pharmacology of antiviral drugs

1. Dr. Hanan
Senior Resident
Department of
Pharmacology
ANTIVIRAL
DRUGS

3. Target – viral enzymes with higher affinity for some antimetabolites
Viral replication is
already at its peak
when symptoms
appear

5. CLASSIFICATION OF ANTIVIRAL DRUGS

6. ANTI-HERPES VIRUS DRUGS
• Herpes group of viruses
• HSV 1 and 2
• VZV
• EBV
• CMV

7. ANTIHERPES DRUGS
Idoxuridine
Trifluridine
Acyclovir
Valacyclovir
Ganciclovir
Valganciclovir
Famciclovir
Cidofovir
Foscarnet

8. IDOXURIDINE
• Thymidine analogue
• Competes with thymidine
• Incorporated in DNA
• Fraudulent DNA (faulty DNA)
• Breakdown
IDOXURIDINE
USE : SUPERFICIAL DENDRITIC
KERATITIS – 0.1% eye drops

9. ACYCLOVIR

10. ACYCLOVIR
• Preferentially taken up by the virus infected cells
• Greater viral DNA synthesis inhibition
• Low host cell toxicity
• Active only against herpes group of viruses

11. ACYCLOVIR - PK
• Only 20% is absorbed orally
• Good CSF concentration
• Penetrates cornea
• Negligible systemic absorption when applied topically

12. USES OF ACYCLOVIR
1. Genital herpes simplex
2. Mucocutaneous herpes simplex
3. Herpes simplex encephalitis
4. Herpes simplex keratitis
5. Herps zoster
6. Chicken pox

13. ADVERSE EFFECTS
• TOPICAL ACYCLOVIR: stinging and burning sensation
• ORAL ACYCLOVIR: headache, nausea, malaise
• INTRAVENOUS: rashes, sweating, fall in BP
• Dose dependent increase in GFR
• Higher doses: neurological manifestations – Tremors, lethargy,
disorientation, etc.
• No teratogenic potential has bee noted

14. VALACYCLOVIR
• Valyl ester prodrug of acyclovir, with improved oral bioavailability
• During passage through intestine and liver – completely converted to
acyclovir
• Drug of choice in herpes zoster
• OTHER USES:
• Orolabial herpes
• Genital herpes

16. DRUGS FOR CMV- GANCICLOVIR
• Most active against CMV
• Activated intracellularly by viral thymidine kinase
• inhibit viral DNA polymerase
• Bone marrow toxicity
• Restricted for :
• Prophylaxis and treatment of severe CMV infection in immunocompromised patients

17. VALGANCICLOVIR
• Valyl prodrug of ganciclovir
• Improved bioavailability
• CMV retinitis

18. CIDOFOVIR
• Cytidine analogue
• Inhibit most DNA viruses
• Converted to active form diphosphate by cellular kinases
• USES:
• CMV retinitis in AIDS patients
• Anogenital warts (topical)
• Adverse effects:
• Dose related renal toxicity
• Uveitis

19. FOSCARNET
• Inhibit viral DNA polymerase and reverse transcriptase
• H.simplex, CMV, HIV
• USES:
• CMV retinitis
• Acyclovir resistant mucocutaneous Herpes simplex
• Varicella zoster infection in AIDS patients
• ADVERSE EFFECTS:
• Damages kidney – acute renal failure
• Anemia, phlebitis, tremor, convulsions

20. ANTI
INFLUENZA
VIRUS DRUGS

22. ANTI INFLUENZA
• AMANTADINE
• RIMANTADINE
• OSELTAMIVIR
• ZANAMIVIR
• PERAMIVIR

23. AMANTADINE AND RIMANTADINE
• Inhibits only influenza A virus
• Inhibits viral M2 protein (ion channel) and prevents uncoating of the
viral genome within the infected cell
• Mutation of M2 protein  resistance
• Rimantadine – longer acting and better tolerated

24. OSELTAMIVIR
• Most commonly use anti influenza virus drug
• Broad spectrum – infleunza A, H5N1, H1N1 and influenza B
• Prodrug
• Rapidly and completely hydrolysed to active form, ,oseltamivir
carboxylate during absorption

25. OSELTAMIVIR- MOA
• Inhibit neuraminidase enzyme  prevents release of new virions
• Resistance – mutation of viral neuraminidase enzyme
• Started within 48 hours of onset of symptoms – reduces severity, duration
and complications of illness
• Not effective in children
• Prophylaxis – take within 2 days of exposure

27. OSELTAMIVIR
• ADVERSE EFFECTS
Nausea and abdominal pain – gastric irritation  reduced by taking the
drug with food
Headache, weakness, diarrhea, insomnia
Rashes

28. ZANAMIVIR
• Very low oral bioavailability
• Inhalation
• Powder
• Reserved for oseltamivir resistant cases
• ADVERSE EFFECTS :
• Powder induce bronchospasm in some individuals
• Contraindicated in asthmatics
• headache, nausea, vomiting

