Review Topic
  • A 45-year-old woman presents to the emergency room with painless vision loss. She has a past medical history of HIV infection and has not been on any anti-retroviral medications due to loss of health insurance last year. Her course has been complicated by CMV esophagitis in the past, which was resistant to ganciclovir. Her last CD4+ count was < 50/uL 1 week ago. On physical exam, she is found to be dehydrated with decreased skin turgor and dry mucous membranes. Funduscopic exam shows yellow-white patches of retinal opacification. After fluid resuscitation, she is started on foscarnet. (CMV retinitis)
  • Drugs
    • foscarnet
  • Mechanism of action
    • inhibits viral DNA/RNA polymerase and HIV reverse transcriptase by preventing pyrophosphate from binding
      • the drug is a pyrophosphate (pyroFOSphate, FOScarnet) analog
      • does not need to be activated by a kinase
        • can be used in viral strains resistant to acyclovir and ganciclovir
  • Mechanism of resistance
    • mutation of viral DNA/RNA polymerase
  • Clinical use
    • cytomegalovirus (CMV) infections in immunocompromised patients (e.g., HIV)
      • especially if resistant to ganciclovir
      • can also be given in combination with ganciclovir
    • herpes simplex virus infections
      • especially if resistant to acyclovir
    • varicella zoster virus infections
  • Adverse effects
    • nephrotoxic
      • must correct dehydration prior to therapy
      • acute tubular necrosis
    • cardiac effects
      • QT prolongation
      • torsades de pointes
    • electrolyte abnormalities
      • hypocalcemia
      • hypomagnesemia
      • seizures

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