The document summarizes various antiviral agents used to treat different viral infections. It describes the targets of antiviral drugs and classifies them based on their mechanism of action. It provides details about specific antiviral drugs used to treat herpes viruses, hepatitis viruses, and influenza. These include acyclovir and valacyclovir for herpes, lamivudine and tenofovir for hepatitis B, and oseltamivir and zanamivir as neuraminidase inhibitors for influenza. The document compares the mechanisms, pharmacokinetics, uses and side effects of different antiviral drugs.

1. Antiviral Agents

4. Change in term ending Exam –
Practical
Parmac Patho Micro FMT Marks
30- 7-2020 Thu 10-12 pm D A B C 40
2-4 pm H E F G 40
31 July
2020
Fri 10-12 pm Community Medicine

5. Objectives
• Identify the targets of anti-viral agents
• Classify anti-viral agents
• Describe the pharmacology of acyclovir
Compare the different anti-herpes agents

7. Virus specific steps:
Possible Targets Target Examples
• 1 Enfuvirtide, Maraviroc (HIV)
• 2 Interferon-alpha (HBV, HCV)
• 3 Amantadine, Rimantadine (Influenza)
• 4 NRTI, NNRTI (HIV); Nucleoside/ Nucleotide
analogues (HSV, HBV)
• 5 INSTIs (HIV)
• 6 Protease Inhibitors (HIV)
• 7 Neuraminidase inhibitor (Influenza)

8. 1. Anti-Herpes drugs
- Idoxuridine, Trifluridine
- Acyclovir, Valacyclovir
- Ganciclovir, Valganciclovir
- Famciclovir
- Cidofovir
- Foscarnet
2. Anti-influenza drugs
• - Amantadine, Rimantadine
• - Oseltamivir
• - Zanamivir
3. Anti-Hepatitis
drugs (Non-selective
antiviral drugs
 Primarily for Hepatitis B
Lamivudine
Adefovir dipivoxil
Tenofovir
Primarily for Hepatitis C
Ribavirin
Interferon alpha

9.  Idoxuridine, Trifluridine
 Acyclovir, Valacyclovir
 Ganciclovir, Valganciclovir
 Famciclovir
 Cidofovir
 Foscarnet
Anti-Herpes drugs

10. Idoxuridine, Trifluridine
• Thymidine analogue
• - Competes with thymidine
• - Gets incorporated into DNA
• - Faulty DNA formed, that breaks easily
• Trifluridine: fluorinated nucleoside
• Problems:
• Low virus selectivity
• Rapid development of viral resistance
• Use:
• Herpes simplex keratitis (superficial) - Trifluridine: higher
efficacy
Side effects:
Ocular irritation
Lid oedema

11. Acyclovir-Deoxyguanosine
analogue
Selective toxicity:
- Preferentially taken up by virus infected cells
- Herpes virus specific thymidine kinase required for its
action
- Acts by inhibiting viral DNA polymerase reversibly
and irreversibly
- Because it requires the viral kinase for initial
phosphorylation, acyclovir is selectively activated—
and the active metabolite accumulates only in
infected cells.

12. Pharmacokinetics
• • Bioavailability – Acyclovir low 15-20% Decreases with
increasing dose
• Valacyclovir: 55-70%
• Low percutaneous absorption
• • Widely distributed
• • T ½ - 2.5 – 3hrs
• • Clearance – Eliminated unmetabolized via glomerular
filtration & tubular secretion
• • 20 hrs in patient with anuria
• (Anuria - Anuria means nonpassage of urine, in practice is
defined
• as passage of less than 50 milliliters of urine in a day.)
• • Route – topical, oral and IV

13. Therapeutic uses
Oral –
Genital herpes (recurrent, first episode (Primary)),
Mucocutaneous - Herpes labialis, Cutaneous zoster, (
decreases the total number of lesions, duration of symptoms and viral
shedding) also reduces the post-herpetic neuralgia.
Keratitis
Porphylactically –
Organ transplant patients to prevent HSV reactivation.
IV –
HSV- Encephalitis (doc), Neonatal HSV, Serious HSV
VZV - Herpes zoster or Chickenpox
Topical – less effective than oral for primary HSV infection,
not benefit for recurrent genital HSV

