Antiviral Agents

• Chapter 10 focuses on antiviral agents

Viruses Responsive to Antiviral Therapy

• Viruses responsive to antiviral therapy include Influenza A, herpes viruses, Cytomegalovirus (CMV), Human Immunodeficiency Virus (HIV), Hepatitis B and C, and some viruses causing warts and certain eye infections.

Characteristics of Common Viruses

• A virus needs to attach to and enter a host cell because it cannot replicate on its own
• A virus then uses the host cell's resources to synthesize protein, DNA, and RNA
• Viruses live inside cells making them difficult to target without harming the host
• Drugs that kill viruses may also harm our cells

Stages of Virus Replication

• A virus adheres to a cell surface
• The virus enters by pinocytosis
• The virus sheds its coat
• Replication of viral nucleic acids
• Synthesis of viral protein of capsid
• Assembly of new virions
• Release occurs

Characteristics of Antiviral Drugs

• Antiviral drugs enter cells infected with the virus
• They work by interfering with viral nucleic acid synthesis or regulation
• Some antiviral agents interfere with the ability of viruses to bind to cells
• Other antiviral agents stimulate the body's immune system

Types of Antiviral Agents

• Influenza A & B agents include rimantadine, amantadine, and oseltamivir
• Herpes Virus & CMV agents include acyclovir, famcyclovir, and valacyclovir
• HAART (highly active antiretroviral therapy) agents include NNRTI, NRTI, Protease Inhibitors, Fusion Inhibitors, CCR5 Coreceptor antagonists, and Integrase inhibitors
• Anti-Hepatitis B agents are adefovir and entecavir
• Anti-Hepatitis C agents is simeprivir
• Other locally active agents include docosanol, imiquimod, and penciclovir

Prototype Respiratory Antiviral Agent: Rimantadine

• Rimantadine is indicated for prophylaxis and treatment of illness caused by influenza A virus in adults, and for prophylaxis against influenza A virus in children
• It inhibits viral replication, possibly by preventing the uncoating of the virus
• When taken orally, rimantadine has a slow onset, reaching peak levels in 6 hours
• The half-life of rimantadine is 25.4 hours, and it is excreted unchanged in urine
• Contraindications for rimantadine include allergy, renal impairment, pregnancy, or lactation
• Adverse effects include light-headedness, dizziness, insomnia, nausea, dyspnea, orthostatic hypotension, and depression

Signs and Symptoms of Herpes Virus

• Painful vesicles often occur in clusters on the skin, cornea, or mucous membranes
• The usual course of the primary disease is two weeks
• The duration of recurrences varies

Signs and Symptoms of Cytomegalovirus (CMV)

• Cytomegalovirus (CMV) is usually a problem in immunocompromised patients, such as those with HIV or on immunosuppressants
• Individuals with CMV may be asymptomatic
• Symptoms of CMV includes fatigue, nausea, and jaundice
• CMV, if contracted during pregnancy, can result in stillbirth, brain damage, or birth defects

Herpes and Cytomegalovirus Antivirals

• They inhibits viral DNA replication by competing with viral substrates to form shorter, non-effective DNA chains
• They are readily absorbed in the kidney and GI tract, metabolized in the liver, and excreted primarily in the urine and feces
• Use of these drugs are contraindicated for individuals with known allergies to antiviral agents, and due to being highly toxic in pregnancy and lactation as well as in renal disease
• Adverse reactions includes nausea, vomiting, headache, rash, hair loss, paresthesias, neuropathy and renal dysfunction
• Drug-to-drug interactions of antiviral include nephrotoxic drugs, zidovudine and aminoglycosides

Nursing Considerations for Herpes Virus and Cytomegalovirus

• Assess for a history of allergy to antivirals, physical status, orientation and reflexes, skin condition (color, temperature, and lesions) and renal function

Prototype Herpes and Cytomegalovirus Agent: Acyclovir

• Acyclovir is indicated for the treatment of herpes simplex virus (HSV) 1 and 2 infections, severe genital HSV infections, HSV encephalitis, acute treatment of shingles and chickenpox, genital herpes infections (ointment) and cold sores (cream)
• Acyclovir's action is to inhibit viral DNA replication
• Acyclovir’s onset varies when taken orally, is immediate when taken intravenously, and is not generally absorbed systemically when used topically
• Acyclovir’s peak is in 1.5-2 hours when taken orally and 1 hour when taken intravenously
• Its half-life is 2.5 to 5 hours and is excreted unchanged in the urine
• Adverse effects includes headache, vertigo, tremors, nausea, vomiting, and rash

