1. Know the history of virus!
IVANOVSKY
– 1892
BEIJERINCK-
1898
LANDSTEINER &
POPPER – 1909
RUSKA – 1934
LUC
MONTAGNIER –
1981

2. • They are obligate intracellular parasites.
• Lack cell wall & membrane, metabolism.
• Directs host cells to synthesize new virus
particles.
• Clinical symptoms appears late in course of
diseases at a time where most viruses have
replicated. (contrast to bacteria).
• Responsible for 60% of human diseases.
• Has genome
(DNA/RNA), enzymes, capsid, envelope (lipid
layer).
ULTIMATE MICROBES - VIRUS

3. ABOUT PATHOGENESIS…
2.Release of
viral genes &
enzymes.
3.Replication
of viral
components.
4.Assembly
into complete
viral particles.
5.Release of
viral particles.
1.Attachment
to host cell.

4. VIEW OF VIRUS & DISEASES.
COMMON VIRUSES ITS DISEASES
1. HEPATITIS A,E & B,C. HEPATITIS & CIRRHOSIS.
2. RHINO VIRUS COMMON COLD
3. VARICELLA ZOSTER CHICKEN POX
4. HUMAN IMMUNO DEFICIENCY AIDS
5. INFLUENZA (A) INFLUENZA (BIRD FLU)
6. RUBELLA & PARAMYXO MEASLES & MUMPS
7. HERPES SIMPLEX HERPES SIMPLEX
8. RESPIRATORY SYNCYTIAL RESPIRATORY INFECTION
9. LYSSA & POLIO RABIES & POLIO
10. ANDES & HANTAAN PULMONARY & RENAL SYNDROME
11. HUMAN HERPES 1 & 2 ORAL & GENITAL INFECTIONS
12. SUDAN & RESTON HEMORRHAGIC FEVER
13. RHADINO KAPOSI SARCOMA.

6. PROPERTIES OF ANTI
VIRAL DRUGS:-
Key characteristics of antiviral drugs:
*Able to enter the cells infected with virus.
*Interfere with viral nucleic acid synthesis
and/or regulation.
*Some agents interfere with ability of virus
to bind to cells.
*Some agent stimulate body’s immune system.
Viruses killed by current antiviral therapy:
• cytomegalovirus (CMV)
• herpes simplex virus (HSV)
• human immunodeficiency virus (HIV)
• influenza A (the “flu”)
• respiratory syncytial virus (RSV).

7. RECALL THE CLASSIFICATION!!.
ANTI – HERPES
VIRUS
ANTI –
INFLUENZA
VIRUS
NON SELECTIVE
ANTI VIRALS
*Idoxuridine
*Acyclovir
*Valacyclovir
*Famciclovir
*Ganciclovir
*Foscarnet
*Amantadine
*Rimantadine
*Oseltamivir
*Zanamivir
*Ribavirin
*Lamivudine
*Adefovir dipivoxil
*Interferon.

8. Continued… ANTI-RETRO VIRALS
• STAVUDINE
• ABACAVIR
• LAMIVUDINE
• ZIDOVUDINE
• DIDANOSINE
Nucleoside reverse
transcriptase
inhibitors.
• NEVIRAPINE
• EFAVIRENZ
• DELAVIRDINE
Non nucleoside
reverse transcriptase
inhibitors. • NELFINAVIR
• INDINAVIR
• RITONAVIR
• SAQUINAVIR
• LOPINAVIR
Protease inhibitors.

9. ANTI-HERPES -ACYCLOVIR
 Deoxiguanosine analogue.
 Inhibits DNA synthesis and viral
replication.
 Active only against herpes group
of viruses.
 Acyclovir is taken up by virus
infected cells.
PK:
 Attains good CSF concentration.
 Penetrates cornea well.
 Plasma t ½:- 2-3 hours.
 Excreted unchanged in urine.

