Anti viral agents

1. ANTI-VIRAL AGENTS
G Vijay Narasimha Kumar
Asst. Professor,
Dept. of. Pharmacology
Sri Padmavathi School of Pharmacy

2. Definition:
• Antiviral drugs are a class of medication used
specifically for treating or controlling viral
infections. Like antibiotics for bacteria, specific
antivirals are used for specific viruses. Unlike
most antibiotics, antivirals do not destroy their
target pathogen; instead they inhibit their
development.

3. Classification of Antiviral Drugs
• DNA polymerase inhibitors
Purine Analogues:
Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir,
Famciclovir, Penciclovir, Cidofovir, Adefovir, Entecavir,
Vidarabine.
Pyrimidine analogues:
Idoxuridine, Trifluridine, Telbivudine
Non-nucleosides:
Foscarnet

4. Contd….
• m-RNA synthesis inhibitors
Ribavirin, Fomivirsen
• Adamantase inhibitors:
Amantidine, Rimantidine, Docosanol
• Neuraminidase inhibitors:
Oseltamivir, Zanamivir, Peramivir.
• Immunomodulators:
Interferons, Palivizumab, Imiquimod.

5. DRUG NAME ANALOGUE
ACYCLOVIR Guanosine analogue
VALACYCLOVIR A L- valine ester of Acyclovir
GANCICLOVIR A hydroxymethylated analogue of
Acyclovir.
VALGANCICLOVIR A valine ester of Ganciclovir
PENCICLOVIR Guanine nucleoside analogue
FAMCICLOVIR Diacetyl ester of penciclovir
VIDARABINE Adenine analogue
CIDOFOVIR Cytidine analogue
ADEFOVIR Adenosine monohoshate analogue
ENTECAVIR guanosine nucleoside analogue
IDOXURIDINE iodinated derivative of deoxyuridine
TRIFLURIDINE trifluoromethyl derivative of idoxuridine
TELBIVUDINE thymidine analogue
FOSCARNET an inorganic pyrophosphate derivative

6. DNA polymerase inhibitors
Mechanism of action:
The drug to exhibit it’s action, it should get convert to
its active metabolite via three phosphorylation steps.
 In the presence of enzyme known as viral thymidine
kinase, drug will convert into it’s monophosphate.
 The monophosphate will further convert into
diphosphate by an enzyme called Guanidylate kinase.
 Finally, the diphosphate converts into triphosphate,
which is an active metabolite.

7. The active metabolite inibits viral DNA
polymerase
Thus, preventing the replication of DNA by
terminating the elongation of the viral DNA
chain.

8. PHARMACOKINETICS:
Absorption:
Only about 20% of an oral dose of Acyclovir
is absorbed.

9. DISTRIBUTION:
 It is little plasma protein bound and is widely
distributed attaining CSF concentration that is
50% of plasma concentration.
 It penetrates cornea well.

10. ELIMINATION:
 It is primarily excreted unchanged in urine,
both by glomerular filtration and tubular
secretion.
 It’s plasma half life is 2-3 hours in healthy
persons and 20 hrs in patients with renal failure.

11. THERAPEUTIC USES
 Herpes simplex virus -1 (which causes herpes
labialis,herpes esophagitis,herpes
keratitis,herpes encephalitis and ocular
herpes)
 Herpes simplex virus -2 (genital herpes)
 Varicella Zoster Virus (chicken pox and
shingles)
 Epstein Barr Virus
 Cytomegalovirus

12. ADVERSE EFFECTS
 Topical:
stinging and burning sensation after each
application.
 Oral:
Headache, nausea, malaise and some CNS
effects are reported.
 Intravenous:
Rashes, sweating, emesis, hypotension.

13. DRUG INTERACTIONS
 Cyclosporine and other nephrotoxic agents
may increase the risk of renal toxicity.
 Probencid inhibits the renal excretion of
Acyclovir.

