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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure with reduced ejection fraction (HFrEF) * Post-myocardial infarction (MI) for patients with evidence of left ventricular dysfunction or heart failure. * Diabetic nephropathy ## Adult Dosing Dosing varies significantly by specific ACE inhibitor and indication. Doses are typically initiated low and titrated upwards based on patient response and tolerance. * **Hypertension:** Usual starting doses for common agents include: * Lisinopril: 10 mg once daily, titrate up to 20-40 mg once daily. * Enalapril: 5 mg once or twice daily, titrate up to 10-20 mg once or twice daily. * Ramipril: 2.5 mg once daily, titrate up to 10 mg once daily. * Maximum doses are generally 40 mg daily for lisinopril and enalapril, and 10 mg daily for ramipril, but may be higher in specific situations per local protocol. * **Heart Failure:** * Lisinopril: Initiate at 5 mg once daily, titrate to 20-40 mg once daily. * Enalapril: Initiate at 2.5 mg once or twice daily, titrate to 10-20 mg once or twice daily. * Ramipril: Initiate at 2.5 mg once daily, titrate to 5-10 mg once daily. * Maximum doses typically 40 mg daily for lisinopril and enalapril, and 10 mg daily for ramipril. * **Post-MI:** * Lisinopril: Initiate at 5 mg once daily, with doses of 5-10 mg once daily. * Other ACE inhibitors may be initiated within 24 hours of symptom onset for patients with anterior MI or evidence of heart failure. ## Pediatric Dosing Dosing in pediatric patients varies by agent, age, and indication and is often weight-based. Consult specific pediatric guidelines or formularies. * **Hypertension:** * Enalapril: 0.08 mg/kg/day to 0.58 mg/kg/day divided once or twice daily. * Lisinopril: 0.07 mg/kg/day to 0.61 mg/kg/day once daily. * Specific recommendations for neonates and infants require careful consideration due to potential renal effects. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in patients with severe renal impairment (CrCl < 30 mL/min). Start at a lower dose and titrate cautiously. * **Hepatic Impairment:** Use with caution. Dose adjustments may be needed for agents primarily metabolized by the liver. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, fatigue, hyperkalemia. * **Serious:** Angioedema (facial, lip, tongue, glottis, limbs), acute kidney injury (especially in susceptible individuals), hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May decrease antihypertensive effect and increase risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid in patients with diabetes. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of adverse effects, including renal impairment, hyperkalemia, and hypotension. Avoid concomitant use. * **Lithium:** Reduced lithium clearance, increasing risk of lithium toxicity. ## Monitoring * **Blood Pressure:** Regularly monitor for hypotension. * **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and with dose increases or in patients with renal impairment. * **Potassium Levels:** Monitor serum potassium, particularly in patients with renal impairment, hyperkalemia, or those taking potassium-sparing agents. * **Angioedema:** Educate patients on signs and symptoms and to seek immediate medical attention if they occur. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and is usually reversible upon discontinuation. * ACE inhibitors are generally considered renoprotective in patients with diabetic nephropathy. * Initiate at the lowest effective dose and titrate slowly, especially in patients who are volume-depleted, have heart failure, or renal impairment. * Discontinue immediately if angioedema occurs. *** *Disclaimer: This information is intended for clinical decision support and does not replace professional judgment. Always verify current prescribing information and consult relevant guidelines before initiating or modifying therapy.*