15. Adverse effects
• IVI – reversible Renal toxicity (crystalline nephropathy)
Concurrent use of nephrotoxic agents – enhance potential
of nephrotoxicity. - Dose dependent decrease in GFR
• Can have Neurologic effects (need adequate hydration
and
avoid rapid infusion) - Reversible (lethargy,
disorientation,
hallucinations, convulsions, coma) at higher doses
• Topical: Stinging and burning sensation after each
application
• Oral: Well tolerated, nausea, diarrhoea, Headache,
malaise may occur
• Intravenous: Rashes, sweating, fall in BP

16. Acyclovir

17. Ganciclovir
• Analogue of acyclovir
• Active against: H. simplex, H. zoster, EBV, Cytomegalovirus (CMV, most
sensitive)
• Higher concentration
• Eliminated slowly ( >24 hours)
• Mechanism of action: Similar to acyclovir
• Pharmacokinetics: Oral bioavailability <10%
• Valganciclovir higher oral bioavailability
• Excreted in urine
• Plasma half life 2-4 hrs
• Side effects: Bone marrow toxicity
• Precursor cells quite sensitive to ganciclovir
• Rash, fever, vomiting, neuropsychiatric disturbances
• Uses: Prophylaxis and treatment of severe CMV infections in
immunocompromised
• CMV retinitis in AIDS patients

18. Anti-Hepatitis Agents
(Non-selective antiviral drugs
Primarily for Hepatitis B
Lamivudine
Adefovir dipivoxil
Tenofovir
Primarily for Hepatitis C
Ribavirin
Interferon alpha

19. Interferons
• Interferon Alfa
• Endogenous proteins
• Induce host cell enzymes that inhibit viral RNA translation
and cause degradation of viral mRNA and tRNA
• Bind to membrane receptors on cell surface
• May also inhibit viral penetration, uncoating, mRNA
synthesis, and translation, and virion assembly and release
Pegylated interferon Alfa
- A linear or branched polyethylene gylcol (PEG) moiety is
attached to covalently to interferon
- Increased half-life and steady drug concentrations
- Less frequent dosing
- For treatment of chronic hepatitis C in combination with
ribavirin

20. Ribavirin
• A guanosine analogue
• phosphorylated intracellularly by host enzymes
• inhibits capping of viral messenger RNA inhibits the viral RNA-
dependent RNA polymerase – thus inhibits replication of DNA and RNA
viruses
• Antiviral spectrum : DNA and RNA viruses are susceptible, including
influenza, parainfluenza viruses, RSV, Lassa virus
• PK- Distribution in all body tissues, except CNS
• Administration : Oral, IV, Inhalational in RSV.
• ADR- Anemia and jaundice
• Not advised in pregnancy
• Drug of choice for:
RSV bronchiolitis and pneumonia in hospitalized children (given by aerosol)
Lassa fever
Ribavirin is an alternative drug for: Influenza, parainfluenza,
measles virus infection in immunocompromised patients

22. Anti-nfluenza Agents
 Amantadine
 Rimantadine
 Oseltamivir
 Zanamivir

23. Amantadine and Rimantadine
• Cyclic amines
• Inhibit the uncoating of viral RNA (inhibit viral protein
M2)therefore inhibiting replication
• Resistance due to mutations in the RNA sequence
coding for the structural M2 protein
• Used in the prevention and treatment of Influenza A
• Amantidine has antiparkinsonian effect
• Oral bioavailability ~ 50-90%
• Amantadine cross extensively BBB whereas Rimantadine does not cross extensively
• Administration: Oral

24. Zanamivir and Oseltamivir
Neuraminidase Inhibitors
• Influenza virus contains an enzyme neuraminidase which is essential for
the replication of the virus.
• Neuraminidase inhibitors prevent the release of new virions and their
spread from cell to cell.
• Drugs Inhibit the enzyme neuraminidase
• Inhibit the replication of influenza A and influenza B
• Can be used for both prophylaxis and treatment ( to treat acute &
uncomplicated influenza infections)
• Oseltamivir is orally administered.• Zanamavir is given intranasal.
• Risk of bronchospasm with zanamavir if administered intranasally
• Do not interfere with immune response to influenza A vaccine.

25. Preliminary

26. Preliminary

27. IV Term
Ending

29. Change in term ending Exam –
Practical
Parmac Patho Micro FMT Marks
30- 7-2020 Thu 10-12 pm D A B C 40
2-4 pm H E F G 40
1 Aug 2020 Fri 10-12 pm Community Medicine

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