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Introduction
  • Classification
    • antiviral
      • viral DNA polymerase inhibitors
        • acyclovir
  • Drugs
    • acyclovir
Mechanism
  • Both acyclovir and ganciclovir are guanosine analogs dependent on phosphorylation for activation
    • the main difference between the 2 drugs lies in the mechanism by which they are phosphorylated
  • Action of acyclovir
    • monophosphorylated by HSV/VZV thymidine kinase
      • most herpesviridae have this kinase → kills herpesviridae
      • CMV does not have this kinase → less effective against CMV
      • human cells do not have this kinase → low toxicity to human cells
    • further phosphorylated by host cells to form triphosphate
    • acyclovir-triphosphate is incorporated into DNA molecule and terminates the chain
  • Resistance
    • via lack of thymidine kinase
Uses
  • Generally reserved for serious infections or immunocompromised
  • HSV
    • lesions
    • encephalitis
    • no effect on latent virus
  • VZV (varicella zoster)
    • prophylaxis in immunocompromised
    • reduce symptoms of chickenpox in early stages
    • no effect on latent virus
    • famciclovir preferred for shingles
  • EBV
Adverse effects
  • Usually well tolerated
  • Not hematotoxic (ganciclovir is)
  • Neurotoxicity
  • Renal failure secondary to crystalline nephropathy  
  • Must prehydrate to decrease the risk 
 

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