CHAPTER 40
Antiviral Drugs
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Understanding Viruses

Viral replication
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

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
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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
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Antiviral Drugs

Antiviral drugs kill or suppress the virus by
destroying virions or inhibiting ability to
replicate viruses controlled by current antiviral
therapy
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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)
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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
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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
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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
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Antiviral Drugs (cont’d)

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
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Virus Infections
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Herpes-simplex viruses
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

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)
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Antiviral Drugs (non-HIV)
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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)
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Antiviral Drugs (non-HIV) (cont’d)

Adverse effects


Vary with each drug
Healthy cells are often killed also, resulting in
serious toxicities
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Antiviral Drugs (non-HIV) (cont’d)

amantadine (Symmetrel)




Narrow antiviral spectrum; active only against
influenza A
2008 CDC guidelines do not recommend use for
treatment or prevention of flu
CNS effects: insomnia, nervousness,
lightheadedness
GI effects: anorexia, nausea, others
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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
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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
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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
• Ocular injection (fomivirsen)
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Antiviral Drugs (non-HIV):
Dose-Limiting Toxicities

ganciclovir


Bone marrow toxicity
foscarnet and cidofovir

Renal toxicity
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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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Antiviral Drugs (non-HIV):
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 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
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Four Stages of HIV Infection*
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

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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
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Opportunistic Infections
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Protozoal
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
Fungal
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

Toxoplasmosis of the brain, others
Candidiasis of the lungs, esophagus, trachea
Pneumocystis jirovecii pneumonia, others
Viral

CMV disease, HSV infection, others
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Opportunistic Infections (cont’d)
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Bacterial
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Opportunistic neoplasias
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
Various mycobacterial infections, others
Extrapulmonary TB
Kaposi’s sarcoma, others
HIV wasting syndrome

Major weight loss, chronic diarrhea, chronic fever
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Antiretroviral Drugs
HAART
 Highly active antiretroviral therapy
 Includes at least three medications


“Cocktails”
These medications work in different ways to
reduce the viral load
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Antiretroviral Drugs (cont’d)
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Reverse transcriptase inhibitors (RTIs)
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
Protease inhibitors (PIs)
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
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Inhibit the protease retroviral enzyme, preventing
viral replication
Fusion inhibitors


Block activity of the enzyme reverse transcriptase,
preventing production of new viral DNA
Inhibit viral fusion, preventing viral replication
Entry inhibitor-CCR5 coreceptor antagonists
HIV integrase strand transfer inhibitors
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Antiretroviral Drugs (cont’d)

Reverse transcriptase inhibitors (RTIs)
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

Nucleoside RTIs (NRTIs)
Nonnucleoside RTIs (NNRTIs)
Examples

abacavir (Ziagen)
 delavirdine (Rescriptor)
 didanosine (Videx)
 lefavirenze Sustiva)
 stavudine (Zerit)
 etavirine (Intelence)
 tenofovir (Viread)
 didanosine (Videx)
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Antiretroviral Drugs (cont’d)

zidovudine (Retrovir)




First anti-HIV medication
Nucleoside reverse transcriptase inhibitor
Can be given to pregnant HIV-positive women and
newborn babies to prevent maternal transmission
of HIV
Major dose-limiting adverse effect: bone marrow
suppression
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Antiretroviral Drugs (cont’d)

Protease inhibitors (PIs)

Inhibit the protease retroviral enzyme, preventing
viral replication
 amprenavir (Agenerase)
 indinavir (Crixivan)
 nelfinavir (Viracept)
 ritonavir (Norvir)
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Antiretroviral Drugs (cont’d)
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Fusion inhibitors
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

Inhibit viral fusion, preventing viral replication
A newer class of antiretroviral drugs
Example: enfuvirtide (Fuzeon)
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Antiretroviral Drugs (cont’d)

CCR5 antagonist


maraviroc (Selzentry)
HIV integrase strand transfer inhibitor

raltegravir (Isentress)
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Antiretroviral Drugs (cont’d)
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

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
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Antiretroviral Drugs:
Adverse Effects
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

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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
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Nursing Implications
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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
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Nursing Implications (cont’d)
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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
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Nursing Implications (cont’d)
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

Instruct patients to consult their physician
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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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
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Nursing Implications (cont’d)
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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
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