Antiviral Drugs General Principles of Virology Viral replication o A virus cannot replicate on its own o It must attach to and enter a host cell o It then uses the host cell s energy to synthesize protein DNA and RNA o Viruses are difficult to kill because they live inside the cells Any drug that kills a virus may also kill cells 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 Antiviral Drugs 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 Viruses controlled by current antiviral therapy o Cytomegalovirus CMV o Hepatitis viruses o Herpes viruses o Human immunodeficiency virus HIV o Influenza viruses the flu o Respiratory syncytial virus RSV Key characteristics of antiviral drugs o Able to enter the cells infected with virus o Interfere with viral nucleic acid synthesis and or regulation o Some drugs interfere with ability of virus to bind to cells o Some drugs stimulate the body s immune system o Best responses to antiviral drugs are in patients with competent immune systems o A healthy immune system works synergistically with the drug to eliminate or suppress viral activity Opportunistic infections o Occur in immunocompromised patients o Would not normally harm an immunocompetent person o Require long term prophylaxis and antiinfective drug therapy o Can be other viruses fungi lots of times yeast bacteria or protozoa Antiviral drugs o Used to treat infections caused by viruses other than HIV Antiretroviral drugs o Used to treat infections caused by HIV the virus that causes AIDS Herpes Simplex and Varicella Zoster Virus Infections Herpes simplex viruses o HSV 1 oral herpes o HSV 2 genital herpes Human herpesvirus VZV o Chickenpox and shingles HHV 3 or VZV o Epstein Barr HHV 4 o Cytomegalovirus HHV 5 o Kaposi s sarcoma HHV 8 Antiviral Drugs non HIV Mechanism of action o Inhibit viral replication o Used to treat non HIV viral infections Influenza viruses HSV VZV CMV Hepatitis A B C HAV HBV HCV Adverse effects o Vary with each drug o Healthy cells are often killed also resulting in serious toxicities amantadine Symmetrel o Narrow antiviral spectrum active ONLY against influenza A o Most recent guidelines do not recommend use for treatment or prevention of flu o CNS effects insomnia nervousness light headedness o GI effects anorexia nausea others o Patients that have Parkinson s disease often drool this is a great medication to reduce that rimantadine Flumadine o Same spectrum of activity mechanism of action and indications as amantadine o ONLY for influenza A o Fewer CNS adverse effects o Causes GI upset acyclovir Zovirax o Synthetic nucleoside analog o Used to suppress replication of HSV 1 HSV 2 VZV o Drug of choice for treatment of initial and recurrent episodes of these infections o Oral topical cream for pain parenteral forms When patients use a cream for herpes one and two use glove or wash hands for 3 minutes after application You can move herpes infection somewhere else o VIR is anti viral drug ganciclovir Cytovene o Synthetic nucleoside analog o Used to treat infection with cytomegalovirus CMV o Oral parenteral forms o CMV retinitis Ophthalmic form surgically implanted Vitrasert Dose Limiting Toxicities o ganciclovir Bone marrow toxicity monitor CBC o foscarnet and cidofovir Renal toxicity Neuraminidase Inhibitors o 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 Ribavirin o Synthetic nucleoside analog o Given orally or by oral or nasal inhalation o Inhalation form Virazole used for hospitalized infants with RSV infections o Curative HIV and AIDS Drugs ONLY NEED TO KNOW THIS All cause toxicity most common adverse effect is bone marrow suppression Questions 1 An 82 year old woman is unable to take the influenza vaccine due to 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 Rationale Oseltamivir Tamiflu is the only one indicated for prophylaxis of influenza infection Both oseltamivir and zanamivir can be used to treat active influenza illness Treatment with oseltamivir and zanamivir ideally should begin within 2 days of symptom onset