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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 by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, decreased aldosterone secretion, and reduced sympathetic nervous system activity. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (to improve survival and reduce recurrent MI) * Diabetic nephropathy (to slow progression) * Chronic kidney disease (in select populations) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient factors. Starting doses are typically low and titrated upwards. * **Hypertension:** Common starting doses (e.g., enalapril 5 mg PO QD, lisinopril 10 mg PO QD, ramipril 2.5 mg PO QD). Maximum doses vary by agent (e.g., enalapril 40 mg/day, lisinopril 40 mg/day, ramipril 10 mg/day). * **Heart Failure:** Common starting doses (e.g., enalapril 2.5-5 mg PO BID, lisinopril 5 mg PO QD, ramipril 1.25-2.5 mg PO BID). Doses are titrated upwards based on tolerability and clinical response. Maximum doses are generally higher than for hypertension (e.g., enalapril 20 mg BID, lisinopril 20-35 mg QD, ramipril 5 mg BID). * **Post-MI:** Common starting doses (e.g., captopril 6.25 mg PO TID, ramipril 2.5 mg PO BID). Titration aims for target doses based on clinical trial data (e.g., captopril 50 mg TID, ramipril 5 mg BID). * **Diabetic Nephropathy:** Common starting doses (e.g., enalapril 10 mg PO QD, lisinopril 10 mg PO QD). Doses are often titrated to achieve maximal proteinuria reduction while maintaining tolerability (e.g., enalapril 20 mg/day, lisinopril 20 mg/day). ## Pediatric Dosing Dosing is not well-established for all ACE inhibitors in pediatrics and often relies on adult guidelines or specific pediatric studies. * **Hypertension:** * Enalapril: 0.08 to 0.2 mg/kg/day PO QD or BID; Max 40 mg/day. * Lisinopril: 0.07 to 0.2 mg/kg/day PO QD; Max 40 mg/day. * Ramipril: 0.03 to 0.06 mg/kg/day PO QD; Max 10 mg/day. * *Note: Dosing varies significantly by age and indication. Consult pediatric-specific resources.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally required. The degree of reduction depends on the creatinine clearance and the specific ACE inhibitor. Close monitoring of renal function and serum potassium is essential. * **Hepatic Impairment:** Cautious initiation and slow titration are recommended. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Known hypersensitivity to ACE inhibitors. * Pregnancy (especially the second and third trimesters). ## Adverse Effects * **Common:** Dry cough, dizziness, fatigue, hyperkalemia, headache. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, hypotension, hepatotoxicity, rash. ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid dual therapy unless specifically indicated and closely monitored. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid in patients with diabetes or renal impairment. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to increased serum lithium levels. ## Monitoring * **Renal function (serum creatinine, BUN):** Baseline and periodically thereafter, especially after dose increases or in patients with risk factors for renal impairment. * **Serum potassium:** Baseline and periodically, especially in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics or supplements. * **Blood pressure:** Regular assessment to ensure efficacy and detect hypotension. * **Signs and symptoms of angioedema:** Patient education is crucial. ## Clinical Pearls * Cough is a common, dose-related side effect that usually resolves upon discontinuation. * Angioedema is a rare but serious adverse effect that requires immediate discontinuation and emergency management. Risk is higher in Black patients. * Initiation in patients with heart failure or post-MI should be done cautiously and titrated as tolerated. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. * First-dose hypotension can occur, particularly in patients who are volume-depleted or on diuretics. Consider holding diuretics for 2-3 days prior to initiating ACE inhibitor therapy. *** *This information is intended for healthcare professionals and does not replace the need to consult current prescribing information, clinical guidelines, and individual patient factors before making any treatment decisions.*