ACE INHIBITORS

I. Indications

  1. HTN
  2. CHF
  3. Prevention of Diabetic Nephropathy

II. Differences among them

  1. Captopril* (Capoten)12.5-150mg/d divided BID-TID--the oldest; may have the following adverse effects not noted in others, probably due to a sulfhydryl moiety not present in other ACEIs; however, all these are uncommon at newer, lower doses (<150mg/d) which are just as effective as older high-dose regimens
  1. Mucocutaneous lesions
  2. Taste changes
  3. Neutropenia-dose-related; much more frequent in pts with collagen vascular disease
  4. Pemphigus
  5. Membranous glomerulopathy with proteinuria
  6. Interstitial nephritis (RARE)-rash, fever, eosinophilia, eos in urine, azotemia
  1. Enalapril* (Vasotec) 2.5-40mg/d divided QD-BID
  2. Lisinopril* (Prinivil, Zestril) 5-40 QD-less risk of sig. hypotension than enalapril
  3. Fosinopril (Monopril) 10-40mg/d divided QD-BID
  4. Benazepril* (Lotensin) 10-40 divided QD or BID
  5. Ramipril (Altace) 1.25-20mg/d divided QD-BID
  6. Moexipril* (Univasc) 7.5-30mg/d divided BID
  7. Quinapril (Accupril) 5-80mg/d divided QD-BID
  8. Trandolapril* (Mavik) 1-4mg QD
  9. Perindopril (Aceon) 4-8mg divided QD-BID
  10. Enalaprilat 1.25-5mg Q6h IV
  11. Omapatrilat
    1. Inhibits both ACE and neutral endopeptidase (NEP) which breaks down natriuretic peptides, which have vasodilatory effects
    2. Similar side f/x to other ACEI's
    3. In clinical trials as of 1999
  12. Ramipril may be ass'd with lower mortality than other ACEIs in post-MI patients--Click HERE for details

*--Available in combination with other drugs (diuretics or Ca-blockers) as of 1999

III. Dosing considerations and precautions

  1. All are renally excreted; may need dose adjustment in renal failure
  2. Avoid concomittant treatment with potassium-sparing diuretics
  3. Start with low dose (e.g. Enalapril 2.5 mg QD) & taper upward carefully if any of the following at baseline:
  1. [Na] < 130
  2. [Cr] > 150-300 micromol/l
  3. On K-sparing diuretics
  1. Consider hosp'zing for 1st 24h of tx if:
  1. "Unstable" CHF requiring high-dose diuretics or >1 vasodilator
  2. NYHA class IV
  3. "Marked" hyponatremia
  1. When starting tx, monitor BP, K, Cr (highest risk of renal failure if pt has mild hyponatremia
  2. Don't give during pregnancy

IV. Adverse effects:

  1. Hypotension
  1. Risk factors: elderly; high renin states, i.e. where maintenance of BP is dependent on AII (diuretic tx, pre-tx Na <130)
  2. Us. appears with first dose with captopril but may take sev. weeks to appear with others
  3. To avoid: start with small doses and titrate up
  4. Hypotension may cause deaths in ACEI pts! (CONSENSUS II, NEJM 327:678, 9/92)
  1. Renal effects
  1. ACEIs decrease glomerular pressure by dilating post-glomerular efferent arterioles; thus decreasing proteinuria in pts with DM or hypertensive nephropathy
  2. Can cause azotemia & hyperkalemia, esp. in pts with pre-existing azotemia or volume depletion or hyponatremia (same mech. as below)
    1. Risk factors for hyperkalemia in pts in 1800 outpts on ACEIs (Arch. Int. Med. 158:26, 1998--JW)
      1. BUN > 18
      2. Cr > 1.6
      3. Use of long-acting ACE e.g. enalapril or lisinopril
      4. CHF> 70yo
  1. With bilateral RA stenosis (or unilateral and single kidney), can get SEVERE but reversible renal failure
  1. This is due to dilation of efferent arterioles in the setting of maximal prerenal.preglomerular vasodilation
  2. In this setting, glomerular filtration is maintained by increased efferent (post-glomerular) arteriolar resistance, mediated by AII
  3. Thus ACEI's cause decreased GFR and thus renal failure
  4. Occasionally can cause irreversible renal damage but not consistently
  1. Treatment of ACEI-induced renal failure-decrease dose of any co-administered diuretic (?); increase Na intake (?)
  2. In most instances, increase of serum Cr of < 30% in the first 2wks of ACEI use is not associated with progressive renal insufficiency, according to a review of 12 randomized trials (Arch. int. Med. 160:685, 2000--AFP)
  1. Angioedema
  1. Us. occurs 1-7d after starting; us. stops 3-5d after stopping drug
  2. Prob. a biochemical and not an immunological mechanism
  1. Hypoaldosteronism with hyponatremia and hyperkalemia and metabolic acidosis
  1. More common with pre-existing hyper-renin states (see above), azotemia, concomittant treatment with K, NSAIDs, beta-blockers, or K-sparing diuretics
  1. Cough
  1. 5-30% get it; not much diff. among diff. ACEIs
  2. Can get bronchospasm with asthmatics
  3. Starts 3d-12mo after starting tx
  4. Remits 1d-4wks after stopping
  5. Occurs more often in women than in men
  1. Hypoglycemia in pts on oral hypoglycemics (RARE)
  1. Contraindicated in Pregnancy--may cause serious teratogenic effects

(Source: Crit. Care Clin. 7:555, 1991)