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-Nonretroviral Amantadine (Symmetrel) Narrow antiviral spectrumactive 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-Nonretroviral Rimantadine (Flumadine) Same spectrum of activity, mechanism of action, and indications as amantadine Fewer CNS adverse effects Causes GI upset

Antivirals Drugs-Nonretroviral Acyclovir (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-Nonretroviral Ganciclovir (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-Nonretroviral Dose-Limiting Toxicities ganciclovir and zidovudine Bone marrow toxicity foscarnet and cidofovir Renal toxicity

Antivirals Drugs-Nonretroviral Neuraminidase 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-Nonretroviral Ribavirin 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) Examples Block activity of the enzyme reverse transcriptase, preventing production of new viral DNA Nucleoside RTIs (NRTIs) Nonnucleoside RTIs (NNRTIs) Nucleotide RTIs (NTRTIs) Examples abacavir (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 severe-monitor 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 Implications Patient 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 Implications Patient 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