1. HIV & AIDS Hepatitis Herpes Virus Influenza Chapter 36 1

2. Demographics World-wide in 2006: 65 Million people living with HIV/AIDS U.S.: 1.1 Million cases to date: 40,000 new cases each year 2 nd leading cause of death among 25-44 y.o.’s 1/5 unaware of being infected African Am. 7 X more likely to be infected. CDC 2009 Pharmacology for Nurses 3 rd Ed. 2011 2

3. Landscape World-wide demand to continue the development of new antiviral drugs HIV Transmission: exposed to contaminated body fluids (blood, vaginal/ seminal), sharps & needle punctures, splash to broken skin/mucus membrane. Newborns can be infected during pregnancy, birthing or from brest milk. 3

4. HIV Disease Landscape Causes a gradual destruction of host immune system, uniformly fatal when untreated, demands continuous supply of medications for survival. Rapid rebound of virus if meds are stopped Rapid mutation requires novel approaches of treatment Pharmacology for Nurses 3 rd Ed. 2011 4

5. Pharmacotherapy: Highly Active AntiRetroviral Therapy (HAART) Goal: Lower Viral Load (HIV RNA assay) to undetectable levels or below 50 copies/ml Goal: Maintain CD4 counts >500 cells/ml Goal: Begin HAART if CD4 Count <200 cells/ml 5

6. HAART Continued Goal: Maintain or increase Quality of Life Goal: Decrease Transmission from Mother to Fetus/New Born 6

7. HAART Profile Each Drug Class disrupts a specific phase of the HIV cell replication cycle Multiple Drug Regimen to reduce drug resistance HAART Drugs are specific to HIV Treatment is for remainder of the clients’ life 7

8. HAART Profile Continued Rapid mutation of HIV can make HAART ineffective. HAART can damage the host cell while seeking to kill the intracellular virus or parasite. 70% decline in death rate in U.S. since HAART was instituted. Pharmacology for Nurses 3 rd Ed. 2011 8

9. Case Study Mr. S. is a 56 y.o. male recently admitted to the Medical/Surgical Unit for Left Total Knee Replacement (Lt TKR). He has a history of Coronary Artery Disease, Peptic Ulcer Disease, and smoking. He is HIV+. 9

10. Case Study Cont’ed He had his surgery yesterday (2nd day post op) and is resuming his HIV medications: Zidovudine, Tenofovir & Kaletra. Today’s lab results: WBC’s 4.5, Hemoglobin 11, Hematocrit 30, Platelets 45,000, Na+ 135, K+ 4.5. 10

11. Drug Classifications: 1) Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI/NtRTI) 1) Zidovudine (Retrovir, AZT) (NRTI prototype drug) 100mg PO Q4H on empty stomach Used in combination with other HAART Medications to be effective due to widespread resistance 2) Tenofovir (Viread) 300 mg PO daily 11

12. Adverse Effects Common: Fatigue, generalized weakness, myalgia, n/v/, headache, abdominal pain, anorexia, rash. Serious: bone marrow suppression, neutropenia, anemia, granulocytopenia, lactic acidosis, steatorrhea, neurotoxicity. Contraindications: Hypersensitivity. Use cautiously in patients with pre-existing anemia or neutropenia 12

13. NRTI’s: How do they work? NRTI’s resemble human nucleosides, the building blocks of DNA. The HIV virus incorporates the medications, which are nonfunctioning units, into its DNA chain, stopping HIV synthesis. This action prevents the HIV virus from inserting itself into the human chromosome. Note: High degree of Cross-Resistance among NRTI’s 13

14. NtRTI’s: How do they work? NtRTI’s method of action disrupts the transcriptase enzyme of the HIV virus, thus stopping viral replication. Nursing 2008 Drug Handbook Pharmacology for Nurses 3 rd Ed. 2011 Davis Drug Guide 2011 14

15. Lopinavir/ritonavir (Kaletra) Protease Inhibitor (Prototype drug): 400mg/100mg PO BID with food or after meals (ritonavir prevents hepatic breakdown of lopinavir, increasing it’s blood level and half-life). 15

16. Protease Inhibitors (PI’s) Block the viral enzyme Protease, which is responsible for the final assembly or cleavage of the HIV polyprotein, keeping the HIV virion noninfectious. 16

