1. ANTIVIRAL DRUGS
(NON RETROVIRAL)

2. DNA polymerase inhibitors
 Purine analogues
 Acyclovir , Valcyclovir , Gancyclovir, Valganciclovir,
Famciclovir , Pencyclovir , Cidofovir, Adefovir,
Entacavir , Vidarabine
 Pyramidine analogues
 Idoxuridine , Trifluridine Telbivudine
 Non-nucleosides
 Foscarnet

3. M-RNA synthesis inhibitors
Ribavirin, Fomiversen
Inhibitors of viral penetration and uncoating
Amantidine and Rimantidine, Docosanol
Neuraminidase inhibitors
Zanamavir , Oseltamavir, Peramavir
Immunomodulators : Interferons, Palivizumab ,
Imiquimod

6. Life cycle of viruses and
steps blocked by medicines

7. Guanine nucleoside analogue
Effective against HSV-1 and HSV-2,
VZV, CMV, and EBV.
The active metabolite of acyclovir
inhibits herpes virus DNA replication
in two ways.
Acyclovir triphosphate - competitive
Inhibitor deoxyguanosine triphosphate
(dGTP) into the viral DNA.
 Acts as a chain terminator -because it lacks the 3 -hydroxy group
necessary for further chain elongation.

8.  Pharmacokinetics :Acyclovir absorption is variable
and incomplete following oral administration.
 20% bound to plasma protein
 Amniotic fluid, placenta, and breast milk.
 Acyclovir is both filtered at the glomeruli and
actively secreted.
 The plasma half-life of acyclovir is 3 to 4 hours in
patients with normal kidney function and up to 20
hours in patients with renal impairment

9.  Oral acyclovir - HSV-1 and HSV-2 infections, such as
genital herpes, herpes encephalitis, herpes keratitis,
herpes labialis, and neonatal herpes.
 long-term suppression of recurrent HSV.
 Intravenous acyclovir -herpes simplex encephalitis,
neonatal HSV infection, and mucocutaneous HSV
infection in immunocompromised individuals.
 Acyclovir ointment is used in the treatment of
initial genital herpes but is not effective for recurrent
disease.

10.  Ophthalmic acyclovir formulations are effective in
the treatment of herpes keratoconjunctivitis.
 Acyclovir reduces the extent and duration of VZV
lesions
 chickenpox treatment and prophylaxis in high- risk
individuals.
 Herpes zoster (shingles),
 Does not affect post herpetic neuralgia.

11.  Headache, nausea, and diarrhea.
 Skin rash, fatigue, fever, hair loss, and
depression.
 Reversible renal dysfunction (azotemia) and
neurotoxicity (tremor, seizure, delirium) are
dose- limiting toxicities of intravenous acyclovir.
 Adequate hydration and slow drug infusion can
minimize the risk of renal toxicity
 Thrombotic thrombocytopenic purpura–
hemolytic uremic syndrome (TTP–HUS)
 Safe in Pregnancy

12.  Drug interaction –Probenacid , cyclosporine
 Resistance –Mutations resulting in decrease
in thymidine kinase activity.
 Altered substrate specificity
 Decreased affinity of viral DNA polymerase

13.  - acyclic phosphonate cytosine analogue
 - Herpes viruses including CMV, HSV-1, HSV-2, EBV,
and VZV. adenoviruses, papillomaviruses,
polyomaviruses, and poxviruses.
 Activation- requires metabolism to a diphosphate.
 -competes with deoxycytidine triphosphate (dCTP)
for access to viral DNA polymerase and also acts
as an alternative substrate.
 - slows replication
 - halts DNA polymerase activity.

14.  Pharmacokinetics :
 low oral bioavailability. T1/2- 2.6 hours,
 the diphosphate form -half life of 17 to 65 hours.
 A phosphocholine metabolite half-life 87 hours .
 is excreted unchanged by the kidney. Glomerular
filtration and probenecid-sensitive tubular
secretion are responsible for cidofovir elimination
 Weekly dosage

15.  -Treatment and prophylaxis of
CMV retinitis in AIDS patients.
 -Treatment of acyclovir-resistant (viral thymidine
kinase-deficient) HSV infections,
 -Polyomavirus associated progressive multifocal
leukoencephalopathy,
 condylomata acuminata (anogenital warts), and
molluscum contagiosum.

