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 waterPGE2: 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 2PGE2 & PGF2a: Inflammation anti-inflammatory effect- monitor for efficacy, therapeutic

Nonselective COX InhibitorsAcetic Acid Propionic Acid Fenamate Salicylate Naphthylalkanone Oxicam Choline

magnesium trisalicylate

DiclofenacEtodolacIndomethacinSulinclacTolmetin

FenoprofenFlurbiprofenIbuprofenKetoprofenNaproxenOxaprozin

MeclofenamateMeclofenamic acid

AspirinDiflunisal

Nabumetone PiroxicamMeloxicam

Salsalate

Selective COX-2 Inhibitors CelecoxibRofecoxib

*Lesser side effects Don’t take if at risk for blood clots! Risks for clotting-HA, stroke, etc.

Aspirin- Salicylate NSAID

o Antipyretico Analgesico Anti-inflammatoryo 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 Function InhibitorCox 1 Organ pain, platelet function, stomach

protectionNSAIDs including aspirin

Cox 2 Inducible: inflammation, pain, fever NSAIDs, COX 2 inhibitors including celebrex

Cox 3 Pain pathways, not inflammation pathways

Acetaminophen & some NSAIDs

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 child…Avoid taking NSAIDs at all during the 3rd trimester. Prolongation of gestation and inhibitor of labor. Risk for Patent Ductus Arteriousus

2. ImmunosuppressantsCorticosteroidAdverse Effects:

- All commonly occur because high doses used for immunosuppression:o Cushing’s Syndrome

Hyperglycemia (Gluconeogenesis) Weight gain (Na & H2O retention) Abnormal fats distribution Hypertension Hypokalemia

o Gastric Ulcero Euphoric personality changeso Osteoporosis

Inhibition of osteoblastic activity, decreased calcium absorption, increased urinary calcium excretion

o Cataracts

Calcineurin Inhibitors : interleukin 2 production blockersCyclosporine (Sandimmune) Tracolimus (Prograft) Sirolimus (Rapamune)Adverse Effects:

- Nephrotoxicity- Hepatotoxicity- Hirsutism- Neurotoxicity- Lymphoma- Anaphylaxis

Drug Interactions:- Induction and inhibition of

hepatic cytochrom: P450- Nephrotoxic drugs- Grapefruit juice (inhibits

p450)

Adverse Effects: - Nephrotoxicity- Increased risk of lymphoma- Hypersensitivity- GI complaints- Hypertention

Drug Interactions:- Agents that inhibit CYP3A (an

isozyme of cytochrome P450)- Grapefruit juice- NSAIDs

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 AgentsT-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 & Uses1. Blocks all T cell function2. Inhibits cytotoxic T killer cell function3. Opsonizes circulating T lymphocytes and enhances their removal

a. Depletes T cells prior to bone marrow transplantb. 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 Globulin3) Antithymocyte Globulin-Rabbit- Used to treat acute rejection transplant- Mechanisms

o Removal of T cells from circulationo Decrease cytokine induced reactions

- Adverse Effectso 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 functiono Baseline CBCo 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 Masko Use of strict aseptic technique in caring for IV lines, urinary catheter & wound careo 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 transfusiono Administer Procrit as orderedo Supplemental oxygen

Platelet <75,000o Bleeding precautiono Monitor for abnormal bleedingo 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 Rhinitiso Prevention of anaphylaxiso Allergic conjunctivitiso Drug Allergieso Allergic dermatologic conditionso Blood Transfusion

First Generation Second GenerationBind to both central and peripheral H1 receptorsCauses drowsinessPossess anticholinergic effectsSome are used for motion sickness (30-60 min)

- Dipenhydramine- Promethazine

Bind to peripheral H1 receptorDoes not cross BBBNon-sedating

BrompheniramineDiphenhydramineChlorpheniramineDexchlorpheniramineCyproheptadineHydroxyzineClemastinePromethazineTripolidine

AzlastineCetirizineDesloratidineLoratadineFexofenadine

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 Bronchioleso Constricts Blood Vesselso Decreases capillary permeabilityo 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 pressureTo 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 thrombosiso 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, Cushing’s Syndrome, Ulcerogenic, Osteoporosis, Cataracts

o Immunosuppresants : may be used alone or in combination with corticosteroids Azathioprine (Imuran) Cyclophosphamide (Cytoxan) Cyclophosphamide (Sandimmune) Mycophenolate (CellCept)

Side Effectso Bone Marrow suppression

Anemia Administer Procrit as ordered

Risk for infection Risk for bleeding

*Avoid aspirin & NSAIDs

7. HIV:Opportunistic Infections

- PCPo 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 Inhibitorsi. Zidovudin AZT (Retrovir, Zidobudin)

ii. Didanosine (DDI) (Videx)iii. Zalcitabine (DDC) (Hivid)

2) Protease Inhibitorsa. Inhibit the viral proteases thus preventing viral maturation

i. Saquinavirii. Ritonavir

iii. Intinavir3) Entry/Fusion Inhibitors

a. Interfere with HIV CD4 receptor site binding and entry into cells i. Enfuvirtide (Fuzeon)

4) Nucleoside reverse transcriptase inhibitors- 1st druga. Zidovudin AZT (Retrovir) first drug approved for HIVb. Aslo used prophylactically for exposuresc. Must be taken q4-6 hours round the clock to keep increased blood

i. Adverse Effects1. Bone Marrow toxicity; drug resistance with long term use2. Nausea and HA most common SE3. Take ½ hour before or 1 hour after meals

HAART “Highly Active Anti-retrovial Therapy”- Combine 3-4 antiviral drugs

o Decreases chance of drug resistanceo Does NOT cure disease, can still transmito Many SE often want to stop medso 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 Marinolo 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 lighto Do not mix with other drugs in a syringeo IM or deep SQo 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 lighto Do not mix with other drugs in a syringeo Monitor for hypersensitivityo Interaction: Methotrexate, Phenytonin, contraceptiveso Teach to avoid alcohol and tobaccoo 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 counselingo 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 SubQo Epogen Alfa (Procrit & Epogen)

Half-life: 4-13 hours peak within 24 hours (IV) peak 5-24 hourso Darbepoetin Alfa (Aranest)

Half-life is 49 hours-long termo 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 patient’s 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 fireo Unless life threatening bleeding is presento 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 reproductiono 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

o 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 can’t 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

o 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, Vinblastineo Structurally related compounds derived from the

periwinkle plant, Vinca rosea (vinca alkaloids) o Binds to the microtubular protein, tubulino 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” B-lymphocyte 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 TBo How will this kill tumor cells?

Immune system attacks cancer cells

*Know Chemo Man!!Cell Cycle Non-Specific Cell Cycle SpecificAlkylating AgentsAntibioticsCisplatinNitrosureas

- Effective for both low-growth fraction malignancies (Solid-tumors) as well as high growth fraction malignancies.

- Slow growing

AntimetabolitesBleomycin antibioticsVinca alkaloidsEtoposide

- Effective for high growth fraction malignancies (hematologic cancers)

- Rapidly growing