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Antiviral drugs(non retro-viral)
- 2. Anti Viral Drugs Dr Bikash Meher Asst. Prof AIIMS,Bhubaneswar
- 3. Contents Introduction Classification of antiviral drugs Major site of action of antiviral drugs Individual drugs M.O.A Uses Adverse effects
- 4. Introduction
- 5. Steps of Viral replication
- 7. Antiviral therapy Vaccination Stimulating host immune mechanism Antiviral drug therapy
- 8. Problems in antiviral drug therapy Antiviral drug is toxic to host cells Some viruses multiply in both cytoplasm as well as nucleus Antiviral drugs most effective during rapid multiplications Latent virus not affected by antiviral drugs
- 9. Ideal antiviral agents Low toxicity to host Greater selectivity Should kill latent viruses as well
- 10. Classification of antiviral drugs 1.Based on mechanism of action 2.Based on type of virus against which active
- 11. Based on mechanism Inhibitors of attachment Enfuvirtide Dosaconol Inhibitors of un coating Amantadine Inhibitors of Reverse transcriptase Zidovudine Lamivudine Nucleic acid synthesis inhibitors Acyclovir Ribavarin Inhibition of release of progeny virus Oseltamivir Zanamivir Other Interferons
- 14. Acyclovir Guanine derivative pro drug
- 16. P/K 20% bioavailability Bioavailability not affected by food Widely distributed in most tissue CSF conc. Is 50% of plasma conc. T1/2- 3hr
- 17. Uses • 5% ointment locally 6 times a day for 10 days • 1gm/day in 5 divided doses Primary genital herpes • 5mg/kg IV infused over 1 hr • Repeated 8 hrly for 10 days Recurrent genital herpes • 5% ointment locally 6 times a day for 5days • 1gm/day in 5 divided doses Mucocutaneous herpes Keratoconjuctivitis
- 18. • 15mg/kg/day for 7days Chickenpox • 15mg/kg/day for 7days • 10mg/kg/8hr IV for 10 days Varicella zoster • Acyclovir 10mg/kg/8hr IV for 10 days Herpes simplex encephalitis
- 19. Adverse effects Stinging and burning sensation Nausea,Vomiting,Diarrhea,Headache,Malaise Vomiting,Rash,Sweating,Hypotension Renal dysfunction,Nerotoxicity
- 20. Q.Tick the unwanted effects of intravenous acyclovir infusion A. Renal insufficiency, tremors, delirium B. Rash, diarrhea, nausea C. Neuropathy, abdominal pain D. Anemia, neutropenia, nausea, insomnia
- 21. Valcyclovir L-Valyl ester of acyclovir Bioavailability is 50-75% More effective in herpes zoster Dose -1gmBD for 1 week Use in prevention CMV infection A/E GI intolerance in AIDS Neurotoxicity,TTP,HUS in organ transplant pts
- 22. Ganciclovir Guanine analogue of acyclovir Poor bioavailability(8-10%) More active against CMV Accumulated in vitreous humor Use in CMV infection,Acyclovir resistant HSV infection For prevention of CMV in organ transplant patients Dose 5mg/kg BD IV
- 23. A/E Myelosuppresion Zidovudine potentiate myelosuppresion Cyclosporine potentiate nephrotoxicity Probencid increase ganciclovir level
- 24. Foscarnet Inorganic pyrophosphate derivative Doesn't require phopsphorylation Inhibits DNA polymerase activity Poor bioavailability Acyclovir resistant HSV infections,CMV retinitis A/E Renal toxicity Electrolyte disturbance,anemia,lekopenia
- 25. Cidofovir Cytidine analogue Cidofovir diphosphate Inhibits DNA polymerase Poor bioavailability Not metabolized significantly and excreted in urine unchanged For CMV retinitis,HSV mucocutaneous reaction PML,Molluscum contgiosom A/E Nephrotoxicity,↓IOP,Uveitis,Neutropenia
- 26. Adefovir dipivoxil Adenosine analogue For HBV Absorption is NOT affected by food Active against lamivudine resistant strain of HBV A/E Sore throat,Headache,Abdominal pain, Flu syndrome Nephrotoxicity,Lactic acidosis,Hepatomegaly Dose 10 mg OD
- 27. Amantadine Tricycline amine Influenza A specific No Cross resistance with zanamivir and oseltamivir
- 28. M.O.A
- 29. Adverse Effects GI intolerance CNS side effects Anticholinergic effects Teratogenic CI in gastric ulcer and CNS disease
- 30. Uses Prophylaxis of influenza A2 Treatment of influenza A2 Dose 100mg BD
- 31. Rimantadine Methyl derivative of amantadine More potent, Long acting Less neurotoxic,High GIT intolerance Dose 100mg BD
- 32. Zanamivir Inhibits neuraminidase Effective for both influenza A and B Treatment should be started within 1-2 days Poor bioavailability, Poor plasma protein binding Used as inhalation Dose -10mg BD a day for 5 days Precipitate bronchospasm Nasal and throat discomfort, GI disturbance
- 33. M.O.A
- 34. Oseltamivir Prodrug Oseltamivir carboxylate-active form Dose 75 mg BD for treatment and 75 mg OD for prevention A/E Nausea,Vomiting,Dirrhea,Abdominal pain,Seizures Aggravation of diabetes
- 35. Telbivudine Thymidine nucleoside analogue Undergoes triple phophorylation Inhibits HBV DNA polymerase Bioavailability is NOT altered by food No known interaction with drugs affecting CYPp-450 More effective than lamivudine A/E Abdominal pain,headache Lactic acidosis,hepatomegaly,steatosis
- 36. Ribavarin Purine nucleoside analogue Broad spectrum antiviral activity Bioavailability -50% Inhibits Viral RNA polymerase
- 37. Uses Influenza Hepatitis C Bronchiolitis Dose 200mg QID A/E Anemia,BMD,Hemolysis Teratogenic
- 38. Interferon Low molecular weight glycoprotein Nonspecific antiviral Affect viral replication at multiple levels Viral protein synthesis Host specific
- 39. Uses Chronic hepatitis B AIDS related kaposi sarcoma Chronic hepatitis C Condyloma acuminata H.simple,H zoster,CMV
- 40. Side effects Flu like symptoms Neurotoxicity Myelosuppression Thyroid dysfunction Alopecia
- 41. Thank You
- 42. Fomivirsen • Oligonucleotide • Anti CMV agent • Inhibits m-RNA synthesis • Selective accumulation in retina and vitreous humor • Use in CMV retinitis • A/E • Iritis vitreitis IOP • Cidofovir increase risk of occular inflammation