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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 decreased aldosterone secretion, which reduces sodium and water retention. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (MI) * Diabetic nephropathy (proteinuria) ## Adult Dosing Dosing varies by specific ACE inhibitor and indication. Titration is common, guided by patient response and tolerability. * **Hypertension:** Initial doses are typically low, with gradual increases every 1-4 weeks as needed. Examples: * Lisinopril: 10 mg orally once daily, may increase to 40 mg daily. * Enalapril: 5 mg orally once or twice daily, may increase to 40 mg daily. * Ramipril: 2.5 mg orally once daily, may increase to 10 mg daily. * **Heart Failure:** Often initiated at lower doses than for hypertension. * Lisinopril: 5 mg orally once daily, target 10-40 mg daily. * Enalapril: 2.5 mg orally twice daily, target 10-20 mg daily. * Ramipril: 1.25 mg orally once daily, target 10 mg daily. * **Post-MI:** Typically started within 24 hours of symptom onset if no contraindications. * Captopril: 6.25 mg orally three times daily, titrate up to 50 mg three times daily. * Lisinopril: 5 mg orally once daily, target 10 mg daily. * **Diabetic Nephropathy:** * Lisinopril: 10 mg orally once daily, may increase to 20 mg daily. * Ramipril: 1.25 mg orally once daily, may increase to 5 mg daily. ## Pediatric Dosing ACE inhibitor use in pediatrics is less well-established than in adults and often relies on expert consensus or institutional protocols. Dosing is typically weight-based. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/dose orally every 12-24 hours. Maximum dose generally 0.61 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/dose orally once daily. Maximum dose generally 40 mg/day. * Captopril: 0.3-0.5 mg/kg/dose orally every 8 hours. Maximum dose generally 150 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in severe renal insufficiency. Specific recommendations vary by drug and creatinine clearance. For example, captopril and enalapril require dose adjustments. Lisinopril may require less adjustment due to its elimination profile. * **Hepatic Impairment:** Use with caution. Ester prodrugs (e.g., enalapril, ramipril) may have reduced efficacy due to decreased conversion to active metabolites. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (teratogenic effects, especially in the second and third trimesters). * Known hypersensitivity to ACE inhibitors. * History of hereditary or idiopathic angioedema. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, headache, hyperkalemia, fatigue, renal dysfunction. * **Less Common/Serious:** Angioedema (including laryngeal edema, potentially fatal), acute kidney injury, severe hypotension, rash, neutropenia, taste disturbances. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) & Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs & COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in volume-depleted patients. * **Diuretics:** Additive hypotensive effect; risk of hypovolemia and hyperkalemia. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. * **mTOR Inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. * **ARBs & Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Concomitant use with aliskiren in patients with diabetes is contraindicated. ## Monitoring * **Blood Pressure:** Assess at baseline and regularly during therapy. * **Serum Potassium:** Monitor at baseline, within 1-2 weeks of initiation or dose adjustment, and periodically thereafter. * **Renal Function (Serum Creatinine/BUN):** Monitor at baseline, within 1-2 weeks of initiation or dose adjustment, and periodically thereafter, especially in patients with renal insufficiency or heart failure. * **Angioedema:** Educate patients on signs and symptoms and to seek immediate medical attention. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and may occur months after initiation. Discontinuation typically resolves the cough. * Angioedema is a rare but life-threatening side effect. It can occur at any time during treatment, even after prolonged use. Patients should be advised to stop the medication and seek emergency care immediately if symptoms develop. * Initiate at low doses and titrate slowly, particularly in patients who are volume-depleted, elderly, or have renal impairment, to minimize the risk of symptomatic hypotension. * ACE inhibitors are generally considered safe and effective in patients with diabetes, and can offer renal protection by reducing proteinuria. * Discontinue ACE inhibitors during pregnancy due to the risk of fetal harm. *** *This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and local institutional protocols before making clinical decisions.*