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Chapter 40
Antiviral Drugs
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2. 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.
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Virus replication
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4. General Principles of Virology (Cont.)
Viruses are difficult to kill because they live inside the cells.
Any drug that kills a virus may also kill cells.
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Viral Illnesses
Smallpox (poxviruses)
Sore throat
Conjunctivitis (adenoviruses)
Warts (papovaviruses)
Influenza (orthomyxoviruses)
Respiratory infections (coronaviruses, rhinoviruses)
Gastroenteritis (rotaviruses, Norwalk-like viruses)
Human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) (retroviruses)
Herpes (herpesviruses)
Hepatitis (hepadnaviruses)
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6. Viral Illnesses (Cont.)
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.
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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.
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8. Antiviral Drugs (Cont.)
Viruses controlled by current antiviral therapy
Cytomegalovirus (CMV)
Hepatitis viruses
Herpesviruses
HIV
Influenza viruses (the “flu”)
Respiratory syncytial virus (RSV)
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9. Antiviral Drugs (Cont.)
Key characteristics of antiviral drugs
Able to enter the cells infected with virus
Interfere with viral nucleic acid synthesis, regulation, or both
Some drugs interfere with ability of virus to bind to cells.
Some drugs stimulate the body’s immune system.
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10. Antiviral Drugs (Cont.)
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.
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11. Audience Response System Question
An 82-year-old woman is unable to take the influenza vaccine because of 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.
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12. Antiviral Drugs (Cont.)
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
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13. Antiviral Drugs (Cont.)
Used to treat infections caused by viruses other than HIV
Antiretroviral drugs
Used to treat infections caused by HIV, the virus that causes AIDS
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14. Herpes Simplex and Varicella Zoster Virus Infections
Herpesviridae
HSV-1 (oral herpes)
HSV-2 (genital herpes)
Chickenpox and shingles (HHV-3 or VZV)
Epstein-Barr (HHV-4)
CMV (HHV-5)
Human herpesviruses 6 and 7 are not especially clinically significant; immunocompromised patients
Kaposi’s sarcoma (HHV-8)
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15. Herpes Simplex and Varicella Zoster Virus Infections (Cont.)
Herpesviridae (Cont.)
HSV-2 (genital herpes)
Highly transmissible
“Neonatal” herpes
Chickenpox (HHV-3 or VZV): varicella virus vaccine
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16. Herpes Simplex and Varicella Zoster Virus Infections (Cont.)
Herpesviridae (Cont.)
Shingles (HHV-3 or VZV)
Painful: opioids for pain control
Postherpetic neuralgias
Acyclovir may speed recovery; best results are generally seen when the antiviral drug is started within 72 hours of symptom onset
Zostavax
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Hepatitis B
Mild, without symptoms or chronic hepatitis or liver failure and death
Transmission of hepatitis B virus occurs through blood and body fluid exposure.
Transmission to infants
Hepatitis B vaccine
Antiviral drug therapy for hepatitis B: lamivudine, tenofovir, and telbivudine, and alfa-interferon
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Hepatitis C
Leading cause of liver failure leading to liver transplantation
Symptoms
Transmission: infected blood and sexual contact
Alcoholic disease can lead to development of hepatitis C
Treatment: interferon, ribavirin, simeprevir, and sofosbuvir
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19. Antiviral Drugs (Non-HIV)
Mechanism of action
Most of the current antiviral drugs work by blocking the activity of a polymerase enzyme that normally stimulates the synthesis of new viral genomes.
Used to treat non-HIV viral infections
Influenza viruses
HSV, VZV
CMV
Hepatitis
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20. Antiviral Drugs (Non-HIV) (Cont.)
Adverse effects
Vary with each drug
Healthy cells are often killed also, resulting in serious toxicities.
Interactions
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21. Antiviral Drugs (Non-HIV) (Cont.)
Amantadine (Symmetrel)
Narrow antiviral spectrum; active only against influenza A
Most recent guidelines do not recommend use for treatment or prevention of flu
Central nervous system (CNS) effects: insomnia, nervousness, light-headedness
Gastrointestinal (GI) effects: anorexia, nausea, others
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22. Antiviral Drugs (Non-HIV) (Cont.)
Rimantadine (Flumadine)
Same spectrum of activity, mechanism of action, and indications as amantadine
Fewer CNS adverse effects
Causes GI upset
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23. Antiviral Drugs (Non-HIV) (Cont.)
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
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24. Antiviral Drugs (Non-HIV) (Cont.)
Ganciclovir (Cytovene)
Synthetic nucleoside analog
Used to treat infection with CMV
Oral, parenteral forms
CMV retinitis
Ophthalmic form surgically implanted (Vitrasert)
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25. Antiviral Drugs (Non-HIV): Dose-Limiting Toxicities
Ganciclovir
Bone marrow toxicity
Foscarnet and cidofovir
Renal toxicity
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26. 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.
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27. Antiviral Drugs (Non-HIV): Ribavirin (Virazole)
Synthetic nucleoside analog
Given orally, or by oral or nasal inhalation
Inhalation form (Virazole) used for hospitalized infants with RSV infections
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28. Antiviral Drugs (Non-HIV): Simeprevir (Olysio)
Protease inhibitor (PI)
Chronic hepatitis C
Approved in 2013
Used in conjunction with standard hepatitis C treatments: interferon and ribavirin
Not to be used as monotherapy
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29. Antiviral Drugs (Non-HIV): Sofosbuvir (Solvald)
First-in-class RNA polymerase inhibitor for the treatment of chronic hepatitis C
Sofosbuvir is considered “break-through” therapy.