16.  Probenecid with cidofovir . Probenecid carries its own
adverse effects, including gastrointestinal upset.
 Nephrotoxic agents (e.g., aminoglycosides, NSAIDs,
amphotericin B, foscarnet) should not be given
within 7 days of cidofovir administration.
 ADR-Hypersensitivity reactions, Anterior uveitis and
Neutropenia
 Potential human carcinogen- Embryotoxic and
teratogenic effects and to impair fertility .
 Nephrotoxicity, Proteinuria, azotemia, glycosuria,
elevated serum creatinine, and
 Rarely, Fanconi’s syndrome.


17.  -diacetyl ester prodrug of the acyclic guanosine analogue 6-
deoxypenciclovir.
 - HSV-1, HSV-2, VZV, and HBV.
 - After oral administration, famciclovir is converted to
penciclovir by first-pass metabolism.
 Penciclovir triphosphate acts as a competitive inhibitor of
viral DNA polymerase
 Resistance : Mutations in DNA polymerase or thymidine
kinase may result in resistance. Acyclovir-resistant HSV strains

18.  Penciclovir is available as a topical cream
 Famciclovir ->converted to penciclovir by hepatic first-
pass metabolism ->Bioavailability 77%.
 Penciclovir-t1/2 is 2 to 3 hours; however, the intracellular
half-life of penciclovir triphosphate is 7 to 20 hours in
infected cells.
 Eliminated unchanged by the kidney via glomerular
filtration and active tubular secretion.
 The plasma half-life is increased in individuals with renal
insufficiency.

19.  Herpes labialis.
 Shortens the duration of lesion presence and pain
 Famciclovir -acute herpes zoster (shingles)
 Famciclovir -treatment of HSV
 Famciclovir -Recurrent genital herpes.
 For HIV-infected individuals- all recurrent
mucocutaneous HSV infections

20.  Headache, nausea, and diarrhea.
 Hallucinations and urticaria
 Animal studies -Tumorigenic and impair
spermatogenesis.
 Dosage adjustment is necessary in individuals with
renal impairment.
 Famciclovir interact with probenecid -drugs
eliminated by renal tubular secretion.
 Increased blood levels of penciclovir or other
agents.

21.  Ganciclovir is an acyclic analogue of 2 de-oxyguanosine
especially CMV.
 Valganciclovir is the L-valyl ester prodrug of ganciclovir.
 Activation of ganciclovir --ganciclovir monophosphate
 Protein kinase pUL97 in CMV or thymidine kinase in
HSV.
 additional phosphorylations ganciclovir
triphosphate  competes with dGTP incorporation
into DNA  chain termination
 Ganciclovir triphosphate is up to 100-fold more
concentrated in CMV-infected cells than in normal cells .

22.  Resistance : Exposed to the drug for long periods .
 -Mutation of the protein kinase gene.
 -Mutations in the DNA polymerase .
 Pharmacokinetics : - Orally or intravenously
 Valganciclovir –orally - rapidly metabolized to
ganciclovir60%
 Intravenous -Ganciclovir -vitreous humor
 Ganciclovir- eliminated by glomerular filtration and
active tubular secretion.
 The T1/2-ganciclovir -3.5 hours (iv)and 4.8 hours (oral)
 Oral valganciclovir -4 hours. The intracellular half-life
of ganciclovir triphosphate is over 24 hours.

23.  CMV retinitis in immunocompromised
individuals, including those with AIDS, CMV
infection in organ transplant recipients.
 -CMV retinitis in AIDS ,
 Ganciclovir -intravitreal implant -CMV retinitis
in AIDS patients.
 Resistance : Exposed to the drug for long
periods .
 -Mutation of the protein kinase gene.
 -Mutations in the DNA polymerase .

24.  -Myelosuppression
 Neutropenia and anemia (25 to 30% ) and
Thrombocytopenia( 5 to 10%).
 sperm production, teratogenesis, and tumor formation.
 Severe neutropenia -with zidovudine.
 Ganciclovir increases serum levels of didanosine,
whereas probenecid decreases ganciclovir elimination.
 Nephrotoxicity (e.g., amphotericin B, cyclosporine,
NSAIDs) are administered in conjunction with ganciclovir

25.  Idoxuridine -is a water-soluble iodinated derivative of deoxyuridine
 -Inhibits several DNA viruses including HSV, VZV, vaccinia, and
polyoma virus.
 MOA:The triphosphorylated metabolite of idoxuridine inhibits
both viral and cellular DNA synthesis
 Host cytotoxicity,
 Pharmacokinetics: Idoxuridine topical ophthalmic use
 Uses : treatment of herpes simplex infections of the eyelid,
conjunctiva, and cornea. soft tissue sarcoma
 Adverse Events: local irritation, mild edema, itching, and
photophobia. Corneal clouding and small punctate defects
 in the corneal epithelium .

