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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used for managing hypertension and heart failure. They work by inhibiting the renin-angiotensin-aldosterone system (RAAS), leading to vasodilation and reduced sodium and water retention. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (MI) with reduced ejection fraction * Diabetic nephropathy (proteinuria) * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosage varies significantly by specific ACE inhibitor, indication, and patient response. Dosing typically starts low and is titrated upwards based on blood pressure, renal function, and tolerability. * **Hypertension:** Initial doses vary by agent (e.g., lisinopril 5-10 mg once daily, enalapril 2.5-5 mg twice daily). Titration typically occurs every 2-4 weeks. Maximum doses also vary by agent (e.g., lisinopril up to 40 mg once daily, enalapril up to 20 mg twice daily). * **Heart Failure:** Initial doses are usually lower than for hypertension (e.g., lisinopril 2.5-5 mg once daily, enalapril 2.5 mg twice daily). Titration aims for target doses or the maximum tolerated dose (e.g., lisinopril 32.5 mg once daily, enalapril 10 mg twice daily). * **Post-MI:** Dosing initiated within 24 hours of MI in patients with no contraindications. Similar titration strategies to heart failure. * **Diabetic/CKD Nephropathy:** Initiated at low doses and titrated to achieve target blood pressure or proteinuria reduction, often up to the maximum recommended dose for that agent. ## Pediatric Dosing Dosing in pediatric patients is less established and requires careful consideration. Generally, it is weight-based and initiated at low doses. Specific recommendations vary by agent and age group. For example: * **Enalapril:** 0.07 mg/kg/day to 0.75 mg/kg/day divided every 12-24 hours. Uncertainty exists regarding optimal dosing and long-term safety in all pediatric age groups. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in moderate to severe renal impairment (CrCl < 30 mL/min). Initial doses should be reduced, and titration should be slower. * **Hepatic Impairment:** Generally, dose adjustments are not routinely required unless severe hepatic impairment is present. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary angioedema or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to ACE inhibitors. ## Adverse Effects * **Common:** Dry cough, dizziness, headache, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in susceptible individuals), severe hypotension, hepatotoxicity (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in volume-depleted patients. * **Diuretics (thiazide and loop):** Increased risk of hypotension, especially with concurrent volume depletion. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use, especially in patients with diabetes or renal impairment. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal impairment. Concurrent use is generally not recommended. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. Monitor lithium levels closely. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor blood pressure, especially after initiation and dose adjustments. * **Renal Function:** Monitor serum creatinine and estimated glomerular filtration rate (eGFR) periodically, particularly at baseline and after dose increases. * **Electrolytes:** Monitor serum potassium levels, especially in patients with renal impairment, diabetes, or those taking potassium-sparing agents. * **Angioedema:** Educate patients to report any signs of swelling, especially of the face, lips, tongue, or throat. ## Clinical Pearls * The dry cough associated with ACE inhibitors is due to bradykinin accumulation and typically resolves after discontinuation. * Angioedema is a medical emergency; patients should seek immediate medical attention if symptoms occur. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. * Initiation in elderly patients or those with volume depletion should be done cautiously with lower starting doses due to increased risk of hypotension. * Discontinuation of ACE inhibitors is recommended prior to initiating therapy with neprilysin inhibitors (e.g., sacubitril/valsartan) due to the risk of angioedema. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive guidance on drug use.