Angiotensin Converting Enzyme (ACE) Inhibitors

Indications

Clinical Aspects

  • Decrease renal dysfunction, need for HD or CRT, and mortality rate in type 1 DM + nephropathy
  • Decrease proteinuria and mortality in blacks with modest CRI due to hypertensive nephrosclerosis
  • 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

Agents

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

Pharmacology

  • Angiotensin Converting Enzyme (ACE) Inhibition
    • Antihypertensive Effect

Adverse Effects

Allergic Adverse Effects

Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])

  • Epidemiology: xxx
  • Treatment: see see Anaphylaxis, [[Anaphylaxis]]

Angioedema (see Angioedema)

  • Epidemiology
    • Occurs in 0.1-0.2% of 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, [[Lingual Edema]])
    • Facial Edema (see Facial Edema, [[Facial Edema]])
  • Treatment
    • Airway Protection: as required
    • Antihistamines (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])
      • Diphenhydramine (Benadryl) (see Diphenhydramine, [[Diphenhydramine]]): 25-50 mg IV PRN
    • Epinephrine (see Epinephrine, [[Epinephrine]])
    • Corticosteroids (see Corticosteroids, [[Corticosteroids]])
    • Icatibant (Firazyr) (see Icatibant, [[Icatibant]])
    • Withdrawal of ACE-Inhibitor: rechallenge is contraindicated

Endocrinologic Manifestations

Gastrointestinal Adverse Effects

Pulmonary Adverse Effects

Cough (see Cough, [[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 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, [[Drug-Induced Pulmonary Eosinophilia]])

  • Associated Agents
    • Captopril (see Captopril, [[Captopril]])
    • Fosinopril (see Fosinopril, [[Fosinopril]])
    • Perindopril

Exacerbation of Bronchospasm (see Obstructive Lung Disease, [[Obstructive Lung Disease]])

  • Epidemiology: very rare

Renal Adverse Effects

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

References

  • xxx