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ANTI VIRAL DRUGS
DR.MINU BABY
ANTIVIRAL DRUGS-CLASSIFICATION
Anti-Herpes Virus Drugs
Anti-Influenza Virus Drugs
Anti-Hepatitis Virus Drugs
Anti-Retroviral Drugs
Anti-Herpes Virus Drugs
• Acyclovir ,
• Valacyclovir ,
• Famciclovir
• Penciclovir ,
• Ganciclovir
• Cidofovir ,
• Foscarnet,
• Fomivirsen
• Structural analogues of nucleosides
• Activated to triphosphate forms
• Competitive inhibition of viral thymidione
kinase and DNA/RNA polymerase
ANTI-INFLUENZA DRUGS
DRUGS FOR HEPATITIS
Are drugs which are effective against
 Hepatitis B Virus(HBV)-DNA virus
 Hepatitus C Virus (HCV)-RNA virus
DRUGS FOR HEPATITIS B
Hepatitis B Virus is a DNA virus
It integrates into chromosomal DNA
Causes permanent infection
It is unable to eradicate the viral antigen from the body
GOAL OF TREATMENT
 Suppress viral replication.
To reduce its inflammatory & hepatocyte damaging process.
 Prevent progression of hepatic disease & complications like cirrhosis and
hepatic carcinoma
DRUGS FOR HEPATITIS B
LAMIVUDINE
ENTECAVIR
ADEFOVIR DIPIVOXIL
TENOFOVIR
TELBIVUDINE
INTERFERON
Not to be stopped suddenly as it can result in acute exacerbation of
hepatitis
To be continued till 6 months after seroconversion to minimize
reactivation
LAMIVUDINE
A cytosine analogue
Effective for both HIV & Hep B
Mechanism OF ACTION
Inhibit HBV DNA Polymerase
Also get incorporated in the viral DNA and causes chain
termination
Inhibit HIV reverse transcriptase
LAMIVUDINE
USES
Hepatitis B: Chronic hepatitis
HIV
DISADVANTAGES
Resistance
Tenofovir & Adefovir preferred in Lamivudine resistant cases
ADVERSE EFFECTS:
Headache,nausea,anorexia,abdominal pain,rashes
Pancreatitis,neuropathy  Rare
TENOFOVIR
Nucleotide analogue
Active against HIV & Hepatitis B
Is used as disoproxil ester PRODRUG
better Oral absorption
better viral entry
TENOFOVIR
Mechanism of Action
Nucleotide analogue
Tenofovir undergoes diphosphorylation by cellular kinase
Tenofovir diphosphate inhibits HBV DNA polymerase
It also gets incorporated in the viral DNA to cause chain termination
Inhibits HIV Reverse Transcriptase enzyme
TENOFOVIR
ADR:
GIT:Nausea,flatulence,loose stools,pain abdomen
Renal: proximal tubular disease
Slight increase in creatinine,acute/chronic renal disease
Fanconi Syndrome
USES
DOC for Hepatitis B – active even for lamivudine resistant cases
HIV
ENTECAVIR
Guanosine nucleoside analogue
Currently the first line drug for treatment of Chronic Hepatitis B
MOA :
Inhibits HBV DNA polymerase
Need to be taken in empty stomach ,food decreases oral
bioavailability
Long acting,half life is 128-148 hrs
Well tolerated,mild dyspepsia,disturbed sleep
Lactic acidosis in decompensated cirrhosis
Adefovir Dipivoxil
Prodrug of Adefovir
Adefovir  adenosine analogue
 MOA:Competitive inhibition of HBV DNA Polymerase
USES:Chronic Hepatitis B
Effective in Lamivudine resistant cases
Effective in patients with concomitant HIV infection
ADR:Nephrotoxicity
Flu syndrome,Sore throat
TELBIVUDINE
Newer anti-HBV drug
Thymidine analogue
MOA:Inhibits HBV DNA polymerase
Adavantages
Long acting
Orally effective
Faster & more complete suppression of HBV DNA titre
Disadvantages
Resistance
ADR: Well tolerated
Serum amylase may rise
DRUGS FOR HEPATITIS C
RIBAVIRIN
INTERFERON
NEWER DRUGS
i.NS5B Polymerase Inhibitor: Sofosbuvir
ii.NS3/4A Protease Inhibitor: Simepravir
iii.NS5A Inhibitors: Daclatasvir
Ledipasvir
Velpatasvir
INTERFERONS (IFN)
Interferons are cytokines produced by host cells in response to viral
infections
Three types of Interferons : IFN α, β, γ
Antiviral action  IFN α
Only IFN α2A & INF α2B are produced by recombinant technology &
are used clinically
