Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 40 Antiviral Drugs

2 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Understanding Viruses  Viral replication  A virus cannot replicate on its own  It must attach to and enter a host cell  It then uses the host cell’s energy to synthesize protein, DNA, and RNA

3 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

4 Understanding Viruses (cont’d)  Viruses are difficult to kill because they live inside the cells  Any drug that kills a virus may also kill cells

5 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Viral Illnesses  Most viral illnesses are bothersome, but survivable  Effective vaccines have prevented some illnesses  Effective drug therapy is available for a small number of viral infections

6 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs  Antiviral drugs kill or suppress the virus by destroying virions or inhibiting ability to replicate viruses controlled by current antiviral therapy

7 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (cont’d) Viruses controlled by current antiviral therapy  Cytomegalovirus (CMV)  Hepatitis viruses  Herpes viruses  Human immunodeficiency virus (HIV)  Influenza viruses (the “flu”)  Respiratory syncytial virus (RSV)

8 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (cont’d) Key characteristics of antiviral drugs  Able to enter the cells infected with virus  Interfere with viral nucleic acid synthesis and/or regulation  Some drugs interfere with ability of virus to bind to cells  Some drugs stimulate the body’s immune system

9 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (cont’d)  Best responses to antiviral drugs are in patients with competent immune systems  A healthy immune system works synergistically with the drug to eliminate or suppress viral activity

10 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (cont’d) Opportunistic infections  Occur in immunocompromised patients  Would not normally harm an immunocompetent person  Require long-term prophylaxis and antiinfective drug therapy  Can be other viruses, fungi, bacteria, or protozoa

11 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (cont’d)  Antiviral drugs  Used to treat infections caused by viruses other than HIV  Antiretroviral drugs  Used to treat infections caused by HIV, the virus that causes AIDS

12 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Virus Infections  Herpes-simplex viruses  HSV-1 (oral herpes)  HSV-2 (genital herpes)  Human herpesvirus/VZV  Chickenpox and shingles (HHV-3 or VZV)  Epstein-Barr (HHV-4)  Cytomegalovirus (HHV-5)  Kaposi’s sarcoma (HHV-8)

13 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV)  Mechanism of action  Inhibit viral replication  Used to treat non-HIV viral infections  Influenza viruses  HSV, VZV  CMV  Hepatitis A, B, C (HAV, HBV, HCV)

14 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV) (cont’d)  Adverse effects  Vary with each drug  Healthy cells are often killed also, resulting in serious toxicities

15 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV) (cont’d)  amantadine (Symmetrel)  Narrow antiviral spectrum; active only against influenza A  2008 CDC guidelines do not recommend use for treatment or prevention of flu  CNS effects: insomnia, nervousness, lightheadedness  GI effects: anorexia, nausea, others

16 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV) (cont’d)  rimantadine (Flumadine)  Same spectrum of activity, mechanism of action, and indications as amantadine  Fewer CNS adverse effects  Causes GI upset

17 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV) (cont’d)  acyclovir (Zovirax)  Synthetic nucleoside analog  Used to suppress replication of: HSV-1, HSV-2, VZV HSV-1, HSV-2, VZV  Drug of choice for treatment of initial and recurrent episodes of these infections  Oral, topical, parenteral forms

18 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV) (cont’d)  ganciclovir (Cytovene)  Synthetic nucleoside analog  Used to treat infection with cytomegalovirus (CMV)  Oral, parenteral forms  CMV retinitis Ophthalmic form surgically implanted Ophthalmic form surgically implanted Ocular injection (fomivirsen) Ocular injection (fomivirsen)

19 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV): Dose-Limiting Toxicities  ganciclovir  Bone marrow toxicity  foscarnet and cidofovir  Renal toxicity

20 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV): Neuraminidase Inhibitors  oseltamivir (Tamiflu) and zanamivir (Relenza)  Active against influenza types A and B  Reduce duration of illness  Oseltamivir: causes nausea and vomiting  Zanamivir: causes diarrhea, nausea, sinusitis  Treatment should begin within 2 days of influenza symptom onset

21 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs (non-HIV): Ribavirin  Synthetic nucleoside analog  Given orally, or oral or nasal inhalation  Inhalation form (Virazole) used for hospitalized infants with RSV infections