10. USES OF ACYCLOVIR
GENITAL HERPES SIMPLEX
TYPE 2
PRIMARY DISEASE
(TOPICAL & ORAL) -
RECURRENT DISEASE(I.V.) -
6 TIMES/DAY X 10 DAYS
400mg/TDS X 10 DAYS
5mg/kg(1 hr.) rep. 8hrly x 10D
MUCOCUTANEOUS HERPES
SIMPLEX- TYPE 1
LOCALISED TO LIPS & GUMS.
ORAL/I.V. ACYCLOVIR
15mg/kg/day x 7 DAYS
HERPES SIMPLEX
ENCEPHALITIS-TYPE 1
EARLY TREATMENT IS
EFFECTIVE.(I.V.)
20mg/kg/8hr. X 10 days
HERPES SIMPLEX KERATITIS –
TYPE 1
EFFECTIVE IN SUPERFICIAL
DENDRITIC CORNEAL ULCER –
EYE OINTMENT
5 TIMES DAILY X 3 DAYS
HERPES ZOSTER HIGHER DOSES REQUIRED.
I.V./ORAL
10 mg/kg/8hr. X 7 DAYS
800 mg (5times daily)
CHICKEN POX REDUCES FEVER,ERUPTION.
HASTENS HEALING &PREVENT
VISCERAL COMPLICATIONS.
15 mg/kg/day x 7 DAYS
400mg / q.i.d x 7 DAYS

11. ADVERSE EFFECTS:
TOPICAL:
 Stinging & burning sensation after each application.
ORAL:
 Headache, nausea, malaise, some CNS effects.
Intravenous:
 Rashes, sweating, emesis, fall in B.P.
 Dose dependent decrease in G.F.R – important toxicity.
 Reversible neurological manifestations- tremors, hallucinations,
lethargy, convulsion, coma.(higher doses).

12. IDOXURIDINE:
• 5iodo 2deoxyuridine.
• Thymidine analogue.
• Effective against DNA viruses.
• Treatment of H.Simplex
keratitis, labial & genital
herpes.
• Not used now.
VALACICLOVIR:
• Ester prodrug of Aciclovir.
• Converted to aciclovir by
esterases
• Effective in herpes zoster
treatment.
• Plasma t ½: 3 hrs.
• Genital herpes simplex:1 gm
bdx10d
• Orolabial herpes: 2gm bd x 1
day.

13. FAMCICLOVIR:-
Ester prodrug of
guanine nucleoside
analogue.
Metabolised to
active penciclovir.
Active DNA
polymerase inhibitor.
Used as an
alternative to acyclovir
in genital herpes &
herpes zoster.
Side effects: nausea,
headache loose
motions, itching,
rashes & mental
confusions.
GANCICLOVIR:-
Analogue of
aciclovir.
Active against all
herpes viruses.
Given
I.V., penetrates CSF.
Excreted in urine
T1/2: 2 to 4 hrs.
Used in CMV
retinitis.
(10mg/kg/day).
Side
effects:rash, fever, vo
mitting, bone marrow
depression, neuro
psychiatric
disturbances.
FOSCARNET:-
Pyrophosphate
derivative.
Inhibits viral DNA
polymerase & reverse
transcriptase.
Active against
H.Simplex, CMV, HIV.
Given I.V., t 1/2:- 4
to 8 hours.
Used in CMV
retinitis, other CMV
infections in AIDS pt
Side effects:
anemia, phlebitis, trem
or, convulsions,damage
s kidney.

14. ANTI-INFLUENZA VIRUS DRUGS –
AMANTADINE:
Inhibits replication(viral uncoating) of influenza A virus.
MOA: blocks viral membrane protein M2 which functions as
channel for H2 ion.
(this channel is required for fusion of viral membrane with cell
membrane)
PK:
Well absorbed orally, penetrates CNS, eliminated in urine.
Plasma t ½ : 16 hrs.
RESISTANCE:
Due to mutation in the M2 matrix protein.
ADVERSE EFFECTS:
Insomnia, dizziness, ataxia, nausea, anorexia, ankle edema.
It is embryo toxic.
Rimantadine t ½ is 30 hrs.(long acting).

15. USES OF AMANTADINE:
 Prophylaxis of influenza A2.
Treatment of influenza A2.(5 days
treatment).
In parkinsonism: Acts on NMDA
type of glutamate receptors, by
promoting pre-synaptic synthesis &
release of DA in brain.
Dose:100mg B.D(lasts 12 hrs.)
SIDE EFFECTS:
Livedo reticularis(due to release
of CA resulting in vasoconstriction)
Ankle edema.