Interferons bind to receptors(JAK-STAT tyrosine
kinase receptors)
Induces expression of interferon induced
proteins
Inhibit viral replication at multiple steps
:penetration, synthesis of viral mRNA and
viral proteins, release of progeny virus
INTERFERONS-MECHANISM OF ACTION
Interferon Alfa
No oral BA- polypeptide
s/c or im
Pegylated Interferons:
Obtined by attachment of IFN to polyethylene glycol (PEG)
molecules – pegylation
Increase duration of action
Enable once-weekly dosing
Enhanced clinical effiacy
Interferon α - USES
1.Chronic Hepatitis B
2.Chronic Hepatitis C
3.AIDS related Kaposi sarcoma
4.Condyloma Acuminata:caused by papilloma virus
Treated with topical podophyllin
Intralesional interferon in resistant cases
5.Herpes infection:IFN my be added to acyclovir in
immunocompromised patients
6.Hematological Malignancy:CML,Follicular lymphoma,Cutaneous T cell
Lymphoma,Multiple Myeloma
IFN-ADVERSE EFFECTS
IFN cause frequent & distressing adverse effects
IV infusion  Flu like symptoms
Thyroid dysfunction
Neurotoxicity , bone marrow toxicity,alopecia
Reversible Liver & kidney damage
Hypotension,transient arrhythmias
Alopecia
May impair fertility
Autoimmune diseases
Depression
RIBAVIRIN
A broad spectrum antiviral drug
Spectrum: HCV, Influenza A & B
Respiratory syncytial virus
MOA :Inhibits GTP synthesis& viral RNA synthesis
Long t1/2>10days,accumulates in body on daily dosing
RIBAVIRIN
USE: Chronic Hepatitis C , Influenza, Measles,
RSV-nebulised Ribavirin
NIPAH VIRUS
ADR: Dose dependent Hemolytic anemia,
Bone marrow supression
Cough,Dyspnoea,bronchospasm on nebulization
Teratogenicity
NEWER DRUGS FOR HEPATITIS C
NOVEL DIRECTLY ACTING AGENTS
They target NONSTRUCTURAL VIRAL PROTEINSreplication
Used in combination:Development of resistance
Advantages
-Better viral response
-Shorter duration of treatment
-Less toxic
-Delayed onset of resistance
Disadvantages
-More drug interactions
NON-STRUCTURAL PROTEINS
NS5B Polymerase Inhibitor:SOFOSBUVIR
It is a uridine analogue
Prodrug
Inhibits NS5B (HCV RNA polymerase )
PHARMACOKINETICS
Oral bioavailability is 80%improved with fatty meal
It is a substrate of Pgp efflux transporter should not be used with Pgp
inducers like Phenytoin, Rifampicin
ADR: Fatigue,pain abdomen,joint pain,anemia
Sever bradycardia if used with Amiodarone
NS3/4A PROTEASE Inhibitor:SIMEPRAVIR
Mechanism of Action
 NS3/4A protein helps to form functional viral polypepetides
 InhiBItion of this protein blocks viral replication
Pharmacokinetics
Orally effectiveabsorption increases when taken with meals
Metabolised by CYP3A4
Substrate for Pgp
USES:Chronic Hepatitis C
Given as Simepravir –Sofosbuvir combination for 12-24weeks
ADR:Photosensitivity,Rashes,dyspnea
DRUG INTERACTIONS
NS5A INHIBITORS
NS5A is a multifunctional protein essential for viral replication
I.DACLATASVIR
II.LEDIPASVIR
III.VALPATASVIR
Features
Used as combination therapy with SOFOSBUVIR
Metabolisd by CYP
Substrates of Pgp DRUG INTERACTIONS
Needs gastric acidity for
absorption
Drugs for Corona virus-COVID-19
Remdesivir
Baricitinib
Tocilizumab
Sotrovimab
Casirivimab + Imdevimab
Immune-based therapy: Convalescent plasma
THANK YOU

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antivirals 2 (1).pptx

  • 2. ANTIVIRAL DRUGS-CLASSIFICATION Anti-Herpes Virus Drugs Anti-Influenza Virus Drugs Anti-Hepatitis Virus Drugs Anti-Retroviral Drugs
  • 3. Anti-Herpes Virus Drugs • Acyclovir , • Valacyclovir , • Famciclovir • Penciclovir , • Ganciclovir • Cidofovir , • Foscarnet, • Fomivirsen • Structural analogues of nucleosides • Activated to triphosphate forms • Competitive inhibition of viral thymidione kinase and DNA/RNA polymerase
  • 4.
