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Antiviral agents. Viruses treatable with antiviral drugs. HSV VZV CMV HIV Influenza A and B Respiratory syncytial virus (RSV) Hepatitis A, B, and C viruses (HAV;HBV;HCV) Papilloma Picornavirus. Agents active against Herpesviruses-I. Acyclovir Cidofovir Famciclovir and penciclovir
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Viruses treatable with antiviral drugs • HSV • VZV • CMV • HIV • Influenza A and B • Respiratory syncytial virus (RSV) • Hepatitis A, B, and C viruses (HAV;HBV;HCV) • Papilloma • Picornavirus
Agents active against Herpesviruses-I • Acyclovir • Cidofovir • Famciclovir and penciclovir • Foscarnet • Fomivirsen
Agents active against Herpesviruses-II • Ganciclovir • Valacyclovir • Valganciclovir • Vidarabine • Topical agents: -Trifluridine -Vidarabine
Revolution in the field of Infectious diseases: • The availability of • Increasing number of antiviral agents • Against a broadening spectrum of viral pathogens
Mechanism of action of antiviral agents • is essential , • for appropriate clinical use and • for understanding and managing antiviral resistance !
Acyclovir • HSV encephalitis • Neonatal HSV infection • Primer genital HSV • Mucosal and cutaneous HSV-1 and HSV-2 infections in immunocompromised patients • VZV infection • Recurrent genital herpes
Acyclovir resistance • Mutation • either in viral TK or • DNA polymerase genes.
Cidofovir • Broad activity: -adenoviruses -herpesviruses -papovaviruses -poxviruses
Cidofovir • Prophylaxis and treatment of CMV retinitis in patients with AIDS • Acyclovir and foscarnet resistent HSV infections
Famciclovir and Penciclovir • DNA polimerase inhibitor • Nucleoside analogue • Famciclovir: synthetic • Active metobolite: penciclovir • 1% topical penciclovir
Famciclovir • Singles (acute zoster) • Genital HSV • Mucocutaneous HSV in HIV infected patients
Foscarnet • Pyrophosphate analogue • DNA polymerase inhibitor • RT inhibitor • Active agains all herpesviruses, HIV, HBV
Foscarnet • CMV retinitis in AIDS patients • Acyclovir resistant mucuccutaneous HSV infections in AIDS patients • Gancyclovir resistant CMV pulmoner infections in AIDS patients • Acyclovir resistant VZV infections in AIDS patients
Fomivirsen • Inhibits viral replication by antisense mechanism: its a nucleotide sequence which is complementary to a sequence in mRNA transkript and translation is inhibited. • Intravitreal injection for CMV retinitis
Ganciclovir • Guanoside analogue • DNA polimerase inhibitor • Similar to acyclovir • i.v, oral and intraocular application
Ganciclovir • Prevention and treatment of • CMV retinitis in AIDS patients • CMV disease in transplant patients
Valacyclovir • Active metobolite= acyclovir
Vidarabine • Nucleosid analogue • First licensed systemic antiviral agent • Acyclovir has supplanted vidarabine
Topical agents for HSV keratitis • Trifluridine • Vidarabine
Interferons • Low molecular weight proteins • With complex antiviral, immunomodulating, antiproliferative activities. • Produced by eucaryotic cells in response to various inducers: viruses • 3 types: IFN-a, IFN-β , INF- δ • IFN-a2b: widest application • Pegilated- IFN-a: + polyethylene glycol to the interferon, through a process known as pegylation, enhances the half-life of the interferon when compared to its native form.
HIV(Human immunodeficeincy virus) • Nucleoside analogue reverse transcriptase inhibitors:Zidovudine (azidothymidine) • Non- Nucleoside analogue reverse transcriptase inhibitors • Protease inhibitors • Fusion inhibitors • Integrase inhibitors
Hepatitis C: Interferon-a, ribavirin • Hepatitis B: INF-a, lamivudine (reverse transcriptase inhibitor), adefovir, … • Papillomavirus: Interferon-a • RSV: Ribavirin • CMV:ganciclovir, foscarnet • VZV: valacyclovir, famciclovir • Picornavirus: pleconaril
Anti-influenza drugs • Influenza A: • Amantadine • Rimantadine 2. Influenza A and B • Zanamivir: enzyme inhibitors of neurominidase, virus release is inhibited. • Oseltamavir: the same • The length of disease is reduced if taken within the first 48hours