ANTIVIRAL DRUGS

Understanding Viruses

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

Understanding Viruses

Viruses are difficult to kill because they live inside the cells

Any drug that kills a virus may also kill cells

Viral Infections

Competent immune system:

Best response to viral infections A well-functioning immune system will eliminate or

effectively destroy virus replication

Immunocompromised patients have frequent viral infections

Cancer patients, especially leukemia or lymphoma Transplant patients, due to pharmacologic therapy AIDS patients, disease attacks immune system

Antivirals

Viruses controlled by current antiviral therapy

Cytomegalovirus (CMV) Hepatitis viruses Herpes viruses Human immunodeficiency virus (HIV) Influenza viruses (the “flu”) Respiratory syncytial virus (RSV)

Antivirals

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

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

Antivirals

Opportunistic infections

Occur in immunocompromised patients

Infections that would not normally harm an immunocompetent person

Require long-term prophylaxis and anti-infective drug therapy

Can be other viruses, fungi, bacteria, or protozoa

Antiviral Medications

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

Herpes-Simplex Viruses HSV-1 (oral herpes) HSV-2 (genital herpes)

Varicella Zoster Virus Chickenpox Shingles

Antiviral Drugs: Nonretroviral Mechanism of action

Inhibit viral replication Used to treat non-HIV viral

infections Influenza viruses HSV (herpes simplex virus), VZV (vericella zoster

virus) CMV (cytomegalovirus) Hepatitis A, B, C (HAV, HBV, NCV)

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

serious toxicities

Antivirals Drugs-NonretroviralAmantadine (Symmetrel)

Narrow antiviral spectrumactive only against influenza A

Used prophylactically when vaccine is not available or cannot be given

Therapeutic use can reduce recovery time

CNS effects: insomnia, nervousness, lightheadedness

GI effects: anorexia, nausea, others

Antivirals Drugs-NonretroviralRimantadine (Flumadine)

Same spectrum of activity, mechanism of action, and indications as amantadine

Fewer CNS adverse effects

Causes GI upset

Antivirals Drugs-NonretroviralAcyclovir (Zovirax)

Synthetic nucleoside analog

Used to suppress replication of: HSV-1(oral herpes), HSV-2(genital herpes), VZV (Varicella – chickenpox or shingles)

Drug of choice for treatment of initial and recurrent episodes of these infections

Oral, topical, parenteral forms

Antivirals Drugs-NonretroviralGanciclovir (Cytovene)

Synthetic nucleoside analog

Used to treat infection with cytomegalovirus (CMV)

Oral, parenteral forms

CMV retinitis Ophthalmic form surgically implanted Ocular injection (fomivirsen)

Antivirals Drugs-NonretroviralDose-Limiting Toxicities

ganciclovir and zidovudine Bone marrow toxicity

foscarnet and cidofovir Renal toxicity

Antivirals Drugs-NonretroviralNeuraminidase Inhibitors

oseltamivir (Tamiflu) and zanamivir (Relenza) Active against influenza types A & B

Use: Reduce duration of illness

oseltamivir: causes nausea & vomiting

zanamivir: causes diarrhea, nausea, sinusitis

Treatment should begin within 2 days of influenza symptom onset

Antivirals Drugs-NonretroviralRibavirin

Synthetic nucleoside analog

Given orally, or oral or nasal inhalation

Inhalation form (Virazole) used for hospitalized infants with RSV (respiratory syncytialvirus) infections

HIV

Human immunodeficiency virus infection 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

Five 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

WHO model stages

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

Bacterial Various mycobacterial infections, others Extrapulmonary TB

Opportunistic neoplasias Kaposi’s sarcoma, others

Antiretroviral Drugs

HAART - Highly active antiretroviral therapy

Includes at least three medications “cocktails”

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 Reverse transcriptase inhibitors (RTIs)

Nucleoside RTIs (NRTIs) Nonnucleoside RTIs (NNRTIs) Nucleotide RTIs (NTRTIs)

Examplesabacavir (Ziagen) delavirdine (Rescriptor)didanosine (Videx) lamivudine (Epivir)stavudine (Zerit) tenofovir (Viread)

Antiretroviral Drugs

Protease inhibitors (PIs) Inhibit the protease retroviral enzyme,

preventing viral replication Examples: amprenavir (Agenerase) indinavir

(Crixivan) nelfinavir (Viracept) ritonavir (Norvir) saquinavir (Invirase)

Antiretroviral Drugs

Fusion inhibitors

Inhibit viral fusion, preventing viral replication

Newest class of antiretroviral drugs

Example: enfuvirtide (Fuzeon)

Antiretroviral Drugs

Combinations of multiple antiretroviral medications are common

Adverse effects vary with each drug and may be severemonitor for dose-limiting toxicities

Monitor for signs of opportunistic diseases

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

Nursing Implications

Before therapy, assess underlying disease, history, allergies

Assess baseline VS and nutritional status

Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions

Nursing ImplicationsPatient Education

Consult their physician before taking other medication, including OTCs

Good hygiene

Antiviral drugs are not cures but help manage symptoms

Take these medications exactly as prescribed

Take medications for the full course of treatment

Nursing ImplicationsPatient Education

Teach each proper application for ointments, aerosol powders

Hand washing before and after administration of medications

Wear glove or finger cot when applying ointments

Start therapy with antiviral drugs at the earliest sign of recurrent episodes of genital herpes or herpes zoster

Nursing Implications

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 flu-like symptoms, decrease in frequency of herpes-like flare-ups, or crusting over of herpetic lesions

Monitor for adverse effects Effects are varied and specific to each drug