This document discusses antiviral drugs used to treat viral infections. It begins with an introduction to viruses and their parasitism of host cells. The history of antiviral development is covered from the 1960s onwards. Viruses are classified and several antiviral drug classes are described including anti-herpes drugs like acyclovir and famciclovir, anti-retrovirals for HIV like zidovudine and lamivudine, and the non-selective antiviral interferon. Specific viruses and the doses, mechanisms, and adverse effects of antiviral treatments are outlined. The document concludes with a discussion of herpes virus classification and post-exposure prophylaxis for preventing HIV infection.

1. ANTIVIRAL DRUGSANTIVIRAL DRUGSANTIVIRAL DRUGSANTIVIRAL DRUGS
GUIDED BYGUIDED BY--
DR. ANIL GOVINDRAO GHOM
DR. AJIT MISHRA
DR. SHWETA SINGH
DR. SAVITA GHOM
PRESENTED BYPRESENTED BY--
DR. BRATATI DEY (PG-II)
DEPT. OF OMR

2. CONTENTSCONTENTS
⁎ Introduction to virus
⁎ History
⁎ Classification
⁎ Mode of action
⁎ Pharmacokinetics
⁎ Uses
⁎ Doses
⁎ Adverse effect
⁎ Infection caused by virus
⁎ Conclusion
⁎ References

3. INTRODUCTIONINTRODUCTION
⁂Viruses have been defined as submicroscopic entities
which reproduce within the specific living cells.
⁂Virus may contain either ribonucleic acid (RNA) or
deoxyribonucleic acid (DNA)

4. INTRODUCTIONINTRODUCTION
⁂ Viruses are the ultimate expression of parasitism.
⁂ They not only take nutrition from the host cell, but also direct
its machinery to synthesize new virus particle.
⁂ In majority of acute infections viral replication is already at its
peak when symptoms appear.
⁂ To be effective, therefore, therapy has to be started in the
incubation period, i.e. has to be prophylactic.

6. HISTORYHISTORY
 From 1972 to date, >50 new viruses have been found
as etiologic agents of disease.
 However, it took almost 60 years for antiviral
development to reach its current status of
effectiveness.
 In 1967, Kates and McAuslan described the first viral
enzyme, pox virus DNA-dependent RNA polymerase.

7. HISTORYHISTORY
 In 1963, Iododeoxyuridine, described earlier by
Prusoff had been shown to be active against herpes
simplex.
 Secondly, amantadine had been shown not only to
inhibit influenza virus, but also to cause resistance
development.
 Finally, interferon were extensively discussed as
potential antiviral drugs against several viral
infections.

8. HISTORYHISTORY
 The field of antiviral drugs grew rapidly in the herpes
area with the development of acyclovir (Schaffer et
al., 1978) and other inhibitors.
 Development of drugs against hepatitis B virus
(HBV) has been successful and there is a large effort
to discover drugs against hepatitis C virus.

9. CLASSIFICATIONCLASSIFICATION
Anti-herpes virus
Acyclovir, Famcyclovir
gancyclovir
Anti-retrovirus
Nucleoside reverse transcriptase
inhibitor
Zidovudine, Lamivudine, Abacavir
Nonnucleoside reverse
transcriptase inhibitors
Nevirapine
Protease inhibitors
Ritonavir, Indinavir
Anti influenza
virus
Amantadine
Nonselective
antiviral
Interferon α

10. Mechanism Of Action Of Antiviral Drugs

11. ANTIHERPES VIRUSANTIHERPES VIRUS
AcyclovirAcyclovir
 It requires a viral specific enzyme for conversion to the active
metabolite that inhibit DNA synthesis.
Acyclovir
Herpes virus specific thymine kinase
Acyclovir monophosphate
Cellular kinase
Acyclovir Triphosphate
Inhibit herpes virus DNA
polymerase completely.
Gets incorporated in viral
DNA and stops lengthening of
DNA strand. The terminate
DNA inhibit DNA polymerase
irreversibly.

12. Mode of action of Acyclovir

13. • Acyclovir active against H. simplex Type IH. simplex Type I
Herpes simplex type IIHerpes simplex type II
Varicella ZosterVaricella Zoster
EpsteinEpstein--barr Virusbarr Virus
CytomegaloVirus (CMV)CytomegaloVirus (CMV)

14. PharmacokineticsPharmacokinetics
 Only 20% of oral dose of acyclovir is absorbed.
 Little plasma protein bound, and widely distributed
attending CSF conc. 50% of plasma conc.
 It penetrate cornea well.
 Excreted in urine.
 Plasma t1/2 2-3hours.

