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Updated: Dec 25 2021

Protease Inhibitors

  • Snapshot
    • A 34-year-old man presents to the emergency room with acute epigastric pain. He denies any alcohol use. He is HIV-positive currently on highly active antiretroviral therapy. His past medical history is significant for a cholecystectomy 5 years ago without any complications. Laboratory evaluation reveals normal electrolytes, including calcium. A CT scan of his abdomen reveals acute pancreatitis. Upon careful review of his medications, 1 antiretroviral medication in particular increased this patient’s risk for acute pancreatitis. (Acute pancreatitis induced by a protease inhibitor)
  • Introduction
    • Drugs
      • atazanavir
      • darunavir
      • fosamprenavir
      • indinavir
      • lopinavir
      • nelfinavir
      • ritonavir
      • saquinavir
      • tipranavir
    • Mechanism of action
      • inhibits HIV-1 protease (pol gene), which cleaves HIV mRNA
      • prevents complete development of new viruses
    • Mechanism of resistance
      • usually requires multiple mutations in the pol gene
    • Clinical use
      • highly active antiretroviral therapy (HAART)
      • second-line therapy for patients resistant to first-line therapies
    • Adverse effects
      • hyperglycemia
      • gastrointestinal upset
        • saquinavir
      • acute pancreatitis
      • fat redistribution/lipodystrophy
        • Cushing-like syndrome with “buffalo hump” on the upper back
      • indinavir-specific side effects
        • nephropathy
        • kidney stones
        • hematuria
        • thrombocytopenia
      • interaction with rifampin (CYP450 inducer)
        • rifampin decreases concentrations of protease inhibitors in the body
        • rifabutin is recommended in patients on HAART
      • ritonavir
        • CYP450 inhibitor
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