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# ACE Inhibitors ## Overview ACE inhibitors are a class of medications that block the action of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (for certain agents and indications) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Doses should be titrated gradually to the lowest effective dose. * **Hypertension:** * Benazepril: Start at 5-10 mg once daily. Max: 40 mg/day. * Captopril: Start at 6.25-12.5 mg TID. Max: 50 mg TID. * Enalapril: Start at 2.5-5 mg once daily. Max: 40 mg/day. * Fosinopril: Start at 10 mg once daily. Max: 80 mg/day. * Lisinopril: Start at 5-10 mg once daily. Max: 40 mg/day. * Moexipril: Start at 7.5 mg once daily. Max: 30 mg/day. * Perindopril: Start at 2.5-5 mg once daily. Max: 10 mg/day. * Quinapril: Start at 5-10 mg BID. Max: 80 mg/day. * Ramipril: Start at 2.5-5 mg once daily. Max: 10 mg/day. * Trandolapril: Start at 0.5-1 mg once daily. Max: 4 mg/day. * **Heart Failure:** * Enalapril: Start at 2.5 mg BID. Titrate up to target dose, typically 10 mg BID. Max: 20 mg BID. * Lisinopril: Start at 5 mg once daily. Titrate up to target dose, typically 10-20 mg once daily. * Ramipril: Start at 1.25-2.5 mg once daily. Titrate up to target dose, typically 5 mg BID or 10 mg once daily. * Captopril: Start at 6.25 mg TID. Titrate up to target dose, typically 50 mg TID. * **Post-MI:** (e.g., Ramipril, Lisinopril) Dosing and initiation time depend on specific guidelines and patient stability. Typically starts within 24 hours of STEMI in patients with anterior MI, LV dysfunction, or heart failure. * **Diabetic Nephropathy:** Dosing often similar to hypertension, aiming for maximal tolerated dose to reduce proteinuria. ## Pediatric Dosing * **Hypertension:** Dosing varies significantly by age and weight. Often initiated at lower doses and titrated. Specific recommendations are highly dependent on the agent and often based on expert consensus or guidelines. For example: * Enalapril: 0.07-0.1 mg/kg/dose every 12-24 hours. Max: 0.5 mg/kg/day. * Lisinopril: 0.07-0.2 mg/kg/day once daily. Max: 20 mg/day. * Captopril: 0.3 mg/kg/dose every 8 hours. Max: 6 mg/kg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in moderate to severe renal impairment. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Some agents (e.g., enalapril, lisinopril) undergo minimal hepatic metabolism and may not require significant dose adjustment. Others may need caution. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * Cough (dry, persistent): Most common, may be dose-dependent. * Angioedema: Rare but life-threatening; can occur at any time. * Hyperkalemia: Risk increased with renal impairment, potassium supplements, or potassium-sparing diuretics. * Hypotension: Especially with the first dose or in volume-depleted patients. * Acute kidney injury: Risk increased in patients with bilateral renal artery stenosis. * Dizziness, fatigue, headache. * Rash, altered taste. * Neutropenia/agranulocytosis: Rare. ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride), potassium supplements, and salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May blunt antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially loop and thiazide):** Increased risk of hypotension, particularly after initiation. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment; generally contraindicated in combination with ACE inhibitors in diabetic patients. ## Monitoring * Blood pressure: Before and during treatment. * Serum creatinine and potassium: Baseline and periodically, especially with dose changes, renal impairment, or other risk factors. * Renal function: Assess for signs of worsening renal function. * Signs and symptoms of angioedema. * Complete blood count (CBC): Consider baseline and periodically if risk factors exist (e.g., autoimmune disease). ## Clinical Pearls * Initiate at a low dose and titrate gradually to minimize side effects like hypotension and cough. * ACE inhibitors are generally renoprotective in diabetic patients with proteinuria. * Discontinue immediately if angioedema occurs and never re-challenge. * Patients with a dry cough may benefit from switching to an ARB. * First-dose hypotension is more likely in patients taking diuretics or with heart failure. Consider holding diuretics for 2-3 days prior to initiating ACE inhibitor therapy. *** *This information is intended for healthcare professionals. Always consult the official prescribing information and current clinical guidelines for the most up-to-date and complete drug information.*