16. OSELTAMIVIR-TAMIFLU
 Sialic acid analogues, inhibits
viral neuraminidase enzyme.
 Has broad spectrum activity
against influenza A & B.
 In liver hydrolysed to active
form oseltemavir carboxylate.
 Active orally . t ½ 6-10 hrs. ,
eliminated in urine.
 Side effects –nausea, headache,
diarrhoea, cough, g.i. irritation,
insomnia.
 Resistance occurs by mutation
of neuraminidase.
ZANAMIVIR-RELENZA
 Sialic acid analogue, inhibits
viral neuraminidase enzyme.
 Against influenza A &
B, avian influenza.
 Administered intra-
nasally(inhaled).
 T ½ 2-5 hrs. , eliminated in
urine.
 Side effects – induce
bronchospasm, headache, di
zziness, nausea, rashes.
 Avoided in asthma & COPD
patients.

17. NON-SELECTIVE ANTI-VIRALS:
RIBAVIRIN:
Synthetic guanosine analogue has broad spectrum
anti-viral activity, including DNA & RNA virus.
Used in treating infant & childrens with RSV
infection.
Also effective in influenza(A & B), measles, herpes
infection & acute hepatitis.{combined with interferon
used in chronic hepatitis C infection}.
PK:
Oral bioavailability is approximately 50%.
Absorption is increased when drug is taken with
fatty meal.
Nebulized ribavirin is used in RSV broncholitis in
children.
Adverse effects:
Dose dependent anemia, elevated
bilirubin, hemolysis.
Aerosol causes irritation of mucosa & bronchospasm.
Contraindicated in pregnancy.(teratogenic effects)

18. DOSE:
200mg qid (children 10mg/kg/day)
RIBAVIRIN
RIBAVIRIN
TRI-
PHOSPJATE
INHIBIT
GUANOSINE
TRI-PHOSPHATE
FORMATION
PREVENTS
VIRAL mRNA
capping
BLOCKS RNA
DEPENDENT
RNA
POLYMERASE

19. ADEFOVIR DIPIVOXIL:
Nucleotide analogue, active
against hepatitis B virus & other
DNA viruses.
Oral availability is
approximately 60%.
Plasma t ½ is 7 hrs. , excreted
in urine.
Dose 10mg/day.
ADVERSE EFFECTS:
Sore throat, headache
, weakness, abdominal pain, flu
syndrome, nephrotoxicity(in
high doses) .
ADEFOVIR
MONO-
PHOSPHATE
ADEFOVIR
DI-
PHOSPHATE
INCORPORATE
INTO VIRAL
DNA
TERMINATION
OF FURTHER
DNA
SYNTHESIS
PREVENTS
VIRAL
REPLICATION
MECHANISM

20. INTERFERON:
Low molecular weight glycoprotein.
Only naturally occuring anti-viral.
Inhibit many RNA & DNA viruses.
Not active orally.
Administered s.c. /i.v./i.m
Plasma t ½ : 24 hrs.

21. CHRONIC
HEPATITIS
B & C (HBV-DNA
DISAPPEARS
FROM PLASMA)
AIDS RELATED
KAPOSI’S
SARCOMA.
RHINO VIRAL
COLD
HERPES
SIMPLEX, HERPES
ZOSTER, CMV
INFECTIONS IN
IMMUNOCOMPRO
MI-SED PATIENTS
CONDYLOMA
ACUMINATA
CAUSED BY
PAPILLOMA
VIRUS
MULTIPLE
MYELOMA &
CHRONIC
MYELOGENOUS
LEUKAEMIA
ADVERSE EFFECTS:
FLU-LIKE SYMPTOMS-
fatigue, malaise, fever, dizziness, anorexia, aches.
Neurotoxicity-
tremor, numbness, sleepiness, neuropathy, rarely
convulsions.
Myelosuppression-
neutropenia, thrombocytopenia.
Thyroid dysfunction(hypo & hyper).
Hypotension, alopecia, transient arrythmia, liver
dysfunction.

23. :-
First anti
retro viral is
ZIDOVUDINE.
DRUGS USED
IN
POSTPONING
COMPLICATION
OF AIDS or AIDS
RELATED
COMPLEX.
1. NRTI’ s
2. NNRTI ‘s
3. PI’ s
4. Entry
Inhibitors.
5. Integrase
Inhibitors.

