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Updated: Jan 26 2020


  • 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
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