26.  Trifluridine is a fluorinated pyrimidine nucleoside
 -HSV-1 and HSV-2, vaccinia, adenoviruses.
 MOA: Activation of trifluridine  5
monophosphate inhibits the conversion of
deoxyuridine monophosphate (dUMP) to
deoxythymidine monophosphate (dTMP) by
thymidylate synthetase.
 Resistance alterations in thymidylate synthetase
specificity.

27.  Pharmacokinetics :- topical instillation of trifluridine into
the eyes. Its half-life is approximately 12 minutes.
 Uses:
 Trifluridine (topical ophthalmic solution)- primary
keratoconjunctivitis, recurrent keratitis due to HSV-1 or
HSV-2.
 Unresponsive or intolerant to topical idoxuridine or
vidarabine.
 Adverse effects:Transient burning or stinging and
palpebral edema.
 -Superficial punctate keratopathy, epithelial keratopathy,
hypersensitivity, stromal edema, irritation, keratitis
sicca, hyperemia, and increased intraocular pressure.

28.  Foscarnet is an inorganic pyrophosphate analogue
 HSV-1, HSV-2, VZV, CMV, EBV, HBV, and HIV.
 Noncompetitive inhibitor of viral DNA polymerase
and reverse transcriptase
 Resistance -mutation of viral DNA polymerase.
 Pharmacokinetics : IV -14 to 17% bound to plasma
proteins.
 -accumulates in bone bimodal initial half-life of 4
to 8 hours and prolonged terminal elimination half-life
of 45 to 130 hours.
 - eliminated as unchanged drug  glomerular
filtration and active tubular secretion.

29.  Uses
 CMV retinitis in AIDS patients.
 refractory retinitis, Kaposi’s sarcoma
 Acyclovir- resistant mucocutaneous HSV infections in
immunocompromised individuals.
 Acyclovir-resistantVZV and nonretinitis forms of CMV
infection
 Adverse effects
 Nephrotoxicity -second week of induction therapy
 Serum creatinine levels may be elevated in up to 33 to 50%
of patients;
 Dehydration, previous renal impairment, and concurrent
administration of other nephrotoxic drugs increase the
risk of renal toxicity.

30.  -synthetic guanosine analogue
 -Influenza A and B, parainfluenza, RSV, HCV, HIV-1, and
various herpesviruses, arena viruses, and paramyxo viruses.
 -inhibits the synthesis of viral mRNA
 ribavirin  monophosphate, diphosphate, and
triphosphate forms.
 Ribavirin monophosphate-- inhibits the guanosine
triphosphate (GTP) synthesis Ribavirin triphosphate
inhibits the 5 capping of viral mRNA with GTP increasing
the mutation rate of RNA viruses nonviable progeny virions

31.  Resistance has not been documented in clinical isolates.
 Pharmacokinetics : Aerosol respiratory tract secretions
approximately 100 times
 Oral absorption is rapid, and first-pass metabolism is
extensive;
 Ribavirin’s oral bioavailability is 64% -high-fat meal.
 Steady-state levels are reached after 4 weeks.
 Ribavirin triazole carboxylic acid metabolite urine
 The plasma half-life -9.5 hours
 The drug accumulates in erythrocytes, with a half-life of 40
days.

32.  Uses :
 Severe bronchiolitis or pneumonia due to RSV infection.
 Oral ribavirin in combination with interferon- α
 Intravenous ribavirin -Hantaan virus infection, Crimean or
Congo virus hemorrhagic fever, Lassa fever, and severe
adenovirus infection.
 Ribavirin monotherapy
 Adverse effects
 Local adverse effects.
 Pulmonary function -chronic obstructive lung disease or
asthma.
 Headache, conjunctivitis, rash, and rarely, bronchospasm.
 Oral and intravenous- hemolytic anemia

33.  With interferon-α - fatigue, nausea, insomnia,
depression, and anemia, fatal or nonfatal
pancreatitis.
 Ribavirin is mutagenic, teratogenic, and embryotoxic
 C/I- pregnant women ,Effective forms of
contraception during ribavirin treatment .
 Sickle cell anemia and other
hemoglobinopathies,coronary disease ,severe renal
impairment.
 D/I-In vitro, ribavirin inhibits the phosphorylation
reactions zidovudine and stavudine

34.  First antisense oligonucleotide immediate early
region 2 (IE2) of CMV mRNA.
 By binding to IE2 mRNA, fomivirsen prevents its
translation to protein and thereby blocks viral
replication. Because this mechanism of action is
different from that of other antiviral agents, cross-
resistance with other drugs used to treat CMV is
unlikely.
 Pharmacokinetics: Fomivirsen is injected directly
into the vitreous humor of the eye.-->retina and iris
over 3 to 5 days and is cleared from the vitreous
humor within 7 to 10 days.

