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# ACE Inhibitors ## Overview ACE inhibitors (e.g., lisinopril, enalapril, ramipril) are a class of medications that block the renin-angiotensin-aldosterone system (RAAS) by inhibiting angiotensin-converting enzyme (ACE). This leads to vasodilation and reduced sodium and water retention, thereby lowering blood pressure. ## Primary Indications * Hypertension * Heart Failure (HF) with reduced ejection fraction (HFrEF) * Post-myocardial infarction (MI) to improve survival * Diabetic nephropathy * Certain chronic kidney diseases (CKD) ## Adult Dosing * **Hypertension:** Initial doses vary by agent. For example: * Lisinopril: 10 mg once daily. * Enalapril: 5 mg once daily. * Ramipril: 2.5 mg once daily. * Titrate based on blood pressure response. Usual maintenance doses range from 10-40 mg daily for lisinopril, 10-40 mg daily for enalapril, and 5-10 mg daily for ramipril. Maximum doses vary by agent and indication. * **Heart Failure (HFrEF):** Initial doses are typically lower than for hypertension to minimize risk of hypotension. For example: * Lisinopril: 2.5-5 mg once daily. * Enalapril: 2.5 mg twice daily. * Ramipril: 1.25-2.5 mg twice daily. * Titrate upwards as tolerated over weeks to months. Typical target doses for maintenance therapy are: * Lisinopril: 35-40 mg once daily. * Enalapril: 10 mg twice daily. * Ramipril: 5 mg twice daily. * **Post-MI:** Initiated within 24 hours in stable patients. * Lisinopril: 5 mg once daily, increased to 10 mg once daily. * Enalapril: 2.5 mg twice daily, increased to 5 mg twice daily, then 10 mg twice daily. * Ramipril: 1.25 mg once daily, increased to 2.5 mg twice daily, then 5 mg twice daily. * **Diabetic Nephropathy/CKD:** Doses are similar to hypertension, titrated to achieve target blood pressure and/or reduce proteinuria. ## Pediatric Dosing Dosing in children is weight-based and depends on the specific ACE inhibitor and indication. Due to variability and limited data for some agents, consultation with a pediatric specialist or pharmacist is recommended. Examples: * **Hypertension (Enalapril):** 0.08 mg/kg/day to 0.58 mg/kg/day divided once or twice daily. * **Hypertension (Lisinopril):** 0.07 mg/kg/day to 0.61 mg/kg/day once daily. ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally required in patients with significant renal impairment (creatinine clearance < 30 mL/min). Specific reductions depend on the agent and degree of renal dysfunction. Monitor potassium closely. * **Hepatic Impairment:** Use with caution. No specific dose adjustments are usually recommended for mild to moderate impairment, but initiation at lower doses is prudent. ## 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. * Second or third trimester of pregnancy. * Hypersensitivity to the specific ACE inhibitor or its components. ## Adverse Effects * **Common:** Dry cough, dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (can be life-threatening, involving face, lips, tongue, throat, intestines), acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), hypotension, rash, elevated liver enzymes. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension, particularly after initiation. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment. * **ARBs, Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use, especially in patients with diabetes or renal impairment. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), complete blood count (CBC). * **During Therapy:** * Blood pressure regularly. * Renal function (serum creatinine) within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Serum potassium within 1-2 weeks of initiation or dose increase, and periodically thereafter, especially in patients with risk factors for hyperkalemia. * Monitor for signs/symptoms of angioedema and cough. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and typically resolves within 1-4 weeks after discontinuation. * Angioedema is a medical emergency. Discontinue ACE inhibitor immediately if suspected. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, on diuretics, elderly, or have heart failure or renal impairment, to avoid excessive hypotension. * In patients with HFrEF, ACE inhibitors are a cornerstone of therapy and should be initiated and titrated as tolerated to target doses unless contraindicated. * Switching to an ARB may be an option for patients who develop a cough with ACE inhibitors, though cross-reactivity for angioedema exists. --- *This information is intended for healthcare professionals and should not be considered a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.*