  • 6. DRUGS FOR HEPATITIS Are drugs which are effective against  Hepatitis B Virus(HBV)-DNA virus  Hepatitus C Virus (HCV)-RNA virus
  • 7. DRUGS FOR HEPATITIS B Hepatitis B Virus is a DNA virus It integrates into chromosomal DNA Causes permanent infection It is unable to eradicate the viral antigen from the body GOAL OF TREATMENT  Suppress viral replication. To reduce its inflammatory & hepatocyte damaging process.  Prevent progression of hepatic disease & complications like cirrhosis and hepatic carcinoma
  • 8. DRUGS FOR HEPATITIS B LAMIVUDINE ENTECAVIR ADEFOVIR DIPIVOXIL TENOFOVIR TELBIVUDINE INTERFERON Not to be stopped suddenly as it can result in acute exacerbation of hepatitis To be continued till 6 months after seroconversion to minimize reactivation
  • 9.
  • 10. LAMIVUDINE A cytosine analogue Effective for both HIV & Hep B Mechanism OF ACTION Inhibit HBV DNA Polymerase Also get incorporated in the viral DNA and causes chain termination Inhibit HIV reverse transcriptase
  • 11. LAMIVUDINE USES Hepatitis B: Chronic hepatitis HIV DISADVANTAGES Resistance Tenofovir & Adefovir preferred in Lamivudine resistant cases ADVERSE EFFECTS: Headache,nausea,anorexia,abdominal pain,rashes Pancreatitis,neuropathy  Rare
  • 12. TENOFOVIR Nucleotide analogue Active against HIV & Hepatitis B Is used as disoproxil ester PRODRUG better Oral absorption better viral entry
  • 13. TENOFOVIR Mechanism of Action Nucleotide analogue Tenofovir undergoes diphosphorylation by cellular kinase Tenofovir diphosphate inhibits HBV DNA polymerase It also gets incorporated in the viral DNA to cause chain termination Inhibits HIV Reverse Transcriptase enzyme
  • 14. TENOFOVIR ADR: GIT:Nausea,flatulence,loose stools,pain abdomen Renal: proximal tubular disease Slight increase in creatinine,acute/chronic renal disease Fanconi Syndrome USES DOC for Hepatitis B – active even for lamivudine resistant cases HIV
  • 15. ENTECAVIR Guanosine nucleoside analogue Currently the first line drug for treatment of Chronic Hepatitis B MOA : Inhibits HBV DNA polymerase Need to be taken in empty stomach ,food decreases oral bioavailability Long acting,half life is 128-148 hrs Well tolerated,mild dyspepsia,disturbed sleep Lactic acidosis in decompensated cirrhosis
  • 16. Adefovir Dipivoxil Prodrug of Adefovir Adefovir  adenosine analogue  MOA:Competitive inhibition of HBV DNA Polymerase USES:Chronic Hepatitis B Effective in Lamivudine resistant cases Effective in patients with concomitant HIV infection ADR:Nephrotoxicity Flu syndrome,Sore throat
  • 17. TELBIVUDINE Newer anti-HBV drug Thymidine analogue MOA:Inhibits HBV DNA polymerase Adavantages Long acting Orally effective Faster & more complete suppression of HBV DNA titre Disadvantages Resistance ADR: Well tolerated Serum amylase may rise
  • 18. DRUGS FOR HEPATITIS C RIBAVIRIN INTERFERON NEWER DRUGS i.NS5B Polymerase Inhibitor: Sofosbuvir ii.NS3/4A Protease Inhibitor: Simepravir iii.NS5A Inhibitors: Daclatasvir Ledipasvir Velpatasvir
  • 19. INTERFERONS (IFN) Interferons are cytokines produced by host cells in response to viral infections Three types of Interferons : IFN α, β, γ Antiviral action  IFN α Only IFN α2A & INF α2B are produced by recombinant technology & are used clinically
