Acyclovir

Snapshot

• A 36-year-old man presents to the emergency department with lethargy and confusion. His symptoms began approximately 2 days ago when he experienced a headache, memory impairment, vomiting, and fever. His temperature is 101°F (38.3°C), blood pressure is 144/95 mmHg, pulse is 104/min, and respirations are 18/min. The patient has an altered level of consciousness on the physical exam. A non-contrast CT scan of the head is unremarkable. A lumbar puncture is performed and the patient is started on antibiotics. Cerebrospinal fluids results return with a mononuclear pleocytosis, elevated red blood cells and protein, and normal glucose. A polymerase chain reaction (PCR) is positive for herpes simplex virus 2. The patient’s empiric treatment has been narrowed to acyclovir. (Herpes simplex encephalitis)

Introduction

• Mechanism of action
  • acyclovir is phosphorylated by a virally-encoded thymidine kinase 
    • acyclovir triphosphate acts as a guanosine analog, which impairs viral DNA polymerase, impairing viral DNA synthesis 
      • acyclovir is not phosphorylated in uninfected cells, resulting in a favorable adverse effect profile
• Mechanism of resistance
  • altered virally-encoded thymidine kinase 
  • altered viral DNA polymerase
• Clinical use
  • herpes simplex virus 1 and 2 infection
  • varicella-zoster virus
• Adverse effects
  • acute renal failure 
    • acyclovir can precipitate into crystals in the renal tubules  
      • slow drug infusion and pre-hydration decreases this risk