Nursing Considerations for Acyclovir

• Assess for history of allergies to antivirals, physical status, orientation and reflexes, skin (color, temperature, and lesions), renal function (nephrotoxicity), CBC (blood dyscrasia)
• Administer IV infusion slowly over an hour
• Ensure adequate hydration

Client Teaching for Acyclovir

• Emphasize adequate hydration
• Relief of symptoms, but not a cure, can be expected for herpes infections
• With topical administration, use tuber gloves to avoid transfer of the virus to other parts of the body
• Refrain from sexual contact while lesions are present

Signs and Symptoms of HIV/AIDS

• HIV/AIDS attacks helper T-cells in the immune system
• An acute infection manifests as fever, rash, and myalgia
• The asymptomatic infection phase follows the acute infection, the duration of which varies
• Persistent Generalized Lymphadenopathy - Adenopathy persists more than 3 months
• Constitutional symptoms includes fever lasting for more than a month, involuntary weight loss, and chronic fatigue
• Can cause neurological Disease, like dementia
• Secondary infections such as Pneumocystis carinii and disseminated herpes simplex, are common

Drugs Used to Treat HIV/AIDS

• Reverse Transcriptase Inhibitors

• Protease Inhibitors

• Nucleosides- NNRTI and NRTI

• Fusion Inhibitors

• CCR5 Coreceptor Antagonist

• Integrase Inhibitors

• Most drugs used to treat HIV/AIDS inhibit enzymes required for viral replication in host cells, and prevent HIV from entering cells to prevent infection. HAART does not prevent viral mutations or inhibit viral protein synthesis

• CCR5 coreceptor antagonists work by preventing HIV-1 from entering the cell

• Fusion inhibitors work by blocking the fusion of the viral membrane with the host cell membrane

Integrase Inhibitors

• They -inhibit the activity of the virus-specific enzyme integrase, an encoded enzyme needed for viral replication
• It is contraindicated for individuals with hypersensitivity to any component of the drug as well as nursing mothers
• Adverse reactions include headache, dizziness, and an increased risk for the development of rhabdomyolysis and myopathy
• There are drug-to-drug interactions such as decreased serum levels of either drug if combined with rifampin

Nursing Considerations for HIV/AIDS Antiviral Therapy

• Assess for a history of allergy to antivirals and perform a physical assessment
• Check the level of orientation, skin (color, temperature, and lesions)
• Monitor temperature for infections as well as hepatic and renal function tests and CBC

Evaluation of Effectiveness of HIV Meds

• Assess symptoms, basic metabolic panel and CBC
• Monitor CD4 counts– how well their immune system is functioning
• CD4 cells are white blood cells that fight infection, and more you have, the better.

Prototype HIV/AIDS Antiviral Agent: NNRTI (Nevirapine)

• Nevirapine is indicated for the treatment of HIV-1-infected patients with clinical or immunological deterioration in combination with other antiretrovirals
• It binds to HIV-1 reverse transcriptase and blocks replication of HIV by changing the structure of the HIV enzyme
• Nevirapine is taken orally, it has a rapid onset and reaches peak levels in 4 hours
• Drug half life is 45 hours, then 25 to 30 hours, it is metabolized in the liver and excreted in the urine
• Adverse effects of the drug are: Headache, nausea, vomiting, diarrhea, rash, liver dysfunction, chills, fever

Prototype HIV/AIDS Antiviral Agent: NRTI (Zidovudine)

• Zidovudine is indicated for the management of adults with symptomatic HIV infection in combination with other antiretrovirals and for the prevention of maternal fetal HIV transmission
• Zidovudine is a thymidine analogue that is activated to a triphosphate form that inhibits the replication of various retroviruses, including HIV.
• When taken orally, Zidovudine’s onset varies, when taken intravenously, its onset is rapid
• Zidovudine peaks between 30-90 minutes when taken orally, and at the end of infusion when taken intravenously
• The half life is 30 to 60 minutes, it is metabolized in the liver and excreted in the urine
• Adverse effects of Zidovudine include headache, insomnia, dizziness, nausea, diarrhea, fever, rash, and bone marrow suppression

