Indications

Congestive Heart Failure (CHF) (see Congestive Heart Failure)

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Diabetic Nephropathy

• Clinical Efficacy
  • Decrease renal dysfunction, need for HD or CRT, and mortality rate in type 1 DM + nephropathy

Hypertension (see Hypertension)

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Proteinuria (see Proteinuria)

• Clinical Efficacy
  • Decrease proteinuria and mortality in blacks with modest CRI due to hypertensive nephrosclerosis

Other Aspects

• If >20% increase in Cr with use of ACE-I -> highly suggestive of renal artery stenosis
  • Lesser decreases in Cr are commonly seen and usually resolve spontaneously
  • With high-grade unilateral or bilateral renal artery stenosis, >20% increase in Cr with use ACE-I has 100% sensitivity/70% specificity for detection

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Agents

• Benazepril (Lotensin) (see Benazepril)
• Captopril (Capoten) (see Captopril)
• Enalapril (Vasotec, Enalaprilat) (see Enalapril)
• Fosinopril (Monopril) (see Fosinopril)
• Lisinopril (Zestril) (see Lisinopril)
• Moexipril (Univasc) (see Moexipril)
• Perindopril (Coversyl, Coversum, Preterax, Aceon) (see Perindopril)
• Quinapril (Accupril) (see Quinapril)
• Ramipril (Altace) (see Ramipril)
• Trandolapril (Mavik) (see Trandolapril)

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Pharmacology

• Angiotensin Converting Enzyme (ACE) Inhibition
  • Antihypertensive Effect

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Administration

Concomitant Administration of ACE Inhibitors and ARB’s (see Angiotensin II Receptor Blockers)

• Combination ACE Inhibitor and ARB Therapy Increases the Risk of Adverse Effects (Arch Intern Med, 2007) [MEDLINE]: including hyperkalemia, medication discontinuation due to adverse effects, worsened renal function, and symptomatic hypotension
  • Combination ACE Inhibitor and ARB Therapy Does Not Increase the Rate of Malignancy (J Hypertens, 2001) [MEDLINE]
  • Recommendation: it is recommended to not use combination ACE inhibitor and ARB therapy

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Adverse Effects

Allergic Adverse Effects

Anaphylaxis (see Anaphylaxis)

• Epidemiology: xxx
• Treatment
  • xxx

Angioedema (see Angioedema)

• Epidemiology
  • Occurs in 0.1-0.2% of ACE inhibitor-treated patients
• Physiology
  • Mediated by bradykinins
  • Possibly mediated by autoantibodies and complement activation
• Clinical
  • Time of Onset: onset can occur from hours-months after starting ACE-Inhibitor
    • However, most cases within hrs-1 week after starting ACE-Inhibitor
  • Lingual Edema (see Lingual Edema)
  • Facial Edema (see Facial Edema)
• Treatment
  • Airway Protection: as required
  • Antihistamines (see H1-Histamine Receptor Antagonists)
    • Diphenhydramine (Benadryl) (see Diphenhydramine): 25-50 mg IV PRN
  • Epinephrine (see Epinephrine)
  • Corticosteroids (see Corticosteroids)
  • Icatibant (Firazyr) (see Icatibant)
  • Withdrawal of ACE-Inhibitor: rechallenge is contraindicated

Endocrinologic Manifestations

• Hypoaldosteronism (see Hypoaldosteronism)

Gastrointestinal Adverse Effects

• Elevation of Hepatic Transaminases with Hepatocellular Injury (see Drug-Induced Hepatotoxicity)

Pulmonary Adverse Effects

Cough (see Cough)

• Epidemiology: occurs in 5-20% of treated patients
• Physiology: likely related to accumulation of kinins and substance P (which are usually degraded by ACE and other endopeptidases)
• Clinical: dry cough with onset typically within the first few weeks of therapy (although some cases do not present with cough until months later)
• Treatment: 50% of cases with cough ultimately need to have ACE-I discontinued -> cough usually stops within 4 days of discontinuation of ACE-I
  • Rechallenge with ACE-I is not recommended, as cough will usually recur
  • However, since ARB’s have much lower incidence of cough, one of these may be substituted

Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia)

• Associated Agents
  • Captopril (see Captopril)
  • Fosinopril (see Fosinopril)
  • Perindopril

Exacerbation of Bronchospasm (see Obstructive Lung Disease)

• Epidemiology: very rare

Renal Adverse Effects

• Hyperkalemia (see Hyperkalemia): due to drug-induced hypoaldosteronism (see above)

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References

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