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ACE Inhibitor

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ACE Inhibitor, Angiotensin Converting Enzyme Inhibitor, Captopril, Capoten, Lisinopril, Prinivil, Zestril, Enalapril, Vasotec, Fosinopril, Monopril, Benzapril, Lotensin, Moexipril, Univasc, Perindopril, Aceon, Quinapril, Accupril, Ramipril, Altace, Trandopril, Mavik

  • Contraindications
  1. Absolute Contraindications
    1. Angioedema history
      1. Regardless of cause (even if not due to ACE Inhibitor)
    2. Pregnancy (serious Teratogenicity - black box warning)
    3. Renal Artery Stenosis
    4. ACE Inhibitor related Allergic Reaction
  2. Relative Contraindications
    1. Aortic Stenosis
    2. Hypertrophic Cardiomyopathy
  • Indications
  1. Hypertension
    1. Useless in low renin patients (esp. Black ethnicity)
    2. Low renin patients respond better to Diuretics
  2. Myocardial Infarction
    1. Early ACE Inhibitor in acute Myocardial Infarction
      1. Started within 24 hours of Anterior MI
      2. Significant reduction in CHF and death
      3. Significantly lower mortality at 1 year
    2. Reference
      1. Ambrosioni (1995) N Engl J Med 332:80-5 [PubMed]
      2. Stenestrand (2001) JAMA 285:430-6 [PubMed]
  3. Congestive Heart Failure
    1. Left ventricle Systolic Dysfunction
  4. Diabetic Nephropathy
  5. Renal Insufficiency
  • Preparations (Choose once daily dosing if possible)
  1. Captopril (Capoten)
    1. Hypertension: 25 mg orally twice to three times daily (maximum 450 mg/day)
    2. CHF: 6.25 - 12.5 mg orally three times daily (maximum 450 mg/day)
  2. Enalapril (Vasotec)
    1. Hypertension: 5 mg orally daily (maximum 40 mg/day)
    2. CHF: 2.5 mg orally daily to twice daily (maximum 40 mg/day)
    3. IV: 1.25 mg IV every 6 hours
  3. Lisinopril (Prinivil, Zestril)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. CHF: 5 mg orally daily (target 20 mg/day)
    3. Acute MI: 5 mg orally daily for 2 days then 10 mg orally daily
    4. Maximum 40 mg/day
  4. Fosinopril (Monopril)
    1. Hypertension: 10 mg orally daily (target 40 mg/day)
    2. CHF: 10 mg orally daily (target 20-40 mg/day)
    3. Maximum: 80 mg/day
  5. Benzapril (Lotensin)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. Maximum: 80 mg/day
  6. Moexipril (Univasc): Take one hour before meals
    1. Hypertension: 7.5 mg orally daily (maximum 30 mg/day)
  7. Perindopril (Aceon)
    1. Hypertension: 4 mg orally daily (target 4-8 mg/day)
    2. Maximum 16 mg/day
  8. Quinapril (Accupril)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. CHF: 5 mg orally twice daily, titrating weekly to 20-40 mg/day
    3. Maximum: 80 mg/day
  9. Ramipril (Altace)
    1. Hypertension: 2.5 mg orally daily (target 2.5-20 mg orally daily)
    2. CHF: 2.5 mg orally twice daily (target 5 mg orally twice daily)
    3. Maximum 20 mg/day
  10. Trandopril (Mavik)
    1. Hypertension: 1 mg orally daily (target 2 to 4 mg orally daily)
    2. CHF: 1 mg orally daily (target 4 mg orally daily)
    3. Maximum: 8 mg/day
  • Adverse Effects
  1. Cough (dry and irritating)
    1. Characteristics
      1. Occurs in 5 to 20% of patients
        1. More common in women
        2. More common in black patients
      2. Not dose related
      3. Stops within 4 days of medication cessation
    2. Alternative medications
      1. Angiotensin Receptor Blocker (e.g. Losartan)
    3. Inhalers may relieve cough
      1. Tilade 2 puffs inhaled four times daily
      2. Cromolyn 20 mg inhaled four times daily
  2. Hyperkalemia (5% of patients)
    1. See Drug Interactions below
    2. Asociated with Renal Insufficiency, Diabetes Mellitus
  3. Teratogenicity in second or third trimester
    1. Fetal injury or death
    2. Pregnancy Class C if discontinued in first trimester
  4. Renal Insufficiency
    1. Renal Artery Stenosis (see monitoring below)
    2. No Creatinine level is absolute contraindication
    3. Baseline Serum Creatinine <3.0 mg/dl is safe
  5. Hypotension
    1. Restart ACE Inhibitor at half prior dose
    2. Decrease or hold dose of any concurrent Diuretic
  6. Angioedema
    1. ACE-Inhibitor induced Angioedema is not an Allergic Reaction (unlike typical Angioedema)
      1. Related to bradykinin accumulation
      2. Does not respond to typical Angioedema management (e.g. Corticosteroids, Antihistamines)
    2. Occurs in 1 of 300 patients
      1. More common in african american patients by factor of 2-4 fold
    3. Reaction can occur months to years after starting an ACE Inhibitor
    4. Treatment is withdrawal of medication and supportive care
      1. See Angioedema for management
      2. Reactions may be severe and life threatening with complete airway closure
      3. May respond to agents used for Hereditary Angioedema (e.g. Icatibant, Berinert)
    5. Do not re-challenge with ACE Inhibitor
      1. ACE-Inhibitor Angioedema will recur with ARB agents in 8% of patients
      2. Avoid Angiotensin Receptor Blocker (ARB) unless a very compelling reason exists
        1. If ARB is used, wait at least 4 weeks after ACE Inhibitor has been discontinued
        2. Avoid using ARB in moderate to severe ACE Inhibitor Angioedema episode
  7. Rare Adverse Reactions
    1. Rash
    2. Agranulocytosis
    3. Neutropenia
      1. Associated with comorbid Renal Insufficiency
      2. Associated with comorbid collagen vascular disease
  • Drug Interactions
  1. Increases Lithium levels (follow levels)
  2. Decreased ACE Inhibitor levels with concurrent Antacids
  3. Decreased Renal Function with concurrent NSAID use
  4. Agents predisposing to Hyperkalemia
    1. Bactrim
    2. Potassium supplements or salt substitute
    3. Beta Blockers
    4. NSAIDs
    5. Potassium sparing Diuretics
      1. Triamterene
      2. Spironolactone
  • Monitoring
  1. Serum Potassium (if patient at risk)
  2. Serum Creatinine
    1. Timing
      1. Baseline
      2. Recheck in 4 days to 2 weeks
    2. Expect an increase in Chronic Kidney Disease
      1. Despite this, renal protective effect outweighs mild to moderate Creatinine increase
    3. Indication to consider stopping ACE Inhibitor
      1. Serum Creatinine increased >20% in 4 days
    4. Additional precautions when increasing dose
      1. Serum Creatinine should not increase >30%