Indications

• Acute Myocardial Infarction (see Coronary Artery Disease)
• Congestive Heart Failure (CHF) (see Congestive Heart Failure): aterload reduction
• Hypertension (see Hypertension)

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Pharmacology

• Angiotensin Converting Enzyme (ACE) Inhibitor (see Angiotensin Converting Enzyme (ACE) Inhibitors)

Metabolism

• xxx

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Administration

• PO:

Dose Adjustment

• Hepatic
• Renal

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

• Combination ACE Inhibitor and ARB Therapy Increases the Risk of Adverse Effects (Arch Int 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, 2011) [MEDLINE]
  • Recommendation: it is recommended to not use combination ACE inhibitor and ARB therapy

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Adverse Effects

Allergic/Immunologic Adverse Effects

Anaphylaxis (see Anaphylaxis)

• Epidemiology: xxx
• Treatment: see Anaphylaxis

Angioedema (see Angioedema)

• Epidemiology: occurs in 0.1-0.2% of ACE-Inhibitor treated patients
• Physiology: class effect (common to all ACE inhibitors)
  • Mediated by bradykinins (and possibly 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, [[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

Cardiovascular Adverse Effects

Hypotension (see Hypotension)

• Physiology: class effect (common to all ACE inhibitors)

Endocrinologic Manifestations

Hypoaldosteronism (see Hypoaldosteronism)

• Physiology: class effect (common to all ACE inhibitors)

Gastrointestinal Adverse Effects

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

• xxx

Pulmonary Adverse Effects

Cough (see Cough)

• Epidemiology: occurs in 5-20% of treated patients
• Physiology: class effect (common to all ACE inhibitors)
  • Likely related to accumulation of kinins and substance P (which are usually degraded by ACE and other endopeptidases)
• Clinical: dry cough with onset typically wihtin 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)

• Physiology: class effect
  • Associated Agents
    • Captopril (see Captopril)
    • Fosinopril (see Fosinopril)
    • Perindopril (Coversyl, Coversum, Preterax, Aceon) (see Perindopril)

Exacerbation of Bronchospasm (see Obstructive Lung Disease)

• Epidemiology: very rare
• Physiology: class effect (common to all ACE inhibitors)

Renal Adverse Effects

Acute Kidney Injury (AKI) (see Acute Kidney Injury)

• xxxx

Hyperkalemia (see Hyperkalemia)

• Physiology: class effect (common to all ACE inhibitors)
  • Due to drug-induced hypoaldosteronism (see above)

Rheumatologic Adverse Effects

Drug-Induced Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)

• Epidemiology: low-moderate risk of developing drug-induced SLE
• Physiology: class effect (common to all ACE inhibitors)

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References

• xxx