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Chapter 92

Chapter 92. Antiviral Agents I: Drugs for Non-HIV Viral Infections. Antiviral Therapy. Our ability to treat viral infections remains limited Viruses use biochemical machinery of host cells to reproduce Difficult to suppress viral replication without doing significant harm to the host

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Chapter 92

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  1. Chapter 92 Antiviral Agents I: Drugs for Non-HIV Viral Infections

  2. Antiviral Therapy • Our ability to treat viral infections remains limited • Viruses use biochemical machinery of host cells to reproduce • Difficult to suppress viral replication without doing significant harm to the host • Antivirals suppress biochemical processes unique to viral reproduction

  3. Herpesvirus • Herpes simplex virus (HSV) • Causes infection of the genitalia, mouth, face, and other sites • Varicella-zoster virus (VZV) • Cause of varicella (chickenpox) and herpes zoster (shingles)

  4. Acyclovir (Zovirax) • Active only against members of the herpesvirus family • Agent of first choice for HSV or VZV infections • Herpes simplex genitalis • Mucocutaneous herpes simplex infections • Varicella-zoster infections

  5. Acyclovir (Zovirax) • Herpesvirus develops resistance to acyclovir • Decreased thymidine production • Alteration in thymidine kinase • Alteration of viral DNA polymerase

  6. Acyclovir (Zovirax) – Adverse Effects • Intravenous therapy • Phlebitis • Reversible nephrotoxicity • Oral therapy • Gastrointestinal • Vertigo • Topical • Stinging sensations

  7. Valacyclovir (Valtrex) • Prodrug form of acyclovir • Herpes zoster • Herpes simplex genitalis • Herpes labialis • In some immunocompromised patients • Thrombotic thrombocytopenic purpural/hemolytic uremic syndrome (TTP/HUS)

  8. Famciclovir (Famvir) • Prodrug used to treat acute herpes zoster and genital herpes infection • Benefits are equivalent to those of acyclovir • Adverse effects are minimal

  9. Topical Drugs • Herpes labialis • Penciclovir (Denavir) • Docosanol (Abreva) • Ocular herpes infections • Trifluridine (Viroptic) • Vidarabine (Vir-A)

  10. Cytomegalovirus Infection • CMV – member of herpesvirus group • Transmitted direct contact with body fluids • 50%-80% of Americans age 40 and older harbor the virus • Can remain dormant for life • Immunosuppressed patients at high risk to reactivate dormant virus

  11. Ganciclovir (Cytovene, Vitrasert) • Synthetic antiviral agent • Uses • Herpes simplex viruses – including CMV • Prevention and treatment of CMV infection in immunocompromised patients • Serious side effects • Granulocytopenia • Thrombocytopenia

  12. Ganciclovir (Cytovene, Vitrasert) • Adverse effects • Granulocytopenia • Thrombocytopenia • Reproductive toxicity • Nausea, fever, rash, anemia, liver dysfunction, confusion, and other CNS symptoms

  13. Valganciclovir (Valcyte) • Prodrug version of ganciclovir • Used for CMV retinitis • Oral is just as effective as IV • Adverse effects • Blood dyscrasias • Bone marrow suppression • Granulocytopenia, anemia, thrombocytopenia

  14. Valganciclovir (Valcyte) • Adverse effects (cont’d) • Diarrhea, nausea, vomiting • Potential for mutagenesis and carcinogenesis • Direct contact with broken tablet should be avoided • Should be disposed of in the same manner as a cytotoxic drug

  15. Cidofovir (Vistide) • IV with just one indication – CMV retinitis in patients with AIDS who have failed on ganciclovir or foscarnet • Adverse effects • Nephrotoxicity • Neutropenia • Ocular disorders

  16. Foscarnet (Foscavir) • IV drug active against all known herpesviruses • Compared with ganciclovir • More difficult to give, less well tolerated, much more expensive • CMV retinitis in patients with AIDS • Acyclovir-resistant mucocutaneous HSV and VZV in immunocompromised host

  17. Fomivirsen (Vitravene) • Unique drug for treating CMV retinitis with HIV-infected patients who are intolerant of or unresponsive to other drugs • Direct injection into the vitreous humor • Adverse effects • Ocular inflammation

  18. Drugs for Hepatitis • Viral hepatitis is the most common liver disorder • Millions of Americans are infected • Six different viruses can cause acute hepatitis (A, B, C, D, E, and G) • Only B, C, and D can also cause chronic hepatitis

  19. Hepatitis C Virus (HCV) • Differences in HCV – 6 genotypes; more than 50 subtypes • Transmission – primarily through exchange of blood; controversy over sexual transmission • No symptoms, but can transmit • Slow progression can lead to liver failure, cancer, and death • Leading reason for liver transplants • Drugs • Pegylated interferon alfa combined with ribavirin

  20. Interferon Alfa • Interferon family • Alpha, beta, gamma • Alphas used to treat hepatitis • None can be administered orally • Conventional versus long-acting interferons • Adverse effects • Flu-like symptoms • Neuropsychiatric effects, especially depression

  21. Ribavirin (Rebetol, Copegus) • Used in combination with subQ peginterferon alfa for treatment of chronic hepatitis C • Adverse effects • Hemolytic anemia • Birth defects – category X

  22. Hepatitis B Virus (HBV) • 1.25 million people have chronic hepatitis B • 11,000 require hospitalization for deep fatigue, muscle pain, and jaundice • Chronic infection develops in 3%-5% infected adults • Chronic infection can lead to cirrhosis, hepatic failure, hepatocellular carcinoma, and death • Transmission – blood and semen

  23. Hepatitis B Virus (HBV) • HBV vaccine • Drugs • Interferon alfa-2b (PEG-Intron) • Peginterferon alfa-2a • Lamivudine (Epivir-HBV) • Adefovir (Hepsera) • Entecavir (Baraclude) • Telbivudine (Tyzeka)

  24. Influenza • Serious respiratory tract infection • Major cause of morbidity and mortality worldwide • 36,000 deaths/year in the United States • Caused by influenza viruses, which are highly variable and undergo constant evolution • Type A – more infectious than B • Type B

  25. Influenza Management • Influenza managed by vaccination (primary strategy) and drugs • Drugs • Adamantanes and neuraminidase inhibitors • Vaccines • Influenza vaccines change yearly based on identification of strains by CDC, FDA, and WHO.

  26. Influenza Vaccine • Two types of flu vaccines • Inactivated influenza vaccine • Live, attenuated influenza vaccine • Protection begins 1-2 weeks after vaccination; generally lasts 6 months or more • Small risk for Guillain-Barré syndrome • Five influenza vaccines on the market

  27. Influenza Vaccine • Precautions and indications • Acute febrile illness – should defer • Minor illnesses with or without fever do not preclude vaccination • Contraindicated for hypersensitivity to eggs – viruses are grown in eggs • Who should be vaccinated • When should vaccines be given

  28. Drugs for Influenza • Neuraminidase Inhibitors • Oseltamivir (Tamiflu) • Zanamivir (Relenza) • Adamantanes • Amantadine (Symmetrel) • Rimantadine (Flumadine)

  29. Drugs for Respiratory Syncytial Virus Infection • Ribavirin (inhaled) • Broad-spectrum antiviral drug • Palivizumab (Synagis) • Monoclonal antibody for preventing RSV infection in newborns

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