Antiviral drugs

1. Dr.Reshmi.T.R
ANTIVIRAL DRUGS

2. VIRUS
 Structure
 Genome: RNA/DNA/neverBoth
 Capsid: Protein shell
 Envelope: Lipoprotein

3. Structure of a virus
Envelope
Capsid
DNA/RNA
3

4. CLASSIFICATION
DNA virus
 Hepatitis B
 Herpes virus
HSV-1,HSV-2
VZV
EBV
CMV
 Poxvirus(Molluscum)
 Parvovirus(Erythema
infectiosum)
 Papilloma virus(Warts)
RNA Virus
 Influenza
 Hepatitis A,C,D,E
 Enterovirus
 Mumps
 Measles

5. Viral replication
Attachment Entry Uncoating
Synthesis of
viral
RNA/DNA
Synthesis of
structural
proteins
Assembly Release

6. DNA VIRUS REPLICATION
DNA polymerase
Entry into nucleus
Attachment
Uncoating

7. Release of virions
Viral
proteins
RNA VIRUS REPLICATION

8. CLASSIFICATION
Antivirals
DNA Polymerase
inhibitors
mRNA inhibitors
Inhibitors of viral
penetration and uncoating
Release inhibitors
Immunomodulators
Docosanol, Amantadine
Palivizumab
Ribavirin,
Fomivirsen
Neuraminidase inhibitors
Interferons
Acyclovir, Ganciclovir

9. ANTIVIRALS AND
DNA VIRUS

10. Docosanol (HSV)
1) INHIBITION OF ATTACHMENT
Aliphatic alcohol
Topical – 10% cream
Use – Herpes labialis

11. IIn
DNAP
Inhibitors
DNA POLYMERASE INHIBITORS

12. Acyclovir
Valacyclovir
Ganciclovir
Valganciclovir
Famciclovir
Penciclovir
Adefovir
Cidofovir
Entecavir
Vidarabine
Idoxuridine
Trifluridine
Telbivudine
Foscarnet
DNA POLYMERASE INHIBITORS

13. MONOPHOSPHATE
TRIPHOSPHATE
DIPHOSPHATE
ACYCLOVIR
PENCYCLOVIR
GANCICLOVIR
CIDOFOVIR
FOSCARNET
INHIBITION OF VIRAL DNA POLYMERASE
INHIBITION OF VIRAL DNA SYNTHESIS
VIRAL KINASE
HOST KINASES
HOST KINASES

14. PK
 BA – 10-30%
 Wide distribution, crosses BBB
 Half life – 2-3hrs
 Renal excretion-dose reduction
ACYCLOVIR &VALACYCLOVIR

15. SPECTRUM AND USE
 HSV-1: Herpes labialis, esophagitis, keratitis ,encephalitis,
Ocular herpes
 HSV-2: Genital herpes,VZV
 EBV,CMV: Weak action HSV-1>HSV-2>CMV>EBV

16. ROA
 HSV-1,HSV-2,VZV:Oral
 400mg tds
 Encephalitis:Parenteral
 Genital ,Ocular Herpes:Topical

17. ADR
 I.V- rash, sweating, emesis, hypotension, CNS effects, renal
insufficiency, phlebitis on extravasation
 Topical-stinging, burning
 Oral-head ache, nausea, malaise

18. VALACYCLOVIR
 L-valyl ester prodrug of acyclovir
 BA more than acyclovir
 Less frequent dosing
 No IV preparation
 Use:
 VZV, Recurrent genital herpes
 Dose:1g BD/TDS 7 days

19. Penciclovir
Topical cream
Persist in infected
cell for long time
Half life -8to20 hrs
Use:Herpes
Labialis
Famciclovir
Prodrug of
penciclovir
Excreted in urine
Use:VZV

20. GANCICLOVIR AND VALGANCICLOVIR
 Selective action to CMV Infections
 Accumulate in vitreous humor
 CMV retinitis
Poor oral Bioavailability
 ROA:
 IV
 Oral
 Intraocular implant

21. ADVERSE EFFECTS
 Myelosuppression
Anemia,neutropenia,thrombocytopenia
 Fever
 Phlebitis

22. VALGANCICLOVIR
 Prodrug of Ganciclovir
 Well absorbed orally
 Oral valganciclovirCMV Retinitis:900 mg BD

23. CIDOFOVIR
 Poor oral bioavailability
Topical, IV
 Phosphorylated by cellular but not viral enzymes
Acyclovir resistant cases
Use:CMV Retinitis,HSV mucocutaneous lesion
 AE:Nephrotoxicity,Uveitis

24.  MOA:No phosphorylation required to inhibit DNAP
 Thymidine kinase mutation not a threat
 Use:Mucocutaneous HSV ,CMV retinitis
 ROA:IV
 Dose:
Induction:90mg/kg IV Q12h
Maintenance:90 mg/kg/day
FOSCARNET

25. Idoxuridine
 Ophthalmic use:HSV
infection
 Trifluridine
 HSV-1 ,HSV-2,CMV
 Ophthalmic use
 AE: Hyperemia

26.  Adefovir
 Use:chronic HBV
 AE:Nephrotoxicity
 Telbivudine
 Use:Chronic HBV
 AE:Headche,vomiting

27. mRNA synthesis
inhibitors
MRNA SYNHTHESIS INHIBITORS
Fomivirsen
Selective accumulation in vitreous
Use: CMV retinitis
AE: Iritis,Vitreitis