First drug treatment for hepatitis C that can be given without interferon
Used in combination with ribavirin
Not to be used as monotherapy
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HIV and AIDS
New cases of HIV have decreased by 33% since 2001
Retrovirus
Transmitted by sexual activity, intravenous drug use, perinatally from mother to child
The risk for transmission to health care workers via percutaneous (needlestick) injuries is currently calculated at approximately 0.3%.
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Human immunodeficiency virus
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32. Life cycle of the human immunodeficiency virus (HIV)
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33. 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
*World Health Organization model.
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34. Timeline for the spectrum of untreated HIV infection
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35. Audience Response System 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.
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36. 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
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37. Opportunistic Infections (Cont.)
Bacterial
Various mycobacterial infections, others
Extrapulmonary TB
Opportunistic neoplasias
Kaposi’s sarcoma, others
HIV wasting syndrome
Major weight loss, chronic diarrhea, chronic fever
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Antiretroviral Drugs
Highly active antiretroviral therapy
Includes at least three medications
These medications work in different ways to reduce the viral load.
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39. Antiretroviral Drugs (Cont.)
Reverse transcriptase inhibitors (RTIs)
Block activity of the enzyme reverse transcriptase, preventing production of new viral DNA
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
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40. 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.
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41. Audience Response System 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.
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42. Antiretroviral Drugs Enfuvirtide (Fuzeon)
Fusion inhibitors
Suppresses the fusion process whereby a virion is attached to the outer membrane of a host T cell before entry into the cell and subsequent viral replication
Used for treatment of HIV infection in combination with other antiretroviral drugs.
Use of this drug in combination with other standard antiretroviral drugs: markedly reduced viral loads
Drug is currently available only in injectable form
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43. Other Viral Infections
Avian flu
West Nile virus infection
Severe acute respiratory syndrome
H1N1 influenza virus (“swine flu”)
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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.
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45. Nursing Implications (Cont.)
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.
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46. Nursing Implications (Cont.)
Instruct patients to consult their prescribers 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.
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47. Nursing Implications (Cont.)
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.
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48. Audience Response System 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.
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49. Nursing Implications (Cont.)
Monitor for adverse effects:
Effects are varied and specific to each drug.
Monitor for therapeutic effects:
Effects vary depending on the type of viral infection.
Effects range from delayed progression of AIDS and other viruses to a decrease in flulike symptoms, decrease in frequency of herpes-like flare-ups, or crusting over of herpetic lesions.
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Case Study (Cont.)
When teaching patients about treatment of viral infection with Acyclovir (Zovirax), which of the following statements will the nurse include?
The drug is used mainly to suppress the replication of HSV-1, HSV-2, and VZV.
Acyclovir (Zovirax) is only effective for initial viral infections.
Acyclovir (Zovirax) is available in topical form only.
Acyclovir (Zovirax) is taken once daily.
Correct answer: A
Rationale: Acyclovir (Zovirax) is a synthetic nucleoside analogue that is used mainly to suppress the replication of HSV-1, HSV-2, and VZV. Acyclovir is considered the drug of choice for the treatment of both initial and recurrent episodes of these viral infections. Acyclovir is available in oral, topical, and injectable formulations. Acyclovir (Zovirax) is taken five times daily.
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Case Study (Cont.)
When reviewing the antiviral medications oseltamivir (Tamiflu) and zanamivir (Relenza) used for treatment of the flu, which of the following statements should the nurse include?
These drugs are effective only for influenza A.
These drugs decrease the effects of the flu by 12 hours.
Zanamivir is currently indicated only for treatment of active influenza.
The most commonly reported adverse events with oseltamivir are diarrhea, nausea, and sinusitis.
Correct answer: C
Rationale: Zanamivir is currently indicated only for treatment of active influenza. These drugs are active against influenza virus types A and B. They have been shown to reduce the duration of influenza infection by several days. The most commonly reported adverse events with oseltamivir are nausea and vomiting.
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Case Study (Cont.)
Which of the following drugs does the nurse include when teaching caregivers about treatment of neonates with RSV?
Telbivudine (Tyzeka)
Sofosbuvir (Solvald)
Ganciclovir (Cytovene)
Ribavirin (Virazole)
Correct answer: D
Rationale: Telbivudine (Tyzeka) is a nucleoside analogue RTI indicated for chronic hepatitis B. Sofosbuvir (Solvald) is the first-in-class RNA polymerase inhibitor for the treatment of chronic hepatitis C. Ganciclovir (Cytovene) is indicated for the treatment of infections caused by CMV. The inhalational form (Virazole) is used primarily in the treatment of hospitalized infants with severe lower respiratory tract infections caused by RSV.
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Case Study (Cont.)
Which statement should the nurse include when teaching the patient about Indinavir (Crixivan) therapy?
The drug must be taken with food.
Patients taking the drug should be encouraged to drink at least 48 ounces of liquid daily.
This drug is best absorbed in an alkaline environment.
Indinavir decreases CD4 cell counts.
Correct answer: B
Rationale: Patients who take indinavir are encouraged to drink at least 48 oz of liquids every day to maintain hydration and help avoid nephrolithiasis. This drug is best dissolved and absorbed in an acidic gastric environment, and the presence of high-protein and high-fat foods reduces its absorption. Therefore, it is recommended that it be administered in a fasting state. Indinavir therapy produces increases in CD4 cell counts and significant reductions in viral load.
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