chapter 40 antiviral drugs copyright © 2014 by mosby, an imprint of elsevier inc

Chapter 40

Antiviral Drugs

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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

General Principles of Virology

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Viruses are difficult to kill because they live inside the cells Any drug that kills a virus may also kill cells

General Principles of Virology (cont’d)

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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

Viral Illnesses

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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

Antiviral Drugs

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Viruses controlled by current antiviral therapyCytomegalovirus (CMV)Hepatitis virusesHerpes virusesHuman immunodeficiency virus (HIV)Influenza viruses (the “flu”)Respiratory syncytial virus (RSV)

Antiviral Drugs (cont’d)

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Key characteristics of antiviral drugsAble to enter the cells infected with virusInterfere with viral nucleic acid synthesis and/or regulationSome drugs interfere with ability of virus to bind to cellsSome drugs stimulate the body’s immune system

Antiviral Drugs (cont’d)

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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

Antiviral Drugs (cont’d)

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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?

A.She should receive the flu vaccine as soon as possible.

B.She should receive zanamivir (Relenza) in the inhalation form.

C.She should begin oral oseltamivir (Tamiflu) therapy when symptoms begin.

D.She should begin oral oseltamivir (Tamiflu) therapy as soon as possible.

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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

Antiviral Drugs (cont’d)

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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

Antiviral Drugs (cont’d)

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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)

Herpes Simplex and Varicella Zoster Virus Infections

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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)

Antiviral Drugs (non-HIV)

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Adverse effects Vary with each drug Healthy cells are often killed also, resulting in serious

toxicities

Antiviral Drugs (non-HIV) (cont’d)

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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

Antiviral Drugs (non-HIV) (cont’d)

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rimantadine (Flumadine) Same spectrum of activity, mechanism of action, and

indications as amantadine Fewer CNS adverse effects Causes GI upset

Antiviral Drugs (non-HIV) (cont’d)

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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

Antiviral Drugs (non-HIV) (cont’d)

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ganciclovir (Cytovene) Synthetic nucleoside analog Used to treat infection with cytomegalovirus (CMV) Oral, parenteral forms CMV retinitis

• Ophthalmic form surgically implanted (Vitrasert)

Antiviral Drugs (non-HIV) (cont’d)

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ganciclovir Bone marrow toxicity

foscarnet and cidofovir Renal toxicity

Antiviral Drugs (non-HIV): Dose-Limiting Toxicities

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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

Antiviral Drugs (non-HIV): Neuraminidase Inhibitors

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Synthetic nucleoside analog Given orally, or by oral or nasal inhalation Inhalation form (Virazole) used for hospitalized

infants with RSV infections

Antiviral Drugs (non-HIV): Ribavirin

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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

HIV and AIDS

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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

Four Stages of HIV Infection*

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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?

A.Stage 1

B.Stage 2

C.Stage 3

D.Stage 4

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Protozoal Toxoplasmosis of the brain, others

Fungal Candidiasis of the lungs, esophagus, trachea Pneumocystis jirovecii pneumonia, others

Viral CMV disease, HSV infection, others

Opportunistic Infections

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Bacterial Various mycobacterial infections, others Extrapulmonary TB

Opportunistic neoplasias Kaposi’s sarcoma, others

HIV wasting syndrome Major weight loss, chronic diarrhea, chronic fever

Opportunistic Infections (cont’d)

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HAART Highly active antiretroviral therapy Includes at least three medications

• “Cocktails”

These medications work in different ways to reduce the viral load

Antiretroviral Drugs

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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

Antiretroviral Drugs (cont’d)

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Examples enfuvirtide (Fuzeon) indinavir (Crixivan) maraviroc (Selzentry) nevirapine (Viramune) raltegravir (Isentress) tenofovir (Viread) zidovudine (Retrovir)

Antiretroviral Drugs (cont’d)

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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

Antiretroviral Drugs: Adverse Effects

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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?

A.Lactic acidosis

B.Bone marrow suppression

C.Hepatomegaly

D.Fatigue

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Avian flu West Nile virus (WNV) infection Severe acute respiratory syndrome (SARS) H1N1 influenza virus (“swine flu”)

Other Viral Infections

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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

Nursing Implications

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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

Nursing Implications (cont’d)

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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

Nursing Implications (cont’d)

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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

Nursing Implications (cont’d)

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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?

A.CD4 count

B.Bone marrow suppression

C.Urinary output

D.Liver function tests

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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

Nursing Implications (cont’d)

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