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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, resulting in lower blood pressure and reduced cardiac workload. ## Primary Indications * Hypertension * Heart Failure (HF) with reduced ejection fraction (HFrEF) * Post-myocardial infarction (MI) * Diabetic nephropathy * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor and indication. Titration is generally recommended. * **Hypertension:** Typical starting doses vary (e.g., lisinopril 10 mg once daily, enalapril 5 mg once or twice daily, ramipril 2.5 mg once daily). Doses are titrated upwards based on blood pressure response. Maximum doses vary by agent (e.g., lisinopril up to 40 mg once daily, enalapril up to 40 mg once daily, ramipril up to 10 mg once daily). * **Heart Failure (HFrEF):** Typical starting doses are lower than for hypertension (e.g., lisinopril 5 mg once daily, enalapril 2.5 mg once or twice daily, ramipril 1.25 mg once daily). Doses are titrated upwards to target doses or maximum tolerated doses, aiming for sustained reduction in morbidity and mortality. * **Post-MI:** Typically initiated within 24 hours in hemodynamically stable patients (e.g., captopril 6.25 mg three times daily, enalapril 2.5 mg twice daily). Doses are titrated upwards over days/weeks. * **Diabetic Nephropathy/CKD with Proteinuria:** Similar starting doses to hypertension, titrated upwards to reduce proteinuria and slow disease progression. ## Pediatric Dosing Dosing in pediatric patients is complex and often requires weight-based calculations. Dosing can vary significantly by age and indication. Consult specific pediatric guidelines or drug monographs. * **Hypertension:** * Enalapril: 0.05 mg/kg/dose to 0.2 mg/kg/dose once or twice daily. Max: 40 mg/day. * Lisinopril: 0.07 mg/kg/dose once daily. Max: 40 mg/day. * Captopril: 0.3 mg/kg/dose three times daily. Max: 4.5 mg/kg/day or 150 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in moderate to severe renal impairment. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Caution advised; may require lower starting doses and slower titration. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to ACE inhibitors. * Bilateral renal artery stenosis. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (facial, lip, tongue, throat, or intestinal), acute kidney injury (AKI), severe hypotension, liver dysfunction. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **Diuretics:** Increased risk of hypotension, especially with initial doses. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use in most patients. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. Monitor lithium levels. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly, especially after dose initiation or titration. * **Renal Function:** Serum creatinine and BUN, particularly in patients with pre-existing renal disease, heart failure, or dehydration. * **Electrolytes:** Serum potassium, especially in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics. * **Angioedema:** Patient education on signs/symptoms and prompt reporting. * **Cough:** Assess for persistence and severity. ## Clinical Pearls * Initiate at a low dose and titrate slowly to achieve therapeutic goals and minimize adverse effects, particularly hypotension and cough. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. * Discontinue immediately if angioedema occurs and never re-challenge. * Advise patients to report signs of angioedema, infection, or worsening renal function. * Consider switching to an Angiotensin II Receptor Blocker (ARB) for patients who develop a persistent cough due to ACE inhibitors. *** *This information is for educational purposes only and does not substitute for professional medical advice. Always verify current prescribing information with a healthcare professional.*