14. FOSCARNET:
 It is an inorganic pyrophosphate derivative.
 It does not require phosphorylation for inhibitting
viral DNA polymerase, but inhibits herpetic DNA
polymerase activity by blocking the pyrophosphate
binding site on the enzyme.
 The cleavage of the pyrophosphate moiety from the
newly attached nucleotide is thus prevented which in
turn inhibits viral chain elongation.
 It is 100 times more selective for Herpes DNA
polymerase than for mammalian DNA polymerase.

15. PHARMACOKINETICS
 It has very poor bio-availability, hence
administered intravenously.
 It accumulates in aqueous humour and
bones.
 It is eliminated unchanged in urine.

16. THERAPEUTIC USES
 Used in the treatment of Acyclovir resistant
mucocutaneous HSV infections in AIDS patients
and CMV retinitis in immunocomprimised
patients.

17. ADVERSE EFFECTS
 Elevated serum creatinine levels.
 Electrolyte disturbances include:
– Hypocalcemia
– Hypomagnesemia
– Hypokalemia
 Malaise, nausea, headache, vomiting,
anaemia, leukopenia.

18. GANCICLOVIR 60% 1-2%
t1/2 – 4.08 hrs
Liver and also
through kidney
by glomerular
filtration and
active tubular
secretion
Through urine
VALCICLOVIR 54.5% + 9.1% 13-18%
t1/2– 2.5 – 3.3
hrs
Intestinal and
hepatic
metabolism
Through urine
FAMCICLOVIR 77% 20-25%
t1/2 – 10 hrs
hepatic urine
CEDOFOVIR 100% 6%
t1/2 – 2.4-3.2
hrs
_ _
ADEFOVIR 59% < 4%
t1/2 – 7.48 hrs
kidney through
glomerular
filtration and
active tubular
secretion
urine
PENCICLOVIR topical < 20%
T1/2 – 2 hrs liver
_
ENTECAVIR 100% 13%
t1/2 –15hrs liver
_

19. DRUG NAME ABSORPTION DISTRIBUTION METABOLISM EXCRETIO
N
VIDARABINE TOPICAL 24-38 % - -
IDOXURIDINE OCCULAR - inactivated by
enzymes
deaminases
-
TRIFLURIDINE OPTHALMIC t1/2 – 12-18 mins - -
TELBIVUDINE ORAL 3.3%
t1/2 – 15 hrs
kidney urine
AMANTIDINE ORAL 67% kidney urine
RIMANTIDINE ORAL 40% liver urine
OSELTAMIVIR 75% 42%
t1/2 – 1 -3 hrs
liver urine
ZANAMIVIR 2% <10%
T1/2 – 2.5-5.1 hrs
not
metabolised
urine
PALIVIZUMAB - t1/2 - 18-20 days Removed by
opsonisation
-
IMIQUIMOD well absorbed
through skin
as a cream
T1/2 -20hrs(topical
dose)
T1/2-2hrs(S.C dose) - -

23. NEURAMINIDASE INHIBITORS
• MECHANISAM OF ACTION:
Viruses enters into host cell.
Multiplication of viral cells.
Viruses releases neuraminidase enzyme.
Which causes lysis of cell membrane and
decrease the spread of infection to new cells.

24. OSELTAMIVIR:
• It is a prodrug which converts to active form in
the liver.
• PHARMACOKINETICS:
• ABSORPTION:
• It can be administered orally.

25. • METABOLISM:
OSELTAMIVIR
hepatic esterases
Oseltamivir carboxylate

26. EXCRETION:
• It has bioavailability 80% .
• Its plasma half life is 8 hrs.
• Excretion via urine.

27. ZANAMIVIR:
ABSORTION:
It is taken as aerosol.
METABOLISM:
Metabolised by liver.
EXCRETION:
Its plasma half life is 3.5 hrs.
Excretion through urine.

28. USES OF OSELTAMIVIR & ZANAMIVIR:
• Used in the treatment of acute uncomplicated
influenza A or influenza B infections.
DOSE:
• OSELTAMIVIR:75 mg BD orally for treatment.
• 75 mg OD orally for prevention
• ZANAMIVIR:10 mg BD inhalation for treatment.
• 10 mg per day for prevention.