15. Available asAvailable as
AcivirAcivir DT 200mg, 400mg,DT 200mg, 400mg,
800mg800mg
HerperaxHerperax 200mg200mg
ZoviraxZovirax 200mg200mg
ZoviraxZovirax 5% ointment5% ointment

16. UsesUses
Acyclovir is effective in patient with normal as well as
deficient immune status.
1. Genital Herpes simplex can be treated by topical, oral, or
parenteral acyclovir.
Primary disease Recurrent Disease Severe cases
5% ointment locally 6
times a day for10 days.
(effective only in mild
cases)
Late and more severe
cases should receive oral
therapy (1g/day in 5
divided dose).
Topical therapy is totally
ineffective.
Response to oral
treatment is slow &
incomplete.
Treated parenterally
5mg/kg iv infused 1 hour
repeated 8 hourly for 10
days.
Suppressive oral therapy
with 200mg 4 times a
day(later TDS or even
BD).
It is recommended to stop treatmentIt is recommended to stop treatment after 1 year.after 1 year.

17. UsesUses
•• MucocutaneousMucocutaneous HerpesHerpes simplexsimplex-- It is a type 1 virus
disease remain localize to lips and gums. May be treated with
10 day oral acyclovir (200mg 5 times/ day).
•• ChickenChicken poxpox-- Patient with immunodeficiency and
neonates calls for specific therapy.
Dose- Acyclovir 15mg/kg/day i.v. for 7days.

18. UsesUses
Herpes simplex encephalitis ( type I virus)Herpes simplex encephalitis ( type I virus)
Treatment –
10 mg/kg 8 hourly iv for 10 days. treatment is effective if
started early.
HerpesHerpes ZosterZoster-- Acyclovir should be used only in
immunodeficient individuals or in severe cases.
Dose –
5 mg/kg 8 hourly i.v. for 7 days. Early started oral therapy is
also beneficial.
complicationcomplication-- post herpetic neuralgiapost herpetic neuralgia

19. Adverse EffectAdverse Effect
1. Topical- stinging and burning sensation after each
application.
2. Oral- well tolerated, headache, nausea, malaise and
some CNS effect.
3. Intravenous- rashes, sweating, fall in BP occurs only
in few patient.
4. Decrease in g.f.r is most dependent toxicity.
5. Reversible neurological disturbances.
6. No teratogenic potential.

20. FamciclovirFamciclovir
 It has good oral bioavailability and prolonged
intracellular t1/2 of the active triphosphate metabolite.
 Mode of action- like acyclovir it needs viral
thymidine kinase for generation of active DNA
polymerase inhibitor.

21. UsesUses
 Famciclovir inhibits H. simplex, H zoster but not acyclovir
resistance stains.
 Some activity against hepatitis B virus (HBV).
 It is alternative to acyclovir for herpes zoster.
PharmacokineticsPharmacokinetics
Plasma t1/2- 2 hours

22. DosesDoses
Genital herpes – 250mg TDS for 5 days.
Recurrent cases – 250mg BD up to 1year.
Herpes zoster – 500mg TDS for 7 days.

23. Adverse EffectAdverse Effect
Headache
Nausea
Loose
motion
Itching &
rashes
Mental
confusion

24. Anti Retroviral Drugs
When to Begin Anti Retroviral therapy?
The CD4 cell
count below 350
cell per microliter,
and those with
rapidly falling
counts
The plasma viral
Load 100000
viral genome
copies per ml
In pregnancy to
reduce risk of
vertical
transformation

25. •• HAARTHAART- Highly Active Anti RetroviralHighly Active Anti Retroviral
TherapyTherapy
(A term coined in the late 1990s to describe the effectiveness
of combination drug therapies used to treat HIV.)
 It causes suppression of HIVHIV replication and prolonging
as well as improving the quality of life of the patient.
The drugs used are zidovudine, didanosine, zalcitabine

26. HAARTHAART
Zidovudine – dose
200mg TDS or
300mg BD
Didanosine – dose
200 mg BD
Zalcitabine – it used
in combination with
Zidovudine, (.75mg
TDS)

27. ANTIRETROVIRALAGENTANTIRETROVIRALAGENT
ZidovudineZidovudine
 It is thymidine analogue (Azidothymine).
ModeMode ofof actionaction – After phosphorylation in the host
cell Zidovudine triphosphate selectively inhibit viral
reverse transcriptase in preference to cellular DNA
polymerase.

