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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity. ## Primary Indications * Hypertension * Heart Failure (HF) * Left Ventricular Dysfunction post-Myocardial Infarction (MI) * Diabetic Nephropathy * Renal Insufficiency in patients with Type 1 diabetes ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is usually required. * **Hypertension:** Starting doses vary by agent. Titrate upwards every 1-4 weeks as needed. Usual maintenance doses vary but generally range from: * Benazepril: 10-40 mg once daily * Captopril: 25-150 mg twice daily * Enalapril: 10-40 mg once daily * Fosinopril: 10-40 mg once daily * Lisinopril: 10-40 mg once daily * Moexipril: 7.5-30 mg once daily * Perindopril: 5-20 mg once daily * Quinapril: 10-80 mg twice daily * Ramipril: 2.5-20 mg once daily * Trandolapril: 1-4 mg once daily * **Heart Failure:** Starting doses are typically lower than for hypertension, with gradual titration. * Captopril: 6.25 mg TID to 50 mg TID * Enalapril: 2.5 mg BID to 10 mg BID (max 20 mg BID) * Lisinopril: 5 mg QD to 10 mg QD (max 20-40 mg QD) * Ramipril: 1.25 mg QD to 10 mg QD (max 10 mg QD) * **Post-MI:** Initiate within 24 hours of symptom onset if stable. * Captopril: 6.25 mg TID, titrate to 50 mg TID * Enalapril: 5 mg QD, titrate to 10 mg BID * Lisinopril: 5 mg QD, titrate to 10 mg QD * **Diabetic Nephropathy:** * Lisinopril: 10-20 mg once daily * Ramipril: 5 mg once daily (max 10 mg once daily) ## Pediatric Dosing Dosing in children is less established and often based on weight. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/day divided BID (max 0.5 mg/kg/day or 40 mg/day) * Lisinopril: 0.07-0.2 mg/kg/day once daily (max 20 mg/day) * Ramipril: 0.05 mg/kg/day once daily (max 10 mg/day) ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly for agents primarily renally eliminated. For moderate to severe renal impairment, start at the lower end of the dose range and titrate cautiously. Specific recommendations vary by agent. * **Hepatic Impairment:** Use with caution; may require dose adjustment, especially for prodrugs like enalapril and ramipril. ## Contraindications * History of angioedema related to ACE inhibitor therapy * Concomitant use with aliskiren in patients with diabetes * Pregnancy (especially second and third trimesters) * Hypersensitivity to ACE inhibitors ## Adverse Effects * **Common:** Cough (dry, persistent), hyperkalemia, dizziness, fatigue, headache, hypotension. * **Serious:** Angioedema (can be life-threatening, affecting face, lips, tongue, larynx), acute kidney injury, severe hypotension, hyperkalemia, neutropenia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Increased risk of hypotension. * **Aliskiren:** Increased risk of hyperkalemia and hypotension; avoid concomitant use, especially in patients with diabetes. * **ARBs:** Increased risk of adverse events, including angioedema and renal dysfunction; use with caution. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Renal function (serum creatinine, BUN)** * **Electrolytes (serum potassium)** * **Blood pressure** * **Signs and symptoms of angioedema** * **Baseline and periodic complete blood count (CBC)**, especially in patients at risk for neutropenia. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * First-dose hypotension can occur, particularly in patients who are volume-depleted or on diuretics. Consider withholding diuretics temporarily prior to starting an ACE inhibitor. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. *** *This information is intended as a reference and does not substitute for professional clinical judgment. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.*