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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used to manage cardiovascular diseases. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI management) * Diabetic nephropathy * Proteinuric chronic kidney disease ## Adult Dosing Dosing varies significantly by agent and indication. Doses are typically initiated low and titrated upwards based on clinical response and tolerability. * **Hypertension:** * Benazepril: Start 10 mg once daily, max 40 mg once daily. * Captopril: Start 25 mg twice daily, max 150 mg three times daily. * Enalapril: Start 5 mg once daily, max 40 mg once daily. * Fosinopril: Start 10 mg once daily, max 80 mg once daily. * Lisinopril: Start 10 mg once daily, max 40 mg once daily. * Moexipril: Start 7.5 mg once daily, max 30 mg once daily. * Perindopril: Start 2.5-5 mg once daily, max 10 mg once daily. * Quinapril: Start 10 mg once daily, max 80 mg once daily. * Ramipril: Start 2.5 mg once daily, max 10 mg once daily. * Trandolapril: Start 0.5-1 mg once daily, max 4 mg once daily. * **Heart Failure:** * Captopril: Start 6.25 mg three times daily, max 50 mg three times daily. * Enalapril: Start 2.5 mg twice daily, max 10-20 mg twice daily. * Lisinopril: Start 5 mg once daily, max 40 mg once daily. * Ramipril: Start 1.25-2.5 mg twice daily, max 10 mg twice daily. * **Post-Myocardial Infarction:** * Enalapril: Start 5 mg, may increase to 10 mg twice daily. * Lisinopril: Start 5 mg once daily, may increase to 10 mg once daily. * Ramipril: Start 1.25 mg once daily, may increase to 5 mg twice daily. * **Diabetic Nephropathy/Proteinuric CKD:** * Dosing is often similar to hypertension, with the goal of reducing proteinuria. ## Pediatric Dosing Dosing for pediatric patients is less standardized and often requires careful titration. Generally, ACE inhibitors are dosed by weight. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/dose every 12-24 hours, max 0.6 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/dose once daily, max 0.6 mg/kg/day or 40 mg/day. * Ramipril: 0.05 mg/kg/day once daily, max 0.1 mg/kg/day or 10 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific guidelines vary by agent and severity of renal impairment (eGFR). * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. * **Volume Depletion/Hyponatremia:** Initiate at a lower dose. * **Concomitant Diuretic Use:** May require lower starting doses. ## 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 (teratogenic effects). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, rash, liver enzyme elevations. ## Key Drug Interactions * **Potassium-Sparing Diuretics/Potassium Supplements/ARBs/Aliskiren:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Lithium:** ACE inhibitors can increase lithium levels, potentially leading to toxicity. * **Diuretics:** Increased risk of symptomatic hypotension, especially with potent diuretics. ## Monitoring * **Baseline:** Renal function (serum creatinine, eGFR), electrolytes (serum potassium), blood pressure. * **During therapy:** Renal function and electrolytes, particularly after dose initiation/titration, with concurrent diuretic use, in patients with renal impairment, or in heart failure. Blood pressure. * **For cough/angioedema:** Patient-reported symptoms. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. It typically resolves after discontinuation of the drug. * Angioedema is a rare but serious side effect and requires immediate discontinuation of the ACE inhibitor and prompt medical attention. * Initiate ACE inhibitors at low doses and titrate slowly, especially in patients who are volume-depleted, on diuretics, elderly, or have heart failure or renal impairment. * Monitor potassium closely, especially in patients with renal insufficiency or those taking potassium-sparing diuretics. * ACE inhibitors are generally not recommended for black patients as initial monotherapy for hypertension due to a lower response rate, but can be effective in combination therapy. *** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient-specific appropriateness.