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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat hypertension, heart failure, and chronic kidney disease. 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) * Myocardial Infarction (post-MI with evidence of LV dysfunction or heart failure) * Diabetic Nephropathy (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Typical starting doses are low and titrated upwards. * **Hypertension:** Common starting doses include: * Lisinopril: 5-10 mg PO once daily * Enalapril: 2.5-5 mg PO once or twice daily * Ramipril: 2.5-5 mg PO once daily * Maximum doses vary by agent, often ranging from 40 mg (lisinopril, enalapril) to 20 mg (ramipril) daily. * **Heart Failure:** Common starting doses include: * Lisinopril: 5 mg PO once daily, titrate up to target dose of 32.5 mg PO once daily * Enalapril: 2.5 mg PO twice daily, titrate up to target dose of 10 mg PO twice daily * Ramipril: 2.5 mg PO twice daily, titrate up to target dose of 10 mg PO once daily * **Post-MI:** Dosing often starts low (e.g., lisinopril 5 mg PO once daily) and is titrated up to a target dose (e.g., lisinopril 10 mg PO once daily) within 24 hours of MI if no contraindications exist. * **Diabetic Nephropathy:** Dosing is similar to hypertension but titration may be slower, aiming for maximal tolerated dose. ## Pediatric Dosing ACE inhibitor dosing in pediatrics is less standardized and often based on weight and clinical response. Doses are typically initiated at the lower end of the range and titrated. * **Hypertension:** * Enalapril: 0.1 mg/kg/dose PO once daily, maximum 20 mg/day. Can be increased to 0.2 mg/kg/dose (max 40 mg/day). * Lisinopril: 0.07-0.2 mg/kg/dose PO once daily, maximum 20 mg/day. * **Note:** Consultation with a pediatric specialist or pharmacologist is recommended for pediatric dosing. ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary in patients with significant renal impairment (CrCl < 30 mL/min). Specific adjustments depend on the agent and degree of renal dysfunction. For example, lisinopril: reduce by 50% if CrCl < 30 mL/min. * **Hepatic Impairment:** Caution is advised, particularly with prodrugs like enalapril, as hepatic metabolism may be reduced. Dose adjustments may be necessary. ## Contraindications * History of angioedema related to ACE inhibitor therapy * Concomitant use of aliskiren in patients with diabetes mellitus * Pregnancy (especially second and third trimesters) * Known hypersensitivity to ACE inhibitors ## Adverse Effects * **Common:** Dry cough (most characteristic), dizziness, hypotension, hyperkalemia, headache, fatigue. * **Serious:** Angioedema (can be life-threatening), acute kidney injury (especially in renal artery stenosis), hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, ARBs, Aliskiren:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce the antihypertensive effect and increase the risk of renal impairment. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. * **Diuretics (Thiazide/Loop):** Increased risk of symptomatic hypotension, especially with initial doses. * **mTOR Inhibitors (e.g., Everolimus, Sirolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor BP to assess efficacy and titrate dose. * **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and with dose changes. * **Potassium Levels:** Monitor serum potassium, particularly in patients with renal impairment, diabetes, or concurrent use of potassium-sparing agents. * **Angioedema:** Educate patients to report any swelling, especially of the face, lips, tongue, or throat, immediately. ## Clinical Pearls * The characteristic dry cough is usually benign and reversible upon discontinuation. * Angioedema is a medical emergency; discontinue the ACE inhibitor immediately and manage airway if necessary. * Initiate at low doses and titrate slowly, especially in elderly patients, those with volume depletion, or renal impairment. * ACE inhibitors are generally contraindicated in pregnancy due to risk of fetal harm. * For patients developing angioedema on an ACE inhibitor, consider switching to an ARB, but be aware of a small risk of cross-reactivity. *** **Disclaimer:** This information is intended for healthcare professionals and does not replace comprehensive drug references or clinical judgment. Always consult current prescribing information and relevant guidelines for the most up-to-date and specific details regarding drug use, including dosage, contraindications, and adverse effects.