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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (in select patients) * Diabetic nephropathy (proteinuria) * Chronic kidney disease (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. * **Hypertension:** Typical starting doses are low and titrated upwards. Common starting doses include: * Enalapril: 2.5-5 mg once or twice daily * Lisinopril: 5-10 mg once daily * Ramipril: 2.5 mg once daily * *Maximum doses vary by agent and indication, but commonly range from 20-40 mg daily for most agents.* * **Heart Failure:** Usually initiated at a lower dose than for hypertension and titrated upwards as tolerated. * Enalapril: 2.5 mg twice daily, titrate to target dose of 10 mg twice daily. * Lisinopril: 2.5-5 mg once daily, titrate to target dose of 20 mg once daily. * Ramipril: 1.25-2.5 mg twice daily, titrate to target dose of 5 mg twice daily. * **Post-MI:** Typically initiated within 24 hours if no contraindications exist. * Captopril: 6.25 mg three times daily, titrated upwards. * Enalapril: 5 mg once or twice daily, titrated upwards. * **Diabetic/Chronic Kidney Disease:** Dosing often starts low and titrates to the maximum tolerated dose to achieve target blood pressure or proteinuria reduction. ## Pediatric Dosing ACE inhibitors are generally not first-line agents in pediatric hypertension. Dosing should be initiated by a specialist. * **Hypertension:** Dosing varies by age and weight. * Enalapril: 0.07-0.1 mg/kg/dose once daily; may increase up to 0.5 mg/kg/day in divided doses. * Lisinopril: 0.07-0.2 mg/kg/dose once daily (max 40 mg/day). * *Exact dosing and maximums depend on the specific agent and available pediatric studies. Uncertainty exists for many pediatric indications.* ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Monitor serum creatinine and potassium. Significant renal impairment may require dose reduction or discontinuation. * **Hepatic Impairment:** No specific dose adjustment is usually required, but caution is advised, especially with agents with short half-lives. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters, Category C in 1st trimester). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (rare but potentially fatal), acute kidney injury, neutropenia/agranulocytosis (rare), hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (especially thiazides):** Increased risk of symptomatic hypotension, especially after first dose. * **Lithium:** Increased lithium levels and toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., saxagliptin, linagliptin):** Increased risk of angioedema. * **ARBs, Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid combination. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), urinalysis. * **During Therapy:** Blood pressure, serum creatinine, electrolytes (especially potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. Monitor for signs/symptoms of angioedema or other adverse effects. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an ARB. * Initiate at a low dose and titrate slowly, especially in patients with heart failure, renal impairment, or those taking diuretics. * First-dose hypotension is a risk, particularly in volume-depleted patients. Consider withholding diuretics temporarily or initiating at a lower dose. * ACE inhibitors are generally safe and effective in diabetic patients and can slow the progression of nephropathy. * Discontinue immediately if angioedema occurs and never re-challenge. *** *This information is intended for healthcare professionals and does not replace professional medical advice. Always consult the most current prescribing information and relevant guidelines before making any clinical decisions.*