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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
  • Safety
  1. Pregnancy: Category D
    1. Category C if stopped in first trimester
    2. Serious Teratogenicity risk to fetus if continued into second or third trimester
  2. Lactation
    1. Unknown
    2. Risk of Hypotension in newborns
  • Preparations (Choose once daily dosing if possible)
  1. Benzapril (Lotensin)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. Maximum: 80 mg/day
    3. Renal Dosing
      1. GFR <30: Start at 5 mg
    4. Primarily renal excretion (as benzeprilat)
    5. Available as unscored generic tablets: 5, 10, 20 and 40 mg
  2. 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)
    3. Primarily Renal Dosing
    4. Available as scored generic tablets: 12.5, 25, 50 and 100 mg
  3. Enalapril (Vasotec)
    1. Hypertension: 5 mg orally daily (maximum 40 mg/day)
    2. CHF, GFR<30: 2.5 mg orally daily to twice daily (maximum 40 mg/day)
    3. IV (Hypertensive Emergency): 1.25 mg IV every 6 hours
    4. Excretion both renal and hepatic
    5. Available as scored tablets: 2.5, 5, 10 and 20 mg
  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. Renal Impairment: 5 mg orally daily at start
    4. Maximum: 80 mg/day
    5. Excretion both renal and hepatic
    6. Available as scored tablets (10 mg) and unscored tablets (20 and 40 mg)
  5. 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. Renal Dosing
      1. GFR 10-30: 2.5 to 5 mg orally daily to start
      2. GFR <10: 2.5 mg orally daily to start
    5. Maximum 40 mg/day
    6. Primarily renal excretion
    7. Available as generic/Prinivil scored tablets (10, 20 and 40 mg)
    8. Available as generic/Zestril unscored tabs (2.5, 5, 10, 20, 30 and 40 mg)
  6. Moexipril (Univasc): Take one hour before meals
    1. Hypertension: 7.5 mg orally daily (maximum 30 mg/day)
    2. Primarily hepatic metabolism
    3. Available as generic scored tablets (7.5, 15 mg)
  7. Perindopril (Aceon)
    1. Hypertension: 4 mg orally daily (target 4-8 mg/day)
    2. Maximum 16 mg/day
    3. Primarily renal metabolism
    4. Available as generic unscored tablets (2, 4, 8 mg)
  8. Quinapril (Accupril)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. CHF: 2.5 mg to 5 mg orally twice daily
      1. Low dose is especially important if concurrent Diuretic use
      2. Titrating weekly to 20-40 mg/day
    3. Renal Dosing
      1. GFR 30-60: 5 mg orally daily to start
      2. GFR 10-30: 2.5 mg orally daily to start
    4. Maximum: 80 mg/day (no benefit above 40 mg/day)
    5. Excretion is 50-60% renal
    6. Available as generic scored tablets (5 mg) and unscored tablets (10,20 and 40 mg)
  9. Ramipril (Altace)
    1. Hypertension: 2.5 mg orally daily (target 2.5-20 mg orally daily)
    2. CHF or MI: 2.5 mg orally twice daily (target 5 mg orally twice daily)
    3. Renal Impairment or Diuretic use: 1.25 mg orally daily to start
    4. Maximum 20 mg/day
    5. Excretion both renal and hepatic
    6. Available as generic capsule (1.25, 2.5, 5, 10 mg)
  10. Trandopril (Mavik)
    1. Hypertension: 1 mg orally daily (target 2 to 4 mg orally daily)
    2. CHF: 0.5 to 1 mg orally daily (target 4 mg orally daily)
    3. Maximum: 8 mg/day
    4. Excretion 66% hepatic and 33% renal
    5. Available as generic scored tablet (1 mg) and unscored tablet (2 and 4 mg)
  • 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%