Anti viral drugs

Introduction to Viruses

• Viruses are composed of nucleic acid, protein

capsid, and host membrane containing virus
proteins
• Viruses live inside host cells and use many host
enzymes.
• viruses have core genome of nucleic acid either
DNA or RNA.
 Types of virus
DNA viruses RNA viruses
• Adenoviruses (upper • Arborvirus-yellow fever
respiratory infections) • Arenaviruses-meningitis
• Hepadnaviruses • Bunya viruses- encephalitis
• Coronaviruses- URI
• Herpes virus(HSV-
• Influenza A and B
1,HSV-2,VZV,CMV)
• Paramyxoviruses – Measles,
• Poxvirus ( small pox) mumps
• Papilloma viruses • Rhabdoviruses-Rabbies
(warts) • Human immunodeficiency
virus (HIV)
 Classification
• DNA polymerase inhibitors
Purine Nucleoside Analogues: Acyclovir, Ganciclovir,
Famiciclovir, Valacyclovir, Penciclovir, Cidofovir
Pyrimidine Nucleoside Analogues: Idoxuridine
Non nucloside- Foscarnet
• Inhibitors of viral penetration, uncoating- Amantadine
Rimantadine
• m-RNA Synthesis inhibitors -Ribvirin Fomivirsen
• Neuraminidase Inhibitors- Zanamivir Oseltamivir
• Immunomodulators Immunoglobulins Interferns
Palivizumab Imiquimod
Nucleoside Analogues General Mechanism of
Action
• Taken up by cells
• Converted by viral and cellular enzymes to the
triphosphate form
• The triphosphate form inhibits:
DNA polymerase
Reverse transcriptase
RNA polymerase
• Or it may get incorporated into growing DNA
leading to abnormal proteins or breakage.
• Antiviral Drugs Nucleoside and Nucleotide Analogs
 Antiviral spectrum :
• Acyclovir: HSV-1, HSV-2, VZV, Shingles.
• Ganciclovir / Cidofovir : CMV
• Famciclovir : Herpes genitalis and shingles
• Foscarnet : HSV, VZV, CMV, HIV
• Penciclovir : Herpes labialis
• Trifluridine : Herpetic keratoconjunctivitis
Pharmacokinetics of Acyclovir :
• Oral bioavailability ~ 20-30%
• Distribution in all body tissues including CNS
• Renal excretion: > 80%
• Half lives: 2-5 hours
• Administration: Topical, Oral , IV
Adverse effects of Acyclovir / Ganciclovir
• Nausea, vomiting and diarrhea
• Nephrotoxicity , crystalluria, haematuria, renal insufficiency
• Myelosuppression, Neutropenia and thrombocytopenia
Anti-viral drugs Therapeutic uses :
Acyclovir is the drug of choice for:
• HSV Genital infections
• HSV encephalitis
• HSV infections in immunocompromised patient
Ganciclovir is the drug of choice for:
• CMV retinitis in immunocompromised patient
• Prevention of CMV disease in transplant patients
Valacyclovir
•L- Valine ester of acyclovir
•Mechanism and clinical use same
•It require less oral dose
•More effective than acyclovir
•No IV formulation

Cidofovir :
• It is approved for the treatment of CMV retinitis in
immunocompromised patients
• It is a nucleotide analog of cytosine – no phosphorylation required.
• It inhibits viral DNA synthesis
• Available for IV, Intravitreal inj, topical
• Nephrotoxicity is a major disadvantage.
Idoxuridine
•First pyrimidine antimetabolite, used as antiviral drug.
•MOA –incorporate in DNA →formed faulty DNA which
breaks down easily →synthesis of wrong viral protein.
Use
•Only topical ophthalmic use
•H. simplex keratoconjunctivitis.
Dose – one drop of 0.1% solution hourly during day time
and two hourly during night time.
•In acute stage- 0.5% eye ointment four hourly for 3
weeks.
Side effect – ocular irritation, lid odema, photophobia.
Foscarnet
• An inorganic pyrophosphate analog
• Active against Herpes (I, II, Varicella, CMV), including those
resistant to Acyclovir and Ganciclovir.
• Direct inhibition of DNA polymerase and RT
• Nephrotoxicity (25%) most common ADR
• Hypocalcemia (chelates divalent cations)
• Others: hypokalemia, hypomagnesemia
• Use: CMV retinitis and other CMV infections instead of
ganciclovir. H simplex resistant to Acyclovir.
Non-selective antiviral drug
RIBAVIRIN
• Has broad spectrum antiviral activity.
• Oral bioavailability-50%
• MAO: Inhibits viral RNA polymerase
USES-
1. Influenza –A,B
2. Measles in immunocompramised pt.,
• Route - aerosol -to treat Respiratory syncitial virus
• DOSE- 200MG/QID
ADVERSE EFFECT
•Anaemia
•haemolysis.
•irritation to mucosa & bronchospasm due to aerosols
Inhibitors of viral penetration and uncoating

•Amantadine and Rimantadine

•Synthetic tricyclic amines
•Active against Influenza-A
•MAO:-Inhibit viral M2 protein
•Amantadine cross extensively BBB whereas Rimantadine
does not cross extensively
•t ½- 17-25hr.
 Neuraminidase inhibitors
• Influenza contains an enzyme neuraminidase which is
essential for the replication of the virus.
• Neuraminidase inhibitors prevent the release of new
virions and their spread from cell to cell.
• Oseltamivir, Zanamivir
• Oral -Oseltamivir carboxylate
• 80% BV
• t ½- 8hrs.
• Effective against influenza
• ADR:
Zanamivir- bronchospasm, Nasal discomfort