17. Lopinavir/ritonavir (Kaletra) Common Adverse Effects: Nausea, vomiting, diarrhea, abdominal pain, headache, dyspepsia. Serious Adverse Effects: Anemia, leukopenia, Deep Vein Thrombosis, pancreatitis, lymphadenopathy, hemorrhagic colitis, hyperglycemia, lipodystrophy. Cautious Use: Hepatic Impairment, Diabetes. Pharmacology for Nurses 3 rd Ed. 2011 Prentice Hall Nurse’s Drug Guide 2009 17

18. Tulane University 18

19. Mr. S. Prior to providing routine 9 AM oral medications and breakfast, the nurse administers Odansetron (Zofran), 4mg IV to help prevent nausea and vomiting, a common side effect of HAART. The nurse begins evaluating the level of understanding Mr. S. and his significant other has regarding goals and expected outcomes, potential and actual nursing diagnosis, and their implementations (interventions and rationales). 19

20. Mr. S. Mr. S. states he would like to spend some quiet time with his partner at this time and asks the nurse if it would be alright to talk about his disease and drug therapy later today. The nurse reply's certainly that it is quite alright and she will come back this afternoon to talk. Mr. S. tolerated his medications and his breakfast well. 20

21. Quality and Safety Education for Nurses (QSEN) QSEN Competency: Patient-centered Care. Recognize the patient or designee as the source of control and full partner in providing compassionate and coordinated care based on respect for the patients preferences, values, and needs. 21

22. QSEN Continued Knowledge: Integrate understanding of multiple dimensions of patient-centered care: education, physical and emotional support, involvement of family and friends. Skills: Elicit pt. values, preferences and needs when implementing and evaluating outcomes of care. Attitudes: Respect and encourage pt.’s / significant other’s expression of needs, preferences, values. Cronenwett, L., Sherwood, G., Barnsteiner, J., et al. 2007. 22

23. Actual/Potential Nursing Diagnosis: Infection Risk for Falls / Risk of Injury Activity Intolerance / Fatigue Pain / Anxiety / Insomnia Imbalanced Nutrition, Less than Body Requirements Deficient Fluid Volume / Diarrhea Ineffective Therapeutic Regimen Management Deficient Knowledge 23

24. 3 rd Day Post Op for Mr. S. Mr. S. has been tolerating his medication and diet well. However, the nurse received a call from the laboratory technician stating his am lab results are: Hemoglobin is 8, Hematocrit is 26. His WBC’s are 2 and his Platelets are 20,000. (All these values are below his baseline). What do we do now? 24

25. 1 st : Verify the lab results (critical values are-by policy-called to the nursing station by the reporting lab). Nurse notifies the Surgeon As the nurse, what orders would you expect to receive? 25

26. Next The Nurse would anticipate: 1) possible transfusion with 1-2 units of Packed Red Blood Cells (PRBC’s) 2)possible change/addition in HAART medications 3) institute protective isolation and observe for signs/symptoms of bleeding and infection 4) continue to assess Mr. S. of his understanding of his condition, educate him as needed, and what is being done to help him 26

27. Ongoing Assessments Assess for Desired Therapeutic Effects: HIV RNA assay (Viral Load) and CD4 levels, CBC, Hepatic and Renal Function, Lipids, Amylase, Glucose remain WNL Tolerate activities of daily living (ADL’s) Absence of signs and symptoms of Infection Watch for Adverse Effects: n/v/d, anorexia, cramping, mental changes, pain, jaundice, dark urine, rash, blistering, 27

28. Neuman System Model Discuss the stressors, Basic Structure and protective concentric rings – Flexible and Normal Line of Defense and Lines of Resistance. 28

29. Follow Up Next Day Mr. S. tolerated a transfusion of 2 Units of PRBC’s, and the AM lab results showed his H&H has increased to 12/32. His WBC’s and Platelets remain low. He is avoiding the use of a razor and is careful to avoid falling/injuring himself by calling for assistance when getting up. He is taking up to 900cc’s of PO fluids each shift and making adequate urine. The hospital staff is maintaining Reverse Isolation to prevent exposing Mr. S. to infections. 29

30. Next Day Continued The Surgeon consulted with Mr. S.’s Attending MD who recommended adding a Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) to his medication regimen and continue to monitor his lab values. The Nurse informs the Attending MD that Mr. S. is compliant with his medications and has a good understanding of his current condition, his vital signs are stable (VSS), he is afebrile, and is not excessively fatigued. 30

31. 3) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) efavirenz (Sustiva), a prototype drug 600mg PO HS Daily on empty stomach. Adverse Effects: Common: Rash, fever, nausea, diarrhea, headache, stomatitis, dizziness, sleep disorders, fatigue Serious: Paresthesia, hepatotoxicity, neutropenia, Stevens-Johnson Syndrome, CNS toxicity. Contraindications: teratogenicity- avoid use in the pregnant pt., use reliable birth control methods. 31

