Chapter_040.pptx

Chapter 40
Antiviral Drugs
Copyright © 2017, Elsevier Inc. All rights reserved.

 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
Copyright © 2017, Elsevier Inc. All rights reserved. 2

Virus replication

 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.)

 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)
Viral Illnesses
Copyright © 2017, Elsevier Inc. All rights reserved.
5

 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 (Cont.)

 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

 Viruses controlled by current antiviral therapy
 Cytomegalovirus (CMV)
 Hepatitis viruses
 Herpesviruses
 HIV
 Influenza viruses (the “flu”)
 Respiratory syncytial virus (RSV)
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.

 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.

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?
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.

 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
 Used to treat infections caused by viruses other than
HIV
 Antiretroviral drugs
 Used to treat infections caused by HIV, the virus that
causes AIDS

 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)
Herpes Simplex and Varicella Zoster
Virus Infections

 Herpesviridae (Cont.)
 HSV-2 (genital herpes)
• Highly transmissible
• “Neonatal” herpes
 Chickenpox (HHV-3 or VZV): varicella virus vaccine
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
Virus Infections (Cont.)

 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
Hepatitis B

 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
Hepatitis C

 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
Antiviral Drugs (Non-HIV)

 Adverse effects
 Vary with each drug
 Healthy cells are often killed also, resulting in serious
toxicities.
● Interactions
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

 Rimantadine (Flumadine)
 Same spectrum of activity, mechanism of action, and
indications as amantadine
 Fewer CNS adverse effects
 Causes GI upset

 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

 Ganciclovir (Cytovene)
 Synthetic nucleoside analog
 Used to treat infection with CMV
 Oral, parenteral forms
 CMV retinitis
• Ophthalmic form surgically implanted (Vitrasert)

 Ganciclovir
 Bone marrow toxicity
 Foscarnet and cidofovir
 Renal toxicity
Antiviral Drugs (Non-HIV):
Dose-Limiting Toxicities

 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.
Neuraminidase Inhibitors

 Synthetic nucleoside analog
 Given orally, or by oral or nasal inhalation
 Inhalation form (Virazole) used for hospitalized
infants with RSV infections
Ribavirin (Virazole)

 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
Simeprevir (Olysio)

 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
Sofosbuvir (Solvald)

 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%.
HIV and AIDS

Human immunodeficiency virus

Life cycle of the human
immunodeficiency virus (HIV)

 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.
Four Stages of HIV Infection*

Timeline for the spectrum of
untreated HIV infection

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?
A. Stage 1
B. Stage 2
C. Stage 3
D. Stage 4

 Protozoal
 Toxoplasmosis of the brain, others
 Fungal
 Candidiasis of the lungs, esophagus, trachea
 Pneumocystis jiroveci pneumonia, others
 Viral
 CMV disease, HSV infection, others
Opportunistic Infections

 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.)

 Highly active antiretroviral therapy
 Includes at least three medications
 These medications work in different ways to reduce
the viral load.
Antiretroviral Drugs

 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
Antiretroviral Drugs (Cont.)

● 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

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

● 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
Antiretroviral Drugs
Enfuvirtide (Fuzeon)

● Avian flu
● West Nile virus infection
● Severe acute respiratory syndrome
● H1N1 influenza virus (“swine flu”)
Other Viral Infections

 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

 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.)

 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.

 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.

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

 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.

When teaching patients about treatment of viral infection
with Acyclovir (Zovirax), which of the following statements
will the nurse include?
A. The drug is used mainly to suppress the replication of
HSV-1, HSV-2, and VZV.
B. Acyclovir (Zovirax) is only effective for initial viral
infections.
C. Acyclovir (Zovirax) is available in topical form only.
D. Acyclovir (Zovirax) is taken once daily.
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?
A. These drugs are effective only for influenza A.
B. These drugs decrease the effects of the flu by 12 hours.
C. Zanamivir is currently indicated only for treatment of
active influenza.
D. The most commonly reported adverse events with
oseltamivir are diarrhea, nausea, and sinusitis.
Case Study (Cont.)

Which of the following drugs does the nurse include
when teaching caregivers about treatment of neonates
with RSV?
A. Telbivudine (Tyzeka)
B. Sofosbuvir (Solvald)
C. Ganciclovir (Cytovene)
D. Ribavirin (Virazole)
Case Study (Cont.)

Which statement should the nurse include when
teaching the patient about Indinavir (Crixivan) therapy?
A. The drug must be taken with food.
B. Patients taking the drug should be encouraged to
drink at least 48 ounces of liquid daily.
C. This drug is best absorbed in an alkaline
environment.
D. Indinavir decreases CD4 cell counts.
Case Study (Cont.)

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