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# ACE Inhibitors ## Overview ACE inhibitors (e.g., captopril, enalapril, lisinopril, ramipril) are a class of medications used primarily to treat hypertension and heart failure. They work by blocking the angiotensin-converting enzyme, which reduces the production of angiotensin II, leading to vasodilation and decreased aldosterone secretion. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Post-myocardial infarction (to reduce mortality and prevent remodeling) * Diabetic nephropathy (proteinuria) * Chronic kidney disease (certain types) ## 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 based on response and tolerability. * **Hypertension:** * **Captopril:** Initial 25 mg once or twice daily; usual range 25-150 mg/day divided BID-TID. Max 450 mg/day. * **Enalapril:** Initial 5 mg once daily; usual range 10-40 mg/day divided QD-BID. Max 40 mg/day. * **Lisinopril:** Initial 10 mg once daily; usual range 10-40 mg/day QD. Max 80 mg/day. * **Ramipril:** Initial 2.5 mg once daily; usual range 5-20 mg/day QD. Max 20 mg/day. * **Heart Failure:** Dosing often starts lower and titrates higher than for hypertension, aiming for maximally tolerated doses. Refer to specific guidelines. * **Post-MI:** Refer to specific guidelines, often starting within 24 hours of MI. * **Diabetic Nephropathy:** Similar ranges to hypertension, aiming for blood pressure control and proteinuria reduction. ## Pediatric Dosing Dosing in children is less established and requires careful titration. Often based on weight. * **Hypertension:** * **Captopril:** 0.3 mg/kg/dose to 0.5 mg/kg/dose every 8-24 hours. Max 6 mg/kg/day. * **Enalapril:** 0.07 mg/kg/dose to 0.2 mg/kg/dose every 12-24 hours. Max 0.61 mg/kg/day. * **Lisinopril:** 0.07 mg/kg/dose (max 5 mg) once daily. Max 0.61 mg/kg/day (or 40 mg). ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary, particularly for renally excreted ACE inhibitors. Monitor renal function closely. * **Hepatic Impairment:** Use with caution; dose adjustments may be needed for prodrugs like enalapril and ramipril. ## Contraindications * History of angioedema related to previous ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (Category D in 2nd and 3rd trimesters; Category C in 1st trimester). Teratogenic effects are well-documented. * Bilateral renal artery stenosis. * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Dry cough (most frequent, dose-related), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening), hypotension, acute kidney injury (especially in patients with bilateral renal artery stenosis or severe volume depletion), hyperkalemia, neutropenia/agranulocytosis (rare, more common with captopril). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive efficacy and increase risk of renal impairment. * **Diuretics (especially loop and thiazide):** Increased risk of hypotension and dehydration. * **Lithium:** ACE inhibitors may decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs, Aliskiren:** Increased risk of hyperkalemia, renal dysfunction, and hypotension. Avoid combination, especially in diabetes. ## Monitoring * **Baseline:** Renal function (serum creatinine, eGFR), electrolytes (serum potassium). Blood pressure. * **During Therapy:** * Blood pressure (especially after dose initiation or titration). * Renal function (within 1-2 weeks of initiation or dose increase, then periodically). * Serum potassium (within 1-2 weeks of initiation or dose increase, then periodically). * Monitor for signs/symptoms of angioedema or hypersensitivity. ## Clinical Pearls * The dry cough is often dose-related and may resolve upon dose reduction or discontinuation. It can occur weeks to months after starting therapy. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. * Initiate with low doses and titrate slowly, especially in elderly patients, those with volume depletion, or impaired renal function. * First-dose hypotension can occur, particularly in patients taking diuretics. Consider holding diuretics prior to initiating ACE inhibitor or starting with a lower dose. * Use with caution in patients with a history of angioedema from other causes. * If angioedema occurs, switch to an ARB, but with extreme caution as cross-reactivity can occur. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive guidance.*