1. Antiviral therapy E.McNamara

2. Challenges Virus parasitize host cells Target the virus specifically Latency, quiescent phase Is treatment necessary? Efficacy of Rx.

3. Current agents Exploit viral : host replication Target viral DNA polymerases Accumulate in viral infected cells Activated by virus encoded enzymes Dose related toxicity

4. Acyclovir Nucleoside analogue Inhibits viral DNA polymerase Stops replicating viral DNA chains Excreted via renal Serum half life 2-3 hrs Good tissue distribution Activated by HSV-TK to triphosphate form

5. Acyclovir toxicities CNS, –Confusion, seizures, coma. –Highest risk Renal impairment Old age Prior mental disability Potential teratogenicity Resistance

6. Acyclovir, uses In-vitro –HSV –VZV –EBV –CMV In-vivo –HSV –VZV

7. Famciclovir Nucleotide analogue Similar spectrum to acyclovir Similar mode of action Inactive prodrug of penciclovir Activated by viral-TK to penciclovir

8. Famciclovir cont. Greater bioavailability Prolonged intracellular half-life TID dosing

9. Famciclovir toxicities No major S/E Potentially teratogenic Potential male infertility Levels increased by probenecid May increase digoxin levels

10. Valaciclovir Valyl ester of acyclovir P.O. metabolised to acyclovir Plasma levels equivalent to IV acyclovir Sustitute for IV acyclovir Bioavailability dependant on GIT and hepatic function

11. Valaciclovir Toxicities similar to acyclovir TTP in immunocompromised on prolonged Rx.

12. Penciclovir Nucleoside analogue Similar activity to acyclovir Topical, Herpes labialis.

13. Herpes infection Rx. Improved PO bioavailability Different mode of action-resistance Improved efficacy Type, –Primary –Secondary/reactivation –Suppressive Rx. Vaccines and immunomodulators

14. Herpes Rx. HSV –Herpes labialis –Genital herpes –Encephalitis –Immunocompromised VZV H.zoster EBV

15. Gangciclovir Competively inhibits viral DNA polymerase Incoporates into viral DNA, chain terminator Major agent for CMV Accumulates in CMV infected cells Excreted renally Crosses Blood Brain Barrior

16. Gangciclovir, toxicity Haematologic/bone marrow –Neutropaenia –Thrombocytopaenia –Interacts with cytotoxic drugs Renal impairment Carcinogenic Potentiated by probenecid

17. Foscarnet Binds viral DNA polymerase and RT. Active v Herpes viruses Not curative Excreted renally Variable half-life Impairs biochem. –Monitor u/e, creatinine

18. Fomivirsen Active v CMV Inactivates CMV mRNA Local, no systemic anti-CMV Rx. Substitute for CMV retinitis Rx. Intra-vitreal injections S/E, intraocular pressure, retinal toxicity

19. CMV management Disseminated disease –Gangciclovir/Foscarnet/ –CMV-Iggs, pneumonitis BMT Prophylaxis/preemptive in Tx. –Gangciclovir/acyclovir/valaciclovir Retinitis –Formiversin/gangciclovir -local

20. Amantadine Inhibits Influ-A uncoating on host cell entry Early Rx. Within 48hrs of symptoms Prophylaxis of unimmunised high risk Combined with vaccine until immunity develops Renal excretion Rapid resistance S/E, CNS- dissyness, seizures

21. Rimantadine Structural analogue of amantadine Fewer CNS S/E

22. Ribavirin Synthetic nucleoside Interferes with viral RNA transcription Acts on RNA viruses –RSV, HCV –Measles –Lassa fever –Hantaviruses

23. Ribavirin uses Ribavirin + alpha-interferon for –Chronic HCV –Monitor Hb + WCC Aerosol route for RSV, infants IV for lassa/hanta

24. Ribavirin toxicities Potentially teratogenic C.I. For 6 months pre-pregnancy Anaemia Exacerbation of COPD via aerosol

25. Interferons Natural glycopeptides Induced by viruses (dsRNA) Affect –Antiviral –Antitumour –Immunomodulators Action, induce cellular enzymes to stop protein synthesis and activate RNA degradation

26. Interferons, types Alpha-interferon, B-lymphocytes Beta-interferon, fibroblasts Gamma-interferon, T-lymphocytes Recombinant –Interferon alfacon-1 –Interferon alfacon-2

27. Interferons, uses Routes, SC, IM, intralesional Chronic HCV Condyloma acuminata-intralesional Chronic HBV, remission

28. Interferons, toxicities Flu-like symptoms Alopecia Exac. Psoriasis Depression Retinal haemorrhages, rare

29. Viral hepatitis HAV, –Supportive –Prophylaxis with HAV IGg –Vaccine HBV –Interferon-alpha –Lamivudine –Vaccine /HBIG HCV –Interferon +ribavirin, Tx.

30. New agents Oseltramavir – PO Zanamivir – topical –Neuraminidase inhibitors –Active v Influenza A+B Sorivudine-VZV+HSV1, 2 step activation Cidofovir, resistant HSV and CMV