29. PERAMIVIR
• Single dose i.v treatment for influenza in adults
• Broad spectrum
• MOA- same as Oseltamivir
• ADVERSE EFFECTS : Nausea, vomiting, diarrhea,

30. ANTI-
HEPATITIS B
DRUGS

31. GENERAL CONSIDERATIONS
• Cannot be eradicated once infected
• Suppression of viral activity
• Improved liver function
• Reduced risk for development of cirrhosis and hepatic carcinoma
• Antiviral drugs – continued until 6 months after seroconversion

32. • Lamivudine
• Entecavir
• Adefovir
• Tenofovir
• Telbivudine

33. ENTACAVIR
• currently the most active and 1st Iine option for treating chronic
hepatitis B
• Guanosine nucleoside analogue
• Inhibits HBV-DNA polymerase after activation by intracellular
phosphorylation
• food decreases bioavailability; it should be taken in empty stomach
• ADVERSE EFFECTS:mild dyspepsia, nausea, diarrhoea, fatigue, and
disturbed sleep.

34. ADEFOVIR
• High affinity for HBV DNA polymerase compared to host cell DNA
polymerase.
• Adefovir itself gets incorporated in the viral DNA resulting in
termination of the DNA chain
• USES:
• chronic hepatitis B
• lamivudine-resistant cases
• HBV + HIV infection

35. TELBIVUDIN
• Newer anti-HBV drug
• Thymidine nucleoside analogue
• Active triphosphate nucleotide competitively inhibits HBV DNA polymerase
• Gets incorporated into HBV-DNA resulting in chain termination
• Better suppression of viremia
• ADVERSE EFFECTS: abdominal pain, diarrhoea, cough, headache. dizziness
and myalgia

36. ANTI-HEPATITIS C
VIRUS
DRUGS

37. • SUSTAINED VIROLOGICAL RESPONSE: undetectable HCV-RNA
in blood for at least 6 months after completion of therapy.

38. RIBAVIRIN
• Purine nucleoside analogue
• Broad-spectrum antiviral activity- HCV, influenza A and B, respiratory
syncytial virus and many other DNA and double stranded RNA viruses
• Inhibit viral RNA synthesis
• USES:
1. Hepatitis C
2. Decompensated cirrhosis
3. RSV bronchiolitis in infants and children(inhaled)

39. • ADVERSE EFFECTS :
1. Haemolytic anaemia
2. Bone marrow depression
3. Teratogenic - female patients should practice contraception during and till 3
months after ribavirin treatment
4. The aerosol can cause irritation of mucosae and bronchospasm.

40. INTERFERON α
• Interferons (IF s) are cytokines produced by host cells
• in response to viral infections, TNF, IL-I and some other inducers
• Affect the viral multiplication at different stages:
• Viral penetration
• Synthesis of viral mRNA
• assembly of viral particles and their release
• inhibition of translation.

41. • IFN α, β, γ
• Recombinant – IFNα2A, IFNα2B
• S.c or i.m injections
• Pegylated forms

42. USES OF INTERFERONS
1. Chronic Hepatitis B
2. Chronic Hepatitis C
3. AIDS related Kaposi’s Sarcoma –zidovudine
4. Condyloma accuminata - intralesional
5. H.simplex, H.zoster and CMV - immunocompromised

43. ADVERSE EFFECTS
• Flu- like symptoms
• Neurotoxicity
• Myelosuppression
• Thyroid dysfunction
• Hypotension , alopecia

44. NEWER ANTI-HCV DRUGS
1. NS5B polymerase inhibitor: Sofosbuvir
2. NS3 protease inhibitor: Simeprevir
3. NS5A inhibitor: Daclatasvir, Ledipasvir, Velpatasvir

45. • Target specific nonstructural (NS) viral proteins
• Used in combination, either among themselves or with Ribavirin ±
Peg lNFa
• Monotherapy: lower efficacy and development of resistance
Replication of HCV inside
hepatocytes

46. SUMMARY
• CLASSIFICATION OF ANTI NONRETROVRAL AGENTS

47. • ANTI HERPES
• ACYCLOVIR - inhibit viral DNA polymerase - used in HSV, VZV – adverse
effects
• VALACYCLOVIR – prodrug- DOC in shingles
• ANTI CMV – GAN, VANGAN
• ANTI INFLUENZA
• AMANTADINE AND RIMANTADINE – M2 channel blocking (only inf.A)
• OSELTAMIVIR – Neuraminidase inhibitor
• ZANAMIVIR- Inhalation

48. • ANTI HEPATITIS B
• ANTI HEPATITIS C
• RIBAVIRIN – inhibit viral RNA synthesis
• INTERFERONE alpha – cytokines – alpha, beta ,gamma – recombinant alpha
2A, 2B - peg – affect viral protein synthesis at different stages- uses, A/E
• NEWER AGENTS- NS proteases – sofosbuvir, simeprevir, daclatasvir,
velpatasvir, ledipasvir

49. THANK YOU………………..!!!!!!!!!!!!!!!!!