicity; drug resistance with long term use 2. Nausea and HA most common SE 3. Take hour before or 1 hour after meals HAART Highly Active Anti-retrovial Therapy - Combine 3-4 antiviral drugs o Decreases chance of drug resistance o Does NOT cure disease, can still transmit o Many SE often want to stop meds o Complicated schedules MUST take many time throughout the day MUST adhere to regimen or viral resistance possible or fatality o Expensive! - If prophylactic for occupational exposure or high risk sexual exposure o 4 week course of treatment started within 72 hours of exposure, preferable 2-3 hour

Others: - Used when clients intolerant to AZT o Stavudin (Zerit) - Used with low CD4 cell counts, 1st line treatment in combo with AZT o Lamividine (Epivar) - Used prophylactically after parenteral exposure to HIV? o Zidovudin (AZT, Retrovir) - How is the effectiveness of treatment determined? o Monitoring viral load and CD4 cell counts - When treatment is working the CD4 cell count sould be? o Above 350 mm3 - Appetite Stimulants: o Marinol o Megace 8. Fe Deficiency Anemia: - Oral Iron Salts: - Ferrous forms better absorbed than ferric (ferrous sulfate, ferrous lactate, ferrous fumarate) IV Iron Dextran: - Can cause allergic reactions *Give Iron supplement 2 hours before tetracycline & antacids-bind to iron 9. B12 Deficiency Anemia: - Vitamin B12 (Cobalamin) injection: o Do not expose crystalline injection to light o Do not mix with other drugs in a syringe o IM or deep SQ o Increase Vit. B12 in the diet- liver, eggs, milk, green leafy products 10. Folic Acid Deficiency Anemia: - Vit. B9 supplement o Do not expose injection to light o Do not mix with other drugs in a syringe o Monitor for hypersensitivity o Interaction: Methotrexate, Phenytonin, contraceptives o Teach to avoid alcohol and tobacco o Increase Vit. B9 in the diet sources-leafy green veggies, oatmeal, peanut butter 11. Aplastic Anemia: - Blood transfusion, bone marrow transplant, immunosuppressive therapy o Oxygenation, bleeding precaution, infection prevention 12. Sick Cell Anemia: - Folic acid supplementation, blood transfusions, genetic counseling o Hydration, Oxygen, Rest, Pain management

13. Hematopoietic Stimulants: - Epoetin Alfa (Procrit & Epogen) & Darbepoetin Alfa (Aranesp) o Synthetic formation of erythropoietin Indications: Anemia caused by several conditions Myelosuppressive anticancer chemotherapy Chronic Renal Failure Used to raise Hgb and reduce the need for BT Administer IV or SubQ o Epogen Alfa (Procrit & Epogen) Half-life: 4-13 hours peak within 24 hours (IV) peak 5-24 hours o Darbepoetin Alfa (Aranest) Half-life is 49 hours-long term o Adverse Effects May make client feel no better than before administration Bone pain-working hard Hypersensitivity Risk of tumor progression in cancer patients HTN Thromboembolism-stroke o Nursing Implications Advise prescriber if the patients Hgb is 12 g/dl or better-stop Assure that there is adequate iron, B9 & B12 in the diet Advise patient about Side Effects Must be refrigerated 14. Neutropenia & Immunostimulants: - Colony Stimulating Factors: synthetic formulation of cytokines used to stimulate production of WBC thus reducing the risk and severity of infection in neutropenic patients. o Drug Formulations: Granulocyte colony-stimulating factor (G-CSF) o Filgastim (Neupogen) & Pegfilgastim (Neulasta) Granulocyte-macrophage colony-stimulating factor (GM-CSF) o Sagramostim (Leukine) Administer IV or Sub Q Must be refrigerated Stopped when WBC normalizes o Indications: Chemotherapy-induced neutropenia Bone marrow transplant (will take 2-4 weeks to mature) G-CSF-can be used to collect stem cell GM-CSF- used to promote arterioles in IHD (promote angiogenesis) o Nursing Implications: Remove from refrigerator 30 minutes before injection. Do not shake the medication. Teach patient about common side effects: Bone Pain

Tenderness at the site of injection Blood test abnormalities (temporary elevation in lactate dehydrogenase, and alkaline phosphatase). These will return to normal once treatment is discontinued.

