Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Chapter 40 Antiviral Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

General Principles of Virology 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

General Principles of Virology (cont’d) Viruses are difficult to kill because they live inside the cells Any drug that kills a virus may also kill cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Antiviral Drugs Antiviral drugs kill or suppress the virus by destroying virions or inhibiting the ability of viruses to replicate; controlled by current antiviral therapy Immunoglobulins are concentrated antibodies that can attack and destroy viruses Copyright © 2014 by Mosby, an imprint 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) Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question An 82-year-old woman is unable to take the influenza vaccine due to allergies, but she has been exposed to the virus through a family reunion. She does not yet have symptoms of the flu. Which option would be best for her? She should receive the flu vaccine as soon as possible. She should receive zanamivir (Relenza) in the inhalation form. She should begin oral oseltamivir (Tamiflu) therapy when symptoms begin. She should begin oral oseltamivir (Tamiflu) therapy as soon as possible. Correct answer: D Rationale: Oseltamivir (Tamiflu) is the only one indicated for prophylaxis of influenza infection. Both oseltamivir and zanamivir can be used to treat active influenza illness. Treatment with oseltamivir and zanamivir ideally should begin within 2 days of symptom onset. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antiviral Drugs (cont’d) Used to treat infections caused by viruses other than HIV Antiretroviral drugs Used to treat infections caused by HIV, the virus that causes AIDS Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Herpes Simplex and Varicella Zoster 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) Copyright © 2014 by Mosby, an imprint 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) Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antiviral Drugs (non-HIV) (cont’d) amantadine (Symmetrel) Narrow antiviral spectrum; active only against influenza A Most recent guidelines do not recommend use for treatment or prevention of flu CNS effects: insomnia, nervousness, light-headedness GI effects: anorexia, nausea, others Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antiviral Drugs (non-HIV) (cont’d) acyclovir (Zovirax) Synthetic nucleoside analog Used to suppress replication of HSV-1, HSV-2, VZV Drug of choice for treatment of initial and recurrent episodes of these infections Oral, topical, parenteral forms Copyright © 2014 by Mosby, an imprint 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 (Vitrasert) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antiviral Drugs (non-HIV): Dose-Limiting Toxicities ganciclovir Bone marrow toxicity foscarnet and cidofovir Renal toxicity Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antiviral Drugs (non-HIV): Ribavirin Synthetic nucleoside analog Given orally, or by oral or nasal inhalation Inhalation form (Virazole) used for hospitalized infants with RSV infections Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 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 Retrovirus Transmitted by sexual activity, intravenous drug use, perinatally from mother to child Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question A patient with HIV infection is seen in the clinic. The nurse notes the patient is experiencing weight loss, chronic diarrhea, fever, and dropping CD4 counts. The nurse anticipates the patient is in which stage of HIV infection? Stage 1 Stage 2 Stage 3 Stage 4 Correct answer: C Rationale: During stage 3, the infection progresses to a moderately symptomatic state. Weight loss, chronic diarrhea, and fever continue, and CD4 counts continue to drop. Opportunistic infections begin, including severe bacterial pneumonias and pulmonary tuberculosis (TB). Pulmonary TB is usually more severe in persons with AIDS and is currently the leading cause of death worldwide for HIV-infected patients. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antiretroviral Drugs (cont’d) Examples enfuvirtide (Fuzeon) indinavir (Crixivan) maraviroc (Selzentry) nevirapine (Viramune) raltegravir (Isentress) tenofovir (Viread) zidovudine (Retrovir) Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question A patient with active HIV has been taking zidovudine (Retrovir). Which potential adverse effect may limit the length of time this medication can be taken? Lactic acidosis Bone marrow suppression Hepatomegaly Fatigue Correct answer: B Rationale: The major dose-limiting adverse effect of zidovudine (Retrovir) is bone marrow suppression, and this is often the reason a patient with an HIV infection must be switched to another anti-HIV drug. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Other Viral Infections Avian flu West Nile virus (WNV) infection Severe acute respiratory syndrome (SARS) H1N1 influenza virus (“swine flu”) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Instruct patients to consult their prescriber 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question The nurse administers maraviroc (Selzentry) to a patient with HIV infection. It is most important for the nurse to monitor which of the following? CD4 count Bone marrow suppression Urinary output Liver function tests Correct answer: D Rationale: The antiretroviral drug maraviroc requires assessment of allergies and liver function as well as review of the list of medications the patient is taking because of the lengthy list of interacting drugs. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.