28. Zidovudine
ZDV-monophosphate
ZDV-diphosphate
ZDV-triphosphate
Inhibit viral replication
Binds reverse transcriptase
Incorporated into viral DNA
Premature chain termination

29. PharmacokineticsPharmacokinetics
 Oral absorption is rapid.
 Bioavailability- 65%
 It is quickly cleared by hepatic glucoronidase.
 T1/2- 1-4 hour
 15-20% of unchanged drug excreted in urine.
 It crosses placenta and found in milk.

30. DosesDoses
Adult- 500mg/day in 2 – 4 divided dose.
Children-180mg/day in 6 – 8 hourly.

31. Adverse effectAdverse effect
Anemia
Granulocytopenia
MyopathyPancreatitis
Lactic acidosis

32. Drug InteractionsDrug Interactions
 Paracetamol increases azidothimidine toxicity, by competing
for glucoronidation.
 Azoles antifungal also inhibit azidothimidine metabolism.
UsesUses
1) Used in HIV infected patients.
2) However, beneficial effect are limited from a few months to a
couple of year after which progressively nonresponsiveness
develops.

33. LamivudineLamivudine
MechanismMechanism ofof actionaction
 It inhibit HIV reverse transcriptase as well as
hepatitis B virus (HBV) DNA polymerase.
 Its incorporation in DNA results in chain termination.
 Most human DNA polymerase are not effected & low
systemic toxicity.

34. UsesUses
• Apart from HIV lamivudine is also effective against
hepatitis B virus as it inhibit DNA polymerase in the
HBV.
• It requires long term treatment.
• It used in combination with other anti-HIV drugs, and
effective as azidothimidine.

35. Adverse effectAdverse effect
 Lamivudine is well absorbed
and well tolerated with no
serious adverse effect in
therapeutic dose.
 It can cause insomnia, fever,
headache, diarrhea.
 Pancreatitis and neuropathy
are rare .

36. NonNon NeucleosideNeucleoside ReversetranscriptaseReversetranscriptase
Inhibitor (Inhibitor (NevirapineNevirapine))
 The NNRT inhibitor bind to reverse transcriptase (are not
converted to triphosphate derivatives) & bring about the
change in the enzyme thereby inactivating the enzyme.
ModeMode ofof actionaction-- Directly inhibit HIV reverse
transcriptase without the need for intracellular phosphorylation
UsesUses- effective only against HIV-1, but do not inhibit HIV-2

37. Adverse effectAdverse effect
It can cause GI disturbances.
allergic reactions (stevensstevens––johnsonjohnson syndromesyndrome)
PharmacokineticsPharmacokinetics
Well absorbed and extensively bound to
plasma protein.
these drugs are metabolized by cytochrome
P450 enzyme.

38. Newer Anti Retroviral DrugsNewer Anti Retroviral Drugs
Fusion inhibitor
It block the entity of HIV
into CD4 cell.
active only against HIV-1
Ex–Enfuvirtide
(Fuzeon)
Integrase inhibitor
It disable the integrase
protein that HIV use to
insert its genetic material
into CD4 cells
Ex – Raltgravir

39. Anti Influenza Virus DrugsAnti Influenza Virus Drugs
AmantadinAmantadin
 Chemically it is tricyclicic amine, unrelated to neucleic acid
precursor, but inhibit replication of influenza A virus.
 A protein designated ‘M2’which act as an ion channel has
been identified as one of its target of action.
 Resistance to amantadine developed by mutation causing
amino acid substitution in the M2 protein.

40. Adverse EffectAdverse Effect
Generally well tolerated
– Nausea
– Anorexia
– Insomnia
– Dizziness
– Nightmare
– Lack of mental concentration
– Postural hypertension have been reported
– Amantadine is contraindicated in epileptic
patients, as it causes convulsion

41. UsesUses
1. Prophylaxis of influenza A2, especially in
high risk patient
2. Treatment of influenza (A2): A modest
therapeutic effect (reduction in fever)
3. Parkinsonism

42. Nonselective antiviral drugs/antiNonselective antiviral drugs/anti--
hepatitis virushepatitis virus

43. WHAT ARE INTERFERON?WHAT ARE INTERFERON?
Interferon are chemical signaling molecule
belong to cytokine.

44. UsesUses
1. Chronic hepatitis B and C
2. Aids related Kaposi’s Sarcoma (But not to
treat HIV as such)
3. H. simplex, H. zoster and CMV infection in
immunocompromised patients as adjuvant to
acyclovir/Gancyclovir

45. Adverse effectAdverse effect
It is not effective orally. s.c. or i.m. injected interferon is
limited by substantial adverse effects.
1.1. Flu like symptomsFlu like symptoms-- Fatigue, pain, malaise, fever,
dizziness, anorexia, taste and visual disturbances
develops few hours after injection
2.2. NeurotoxicityNeurotoxicity – Numbness, neuropathy, tremor.
3.3. MyelosuppressionMyelosuppression (dose limiting).