35.  Fomivirsen exhibits minimal systemic absorption
and is degraded locally by cellular exonucleases.
 Uses
 Fomivirsen -CMV retinitis in patients with AIDS.
 Adverse effects: Iritis, (25%) -topical
corticosteroids.
 - Vitreitis IOT
 C/I- with cidofovir

36.  Amantadine is a synthetic tricyclic amine, and
rimantadine is its α -methyl derivative. Both drugs
inhibit the replication of the three antigenic
subtypes of influenza A (H1N1, H2N2 and H3N2) ,
less activity against influenza B.
 Mechanism Of Action
 - involves inhibition of the viral M2 protein, (H
channel) Blockade  acid-mediated dissociation
of the ribonucleoprotein complex -inhibited
 The pH changes  M2 inhibition alter the
hemagglutinin inhibit viral assembly.

37.  -Viral resistance -30% ,-failure of drug prophylaxis
 -Mutation in the transmembr- M2 protein
 Pharmacokinetics : Amantadine -2 to 5 hours.
 T1/2- 17 hours -29 hours in the elderly.
 Eliminated unchanged by glomerular filtration and
tubular secretion. Rimantadine -5 to 7 hours.
 Its elimination half-life averages 25- 32 hours in the
elderly. -25% -unchanged drug ,75%- hydroxylated or
conjugated metabolites.

38.  Uses :-influenza A strains
 Adverse effects:- Nausea, anorexia, dizziness, and insomnia
 Dose-related effects - amantadine than rimantadine.
 -Depression, impaired coordination, confusion, anxiety,
Cardiac arrhythmias, delirium, hallucinations
 long-term treatment may cause peripheral edema, Abrupt
withdrawal -neuroleptic malignant syndrome.
 -Seizures or worsen preexisting seizure disorders.
 Amantadine is teratogenic and Rimantadine - embryotoxic.
 Pregnancy and lactation.

39.  Drug interactions:- Anticholinergic drugs,
Thiazide–triamterene, trimethoprim–
sulfamethoxazole, quinine, and quinidine
increase plasma amantadine levels.
 Cimetidine decreases rimantadine clearance,
and aspirin and acetaminophen decrease
rimantadine plasma levels.

40.  Docosanol is a long-chain saturated alcohol
 HSV. CMV, influenza virus, and respiratory syncytial
virus.
 -Blocks the entry of the virion
 Docosanol cream -herpes labialis.
 Adverse effects -Skin irritation occurs infrequently.

41.  Oseltamivir phosphate is the ethyl ester prodrug of
oseltamivir carboxylate
 - competitive antagonist of influenza A and B
neuraminidase.
 Neuraminidase -then destroys these hemagglutinin
receptors cleavage of hemagglutinin receptors is
required for the release of progeny virus from the host
cell-inhibited
 Spread of infection  by allowing viral particles to
penetrate the neuraminic acid–rich respiratory mucus
and by preventing the clumping of virus that results from
the binding of hemagglutinins to neuraminic acid residues
on neighboring viral particles –inhibited
  Resistant strains –mutations- neuraminidase

42.  P/KOrally -80%- 2.5 to 5 hours.
 Plasma t1/2 -7 to 9 hours.
 Elimination -active tubular secretion and glomerular
filtration.
 Uses :Oseltamivir - uncomplicated acute influenza in
patients aged 1 year and older. --Prophylaxis of influenza in
individuals aged 13 and older.
 Post- exposure prophylaxis
 Adverse effects:
 -Nausea and vomiting, Bronchitis, insomnia, and vertigo
 -Chronic cardiac or respiratory disease renal insufficiency;
 -Probenecid decreases the elimination of oseltamivir,
 No interference with antibody production in response to
the influenza vaccine.

43.  Zanamivir is a neuraminidase inhibitor with activity
against influenza A and B strains. - reversible
competitive antagonist of viral neuraminidase.
 - inhibits the release of progeny virus,
 Resistant variants with hemagglutinin and/or
neuraminidase mutations
 Pharmacokinetics : bioavailability < 5% oral.
 breath-actuated inhaler device- 12 to 17%, -1.5
hours.
 Eliminated -by the kidneys t1/2.5 to 5 hours.

