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# ACE Inhibitors ## Overview ACE inhibitors (e.g., lisinopril, enalapril, ramipril) are a class of medications that block the activity of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. This results in decreased blood pressure and reduced workload on the heart. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (for certain agents) * Diabetic nephropathy (proteinuric kidney disease) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient factors. Titration is typically required. * **Hypertension:** Initial doses vary (e.g., lisinopril 5-10 mg daily, enalapril 5 mg daily, ramipril 2.5 mg daily). Maximum doses also vary by agent (e.g., lisinopril 40 mg daily, enalapril 40 mg daily, ramipril 10 mg daily). * **Heart Failure:** Initial doses are usually lower than for hypertension to minimize risk of hypotension and renal dysfunction (e.g., lisinopril 2.5-5 mg daily, enalapril 2.5 mg twice daily, ramipril 1.25-2.5 mg daily). Doses are titrated upwards as tolerated based on clinical response and renal function. Maximum doses vary (e.g., lisinopril 20-40 mg daily, enalapril 20 mg twice daily, ramipril 10 mg daily). * **Post-MI:** Typically initiated within 24 hours of MI if no contraindications exist (e.g., captopril 6.25 mg three times daily, escalating to target dose). Specific agents and protocols vary. ## Pediatric Dosing ACE inhibitors are generally not first-line agents for hypertension in children unless secondary to specific conditions (e.g., renovascular hypertension). Dosing is typically based on body weight and requires careful titration. * **Hypertension:** Dosing varies significantly by age and agent. For example, enalapril is often dosed at 0.05 mg/kg/day initially, titrating up to 0.2 mg/kg/day (max 40 mg/day). Lisinopril has been used at 0.07-0.2 mg/kg/day (max 20 mg/day). Consult pediatric guidelines for specific recommendations. ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally required for patients with impaired renal function. Specific recommendations vary by agent and creatinine clearance. * **Hepatic Impairment:** Use with caution. Enalapril is a prodrug converted to its active form in the liver; impaired hepatic function may affect efficacy. ## Contraindications * History of angioedema related to ACE inhibitor therapy * Concomitant use of aliskiren in patients with diabetes mellitus or renal impairment * Pregnancy (teratogenic) * Known hypersensitivity to the specific ACE inhibitor ## Adverse Effects * **Most common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia. * **Less common but serious:** Angioedema (can be life-threatening, especially involving the airway), acute kidney injury, hepatic dysfunction, neutropenia, rash. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May blunt antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients. * **Diuretics (thiazide and loop):** Increased risk of hypotension, particularly after initiation of ACE inhibitor. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use, especially in patients with diabetes or renal impairment. ## Monitoring * **Renal function (serum creatinine, BUN):** Baseline and periodically, especially after dose increases or in patients with risk factors. * **Serum potassium:** Baseline and periodically, particularly in patients with renal impairment or those taking potassium-sparing agents. * **Blood pressure:** Regularly to assess efficacy and guide titration. * **Signs and symptoms of angioedema:** Patients should be counseled to report immediately. * **Baseline complete blood count (CBC):** May be considered in specific populations or with prolonged high-dose therapy. ## Clinical Pearls * Cough is a common, dose-dependent side effect that typically resolves upon discontinuation. * Angioedema is a rare but life-threatening emergency; patients must be educated to seek immediate medical attention if symptoms occur. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, have heart failure, or renal impairment, to minimize risk of hypotension and acute kidney injury. * Monitor potassium closely, especially in patients with risk factors for hyperkalemia. * Discontinue immediately if pregnancy is detected due to teratogenic risks. *** *Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult the most current prescribing information and relevant clinical guidelines for definitive drug information and patient-specific management.*