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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (for specific agents) * Diabetic nephropathy (proteinuria) * Chronic kidney disease (proteinuria) ## Adult Dosing Dosing varies significantly by specific agent and indication. Titration is typically guided by patient response and tolerability. * **Hypertension:** * Benazepril: 5-40 mg once daily * Captopril: 25-150 mg divided twice daily * Enalapril: 5-40 mg once daily (oral), 5 mg every 6 hours IV (max 40 mg/day) * Fosinopril: 10-40 mg once daily * Lisinopril: 10-40 mg once daily * Moexipril: 7.5-30 mg divided twice daily * Perindopril: 2.5-10 mg once daily * Quinapril: 5-80 mg divided twice daily * Ramipril: 2.5-10 mg once daily * Trandolapril: 1-4 mg once daily * **Heart Failure:** * Captopril: 25 mg TID, titrate up to 50 mg TID * Enalapril: 2.5 mg BID, titrate up to 10-20 mg BID * Lisinopril: 5 mg QD, titrate up to 20 mg QD * Ramipril: 2.5 mg BID, titrate up to 5 mg BID * **Post-MI (specific agents like Ramipril):** Ramipril 2.5 mg BID, titrate up to 5 mg BID. ## Pediatric Dosing ACE inhibitors are generally not first-line therapy in pediatric hypertension. Dosing is often weight-based and requires careful titration and monitoring. * **Hypertension (e.g., Enalapril, Lisinopril):** Doses vary. For example, Enalapril: 0.07-0.1 mg/kg/dose PO every 12-24 hours. **Consult pediatric-specific guidelines.** ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in moderate to severe impairment. Monitor serum creatinine and potassium closely. * Captopril: Reduce dose by 50% if CrCl < 30 mL/min. * Lisinopril: Initial dose 5 mg QD if CrCl < 30 mL/min. * Enalapril: Reduce dose by 50% if CrCl < 30 mL/min. * **Hepatic Impairment:** Use with caution. Captopril and enalapril are often preferred. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use of sacubitril/valsartan (within 36 hours of last dose). * Hereditary or idiopathic angioedema. * Pregnancy (especially second and third trimesters). * Bilateral renal artery stenosis. ## Adverse Effects * **Common:** Dry cough, hyperkalemia, dizziness, headache, fatigue, hypotension, rash. * **Serious:** Angioedema (can be life-threatening), acute kidney injury, hyperkalemia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May blunt antihypertensive effect and increase risk of kidney damage. * **Lithium:** ACE inhibitors can increase lithium levels; monitor lithium levels. * **Diuretics:** Additive hypotensive effect. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs:** Increased risk of hyperkalemia, hypotension, and angioedema. ## Monitoring * Blood pressure (before and after dose initiation/titration). * Serum creatinine and potassium (baseline, within 1-2 weeks of initiation/titration, and periodically thereafter). * Renal function in patients with pre-existing renal disease or risk factors. * Signs and symptoms of angioedema. ## Clinical Pearls * The dry cough is thought to be due to increased bradykinin levels and typically resolves within weeks of discontinuation. * Initiate at a low dose and titrate slowly to minimize hypotension and other side effects, especially in volume-depleted patients or those with heart failure. * Monitor potassium closely, particularly in patients with renal impairment or those taking other potassium-elevating medications. * Angioedema is a rare but potentially fatal side effect; discontinue immediately if suspected. * Patients who develop angioedema on an ACE inhibitor should *never* be rechallenged. * In heart failure, ACE inhibitors reduce mortality and hospitalizations. *** **Disclaimer:** This information is intended for clinical use and is not a substitute for comprehensive drug information resources. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.