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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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