Acyclovir

Overview
  • Acyclovir is a generally well-tolerated, topically or orally administered herpes antiviral. Newer analogs of the drug, famciclovir and valacyclovir, are also commonly used and possess the same basic properties as acyclovir.
Antiviral Spectrum
  • Acyclovir is most effective against Herpes Simplex Virus and provides modest protection against Varicella Zoster Virus. The drug is relatively ineffective against EBV and does not provide much protection against cytomegalovirus.
Mechanism of Action
  • Acyclovir is a structural analog of guanosine which lacks a true cyclical sugar, thus giving the drug is "acyclic" namesake. Although host enzymes can effectively distinguish acyclovir from guanosine, the enzymes of certain Herpes Viruses cannot, resulting in its specific herpes antiviral activity. Herpes viruses possess their own thymidine kinase which performs the initial phosphorylation of nucleosides for entry into nucleotide synthesis. Herpes, but not host thymidine kinase, inappropriately phosphorylates acyclovir which then enters the nucleotide synthetic pathway and become tri-phosphorylated. Acyclovir is then inappropriately incorporated, in place of guanosine, by herpes viral DNA polymerase as it replicates the viral genome. However, the acyclic structure of acyclovir does not allow further extension of the DNA chain, causing chain termination and thus inhibiting viral genome replication.
Adverse Effects
  • Nephrotoxicity: High dosages of acyclovir within the context of dehydration may result in crystalization of the drug in renal tubules; however, this effect is reversible.