29. OSELTAMIVIR
ADVERSE EFFECTS:
• Nausea,
• Vomiting,
• Vertigo,
• Seizures,
• Aggravation of diabetes

30. ZANAMIVIR
ADVERSE EFFECTS:
• Bronchospasm,
• Bronchosecretions,
• Nasal discomfort

31. ADAMANTASE DERIVATIVES
AMANTADNE AND RIMANTIDINE:
• Both drugs are effective against influenza A
virus and have negligible activity against
influenza B virus and mumps virus.

32. MECHANISM OF ACTION:
Both the drugs inhibit uncoating of influenza A viral RNA with
in the infected host cells.
which inhibit the viral M2 protein present in the viral
membrane.
Which prevents H+ mediated dissociation of ribonuceloprotein
core segment.
Prevents the viral replication.

33. PHARMACOKINETICS:
ABSORPTION:
Both are absorbed rapidly from GIT.
Plasma half life in
AMANTIDINE:17 hrs in young adults
30 hrs in the elderly.
RIMANTIDINE:25 hrs in young adults
33 hrs in elderly.

34. METABOLISM:
• Metabolism takes place in liver.
EXCRETION:
• AMANTIDINE mostly excreted unchanged in
the urine.
• RIMANTIDINE is partly metabolised in liver.its
conjugated metabolites and some free drug is
excreted in urine.

35. USES:
• Both the drugs are administered orally for prevention
and treatment of influenza A viral infections.
• They reduce the duration of fever and the complaints
by 1 to 2 days.
• Amantadine prophylaxis reduce infection rates by 50%
& illness rate by 60%.
• Amantadine used in the therapy of parkinsons disease.

36. ADVERSE EFFECTS:
• Nausea,
• Anorexia,
• Insomnia,
• Dizziness,
• Nightmares,
• Lack of mental concentration,
• Rarely hallucinatons,
• Ankle edema

37. IMMUNOMODULATORS
• Immunomodulators are the drugs which activate
the immune mechanism to target the virus.
INTERFERONS:
MECHANISM OF ACTON:
• Interferons are mainly produced during the viral
infection.
• Which interferes with the viral infection

38. • virus/bacteria/viralproteins/
exotoxins/endotoxins,viralRNA/DNA
enters into human body.
• Activates the toll like receptors
• Which releases inflammatory mediators
like NF-Kappa betta,IFR-12
• Which releases interferons

39. Interferon's acts against pathogens
Inhibition of activate P53 activates the
translation of gene immune cells
viral mRNA
Viral proteins releases P 53 which MHC-I
cause apoptosis MHC-II

40. PHARMACOKINETICS:
ABSORBTION:
It should be given subcutaneously, intramuscularly, intravenously.
DISTRIBUTION:
Do not cross the blood brain barrier.
METABOLISM:
Metabolised by liver
EXCRETION:
Excretion through bile/kidney.

41. USES:
INTERFERON-ALFA -2a:
• Chronic hepatitis-B infection,
• AIDS related kaposi’s sarcoma,
• Chronic hepatitis-C,
• Hairy cell leukaemia and chronic myelogenous
leukaemia,
DOSE:
• 3mU,thre times weekly; S.C, OR I.M

42. INTERFERON-ALFA-2b:
Hepatitis-C ,
Malignant melanoma;
Condylomata acuminata,
Chronic hepatitis-B,
Chronic hepatitis-C ,
Non-hodgkins lymphoma
DOSE:
3mU,three times weekly; S.C, OR I.M

43. PEGYLATED INTERFERON:
• Used to treat chronic hepatitis-B and C.
• Pegylated interferon alfa-2a and 2b are given through SC.
ADVERSE EFFECTS:
• Fever,
• Weakness,
• Nausea,
• Vomiting,
• Headache,
• Myalgia,
• Flu like symptoms,

44. • Bone marrow depression,
• Rashes,
• Alopecia,
• Cardiovascular, hepatic and thyroid
dysfunction,
• Insomnia,