32. How Do NNRTI’s Work? NNRTI’s bind directly to the HIV viral enzyme reverse transcriptase, blocking RNA & DNA dependant DNA polymerase which disrupts its function. This drug action prevents viral DNA construction. Pharmacology for Nurses 3 rd Ed. 2011 32

33. Mr. S. Post Op Day 5 Mr. S. is progressing in his rehabilitation s/p Lt. TKR. He is ambulating 200 feet in the hall 2X daily using his walker and stand-by assistance only. He knows to take rest between each activity because of the possible side effects of ART along with the fatigue due to being Hospitalized (surgery, pain, prolonged bed rest, muscle wasting, sleep disturbance, etc). 33

34. 5 th Day Continued Lab Values: H&H: 12/31 WBC’s: 5 Platelets: 45,000 Viral Load: Not detectable CD4 Count: 800/ml Liver & Kidney Function Tests: Within Normal Limits (WNL) 34

35. Attending MD Had Considered adding a Fusion Inhibitor (FI) Enfuvirtide (Fuzeon) SubQ 90mg BID Adverse Effects: Common: Pain and inflammation at injection site, nausea, diarrhea, fatigue, abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections Serious: Hypersensitivity, myocardial infarction, neutropenia, thrombocytopenia, nephrotoxicity, hepatotoxicity. Contraindications: Hypersensitivity, lactation. Pharmacology for Nurses 3 rd Ed. 2011 Prentice Hall Nurse’s Drug Guide 2009 35

36. Fuzeon Drug Action Interferes with entry of HIV-1 virus into the host T4 lymphocyte cell by inhibiting fusion or linkage of the virus to the CD4 receptor. 36

37. Attending MD continued MD decides to hold off starting the F.I. at this time due to stable CD4 cell counts and low viral load. He will continue to monitor labs on an out- patient basis along with office visits by Mr. S. every 3 months for now. 37

38. A Newer HIV Drug Class: Integrase Inhibitors Raltegravir (Isentress) blocks HIV integrase, preventing HIV from inserting its genes into uninfected host DNA. Dosage: 400mg PO BID Similar Common and Serious Adverse Effects as the Fusion Inhibitors including myopathy, (nephrotoxicity less common). Pharmacology for Nurses 3 rd Ed. 2011 38

39. Home Mr. S. is to be discharged home Post Operative Day 6. His partner is taking off work for 2 weeks to assist him with ADL’s. An RN from the VNA will visit to remove the staples from his Knee on Post Op. Day 10. He has an appointment with his surgeon in 2 weeks for follow up. What important points need to be covered in the Discharge Instructions by the Nurse prior to going home? 39

40. Discharge Instructions Include: Monitor for symptoms of hypersensitivity or anaphylactic-type reactions Monitor VSS, observe for signs/symptoms of infection, hypotension Watch for mouth ulcers or white patches Comply with scheduled lab draws. (They determine the effectiveness of HAART and/or drug toxicity) 40

41. Discharge Instructions Cont’ed Drug-Drug and Drug-Food interactions (dosing times, no skipping, OTC’s,) Immediately report severe abdominal pain or distension, n/v or fever Support the immune system (adequate rest, sleep, nutrition, hydration) Report numbness/tingling of extremities, using caution to avoid injury 41

42. Discharge Instructions Cont’ed Multidisciplinary Care: Nutritionist, Social Worker, Physical Therapist, etc. PRN Review client’s level of understanding regarding the use and effect of medications. 42

43. Nurse Follow Up Discharge Nurse asks client about HAV, HBV & HCV status. Patient denies history, then nurse confirms via a chart check for up-to-date Immunizations. 43

44. Hepatitis A, B & C 44

45. Viral Hepatitis Hepatitis A Virus(HAV)-acute disease (not chronic) Oral/Fecal Transmission-rare fatalities, few patients develop severe liver disease HAV vaccine (Havrix, VAQTA). 2 step vaccination process-booster giver 6-12 months after initial dose Almost 100% immunity results, lasting 5-8 years, up to 20 years. Pharmacology for Nurses 3 rd Ed. 2011 45

