Antiviral Agents Flashcards
Influenza Virus Replicative Life Cycle
• Binds to the cell surface of an airway epithelial cell - endocytosed and internalized into endosomes
• The acidified endosomal environment promotes a conformational change in hemagglutinin structure that
mediates fusion between the influenza viral envelope and the endosomal membrane.
• Activation of and proton influx through the viral M2 proton channel elicits the release of the RNA genome
and its subsequent replication and assembly into new virus particles.
• Egress of newly synthesized virions results in their being tethered to the plasma member via the interaction
with hemagglutinin and cellular sialic acid moieties. Viral envelope-bound neuraminidases cleave the
sequestered sialic acid moieties, resulting in virion release
Influenza Drugs
1) Inhibition of Viral Neuraminidase (influenza A, B, C)
Oseltamivir, Zanamivir, Peramivir
2) Inhibition of Uncoating (influenza A)
Amantadine, Rimantadine
Herpes Virus Replicative Cycle
• Cellular attachment and entry followed by viral uncoating
• Transfer of viral DNA into host nuclei wherein viral immediate-early genes are transcribed to direct the
synthesis of viral genome replicating genes (e.g., thymidine kinase, DNA polymerase, etc.)
• Upon completion of viral genome replication, late viral encoded genes direct the assembly and packaging of
virion progeny
• Progeny undergo budding to facilitate their ultimate release from host cells
Herpes Drugs
1) Inhibitors of viral DNA polymerase: Acyclovir, Valacyclovir, Penciclovir, Famciclovir 2) Inhibitors of Viral Penetration: Docosanol 3) Inhibitors of viral DNA polymerase: Ganciclovir, Valganciclovir
Cytomegalovirus Drugs
1) Inhibitors of viral DNA polymerase:
Ganciclovir, Valganciclovir
Foscarnet
Respiratory syncitial virus Drugs
1) Inhibits IMP dehydrogenase, viral RNA-dep RNA polymerase:
Ribavirin
Oseltamivir, Zanamivir, Peramivir
1) Mechanism of Action: inhibit viral neuraminidase to decrease viral budding (decrease infectivity) (blocks viral release by cell)
2) Pharmacokinetics: oseltamivir (orally as prodrug); zanamivir (inhalation); peramivir (IV); all renally excreted
3) Spectrum / Uses: prophylaxis/treatment of influenza A, B, C
4) Adverse Reactions: nausea/vomiting (oseltamivir)
bronchospasm (zanamivir)
Amantadine, Rimantadine
1) Mechanism of Action: inhibit viral uncoating by block of viral M2 proton channel
2) Pharmacokinetics: good po, accumulates in lungs, renal [A] or hepatic [R] elimination
3) Spectrum / Uses: prophylaxis/treatment of influenza A [emergence of resistance has been high]
4) Adverse Reactions: A: GI upset, insomnia, confusion, headache (fewer CNS effects with rimantadine)
Acyclovir, Valacyclovir, Penciclovir, Famciclovir
1) Mechanism of Action: phosphorylated by viral thymidine kinase > inhibits viral DNA polymerase plus chain termination (blocks DNA synthesis)
2) Pharmacokinetics: [A]: topical, oral, IV formulations; bioavailability [A: 15-30%, VAL / FAM: 80% (prodrugs), P: topical only]; all renal excretion
3) Spectrum / Uses: HSV-1/HSV-2 (mucosal, genital, encephalitis), also varicella-zoster (higher doses)
4) Adverse Reactions: minor toxicities (headache, n/v); higher levels with valacyclovir may increase risk of CNS / renal side effects
Docosanol (OTC)
1) Mechanism of Action: inhibits fusion between plasma membrane and HSV envelope (blocks viral attachment/entry)
2) Pharmacokinetics: topically applied 5 X daily
3) Spectrum / Uses: HSV-1 labialis
4) Adverse Reactions: well tolerated
Ganciclovir, Valganciclovir
1) Mechanism of Action: phosphorylated by viral thymidine kinase to active form that inhibits viral DNA polymerase
2) Pharmacokinetics: G: poor oral absorption; (good w/valganciclovir), distributes to CNS, renal excretion
3) Spectrum / Uses: HSV, VZV, CMV (more active, but more toxic than acyclovir); sight-threatening CMV retinitis
4) Adverse Reactions: bone marrow depression (neutropenia, thrombocytopenia); CNS (HA, behavioral changes)
Cidofovir
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Foscarnet
1) Mechanism of Action: pyrophosphate analog, (no activation step), inhibits viral/DNA/RNA polymerase and RT (block DNA/RNA sythesis)
2) Pharmacokinetics: poor oral bioavailability; requires continuous infusion
3) Spectrum / Uses: CMV infections ([GAN] resistant) , CMV retinitis, acyclovir resistant herpes infections; VZV; HIV (2nd line)
4) Adverse Reactions: renal impairment, severe n/v; electrolyte imbalance; (esp. hypocalcemia)
Ribavirin
1) Mechanism of Action: triphosphorylated to active form inhibits IMP dehydrogenase, viral RNA-dep RNA polymerase
2) Pharmacokinetics: aerosol administration; well-absorbed orally, long intracellular t1/2
3) Spectrum / Uses: respiratory syncitial virus (RSV) (inh); hepatitis C (oral) (w/interferon) (and pneumonia)
4) Adverse Reactions: low aerosol toxicity, but teratogen,; systemic toxicity includes anemia, bone marrow depression
