Anti Viral Drugs (part 1/2) - respiratory viral infection , hepatic viral infectio with treatment option from lipincott review

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 Treatment of Respiratory Virus Infection




Influenza A & B, RSV(Respiratoy syncytial virus) involved in Respiratory infection

Neuroaminidase inhibitor

Orthomyxovirus cause Influenza contain Neuroaminidase …essential for life cycle…

Oseltamivir & Zanamivir

 Sialic acid analogue… ϴNeuroaminidase,prevent release of virion & their spread….Active against Influenza A & B

Oseltamivir orally prodrug…zanamivir intranasally, cotra in COPD, Asthma

Inhibitor of Viral coating

Amantadine & Rimantadine= only Influenza A virus….Block Viral memb. Protein M2...which act as channel for Hydrogen ion…required for fusion of viral memb with cell memb. 

👍To form ENDOSOME…acidic environment require

S.E= Embryotoxic…

used catiously in patient with Seizure, Athersclrosis, Psychiatric 

Ribavirin

Synthetic Guanosine analogue…

used for RNA, DNA viruses… used in children with 

RSV effective in Chronic Hepatitis… not indicated in Adults with RSV…

MOA: 

convert into 5-Phosphate derivative… Ribavirin-Triphosphate…ϴGTP & mRNA… 

Rhinovirus & Enterovirus already contain mRNA resistant to Ribavirin 

S.E= Anemia, ↑Bilirubin, Teratogenic

Treatment of Hepatic Viral Infection 

Hepatitis virus A,B,C,D,E….involve in replication & destruction of Hepatocytes… 

Hepatitis B & C more common…

Hepatitis A is not chronic disease…

Hepatitis B treated with Peginterferon α-2a S/c once weekly…Interferon α-2b I/M or S/C 3time/week… 

Hepatitis C chronic treated with Peginterferon-α-2a or Pegintereron-α-2b + Ribavirin 

Interferon=Glycoprotein synthesized by Recombinant DNA…α,β,γ forms… 

Interferon-α-2b approved for Hepatitis B & C…Peginterferon contain PEG covalently bonding to Interferon α-2a or α-2b

MOA=induction of host cell enzyme…ϴ of Viral RNA translation 

S.E=Flu-like symptoms, Myalgia, Anthralgia, Bone-marrow suppression, CVS problems, 

Drug-interaction= ↑Myelosuppression by Zidovudine, ↑Theophylline conc.

Lamivudine

Cytosine analogue...ϴHBV DNA polymerase & HIV reverse transcriptase.. 

9hr t1/2…dose reduction in renal impair 

Adefovir=nucleotide analogue...Terminate viral DNA…Contra in Renal pt.

Entecavir=Guanosine analogue...for HBV. ..Reverse transcriptase inhibitor. 

Telbivudine=only HBV...Thymidine analogue. 

Treatment for Herpesvirus Infection 

Herpes virus cause “Cold sore, Viral Encephalitis, Genital infection”

Acyclovir

AcycloGuanosine…Prototype…used for HSV (Herpes simplex virus) 

type1&2, VZV (Voricella zoster virus), EBV (Epstein-Barr virus) 

 MOA=Acyclovir lack Sugar moiety converted into Acycloguanosine-Monophosphate by 

Thymidine kinase….then Acyclo-GTP…compete with d-GTP for incorporation into viral DNA…Premature DNA termination b/c Acyclo-GMP lack 3-OH

S.E= Thrombocytopenic purpura in patient with AIDS

Cidofovir

used for CMV-induced Retinitis in AIDS patient… Contra in Renal impairs or with Nephrotoxic drugs

Fomivirsen

Antisense Oligonucleotide against CMV-mRNA…for CMV-retiniitis

Foscarnet

Phosphonoformate…used for CMV-retinitis in AIDS Pt. & for HSV, Herpes zoster infection…must be given i.v

S.E

 Chelation with cation, Hypomagnessemia, Hypocalcemia, Hypokalemia, Seizure

Ganiciclovir

analog of Acyclovir 8-20time > activity than Acyclovir… used for CMV…

cause dose-dependent Neutropenia, Carcinogenic, Embryotoxic

Penciclovir & Famciclovir

topically used for HSV1, HSV2, and VZV…

Vidaribine

only Ophthhalamic ointment… Arabinofuranosyl adenine…nucleotide analogue…for Keratitis, Junctivitis

Trifluridine= DOC in Keratoconjuctivitis


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