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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI patients with LV dysfunction or clinical signs of HF) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is usually performed every 1-4 weeks. * **Hypertension:** Typical starting doses vary by agent. For example: * Lisinopril: 10 mg once daily. Maximum: 40 mg once daily. * Enalapril: 5 mg once or twice daily. Maximum: 40 mg once or twice daily. * Ramipril: 2.5 mg once daily. Maximum: 10 mg once daily. * **Heart Failure:** Dosing often starts lower and is titrated more slowly than for hypertension. For example: * Lisinopril: 2.5-5 mg once daily. Target doses often 20-40 mg once daily. * Enalapril: 2.5 mg twice daily. Target doses often 10-20 mg twice daily. * **Post-MI:** Typically initiated within 24 hours of symptom onset in hemodynamically stable patients. Starting doses are low, e.g., * Captopril: 6.25 mg three times daily. * Lisinopril: 5 mg once daily. * **Diabetic Nephropathy:** Often initiated at standard doses for hypertension or heart failure, with titration based on proteinuria and blood pressure response. ## Pediatric Dosing ACE inhibitor use in pediatrics is less established and often off-label. Dosing is weight-based and requires careful titration. Consult specialized pediatric guidelines or a pediatric cardiologist/nephrologist. * **Hypertension:** * Enalapril: Generally 0.08-0.1 mg/kg/dose once or twice daily. Maximum doses vary by age and indication. * Lisinopril: Generally 0.07-0.2 mg/kg/dose once daily. Maximum doses vary by age and indication. ## Dose Adjustments * **Renal Impairment:** Dosage reduction is often necessary, especially in moderate to severe renal impairment. Monitor serum creatinine and potassium closely. * Example: For enalapril, if creatinine clearance < 30 mL/min, the usual starting dose is 2.5 mg/day, titrated upwards as tolerated. * **Hepatic Impairment:** Generally less dose adjustment needed, but caution advised, particularly with enalapril (a prodrug requiring hepatic activation). ## 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. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (rare but life-threatening, can occur anytime), acute kidney injury (especially in volume-depleted or renally impaired patients), hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, especially in the elderly or volume-depleted. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction; generally contraindicated in combination, especially in diabetic patients. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor for efficacy and hypotension. * **Renal Function:** Serum creatinine and BUN, particularly at initiation and dose increases, or in patients with risk factors. * **Serum Potassium:** Monitor for hyperkalemia, especially in patients with renal impairment, diabetes, or concomitant use of potassium-sparing agents. * **Angioedema:** Educate patients to report any swelling, especially of the face, lips, tongue, or throat, immediately. ## Clinical Pearls * The characteristic dry cough is a common reason for discontinuation and may be managed by switching to an Angiotensin II Receptor Blocker (ARB). * Initiate at a low dose and titrate slowly, especially in patients who are volume-depleted, have heart failure, renal impairment, or are elderly. * Avoid concomitant use with ARBs and aliskiren unless specifically indicated and closely monitored according to guideline recommendations. * Contraindicated in pregnancy due to risk of fetal harm. *** *Disclaimer: This information is for educational purposes and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for definitive dosing, indications, contraindications, and safety information before prescribing or administering any medication.*