Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 39 Antiviral Drugs

Mosby items and derived items © 2007, 2005, 2002 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

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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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Viral Infections Competent immune system:  Best response to viral infections  A well-functioning immune system will eliminate or effectively destroy virus replication

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Viral Infections (cont’d) Immunocompromised patients have frequent viral infections  Cancer patients, especially leukemia or lymphoma  Transplant patients, due to pharmacologic therapy  AIDS patients, disease attacks immune system

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Viruses controlled by current antiviral therapy  Cytomegalovirus (CMV)  Hepatitis viruses  Herpes viruses  Human immunodeficiency virus (HIV)  Influenza viruses (the “flu”)  Respiratory syncytial virus (RSV)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals (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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals (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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals (cont’d) Opportunistic infections  Occur in immunocompromised patients  Infections that would not normally harm an immunocompetent person  Require long-term prophylaxis and anti- infective drug therapy  Can be other viruses, fungi, bacteria, or protozoa

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Medications  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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Virus Infections  Herpes-Simplex Viruses  HSV-1 (oral herpes)  HSV-2 (genital herpes)  Varicella Zoster Virus  Chickenpox  Shingles

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs: Nonretroviral  Mechanism of action  Inhibit viral replication  Used to treat non-HIV viral infections  Influenza viruses  HSV, VZV  CMV  Hepatitis A, B, C (HAV, HBV, NCV)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antiviral Drugs: Nonretroviral  Adverse Effects  Vary with each drug  Healthy cells are often killed also, resulting in serious toxicities

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral Amantadine (Symmetrel)  Narrow antiviral spectrum  active only against influenza A  Used prophylactically when vaccine is not available or cannot be given  Therapeutic use can reduce recovery time  CNS effects: insomnia, nervousness, lightheadedness  GI effects: anorexia, nausea, others

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral Rimantadine (Flumadine)  Same spectrum of activity, mechanism of action, and indications as amantadine  Fewer CNS adverse effects  Causes GI upset

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral Ganciclovir (Cytovene)  Synthetic nucleoside analog  Used to treat infection with cytomegalovirus (CMV)  Oral, parenteral forms  CMV retinitis  Ophthalmic form surgically implanted  Ocular injection (fomivirsen)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral Dose-Limiting Toxicities  ganciclovir and zidovudine  Bone marrow toxicity  foscarnet and cidofovir  Renal toxicity

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral Neuraminidase Inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza)  Active against influenza types A & B  Reduce duration of illness  oseltamivir: causes nausea & vomiting  zanamivir: causes diarrhea, nausea, sinusitis  Treatment should begin within 2 days of influenza symptom onset

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antivirals Drugs-Nonretroviral Ribavirin  Synthetic nucleoside analog  Given orally, or oral or nasal inhalation  Inhalation form (Virazole) used for hospitalized infants with RSV infections

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HIV  Human immunodeficiency virus infection  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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Five 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 stages

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Opportunistic Infections  Protozoal  Toxoplasmosis of the brain, others  Fungal  Candidiasis of the lungs, esophagus, trachea  Pneumocystis jiroveci pneumonia, others  Viral  CMV disease, HSV infection, others

Mosby items and derived items © 2007, 2005, 2002 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  Others

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Reverse transcriptase inhibitors (RTIs)  Nucleoside RTIs (NRTIs)  Nonnucleoside RTIs (NNRTIs)  Nucleotide RTIs (NTRTIs)  Examples abacavir (Ziagen)delavirdine (Rescriptor) didanosine (Videx)lamivudine (Epivir) stavudine (Zerit)tenofovir (Viread)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Protease inhibitors (PIs)  Inhibit the protease retroviral enzyme, preventing viral replication  Examples: amprenavir (Agenerase)indinavir (Crixivan) amprenavir (Agenerase)indinavir (Crixivan) nelfinavir (Viracept)ritonavir (Norvir) nelfinavir (Viracept)ritonavir (Norvir) saquinavir (Invirase) saquinavir (Invirase)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antiretroviral Drugs (cont’d)  Fusion inhibitors  Inhibit viral fusion, preventing viral replication  Newest class of antiretroviral drugs  Example: enfuvirtide (Fuzeon)

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Before beginning therapy, thoroughly assess underlying disease and medical history, including allergies  Assess baseline VS and nutritional status  Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Be sure to teach proper application technique for ointments, aerosol powders, etc.  Emphasize handwashing before and after administration of medications to prevent site contamination and spread of infection  Patients should wear a glove or finger cot when applying ointments or solutions to affected areas

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Instruct patients to consult their physician before taking any other medication, including OTCs  Emphasize the importance of good hygiene  Inform patients that antiviral drugs are not cures but do help to manage symptoms

Mosby items and derived items © 2007, 2005, 2002 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  Patients should be informed to start therapy with antiviral drugs at the earliest sign of recurrent episodes of genital herpes or herpes zoster

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) Monitor for adverse effects  Effects are varied and specific to each drug

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) 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 flu-like symptoms, decrease in frequency of herpes-like flare-ups, or crusting over of herpetic lesions