46. Classification of
Herpes Virus
Herpes simplex virus 1
Herpes simplex virus 2
Varicella zoster virus
Cytomegalo virus
Epstein-Barr virus
Human herpes virus – 6
Human herpes virus – 7
Human herpes virus – 8
Simian herpes virus B

47. Post-exposure prophylaxis to
prevent HIV infection
 The recommended PEP regimens are
BASIC REGIMENBASIC REGIMEN
Zidovudine 300mg +Lamivudine 150mg
Twice daily for four weeks
EXPANDED REGIMENEXPANDED REGIMENEXPANDED REGIMENEXPANDED REGIMEN
Zidovidune 300mg+ Lamivudine 150 mg twice daily
Zidovudine 300mg+ Lamivudine 150mh +Indinavir 800mg
Thrice daily all for 4 weeks
PEPPEPPEPPEP

48. CONCLUSIONCONCLUSION
 The application of antiviral drugs in dentistry is restricted to
treatment of oropharyngeal herpes simplex and herpes labialis
that occur particularly in immunocompromised patients.
 Dentist run in the risk of accidental exposure to HIV infection,
and should be well informed about its prophylaxis.

49. HerpesHerpes LabialisLabialis 11°° HerpeticHerpetic
GingivoGingivo StomatitisStomatitis
Herpes ZosterHerpes Zoster MumpsMumps
HSV – 1 HSV – 1 Varicella zoster Paramyxovirus
TopicalTopical – 5%
acyclovir, 3%
Penciclovir and 10%
Docosanol 4-6
times/day at the first
prodrome of lesion
Acyclovir 200mg/kg
5times daily for 5 days
Treatment should be
start within 72 hours
of symptoms onset for
maximum
effectiveness.
Treatment of mumps
is symptomatic and
may involve the use of
analgesic and
antipyretics.
SystemicSystemic – Acyclovir
400mg BD for 5 – 10
days
Acyclovir /
Valaciclovir /
Famciclovir
Prophylactic regimen
– Acyclovir
800mg/day
Valacyclovir 500mg or
famcyclovir 250mg
BD/Day for 5days
Systemic doseSystemic dose –
acyclovir 800mg 5
times a day,
Famcyclovir 500mg
TDS and Valacyclovir
1gm TDS
VaccinationVaccination –
prevention with live
attenuated vaccine.
(should be given in 12
– 15 months of life)

50. Viral Hepatitis Erythema
multiforme
Herpangina Infectious
Mononucleosis
Hepatitis A HSV Coxsackievirus Epstein – Barr virus
Prevention measures
to reduce viral
hepatitis spread
include aggressive
vaccination protocol
Supportive care,
Electrolyte, a liquid
diet and nutritional
support
Supportive care,
including hydration
and topical anesthesia
Symptomatic – topical
anesthetic gel, and
hydrogen peroxide
rinse
Supportive- no
antiviral therapy
during an acute
infection
Approved drug
therapy include- IFN-
α, IFN-α2a, Adefovir,
Dipivoxil,
Lamivudine,
entecavir, Telbivudine.
Topical mouthwash or
gel- anesthetic agent
Systemic steroid- for
minor E M 20 – 40
mg/day prednisolone
for 4 – 6 day
Major E M usually
requires 40 – 80
mg/day with gradual
tapering over 2 -3
weeks
Acyclovir 400mg
bd/day indicated in
some recurrent case
Specific antiviral
treatment is not
available
Specific therapy –
Antiviral drug
Gancyclovir and α
interferon inhibit the
replication of virus
Corticosteroid –
indicated only in the
presence of
complication like
airway obstruction,
Hemolytic anemia.

51. REFERENCESREFERENCES
Essentials of medical pharmacology, K D
Tripathi, 5th edition, 725-734
P. N. bennett M. J. Brown, clinical
pharmacology, 10th edition, 208-225
Post-exposure prophylaxis to prevent HIV
infection 1 December 2014
Anil Ghom, textbook of oral medicinr and
radiology, third edition 713-739

52. Thank YouThank You