drug adverse effects of ACE inhibitors

Adverse effects

• cough
  • may occur after several weeks to 1 year
  • dose reduction may alleviate cough
  • switching ACE inhibitor is generally of little benefit
• hyperkalemia & hyponatremia via inhibition of aldosterone secretion*
• hypotension & renal insufficiency with reduced preload
  • may decrease GFR & increase serum creatinine in patients with renal perfusion maintained by increased angiotensin-2
• acute renal insufficiency may develop in patients with bilateral renal artery stenosis*
• rash
• angioedema (1%)
  • generally occurs within 1st week
  • may occur years later
  • more common in blacks than whites; 1% vs 0.3%
  • probably via inhibiting breakdown of bradykinin
  • small intestine angioedema presenting as acute abdominal pain
  • 2% of patients with angioedema on an ACE inhibitor also get angioedema on an ARB
  • standard therapy consists of intravenous prednisolone 500 mg plus clemastine 2 mg
  • icatibant 30 mg SQ is an alternative
  • may not respond to epinephrine
  • wait at least 4 weeks after stopping an ACE inhibitor to start an ARB
• dysgeusia
• increased serum creatinine
  • 15-20% initial increase is acceptable; up to 30% acceptable
  • decline in creatinine within 1 month (2 months), otherwise discontinue
  • increases in serum creatinine after the start of ACE inhibitor or ARB is associated with adverse cardiorenal outcomes, even below the guideline recommended threshold of a 30% increase for stopping treatment
  • <2% with serum creatinine increases of >=30%
    • these patients with increased risk for
      • end-stage renal disease (RR=3.4)
      • myocardial infarction (RR=1.5)
      • heart failure (RR=1.4)
      • all-cause mortality (RR=1.8)
• proteinuria may or may not be present
• contrast nephropathy
• leukopenia
• vasomotor rhinitis
• may exacerbate psoriasis
• congenital malformations when used during 1st trimester of pregnancy
• exposure during the 2nd & 3rd trimesters of pregnancy are associated with neonatal renal failure & death
• associated with increased risk of hospitalization with acute renal failure
• increased risk of lung cancer relative to ARB (1.6 vs 1.2 per 1000 person-years)
• increased risk of stroke 11% & stroke mortality 19% vs diuretic

* Serum creatinine & K+ should be checked within 1 week of starting an ACE inhibitor.

More general terms

• drug adverse effect(s)