24. NUCLEOSIDE/ NULEOTIDE REVERSE
TRANSCRIPTASE INHIBITORS- zidovudine..
• Thymidine analogue.
(azidothymidine)
• Zidovudine inhibits viral
reverse transcriptase
enzyme.
• Also gets incorporated into
growing viral DNA &
terminates chain elongation.
Effective only against
retroviruses.
• PK:- oral bioavailability is
65%. Metabolism by hepatic
glucoronidation, plasma
t 1/2: 1 hour.

25. USES:- In HIV infected persons only in combination with other 2 anti retro virals.
o Reduces neurological manifestations and kaposi’s sarcoma.
o good choice of post exposure prophylaxis & in pregnancy transmissions.
ADVERSE EFFECTS:
oAnaemia & neutropaenia are important side effects.
oNausea anorexia, headache, insomnia, myalgia, abdominal pain.
INTERACTIONS:-
oParacetamol increases AZT toxicity
oStavudine & zidovudine exhibit mutual antagonism.

26. DIDANOSINE STAVUDINE LAMIVUDINE
1. Purine nucleoside analogue. Thymidine analogue. Deoxycytidine anlogue
2.DDL----> DDATP---->
Incorporation into viral DNA
Inhibit HIV revers transcriptase
---->terminates proviral DNA.
Acts same as that of AZT. Terminates synthesis of the
pro- viral DNA chain. Inhibits
reverse transcriptase & hep.B
DNA polymerase.
3. Due to its acid lability,
absorption is best at fasting
state.
Well absorbed orally & rapidly
metabolised.
Oral bio availability is high.
4. Plasma T ½ :- 1 to 1.5 hrs.
Crosses blood brain barrier.
Plasma T ½ :- 1.5 hrs.
Penetrates blood brain barrier.
Plasma T ½ :- 6 to 8 hrs.
5. Used only in combination
regimens. 2nd drug to treat
HIV-1 infection.
Used in combination
regimens. Not combined with
AZT,due to mutual antagonism
Used with other HIV drugs.
Frequently used for chronic
hepatitis B infection.
6.Diarrhoea, abdominal pain,
nausea, peripheral
neuropathy, pancreatitis.
Peripheral neuropathy,
lipodystrophy, rarely
pancreatitis.
Headache, fatigue, nausea,
anorexia, abdominal pain.
7. DOSE- 200 mg BD for > 60
kg b wt.taken 2 hr before meal
DOSE- 40 mg Bd for > 60 kg b
wt.
For HIV- 150 mg BD
For chronic hepB- 100mg OD

27. ADVERSE EFFECTS
Ϫ Guanosine analogue.
Ϫ Converted to carbovir
triphosphate & then acts.
Ϫ Oral bioavailability is 80
%. Eliminated by kidney.
Ϫ Plasma t ½ is 1 to 1.5 hrs.
Intracellular t ½ is > 12hrs.
Ϫ Hypersensitivity
reactions like
rashes, fever, flu-like
symptoms are side effects.
Ϫ Exhibit little cross
resistance with other NRTI
Ϫ DOSE: 300mg BD.

28. NON NUCLEOSIDE REVERSE TRANSCRIPTASE
INHIBITORS – NEVIRAPINE & EFAVIRENZ.
• They are nucleoside unrelated compounds. They directly inhibit
HIV-1 Reverse transcriptase.
• Viral resistance occurs by point mutations.
• They induce CYP 3A4, 2D6 enzymes & enhance their own metabolism
• Are indicated in combination regimens for HIV.
NEVIRAPINE EFAVIRENZ
WELL ABSORBED ORALLY
METABOLISED IN LIVER
PENETRATES CNS.
INCOMPLETE ORAL ABSORPTION
METABOLISED IN LIVER
PENETRATES CNS.
PLASMA T ½ IS – 30 Hrs.
DOSE – 200 mg /day.
PLASMA T ½ IS – 48 Hrs.
DOSE – 600 mg OD on empty stomach.
Side effects- rashes, nausea, headache, fever
raise in liver enzymes.
Side effects – rashes, headache, dizziness,
insomnia, neuropsychiatric symptoms.

29. PROTEASE INHIBITORS:
The structural proteins & enzymes production of the virus
involves an aspartic protease enzyme encoded by HIV.
This protease enzyme acts at a late step(maturation of new virus
particles).RNA genome acquires core protein & genome.
The protease inhibitors bind to protease molecule, interfere with
its cleaving function.
Effective in both newly & chronically infected cells.
Salivary protein “secretory leucocyte protease inhibitor” has some
anti-HIV activity.(HIV doesn’t spread through saliva).
ADVERSE EFFECTS:
G.i. intolerance, headache, dizziness, facial & limb tingling,
numbness, rashes.
Lipodystrophy.(abdominal obesity, buffalo hump, wasting of limbs
& face.
Dyslipidaemia.(raised triglycerides & cholesterol)
Indinavir crystalises in urine- risk of urinary calculi.