22 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

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25 HIV and AIDS  Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS)  ELISA (enzyme-linked immunosorbent assay) Detects HIV exposure based on presence of human antibodies to the virus in the blood Detects HIV exposure based on presence of human antibodies to the virus in the blood  Retrovirus  Transmitted by sexual activity, intravenous drug use, perinatally from mother to child

26 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Four Stages of HIV Infection*  Stage 1: asymptomatic infection  Stage 2: early, general symptoms of disease  Stage 3: moderate symptoms  Stage 4: severe symptoms, often leading to death *WHO model

27 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Opportunistic Infections  Protozoal  Toxoplasmosis of the brain, others  Fungal  Candidiasis of the lungs, esophagus, trachea  Pneumocystis jirovecii pneumonia, others  Viral  CMV disease, HSV infection, others

28 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Opportunistic Infections (cont’d)  Bacterial  Various mycobacterial infections, others  Extrapulmonary TB  Opportunistic neoplasias  Kaposi’s sarcoma, others  HIV wasting syndrome  Major weight loss, chronic diarrhea, chronic fever

29 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs HAART  Highly active antiretroviral therapy  Includes at least three medications  “Cocktails”  These medications work in different ways to reduce the viral load

30 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Reverse transcriptase inhibitors (RTIs)  Block activity of the enzyme reverse transcriptase, preventing production of new viral DNA  Protease inhibitors (PIs)  Inhibit the protease retroviral enzyme, preventing viral replication  Fusion inhibitors  Inhibit viral fusion, preventing viral replication  Entry inhibitor-CCR5 coreceptor antagonists  HIV integrase strand transfer inhibitors

31 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Reverse transcriptase inhibitors (RTIs)  Nucleoside RTIs (NRTIs)  Nonnucleoside RTIs (NNRTIs)  Examples  abacavir (Ziagen)  delavirdine (Rescriptor)  didanosine (Videx)  lefavirenze Sustiva)  stavudine (Zerit)  etavirine (Intelence)  tenofovir (Viread)  didanosine (Videx)

32 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  zidovudine (Retrovir)  First anti-HIV medication  Nucleoside reverse transcriptase inhibitor  Can be given to pregnant HIV-positive women and newborn babies to prevent maternal transmission of HIV  Major dose-limiting adverse effect: bone marrow suppression

33 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Protease inhibitors (PIs)  Inhibit the protease retroviral enzyme, preventing viral replication  amprenavir (Agenerase)  indinavir (Crixivan)  nelfinavir (Viracept)  ritonavir (Norvir)

34 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Fusion inhibitors  Inhibit viral fusion, preventing viral replication  A newer class of antiretroviral drugs  Example: enfuvirtide (Fuzeon)

35 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  CCR5 antagonist  maraviroc (Selzentry)  HIV integrase strand transfer inhibitor  raltegravir (Isentress)

36 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Combinations of multiple antiretroviral medications are common  Adverse effects vary with each drug and may be severe; monitor for dose-limiting toxicities  Monitor for signs of opportunistic diseases

37 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs: Adverse Effects  Numerous and vary with each drug  Drug therapy may need to be modified because of adverse effects  Goal is to find the regimen that will best control the infection with a tolerable adverse effect profile  Medication regimens change during the course of the illness

38 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Before beginning therapy, thoroughly assess underlying disease and medical history, including allergies  Assess baseline vital signs and nutritional status  Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions

39 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Be sure to teach proper application technique for ointments, aerosol powders, and so on  Emphasize hand washing before and after administration of medications to prevent site contamination and spread of infection  Instruct patients to wear a glove or finger cot when applying ointments or solutions to affected areas

40 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Instruct patients to consult their physician before taking any other medication, including over-the-counter medications  Emphasize the importance of good hygiene  Inform patients that antiviral drugs are not cures but do help to manage symptoms

41 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Instruct patients on the importance of taking these medications exactly as prescribed and for the full course of treatment  Instruct patients to start therapy with antiviral drugs at the earliest sign of recurrent episodes of genital herpes or herpes zoster

42 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Monitor for adverse effects  Effects are varied and specific to each drug  Monitor for therapeutic effects  Effects will vary depending on the type of viral infection  Effects range from delayed progression of AIDS and other viruses to decrease in flulike symptoms, decrease in frequency of herpes-like flare-ups, or crusting over of herpetic lesions