15. Thrombocytopenia: ITP - Steroids & Immunosuppressants Plasmapharesis for removal of autoantibodies - Transfusion of platelets - Splenectomy: last resort TTP - Plasmapharesis for removal of large vWF - Cryosupernatant plasma & Solvent-detergent plasma for TTP - Contains no vWF - Do NOT transfuse platelets with TTP! o Adding fuel to the fire o Unless life threatening bleeding is present o MI and strokes have reportedly occurred after transfusion HIT - NO heparin and heparin products - Argatroban, Lepirudin, Fondaparinux (Arixtra) for antithrombotic prophylaxis to patients with history of HIT 16. Cancer: Chemotherapy: - Use of antineoplastic drugs to promote tumor cell death, by interfering with cellular function and reproduction o Cell Cycle Nonspecific: Useful against tumors that have a low percentage of replicating cells Generally have more toxicity in cycling cells *More adverse effects than cell cycle specific Attack anything, any stage o Alkylating Agents Action: Alkylation of DNA is the crucial cytotoxic reaction that is lethal to the tumor cells (Destroy DNA of cancer cells) Do not discriminate between cycling and resting cells Nitrogen Mustard (Mechlorethamine HCl), Cisplatin, Cyclophosphamide, Nitrosureas (Carmustine, Lamustine, Semustine) Toxic Effects: reversible renal tubular necrosis, hemorrhagic cystitis, mutagenic and carcinogenic. Can damage own DNA when touching it. o Anti-tumor Antibiotics Action: owe their cytotoxic action primarily to their interactions with DNA, leading to disruption of DNA function. Damage DNA of cancer cells at any stage. In addition to intercalation, they have the ability to produce free radicals also play a major role in their cytotoxic effect. They are cell cycle nonspecific.

Examples: o Actinomycin D, Bleomycin, Adriamycin (Doxorubicin) Toxic Effect: Damage to cardiac muscle, pulmonary fibrosis

Cell Cycle Specific Chemotherapeutic agents that are effective only against replicating cells-that is, those cells that are cycling Harsher, S or M phase normally Affects rapidly dividing cells more: bone, hair, mucous membranes Anemia, Increased risk of bleeding, increased risk for infection o Antimetabolites Action: structurally related to normal compounds that exist within the cell. Block DNA replication. S-phase. Interfere with the availability of normal purine or pyrimidine nucleotide precursors by inhibiting their synthesis Competing with them in DNA or RNA synthesis Their maximal cytotoxic effects are in S phase (and therefore, cell cycle specific) DNA cant replicate and die. o Examples: Methotrexate-Blocks B9 synthesis Folic Acid deficiency anemia-macrocytic 5 fluorouracil 6 mercaptopurine o Toxic Effects: Nausea, vomiting, stamatitis, diarrhea, alopecia, bone marrow suppression Leucovorin Rescue: Ability to protect normal cells to have normal metabolites, given after increased dose of methotrexate Mitotic Inhibitors Action: Prevent cell division during M phase of cell division The mitotic spindle consists of chromatin plus a system of microtubules composed of the protein tubulin The mitotic spindle is essential for the equal partitioning of DNA when a eukaryotic cell divides. (Prevent microtubules) Examples: o Vincristine, Vinblastine o Structurally related compounds derived from the periwinkle plant, Vinca rosea (vinca alkaloids) o Binds to the microtubular protein, tubulin o Blocks the ability of tubulin to polymerize to form microtubules Toxic Effects: Alopecia, bone marrow suppression, peripheral neuropathy, affects neurotransmission

Hormones - Tumors that are steroid hormone-sensitive may be either: o Hormone responsive- Tumor regresses following treatment with a specific hormone o Hormone dependent- removal of a hormonal stimulus causes tumor regression Tamoxifen (Novaldex) Estrogen antagonist Used for first line therapy in the treatment of estrogen receptor-positive breast cancer Flutamide, Nilutamide, and Bicalutamide Synthetic, nonsteroidal antiandrogens used in the treatment of prostate cancer Immunotherapy - Monoclonal Antibodies o They are created from B lymphocytes (from immunized mice or hamsters) fused with immortal Blymphocyte tumor cells. o Cloned to produce antibodies directed against a single antigen type. o Several monoclonal antibodies are available Trastuzmab, Rituximab, Bevacizmab, and Cetuximab - BCG (Bacillus-Calmette & Guerin) o Injected directly into solid tumor o If exposed to TB o How will this kill tumor cells? Immune system attacks cancer cells *Know Chemo Man!! Cell Cycle Non-Specific Alkylating Agents Antibiotics Cisplatin Nitrosureas Effective for both low-growth fraction malignancies (Solid-tumors) as well as high growth fraction malignancies. Slow growing

Cell Cycle Specific Antimetabolites Bleomycin antibiotics Vinca alkaloids Etoposide Effective for high growth fraction malignancies (hematologic cancers) Rapidly growing