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# ACE Inhibitors ## Overview ACE inhibitors (e.g., lisinopril, enalapril, ramipril) block the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart Failure (reduced ejection fraction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing * **Hypertension:** Initial doses vary by agent. For example, lisinopril 10 mg PO once daily, enalapril 5 mg PO once or twice daily, ramipril 2.5 mg PO once or twice daily. Titrate upwards based on blood pressure response. Maximum doses are agent-specific (e.g., lisinopril 40 mg/day, enalapril 40 mg/day, ramipril 10 mg/day). * **Heart Failure:** Initial doses are typically lower than for hypertension. For example, lisinopril 5 mg PO once daily, enalapril 2.5 mg PO twice daily. Titrate upwards based on patient tolerance and clinical response. * **Post-MI:** Typically initiated within 24 hours of MI if no contraindications exist. For example, captopril 6.25 mg PO three times daily, then titrate as tolerated. * **Diabetic Nephropathy:** Similar starting doses to hypertension, titrating to achieve blood pressure goals and reduce proteinuria. Dosing regimens should be individualized based on the specific agent, patient response, and presence of comorbidities. Local institutional protocols may guide initial dosing and titration schedules. ## Pediatric Dosing ACE inhibitors are generally not first-line agents for pediatric hypertension. Dosing is highly variable and should be guided by specialist recommendations and based on weight. For example, enalapril in pediatric patients has been dosed from 0.04-0.2 mg/kg/day divided BID. ## Dose Adjustments * **Renal Impairment:** Dose reduction is typically required, especially in severe renal insufficiency. Specific guidelines vary by agent and degree of impairment. * **Hepatic Impairment:** Some agents may require dose adjustment, though often used cautiously. ## Contraindications * History of angioedema related to ACE inhibitor therapy * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment * Pregnancy (especially during the second and third trimesters) * Hypersensitivity to the drug ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, headache, fatigue. * **Serious:** Angioedema (can be fatal, especially involving the airway), hyperkalemia, acute kidney injury (especially in patients with bilateral renal artery stenosis), neutropenia, rash. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment. * **Aliskiren:** Increased risk of hypotension, hyperkalemia, and renal impairment. Contraindicated in patients with diabetes. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use. * **Lithium:** Reduced lithium clearance, increasing risk of lithium toxicity. * **Diuretics (especially thiazides):** Increased risk of hypotension, particularly after the first dose. ## Monitoring * **Blood Pressure:** Regularly, especially during initiation and dose titration. * **Renal Function (SCr, BUN):** Before and shortly after initiation, and periodically thereafter. * **Serum Potassium:** Before and shortly after initiation, and periodically thereafter, especially in patients with risk factors for hyperkalemia. * **Angioedema:** Educate patients to report immediately any swelling of the face, lips, tongue, or throat. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and is often reversible upon discontinuation. * Initiate at a low dose and titrate slowly to minimize hypotension and other adverse effects, particularly in volume-depleted patients or those with heart failure. * First-dose hypotension is a concern; monitor closely after the initial dose. * Risk of angioedema is increased in Black patients. * Avoid in pregnancy due to potential for fetal harm. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details.*