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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that primarily 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, resulting in lower blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI with evidence of LV dysfunction or HF) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (non-diabetic, proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is typically done every 1-4 weeks. * **Benazepril:** Hypertension 10-40 mg once daily. Heart failure 5-40 mg once daily. * **Captopril:** Hypertension 25-150 mg twice daily (max 450 mg/day). Heart failure 6.25-12.5 mg TID (max 150 mg/day). MI 6.25 mg TID (may increase to 50 mg TID). * **Enalapril:** Hypertension 10-40 mg once daily. Heart failure 2.5-20 mg BID (max 40 mg/day). MI 5 mg BID (may increase to 10 mg BID). * **Fosinopril:** Hypertension 10-40 mg once daily. Heart failure 5-20 mg once daily (max 40 mg/day). * **Lisinopril:** Hypertension 10-40 mg once daily (max 80 mg/day). Heart failure 5-20 mg once daily (max 40 mg/day). MI 5 mg once daily (may increase to 10 mg once daily). * **Moexipril:** Hypertension 7.5-30 mg once daily. * **Perindopril:** Hypertension 2.5-10 mg once daily. Heart failure 2.5-10 mg once daily. Post-MI 5 mg once daily (may increase to 10 mg once daily). * **Ramipril:** Hypertension 2.5-20 mg once daily. Heart failure 1.25-10 mg once daily. Post-MI 1.25-10 mg once daily. * **Trandolapril:** Hypertension 1-4 mg once daily. Heart failure 0.5-2 mg once daily. * **Quinapril:** Hypertension 10-80 mg once daily or BID. Heart failure 5-20 mg BID (max 80 mg/day). ## Pediatric Dosing ACE inhibitor use in children is less common and generally reserved for resistant hypertension or specific comorbidities. Dosing varies significantly by agent and age. * **Enalapril:** Neonates/Infants 0.01-0.1 mg/kg/dose BID. Children 1 month to <6 years 0.1 mg/kg/dose BID (max 0.5 mg/kg/day). Children 6 years to <12 years 0.1-0.3 mg/kg/dose BID (max 20 mg/day). * **Lisinopril:** Children 6-12 years 0.07-0.2 mg/kg/dose once daily (max 20 mg/day). * **Ramipril:** Children ≥10 years 1.25 mg once daily, titrate up to 2.5 mg once daily (max 5 mg/day for hypertension). *Note: Pediatric dosing may require specific local protocols and expert consultation.* ## Dose Adjustments * **Renal Impairment:** Reduce dose and titrate cautiously. Baseline GFR and serum creatinine are crucial. * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. * **Volume Depletion/Hyponatremia:** Initiate at lower doses (e.g., 5 mg lisinopril, 2.5 mg enalapril). ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use of aliskiren in patients with diabetes mellitus. * Pregnancy (teratogenic). ## Adverse Effects * **Cough:** Dry, persistent cough is common. * **Hypotension:** Especially in volume-depleted or salt-depleted patients. * **Hyperkalemia:** Monitor potassium levels. * **Angioedema:** Rare but life-threatening; can occur at any time. Discontinue immediately. * **Renal Dysfunction:** May worsen renal function, particularly in patients with bilateral renal artery stenosis. * **Dizziness, fatigue, headache.** * **Rash.** * **Taste disturbances (captopril).** ## 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:** Increased lithium levels and toxicity. * **Diuretics:** Additive hypotensive effect; increased risk of hypotension and electrolyte imbalances. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * Blood pressure (seated and standing). * Serum potassium. * Renal function (serum creatinine, GFR). * Signs and symptoms of angioedema. * Signs and symptoms of hyperkalemia. ## Clinical Pearls * Start at a low dose and titrate slowly, especially in patients with heart failure or renal impairment. * Advise patients to report any swelling of the face, lips, tongue, or throat immediately. * A dry cough can be a dose-limiting side effect for some patients; consider switching to an ARB if cough is persistent and bothersome. * ACE inhibitors are generally not recommended for initial monotherapy in Black patients with hypertension unless they have specific comorbidities like heart failure or chronic kidney disease. *** *This information is intended for healthcare professionals. Always refer to the most current prescribing information and consult with a qualified healthcare provider for any medical advice or treatment decisions.*