ACE Inhibitors

Snapshot

• A 67-year-old Caucasian man presents to his primary care physician for follow-up of his hypertension. He was recently started on a lisinopril for chronic hypertension. He has been monitoring his blood pressure at home and they have all been within the normal range. However, he reports a new cough that began a few days after starting lisinopril.

Introduction

• Mechanism of action
  • inhibits angiotensin-converting enzyme (ACE) 
    • ↓ angiotensin II (AT II) 
      • recall that AT II increases blood pressure by constricting renal and peripheral vasculature and increasing sodium reasorption in the kidney
      • ↓ AT II prevents constriction of efferent arterioles and ↓ glomerular filtration rate (GFR)  
    • ↓ negative feedback and ↑ renin
    • ↑ bradykinin, a potent vasodilator
      • ACE normally degrades/inactivates bradykinin 
• Clinical use
  • hypertension
  • myocardial infarction
    • prevents heart remodeling 
  • heart failure (this medication decreases mortality)
  • proteinuria 
  • diabetic nephropathy
• Toxicity
  • cough  
  • angioedema  
    • due to ↑ bradykinin
    • contraindicated in patients with C1 esterase inhibitor deficiency 
  • teratogenic effects on fetuses
    • disrupts fetal renal development
    • contraindicated in pregnant woman
  • ↑ creatinine (↓ GFR) 
    • contraindicated in bilateral renal artery stenosis because ACE inhibitors may further ↓ GFR and cause renal failure 
  • hyperkalemia 
  • hyponatremia
  • metabolic acidosis
  • hypotension
• Medications
  • captopril
  • lisinopril
  • enalapril
  • ramipril