44.  Uses :- Uncomplicated acute influenza A and B virus
 Effective prophylaxis against influenza.
 Adverse effects:
 -Bronchospasm and impaired lung function -
underlying pulmonary disease.
 - Allergic reactions, including angioedema,
 C/I -Severe or decompensated chronic obstructive lung
disease or asthma
 -serious adverse pulmonary reactions. Moderate
asthma
 Severe renal insufficiency

45.  Other antiviral drugs
 Immunoglobin ->( γ-globulin, immunoglobulin [Ig] G)
 -primarily of IgG and contains trace amounts of IgA
and IgM.
 inhibit viral penetration of host cells, opsonize viral
particles, activate complement, and stimulate cell-
mediated immunity.
 Pharmacokinetics: γ-Globulin im/iv - viral disorders.
 Protection lasts for 2 to 3 weeks after a single
injection, although for prolonged infections,
injections can be repeated every 2 to 3 weeks.

46.  Uses :- CMV, HBV, rabies, RSV , and VZV
 - heterogeneous human immune globulin solution- measles,
varicella, or rubella infection
 - adjunctive form of therapy with other therapeutic
approaches.
 Adverse effects : Hypersensitivity reactions
 -Anaphylactoid reaction, urticaria, angioedema, fever, and
injection site reactions.
 - flushing, dizziness, blood pressure changes, palpitations,
abdominal cramps, and dyspnea; Aseptic meningitis
 Interference- live virus vaccines (e.g., measles mumps,
rubella).

47.  -Potent antiviral, immunoregulatory, and
antiproliferative effects
 Interferon-α (type I, leukocyte) and
 Interferon - β (type I, fibroblast)
 Interferon- γ (type II, immune) -natural killer (NK)
cells and T lymphocytes
 inhibition of viral penetration, uncoating, mRNA
synthesis, translation, and/or virion assembly and
release.

48.   Initiate the JAK-STAT signal transduction
pathway 2 -5 –oligo adenylate synthetase (2 -5
OAS)- initiates the activation of a cellular
ribonuclease that cleaves single-stranded RNAs,
 Protein kinase phosphorylates and inactivates an
elongation factor (eIF-2)
 Interferons inflammatory cytokines, biological
oxidants  immune response.

49.  Natural interferons ,recombinant interferons
,Monomethoxy polyethylene glycol (PEG; pegylated
interferons).
 Subcutaneously, intramuscularly, intravenously, or
intralesionally (e.g., into genital warts).
 -peak plasma levels within 4 to 8 hours within 16
to 36 hours.
 Pegylated interferons  15 to 44 hours 48 to 72
hours.
 Eliminated cellular uptake and catabolism in the
kidney and liver

50.  Interferon- α -2a chronic hepatitis C, hairy cell
leukemia, AIDS- related Kaposi’s sarcoma, and
chronic phase Philadelphia chromosome–positive
chronic myelogenous leukemia.
 Interferon-α -2b Hairy cell leukemia, malignant
melanoma, follicular lymphoma, condylomata
acuminata, AIDS-related Kaposi’s sarcoma, and
chronic hepatitis B and C.
 Interferon-α -2b and RibavirinChronic hepatitis C.
 Interferon- α -n3 condylomata acuminata by
intralesional injection.

51.  Interferon alfacon-1 5 times Interferon α -
2a or -2b.
 Interferon alfacon-1 and peg interferon- α -
2b chronic hepatitis C.
 Interferon β -1a and interferon β -1b 
multiple sclerosis.
 Interferon -1b chronic granulomatous
disease , malignant osteopetrosis.

52.  Flu like symptoms fever, chills, weakness,
fatigue, myalgia, and arthralgia, (50% )of
patients CNS complaints  headache,
dizziness, impaired memory and concentration,
agitation, insomnia, and anxiety occur with
regularity.
 Depression  interferon-α and interferon- β .
 Myelosuppression dose limiting
 Gastrointestinal symptoms  nausea, vomiting,
 Elevation of hepatic enzymes
 Injection site reaction alopecia, fertility, cause
miscarriage .

53.  Palivizumab  is a humanized monoclonal antibody F
protein on the surface of RSV.
 It contains 95% human and 5% murine antibody
sequences
 inhibits its ability to fuse with host cell membranes.
 Pharmacokinetics : prophylactically IM/monthly—RSV
season. T1/2- 20 days.
 Uses : Serious LRTI due to RSV.
 bronchopulmonary dysplasia or chronic lung disease
 Premature infants (less than 32 weeks gestation)
 Adverse effects : Mild erythema and pain
 Anaphylactoid reactions –protein.

54.  Imiquimod [1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4
amine]
 Condylomata acuminata, molluscum contagiosum, HPV
infections
 Toll-like receptors TLR7 and TLR8 to boost innate immunity,
interferons

56. THANKYOU
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