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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Congestive Heart Failure (CHF) * Post-myocardial infarction (MI) in patients with decreased left ventricular ejection fraction * Diabetic nephropathy * Proteinuric chronic kidney disease ## Adult Dosing Dosing varies significantly by specific agent and indication. Therapy typically starts at a low dose and titrates upward based on patient response and tolerability. * **Hypertension:** Initial doses are typically low, with titration to a maximum dose based on the specific agent (e.g., lisinopril 10 mg once daily, max 40 mg; ramipril 2.5 mg once daily, max 10 mg). * **Heart Failure:** Initial doses are low, with titration guided by blood pressure, renal function, and symptoms (e.g., enalapril 2.5-5 mg twice daily, max 10 mg twice daily; lisinopril 2.5-5 mg once daily, max 10 mg once daily; ramipril 1.25-2.5 mg once daily, max 10 mg once daily). * **Post-MI:** Commonly initiated within 24 hours of MI if no contraindications exist (e.g., captopril 6.25 mg TID, titrating up to 50 mg TID; ramipril 1.25 mg QD, titrating up to 10 mg QD). * **Diabetic Nephropathy/CKD:** Doses are similar to hypertension, aiming for blood pressure control, often with a target of <130/80 mmHg. ## Pediatric Dosing ACE inhibitor use in children is less established than in adults and often guided by specialist recommendations. Dosing is typically weight-based and may differ by age group. * **Hypertension:** Dosing varies by agent (e.g., enalapril 0.08 mg/kg/day PO divided BID, max 0.59 mg/kg/day or 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally recommended, particularly in moderate to severe renal impairment (CrCl < 30 mL/min). Close monitoring of serum creatinine and potassium is essential. * **Hepatic Impairment:** Generally, dose adjustments are not routinely required, but caution is advised. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment * Hereditary or idiopathic angioedema * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment * Pregnancy (especially in the second and third trimesters) ## Adverse Effects * **Dry cough:** Common, often dose-dependent. * **Hyperkalemia:** Increased risk, especially in patients with renal impairment or those taking potassium supplements/sparing diuretics. * **Hypotension:** Especially with the first dose or in volume-depleted patients. * **Angioedema:** Rare but potentially life-threatening, characterized by swelling of the face, lips, tongue, or throat. * **Renal impairment:** Can worsen pre-existing renal disease, particularly in those with bilateral renal artery stenosis. * **Dizziness, fatigue, headache.** * **Rash.** * **Dysgeusia (altered taste).** ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May decrease antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially loop and thiazide):** Increased risk of hypotension. * **Lithium:** ACE inhibitors can reduce 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 impairment. Avoid concomitant use in high-risk patients. ## Monitoring * **Blood pressure:** Regularly, especially after dose initiation or changes. * **Renal function:** Serum creatinine and BUN, particularly at baseline, after dose increases, and in patients with risk factors for renal dysfunction. * **Serum potassium:** At baseline, after dose increases, and in patients with risk factors for hyperkalemia. * **Signs and symptoms of angioedema.** * **Signs and symptoms of heart failure.** ## Clinical Pearls * Initiate therapy at a low dose and titrate slowly, especially in elderly patients, those with renal impairment, or those on diuretics. * First-dose hypotension can be significant; consider lower starting doses or withholding diuretics temporarily. * Angioedema is a medical emergency; discontinue the ACE inhibitor immediately and manage airway if necessary. * A persistent dry cough is a common side effect and may necessitate switching to an ARB. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. --- *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety.*