ANTIVIRAL DRUGS
(NON RETROVIRAL)
DNA polymerase inhibitors
 Purine analogues
 Acyclovir , Valcyclovir , Gancyclovir, Valganciclovir,
Famciclovir , Pencyc...
M-RNA synthesis inhibitors
Ribavirin, Fomiversen
Inhibitors of viral penetration and uncoating
Amantidine and Rimantidine,...
Life cycle of viruses and
steps blocked by medicines
Guanine nucleoside analogue
Effective against HSV-1 and HSV-2,
VZV, CMV, and EBV.
The active metabolite of acyclovir
inhib...
 Pharmacokinetics :Acyclovir absorption is variable
and incomplete following oral administration.
 20% bound to plasma p...
 Oral acyclovir - HSV-1 and HSV-2 infections, such as
genital herpes, herpes encephalitis, herpes keratitis,
herpes labia...
 Ophthalmic acyclovir formulations are effective in
the treatment of herpes keratoconjunctivitis.
 Acyclovir reduces the...
 Headache, nausea, and diarrhea.
 Skin rash, fatigue, fever, hair loss, and
depression.
 Reversible renal dysfunction (...
 Drug interaction –Probenacid , cyclosporine
 Resistance –Mutations resulting in decrease
in thymidine kinase activity.
...
 - acyclic phosphonate cytosine analogue
 - Herpes viruses including CMV, HSV-1, HSV-2, EBV,
and VZV. adenoviruses, papi...
 Pharmacokinetics :
 low oral bioavailability. T1/2- 2.6 hours,
 the diphosphate form -half life of 17 to 65 hours.
 A...
 -Treatment and prophylaxis of
CMV retinitis in AIDS patients.
 -Treatment of acyclovir-resistant (viral thymidine
kinas...
 Probenecid with cidofovir . Probenecid carries its own
adverse effects, including gastrointestinal upset.
 Nephrotoxic ...
 -diacetyl ester prodrug of the acyclic guanosine analogue 6-
deoxypenciclovir.
 - HSV-1, HSV-2, VZV, and HBV.
 - After...
 Penciclovir is available as a topical cream
 Famciclovir ->converted to penciclovir by hepatic first-
pass metabolism -...
 Herpes labialis.
 Shortens the duration of lesion presence and pain
 Famciclovir -acute herpes zoster (shingles)
 Fam...
 Headache, nausea, and diarrhea.
 Hallucinations and urticaria
 Animal studies -Tumorigenic and impair
spermatogenesis....
 Ganciclovir is an acyclic analogue of 2 de-oxyguanosine
especially CMV.
 Valganciclovir is the L-valyl ester prodrug of...
 Resistance : Exposed to the drug for long periods .
 -Mutation of the protein kinase gene.
 -Mutations in the DNA poly...
 CMV retinitis in immunocompromised
individuals, including those with AIDS, CMV
infection in organ transplant recipients....
 -Myelosuppression
 Neutropenia and anemia (25 to 30% ) and
Thrombocytopenia( 5 to 10%).
 sperm production, teratogenes...
 Idoxuridine -is a water-soluble iodinated derivative of deoxyuridine
 -Inhibits several DNA viruses including HSV, VZV,...
 Trifluridine is a fluorinated pyrimidine nucleoside
 -HSV-1 and HSV-2, vaccinia, adenoviruses.
 MOA: Activation of tri...
 Pharmacokinetics :- topical instillation of trifluridine into
the eyes. Its half-life is approximately 12 minutes.
 Use...
 Foscarnet is an inorganic pyrophosphate analogue
 HSV-1, HSV-2, VZV, CMV, EBV, HBV, and HIV.
 Noncompetitive inhibitor...
 Uses
 CMV retinitis in AIDS patients.
 refractory retinitis, Kaposi’s sarcoma
 Acyclovir- resistant mucocutaneous HSV...
 -synthetic guanosine analogue
 -Influenza A and B, parainfluenza, RSV, HCV, HIV-1, and
various herpesviruses, arena vir...
 Resistance has not been documented in clinical isolates.
 Pharmacokinetics : Aerosol respiratory tract secretions
appr...
 Uses :
 Severe bronchiolitis or pneumonia due to RSV infection.
 Oral ribavirin in combination with interferon- α
 In...
 With interferon-α - fatigue, nausea, insomnia,
depression, and anemia, fatal or nonfatal
pancreatitis.
 Ribavirin is mu...
 First antisense oligonucleotide immediate early
region 2 (IE2) of CMV mRNA.
 By binding to IE2 mRNA, fomivirsen preven...