Prototype HIV/AIDS Antiviral Agent: Protease Inhibitor (Fosamprenavir)

• Fosamprenavir is indicated for the management of adults with symptomatic HIV infection in combination with other antiretrovirals
• It inhibits protease activity, leading to the formation of immature, noninfectious-virus particles
• Fosamprenavir is taken orally with a varied onset, and reaches peak levels in 1.5 to 4 minutes
• The half life is 7.7 hours,It is metabolized in the liver and excreted in the feces and urine
• Adverse effect of this drug include headache, mood changes, nausea, diarrhea, fatigue, rash, Stevens-Johnson syndrome, and redistribution of body fat (buffalo hump, thin arms and legs)

Prototype HIV/AIDS Antiviral Agent: Fusion Inhibitors (Enfuvirtide)

• Enfuvirtide is indicated for the treatment of HIV-1-infected patients who have experienced clinical or immunological deterioration after treatment with other agents, in combination with other antiretrovirals
• It prevents the entry if the HIV-1 virus into cells by inhibiting the fusion of the virus membrane with the cellular membrane
• The subcutaneous route has a slow onset with a peak between 4-8 hours.
• The half life of the drug is 3.2 to 4.4 hours, it is metabolized in the liver, tissues recycle the amino acids, and is not excreted
• Adverse effect of this drug includes headache, nausea, vomiting, diarrhea, rash, anorexia, pneumonia, chills, and injection-site reactions.

Prototype HIV/AIDS Antiviral Agent: CCR5 Coreceptor Antagonist (Maraviroc)

• Maraviroc is indicated for combination antiretroviral treatment of adults infected with CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents
• It selectively binds to the human chemokine receptor CCR5 on the cell membrane, preventing the interaction of HIV-1 and CCR5, which is necessary for the HIV to enter the cell, HIV cannot enter the cell and cannot multiply
• Maraviroc is taken orally, has a slow onset and reaches peak levels in 0.5 to 4 hours
• The half life of Maraviroc is 14 to 28 hours, it is metabolized in the liver and excreted in the feces and urine
• Adverse effects dizziness, paraesthesias, nausea, and vomiting
• Maravioc can also cause diarrhea, cough, upper respiratory infection (URI), fever, musculoskeletal symptoms, and hepatotoxicity.

Prototype HIV/AIDS Antiviral Agent: Integrase Inhibitors (Raltegravir)

• Raltegravir is indicated in combination with other antiviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
• It inhibits the activity of the virus-specific enzyme integrase, an encoded enzyme needed for viral replication. Blocking this enzyme prevents the formation of the HIV-1 provirus and leads to a decrease in viral load and an increase in active CD4 cells
• The onset of action is rapid, reaching peak levels in 3 hours
• The half life is 9 hours, the drug is metabolized in the liver, and excreted in the feces and urine
• Adverse effects of this drug includes: Headache, dizziness, nausea, and vomiting
• Raltegravir can cause diarrhea, fever, and rhabdomyolysis.

Anti-Hepatitis B Agents

• These agents inhibits reverse transcriptase in the hepatitis B virus and causes DNA chain termination
• Contraindications: Known allergy, pregnancy, lactation and known renal and liver dysfunction
• Adverse Effects are headache, dizziness, nausea, diarrhea, and elevated liver enzymes
• Drug-to-Drug Interactions increased risk of renal toxicity if these drugs are taken with other nephrotoxic drugs

Nursing Considerations for Receiving Agents for Hepatitis B

• Assess for: History of allergy to adefovir, entecavir, or telbivudine
• Check Liver and renal function tests
• Perform a physical assessment and take temperature
• Level of orientation and reflexes

Prototype: Entecavir (for hep B)

• Discontinuation of entecavir, a risk for hepatitis B exacerbation exists for those on it
• Teach the client the importance of not running out of the drugs and using extreme caution when discontinuing these drugs because a 1 week course is unusually brief
• The drug must be taken for several months and monitor lab tests

Anti-hepatitis C Agents

• Protease Inhibitors are used for Hep C
• Protease Inhibitors can be used in combination with ribavirin or ribavirin and peginterferon to treat chronic hepatitis C; examples include Technivie and Paritaprevir