Updated: 3/7/2019

Protease Inhibitors

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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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