  • 20. Interferons bind to receptors(JAK-STAT tyrosine kinase receptors) Induces expression of interferon induced proteins Inhibit viral replication at multiple steps :penetration, synthesis of viral mRNA and viral proteins, release of progeny virus INTERFERONS-MECHANISM OF ACTION
  • 21. Interferon Alfa No oral BA- polypeptide s/c or im Pegylated Interferons: Obtined by attachment of IFN to polyethylene glycol (PEG) molecules – pegylation Increase duration of action Enable once-weekly dosing Enhanced clinical effiacy
  • 22. Interferon α - USES 1.Chronic Hepatitis B 2.Chronic Hepatitis C 3.AIDS related Kaposi sarcoma 4.Condyloma Acuminata:caused by papilloma virus Treated with topical podophyllin Intralesional interferon in resistant cases 5.Herpes infection:IFN my be added to acyclovir in immunocompromised patients 6.Hematological Malignancy:CML,Follicular lymphoma,Cutaneous T cell Lymphoma,Multiple Myeloma
  • 23. IFN-ADVERSE EFFECTS IFN cause frequent & distressing adverse effects IV infusion  Flu like symptoms Thyroid dysfunction Neurotoxicity , bone marrow toxicity,alopecia Reversible Liver & kidney damage Hypotension,transient arrhythmias Alopecia May impair fertility Autoimmune diseases Depression
  • 24. RIBAVIRIN A broad spectrum antiviral drug Spectrum: HCV, Influenza A & B Respiratory syncytial virus MOA :Inhibits GTP synthesis& viral RNA synthesis Long t1/2>10days,accumulates in body on daily dosing
  • 25. RIBAVIRIN USE: Chronic Hepatitis C , Influenza, Measles, RSV-nebulised Ribavirin NIPAH VIRUS ADR: Dose dependent Hemolytic anemia, Bone marrow supression Cough,Dyspnoea,bronchospasm on nebulization Teratogenicity
  • 26. NEWER DRUGS FOR HEPATITIS C NOVEL DIRECTLY ACTING AGENTS They target NONSTRUCTURAL VIRAL PROTEINSreplication Used in combination:Development of resistance Advantages -Better viral response -Shorter duration of treatment -Less toxic -Delayed onset of resistance Disadvantages -More drug interactions
  • 28.
  • 29. NS5B Polymerase Inhibitor:SOFOSBUVIR It is a uridine analogue Prodrug Inhibits NS5B (HCV RNA polymerase ) PHARMACOKINETICS Oral bioavailability is 80%improved with fatty meal It is a substrate of Pgp efflux transporter should not be used with Pgp inducers like Phenytoin, Rifampicin ADR: Fatigue,pain abdomen,joint pain,anemia Sever bradycardia if used with Amiodarone
  • 30. NS3/4A PROTEASE Inhibitor:SIMEPRAVIR Mechanism of Action  NS3/4A protein helps to form functional viral polypepetides  InhiBItion of this protein blocks viral replication Pharmacokinetics Orally effectiveabsorption increases when taken with meals Metabolised by CYP3A4 Substrate for Pgp USES:Chronic Hepatitis C Given as Simepravir –Sofosbuvir combination for 12-24weeks ADR:Photosensitivity,Rashes,dyspnea DRUG INTERACTIONS
  • 31. NS5A INHIBITORS NS5A is a multifunctional protein essential for viral replication I.DACLATASVIR II.LEDIPASVIR III.VALPATASVIR Features Used as combination therapy with SOFOSBUVIR Metabolisd by CYP Substrates of Pgp DRUG INTERACTIONS Needs gastric acidity for absorption
  • 32. Drugs for Corona virus-COVID-19 Remdesivir Baricitinib Tocilizumab Sotrovimab Casirivimab + Imdevimab Immune-based therapy: Convalescent plasma