 Fomivirsen exhibits minimal systemic absorption
and is degraded locally by cellular exonucleases.
 Uses
 Fomivirsen -C...
 Amantadine is a synthetic tricyclic amine, and
rimantadine is its α -methyl derivative. Both drugs
inhibit the replicati...
 -Viral resistance -30% ,-failure of drug prophylaxis
 -Mutation in the transmembr- M2 protein
 Pharmacokinetics : Aman...
 Uses :-influenza A strains
 Adverse effects:- Nausea, anorexia, dizziness, and insomnia
 Dose-related effects - amanta...
 Drug interactions:- Anticholinergic drugs,
Thiazide–triamterene, trimethoprim–
sulfamethoxazole, quinine, and quinidine
...
 Docosanol is a long-chain saturated alcohol
 HSV. CMV, influenza virus, and respiratory syncytial
virus.
 -Blocks the ...
 Oseltamivir phosphate is the ethyl ester prodrug of
oseltamivir carboxylate
 - competitive antagonist of influenza A an...
 P/KOrally -80%- 2.5 to 5 hours.
 Plasma t1/2 -7 to 9 hours.
 Elimination -active tubular secretion and glomerular
fil...
 Zanamivir is a neuraminidase inhibitor with activity
against influenza A and B strains. - reversible
competitive antagon...
 Uses :- Uncomplicated acute influenza A and B virus
 Effective prophylaxis against influenza.
 Adverse effects:
 -Bro...
 Other antiviral drugs
 Immunoglobin ->( γ-globulin, immunoglobulin [Ig] G)
 -primarily of IgG and contains trace amoun...
 Uses :- CMV, HBV, rabies, RSV , and VZV
 - heterogeneous human immune globulin solution- measles,
varicella, or rubella...
 -Potent antiviral, immunoregulatory, and
antiproliferative effects
 Interferon-α (type I, leukocyte) and
 Interferon -...
  Initiate the JAK-STAT signal transduction
pathway 2 -5 –oligo adenylate synthetase (2 -5
OAS)- initiates the activati...
 Natural interferons ,recombinant interferons
,Monomethoxy polyethylene glycol (PEG; pegylated
interferons).
 Subcutaneo...
 Interferon- α -2a chronic hepatitis C, hairy cell
leukemia, AIDS- related Kaposi’s sarcoma, and
chronic phase Philadelp...
 Interferon alfacon-1 5 times Interferon α -
2a or -2b.
 Interferon alfacon-1 and peg interferon- α -
2b chronic hepat...
 Flu like symptoms fever, chills, weakness,
fatigue, myalgia, and arthralgia, (50% )of
patients CNS complaints  headach...
 Palivizumab  is a humanized monoclonal antibody F
protein on the surface of RSV.
 It contains 95% human and 5% murine...
 Imiquimod [1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4
amine]
 Condylomata acuminata, molluscum contagiosum, HPV
in...
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Class antiviral drugs 2

  1. 1. ANTIVIRAL DRUGS (NON RETROVIRAL)
  2. 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. 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
  4. 4. Life cycle of viruses and steps blocked by medicines
  5. 5. 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.
  6. 6.  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
  7. 7.  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.
  8. 8.  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.
  9. 9.  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
  10. 10.  Drug interaction –Probenacid , cyclosporine  Resistance –Mutations resulting in decrease in thymidine kinase activity.  Altered substrate specificity  Decreased affinity of viral DNA polymerase
  11. 11.  - 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.
  12. 12.  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
  13. 13.  -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.
  14. 14.  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. 
  15. 15.  -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
  16. 16.  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.
  17. 17.  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
  18. 18.  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.
  19. 19.  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 .
  20. 20.  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.
  21. 21.  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 .
  22. 22.  -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
  23. 23.  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 .
  24. 24.  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.
  25. 25.  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.
  26. 26.  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.
  27. 27.  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.
  28. 28.  -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
  29. 29.  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.
  30. 30.  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
  31. 31.  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
  32. 32.  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.
  33. 33.  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
  34. 34.  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.
  35. 35.  -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.
  36. 36.  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.
  37. 37.  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.
  38. 38.  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.
  39. 39.  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
  40. 40.  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.
  41. 41.  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.
  42. 42.  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
  43. 43.  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.
  44. 44.  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).
  45. 45.  -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.
  46. 46.   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.
  47. 47.  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
  48. 48.  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.
  49. 49.  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.
  50. 50.  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 .
  51. 51.  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.
  52. 52.  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
  53. 53. THANKYOU Download slides from Authorstream/presentations/raghuprasada Slideshare/presentations/raghuprasada Youtube/raghuprasada
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