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# ACE Inhibitors ## Overview ACE inhibitors (e.g., lisinopril, enalapril, ramipril) are a class of medications primarily used to treat cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (left ventricular dysfunction) * Diabetic nephropathy (proteinuric) ## Adult Dosing Dosing is highly individualized and dependent on the specific agent, indication, and patient response. Titration is essential. * **Hypertension:** Typical starting doses include: * Lisinopril: 10 mg once daily. Maximum: 40 mg once daily. * Enalapril: 5 mg once or twice daily. Maximum: 40 mg once daily. * Ramipril: 2.5 mg once or twice daily. Maximum: 10 mg twice daily. * **Heart Failure:** Typical starting doses include: * Lisinopril: 5 mg once daily. Maximum: 40 mg once daily. * Enalapril: 2.5 mg once or twice daily. Maximum: 20 mg twice daily. * Ramipril: 1.25 mg once or twice daily. Maximum: 10 mg twice daily. * **Post-MI:** Typically initiated within 24 hours if stable. Dosing follows heart failure guidelines, with specific target doses for certain agents (e.g., ramipril 5 mg twice daily). * **Diabetic Nephropathy:** Doses are generally similar to hypertension, titrated to achieve target blood pressure and reduce proteinuria. ## Pediatric Dosing * **Hypertension:** Dosing varies by age and weight. * Enalapril: Neonates and infants: 0.1 mg/kg/dose every 8-48 hours. Children: 0.1-0.5 mg/kg/day divided every 8-24 hours. Maximum dose varies. * Lisinopril: Children 6-12 years: 0.07-0.2 mg/kg/dose once daily. Maximum: 20 mg once daily. * Benazepril: Children 1-5 years: 0.1-0.2 mg/kg/day divided every 12-24 hours. Children 6-12 years: 0.1-0.3 mg/kg/day divided every 12-24 hours. Maximum dose varies. * *Note: Pediatric dosing requires careful consideration and may vary based on manufacturer recommendations and local protocols.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially with lower creatinine clearance. Monitor renal function closely. * **Hepatic Impairment:** Generally no dose adjustment needed for most ACE inhibitors, but caution advised due to potential for altered metabolism. * **Volume Depletion:** Initiate at lower doses. Correct volume depletion prior to initiating ACE inhibitor therapy. ## 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), hyperkalemia, dizziness, fatigue, hypotension, headache. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, severe hypotension, hyperkalemia. * **Rare:** Hepatitis, pancreatitis, neutropenia, agranulocytosis. ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 Inhibitors:** May blunt antihypertensive effect and increase risk of renal impairment, particularly in volume-depleted patients or those with pre-existing renal disease. * **Diuretics (Thiazide, Loop):** Increased risk of hypotension and azotemia, especially with initiating ACE inhibitor therapy. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **mTOR Inhibitors (e.g., sirolimus, everolimus), DPP-4 Inhibitors (e.g., sitagliptin):** Increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, serum electrolytes (especially potassium), serum creatinine, BUN. * **During Therapy:** Blood pressure, serum electrolytes, serum creatinine, BUN. Monitor for cough and signs of angioedema. * **Frequent Monitoring:** In patients with heart failure, renal impairment, or initiating therapy. ## Clinical Pearls * The characteristic dry cough is usually non-productive and may resolve upon discontinuation. * Angioedema can occur at any time during therapy and requires immediate discontinuation. * First-dose hypotension is a risk, particularly in patients who are salt or volume depleted or taking diuretics. Consider a lower starting dose or temporary discontinuation of diuretics. * ACE inhibitors are generally considered renoprotective in patients with proteinuria, especially diabetic nephropathy. * Avoid in pregnancy due to potential for fetal harm. *** **Disclaimer:** This information is for educational purposes and is not a substitute for professional medical advice. Always consult with a qualified healthcare provider to ensure accurate diagnosis and treatment, and to review the most current prescribing information for any medication.