Wednesday, November 28, 2007

Chap 49: Antivirals

INTRODUCTION
- needs to block viral entry/exit from host cell
- or active inside host cell
- hence toxicity relates to intefering host cell function

- viral infection --> replication peaks at/before manisfestation of clinical symptoms
- hence the reason for early initiation of therapy OR prevention of infection (chemoprophylaxis for influenzae A using amantidine)

- stages of viral replication


  1. adsorption --> enter host cell
  2. uncoating of viral neucleic acid
  3. systhesis of early regulatory proteins --> nucleic acid polymerases
  4. systhesis of RNA/DNA
  5. systhesis of late, structural proteins
  6. assembly of viral particles
  7. release from cell
AGENTS FOR HSV and VZV
- acyclovir, famvir, valacyclovir
- acyclovir the earliest hence most studied

Acyclovir
- acyclic guanosine derivative
- requires 3 phosphorylation steps for activation --> eventually inhibit viral DNA polymerase
- clinical uses

  • primary genital herpes - shortens duration by 5 days
  • recurrent genital herpes - shortens by 1-2 days
  • VZV - needs higher dosage
- SE

  • generally well tolerated
  • minor GIT SE: N/V
  • neurotoxic - tremor, deliriumm seizure
Valacyclovir
- L-valyl ester of acyclovir
- rapidly converted to acyclovir after po
- serum levels 3-5x higher than with aciclovir

Famcyclovir
Penciclovir
Trifulridine

Agents against CMV
Ganciclovir
- affinity against CMV 100x more than aciclovir
- active against CMV, HSV, VZV, EBV, HHV-8

Valganciclovir
- converted into ganciclovir
- for treatment of CMV retinitis for pt with AIDS

Cidofovir
Foscarnet
Fomivirsen

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