28.  InterferonsDefence against viral infections:
Immunomodulator
 Inhibit viral replication at multiple steps:
1 Penetration
2 Uncoating
3 mRNA synthesis
4 Assembly
5 Release
DNA and RNA viruses are sensitive to interferons
2) INHIBITION OF REPLICATION BY
INTERFERONS

29.  Uses:
 Interferon alpha2a:
 Chronic hepatitis B,Kaposi’s sarcoma,Chronic Hepatitis C
 Interferon alpha2b
 HepatitisC,Chronic hepatitis B,Condyloma acuminata
 Adverse effects:
 Myalgia.fever,rash
 Alopecia,Bone marrow suppression(long term)
INTERFERONS

30. RNA VIRUS

31. 1) ATTACHMENT AND ENTRY
Palivuzumab
Humanized monoclonal antibody
Use: RSV
AE: Fever,Rhinitis,Diarrhoea

32. 2)INHIBITION OF UNCOATING
Uncoating inhibited by
AMANTADINE
RIMANTIDINEResistance:
M2 protein mutation

33. AMANTADINE ,RIMANTADINE
 Rimantadinealpha methyl ester of amantadine
 Amantadine is excreted in urine ,Rimantidineliver
 ROA:Oral,100mg BD
 Rapidly absorbed from GIT
 Use: Treatment of Influenza
 Additional use of Amnatidine:Parkinson’s Disease
InfluenzaA >Influenza B

34. MRNA INHIBITORS
RIBAVIRIN
Broad spectrum
Inhibit RNA and DNA virus
Use: Influenza,HCV
AE: Respiratory distress,hypotension
Resistance: Uncommon

35. Release of virions
Viral
proteins
NEURAMINIDASE INHIBITORS
(INHIBITION OF VIRAL RELEASE)
Neuraminidase
inhibitors

36. Oseltamivir
Zanamivir
Peramivir
NEURAMINIDASE INHIBITORS
Influenza A,B

37. Oseltamivir Zanamivir
MOA Neuraminidase inhibitor Neuraminidase inhibitor
ROA Oral Intranasal
ROE Renal Renal
AE Gastrointestinal Bronchospasm
Dose 75 mg BD for treatment
75mg OD fror prophylaxis
10mg BD inhalation

38.  Recent drug
Use:
Emergency treatment of H1N1
Only IV option for swine flu
PERAMIVIR

39. ANTIHERPES DRUGS

40. HSV-1 Herpes Labialis
Ocular Herpes ,
Herpes encephalitis
HSV-2
Genital herpes
VZV
Chickenpox
Shingles
AGENTS TO TREAT-HSV,VZV INFECTIONS

41. Drug ROA USE
Acyclovir
Valacyclovir (No IV)
Oral
Topical
IV
Genital herpes
Orolabial herpes
Herpes Encephalitis
Varicella
Zoster
Famciclovir Oral Genital herpes
Orolabial herpes
Zoster
Foscarnet IV Acyclovir resistant HSV,VZV
Docosanol Topical Recurrent herpes labialis
Penciclovir Topical Herpes labialis
Herpes Genitalis
Trifluridine Topical Acyclovir resistant HSV

42. AGENTS TO TREAT CMV

43. Agent Route Use
Ganciclovir Oral
IV
Intraocular implant
CMV retinitis
Treatment and prophylaxis
Valganciclovir Oral CMV Retinitis
Treatment and prophylaxis
Foscarnet IV CMV retinitis treatment
Cidofovir IV CMV retinitis treatment

44. AGENTS TO TREAT
HEPATITIS

45. Agent Indication Route
Lamivudine Chronic hepatitis B Oral
Adefovir
Chronic hepatitis B
Oral
Entecavir Chronic hepatitis B Oral
Tenofovir Chronic hepatitis B Oral
Telbivudine Chronic hepatitis B Oral
Interferon alpha Chronic Hepatitis B S/C
Interferon alpha +Ribavirin Chronic hepatitis C S/C

46. Agent Indication Route
Lamivudine Chronic hepatitis B Oral
Adefovir
Chronic hepatitis B
Oral
Entecavir Chronic hepatitis B Oral
Tenofovir Chronic hepatitis B Oral
Telbivudine Chronic hepatitis B Oral
Interferon alpha Chronic Hepatitis B S/C
Interferon alpha +Ribavirin Chronic hepatitis C S/C

47. ANTIINFLUENZA VIRUS

48. Agent Route Mechanism Use
Oseltamivir Oral Neuraminidase inhibitor Influenza A ,B
Zanamivir Inhalation Neuraminidase inhibitor Influenza A,B
Peramivir IV Neuraminidase inhibitor H1N1
Amantadine Oral Inhibtor of penetration Influenza A>B
Rimantidine oral Inhibitor of penetration Influenza A>B
Ribavirin Oral
IV
Aerosol
mRNA inhibitor Influenza A,B
RSV