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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, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Left ventricular dysfunction post-myocardial infarction * Diabetic nephropathy ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Doses are typically started low and titrated upwards every 1-2 weeks as tolerated. * **Hypertension:** Initial doses vary by agent (e.g., lisinopril 5-10 mg PO daily, enalapril 2.5-5 mg PO daily, ramipril 1.25-2.5 mg PO daily). Maximum daily doses also vary by agent (e.g., lisinopril up to 40 mg PO daily, enalapril up to 40 mg PO daily, ramipril up to 10 mg PO daily). * **Heart Failure:** Initial doses are typically lower than for hypertension (e.g., lisinopril 2.5-5 mg PO daily, enalapril 2.5-5 mg PO BID, ramipril 1.25-2.5 mg PO BID). Target doses aim for maximum tolerated doses (e.g., lisinopril 32.5-40 mg PO daily, enalapril 20 mg PO BID, ramipril 5 mg PO BID). * **Post-MI and Diabetic Nephropathy:** Dosing often follows guidelines for heart failure or specific protocols. ## Pediatric Dosing * **Hypertension:** Dosing is weight-based and varies by agent. Examples include: * Captopril: 0.3-1 mg/kg/dose PO TID (max 3 mg/kg/day or 150 mg/day). * Enalapril: 0.07-0.1 mg/kg/dose PO QD (max 0.5 mg/kg/day or 40 mg/day). * Lisinopril: 0.07-0.2 mg/kg/day PO QD (max 20 mg/day). * Ramipril: 0.05 mg/kg/day PO QD (max 2.5 mg/day). * _Note: Pediatric dosing is often based on specific protocols and requires careful titration._ ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Monitor serum creatinine and potassium closely. Specific dose adjustments depend on the degree of renal impairment and the individual ACE inhibitor. * **Hepatic Impairment:** Use with caution. No specific dose adjustments are typically recommended, but titrate slowly and monitor for adverse effects. ## Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Concomitant use of aliskiren in patients with diabetes. * Pregnancy (especially second and third trimesters). * Hypersensitivity to ACE inhibitors. * History of hereditary or idiopathic angioedema. ## Adverse Effects * **Common:** Dry cough (most frequent), dizziness, headache, fatigue, hypotension. * **Serious:** Angioedema (can be life-threatening, especially involving the airway), hyperkalemia, acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), neutropenia/agranulocytosis (rare), severe hypotension. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs, heparin, trimethoprim/sulfamethoxazole:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in elderly or volume-depleted patients. * **Lithium:** Increased lithium levels and risk of toxicity. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Before and regularly after initiation/dose adjustment. * **Serum Potassium:** Before therapy, within the first week, and periodically thereafter, especially in patients with renal impairment or those taking potassium-sparing agents. * **Renal Function (Serum Creatinine, BUN):** Before therapy, within the first week, and periodically thereafter, especially in patients with renal impairment, heart failure, or bilateral renal artery stenosis. * **Signs/Symptoms of Angioedema:** Counsel patients to report immediately. * **Baseline and periodic complete blood count (CBC):** Particularly in patients with collagen vascular disease or renal impairment. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels and is generally reversible upon discontinuation. * ACE inhibitors are generally not recommended in patients with bilateral renal artery stenosis due to the risk of precipitating renal failure. * Starting at a low dose and titrating slowly is crucial to minimize hypotension and other side effects. * In patients with heart failure, ACE inhibitors should be initiated after the patient is stabilized on diuretics and/or inotropes, if necessary. *** _This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making therapeutic decisions._