46. Hepatitis B Hepatitis B Virus (HBV), a chronic disease Transmission via Blood/Body Fluid Greater morbidity and mortality rate than HAV. 10% develop chronic disease (cirrhosis/Liver CA) High Risk factors: IVDU, MSM, Sex with infected partner, health care workers, perinatal & child to child. HBV vaccination (Recombivax HB, Engerix-B): 3 doses confer up to 90% of clients with protection if exposed (Twinrix contains both HAV & HBV vaccine). 46

47. Hepatitis C Virus (HCV) Blood/Body Fluids are primary mode of transmission 70% develop chronic hepatitis, 1/3 of these clients go on to develop end stage cirrhosis Nearly 50% of all clients infected with HIV-AIDS are co-infected with HCV No vaccine yet available 47

48. Chronic Hepatitis C Therapy When the chronic disease becomes active or symptoms appear drug treatment is initiated with: Interferons NonInterferons 48

49. INTERFERONS Interferon alfacon-1 (Infergen): SubQ 9mcg three injections/week for 24 weeks Interferon alfa-2b: 3 million international units SubQ 3 X per week (PEG 1 X week) Common Adverse Effects: Flu-like symptoms, myalgia, fatigue, H/A, anorexia, diarrhea Serious Adverse Effects: Myelosuppression, thrombocytopenia, suicide ideation 49

50. NonInterferons & Combinations Adefovir dipivoxil (Hespera): 10mg PO daily Lamivudine (Epivir HBV): 150mg PO BID Robetron: Ribavirin 200mg PO 5-6 capsules Daily & Interferon alfa 2b Subq 3 million International Units TID/week 50

51. NonInterferons: Adverse Effects : Common asthenia (weakness), H/A, nausea, dizziness, fatigue, nasal disturbances (lamivudine) Serious: Nephrotoxicity & lactic acidosis (adenfovir); pancreatitis, hepatomegaly with steatorrhea (lamivudine); cardiac arrest, hemolytic anemia, apnea (ribaviron). 51

52. New Therapy for HCV Incivek, a Protease Inhibitor In Phase 3 of a clinical research study, in combination with Pegylated-Interferon and Ribaviron, Incivek increased the sustained viral response (SVR, an undetectable level of HCV 24 weeks after completion of drug therapy) from 44% to 79% for a group of 1095 patients. Sutter Health June 23, 2011 52

53. Herpesvirus Family HSV 1 : facial/oral HSV 2 : genital Cytomegalovirus(CMV): multisystem affects for immunocompromised clients Varicella-zoster virus (VZV): chicken pox & shingles 53

54. Herpesvirus Family Continued Epstein-Barr virus: mononucleosis/Burkitt’s lymphoma Herpesvirus 6: roseola in children, hepatitis or encephalitis for immunocompromised clients 54

55. Acyclovir (Zovirax) Prototype Drug For the Immunocompromised patient (ex.: AIDS, geriatric) who develops Herpes Zoster: 800mg PO 5 X daily X 7-10 days. Can prevent or lessen early symptoms (pain, tingling, itching) and lessen the later outbreak of herpes rash and blisters (Shingles). topical preparations are less effective IV: 5-10 mg/kg q8h X 7-14 days 55

56. Acyclovir (Zovirax) Cont’ed Adverse Effects with topical/oral/IV- generally minimal/infrequent : N/V/D, H/A, fatigue, dizziness, tremors, confusion, pain/inflammation at injection site Serious: seizures, acute renal failure, thrombocytopenic purpura. Prentice Hall Nurse’s Drug Guide 2009 56

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58. References Adams, P., Holland, L., Urban, C., Pharmacology for Nurses, A Pathophysiological Approach, 3rd Ed., 2011, Pearson Education, Inc. Nursing 2008 Drug Handbook, 28 th Ed., Wolters Kluwer/Lippincott Williams & Wilkins Prentice Hall Nurse’s Drug Guide 2009, Wilson, B., Shannon, M., Shields, K. Tulane University, Department of Microbiology and Immunology, Big Picture Book of Viruses: RetroviridaeBig Picture Book of Viruses: Retroviridae Cronenwett, L., Sherwood, G., Barnsteiner, J., et al. 2007, Quality and safety education for nurses, Nursing Outlook, 55(3)122-131. http://www.sutterhealth.org/about/news/news11_CPMC-New-Drug- Helps-Hepatitis-C-Patie... Retrieved 7/3/11 http://www.sutterhealth.org/about/news/news11_CPMC-New-Drug- Helps-Hepatitis-C-Patie... Davis’s Drug Guide for Nurses, Deglin, J., Vallerand, A., Sanoski, C., 12 th Ed., 2011 58