30. BUFFALO HUMP

31. INDINAVIR 800mg TDS
• To be taken on empty stomach(g.i. intolerance common).
• Excess fluids intake – avoid nephrolithiasis.
NELFINAVIR 750mg TDS
• Taken with meals.
• Side effects include diarrhoea, flatulence.
RITONAVIR 600mg BD
• Potent protease inhibitor.
• Nausea, diarrhoea, fatigue, lipid abnormalities.
• Lopinavir – available in combination with RTV.improve bioavailability
SAQUINAVIR 1200mg TDS
• Hard gel & soft gel capsules available.
•Side effects include photosensitivity.

32. ANTI-RETRO VIRAL THERAPY:
All cases of symptomatic HIV disease –
treatment necessary.
Asymptomatic HIV disease with CD4
count<200/µl – treatment necessary.
Highly active antiretroviral therapy
involves combination of 3 or more drugs as
indicated.(HAART)
ZIDOVUDINE+LAMIVUDINE+NEVIRAPINE
ZIDOVUDINE+LAMIVUDINE+LOPINAVIR/RTV
ZIDOVUDINE+LAMIVUDINE+NEVIRAPINE
LAMIVUDINE+STAVUDINE+EFAVIRENZ
LAMIVUDINE+STAVUDINE+NEVIRAPINE
LAMIVUDINE+ABACAVIT+NEVIRAPINE
LAMIVUDINE+ZIDOVUDINE+INDINAVIR
LAMIVUDINE+STAVUDINE+RITONAVIR
LAMIVUDINE+ABACAVIR+NELFINAVIR
ZIDOVUDINE+LAMIVUDINE+ABACAVIR
BASIC(2 DRUG)
REGIMEN
LOW
RISK
ZIDOVUDINE 300mg+
LAMIVUDINE 150mg
BD X
4WKS
EXPANDED(3 DRUG)
REGIMEN
HIGH
RISK
ZIDOVUDINE
300mg+LAMIVUDINE
150mg
BD
X 4
WKS
+INDINAVIR 800mg TDS

33. Viral Infections IN OBSTETRICS…..
AGENTS CAUSING VIRAL INFECTIONS IN PREGNANCY:-
Rubella, cyto megala virus, herpes simplex, varicella
zoster, influenza, mumps, HIV, hepatitis and entero viruses.
Incidence of malformations :-
 THE FETAL DEFECTS:- Cataracts, deafness, CNS defects & Heart defects.
Most common fetal viral infection :- cytomegala virus(3rd – 9th week, highly teratogenic)
PARVO VIRUS B- 19 :- erythema infectiosum ( 5th disease of childhood). Leads to non
immune fetal hydrops. ( 2nd or 3rd trimester).
ANTIVIRALS UNSAFE DURING PREGNANCY:-
 Acyclovir, ganciclovir, Foscarnet, Amantadine, Vidarabine, Interferon-a.
ANTI RETRO VIRALS UNSAFE DURING PREGNANCY:-
Didanosine, Abacavir, Indinavir, Ritonavir, Efavirenz.
1st TRIMESTER 2nd TRIMESTER 3rd TRIMESTER
50% 20% 7%

34. PHARMACO ECONOMICS
ACYCLOVIR ACIHERPIN 200mg Rs.60
DIDANOSINE VIROGINE Cap. Rs.42
RITONAVIR RITOMAX Tab. Rs.28
FAMCICLOVIR FAMTREX 250mg Rs.40
GANCICLOVIR GANGUARD 250mg Rs.122
INDINAVIR VIREDIN 400mg Rs.25
INTERFERON SHANFERON 1 vial Rs.810
RIBAVIRIN VIRAZIDE Tab. Rs.56
NELFINAVIR NELVIR Tab. Rs.24
NEVIRAPINE NEVIMUNE 200mg Rs.14
DRUG NAME TRADE NAME DOSE COST

35. FUTURE BEGINS
WITH...
US !