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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, lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is typically done every 1-4 weeks. * **Benazepril:** Hypertension 10-40 mg once daily. Heart failure 5 mg once daily, titrate up to 40 mg once daily. * **Captopril:** Hypertension 25 mg BID-TID, titrate up to 50 mg BID-TID (max 150 mg TID). Heart failure 6.25 mg TID, titrate up to 50 mg TID. * **Enalapril:** Hypertension 10-40 mg once daily. Heart failure 2.5 mg once daily, titrate up to 20 mg BID. * **Fosinopril:** Hypertension 10-40 mg once daily. Heart failure 5 mg once daily, titrate up to 20 mg once daily. * **Lisinopril:** Hypertension 10-40 mg once daily. Heart failure 5 mg once daily, titrate up to 40 mg once daily. Post-MI 5 mg once daily, titrate up to 10 mg once daily. * **Moexipril:** Hypertension 7.5-15 mg once daily, titrate up to 30 mg once daily. * **Perindopril:** Hypertension 5-10 mg once daily. Heart failure 2.5 mg once daily, titrate up to 10 mg once daily. Post-MI 2.5 mg once daily, titrate up to 10 mg once daily. * **Ramipril:** Hypertension 2.5-20 mg once daily. Heart failure 1.25 mg once daily, titrate up to 10 mg once daily. Post-MI 2.5 mg BID, titrate up to 5 mg BID. * **Trandolapril:** Hypertension 1-4 mg once daily. Heart failure 1 mg once daily, titrate up to 4 mg once daily. * **Quinapril:** Hypertension 10-80 mg once daily or BID. Heart failure 5 mg BID, titrate up to 10 mg BID. Maximum doses vary by indication and drug. For hypertension, many agents max out at 40 mg once daily. For heart failure, maximum doses are often lower and titration is slower. ## Pediatric Dosing ACE inhibitor use in pediatrics is primarily for hypertension. Dosing is weight-based and depends on the specific agent and age group. Consult specific pediatric guidelines or drug monographs. * **Enalapril:** Hypertension (2 months to 16 years): 0.07 mg/kg/day once daily, titrate up to 0.57 mg/kg/day (max 40 mg/day). * **Lisinopril:** Hypertension (6 years to 16 years): 0.07 mg/kg/day once daily (max 20 mg/day). * **Ramipril:** Hypertension (10 years to 16 years): 1.25 mg once daily, titrate up to 5 mg once daily. ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally recommended, especially for agents renally excreted (e.g., enalapril, lisinopril). Start at lower doses and titrate cautiously. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Use with caution. Some agents may require dose adjustment (e.g., enalapril, benazepril). ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use of aliskiren in patients with diabetes or renal impairment. * Pregnancy (teratogenic; second and third trimesters). * Known hypersensitivity to ACE inhibitors. ## Adverse Effects * **Angioedema:** Life-threatening swelling of the face, lips, tongue, throat, and intestines. Risk is higher in Black patients. * **Cough:** Dry, persistent cough (non-productive). Usually resolves after discontinuation. * **Hyperkalemia:** Especially in patients with renal impairment or on potassium-sparing diuretics/supplements. * **Hypotension:** Particularly with the first dose or in volume-depleted patients. * **Renal impairment:** Can worsen existing renal insufficiency. * **Dizziness, fatigue, headache.** * **Rash.** * **Dysgeusia (altered taste).** ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride) and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May blunt antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of hypotension and prerenal azotemia. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., saxagliptin, linagliptin):** Increased risk of angioedema. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid dual therapy. ## Monitoring * **Blood pressure:** Before and during therapy, especially after dose changes. * **Renal function:** Serum creatinine and BUN, particularly at baseline, after dose increases, and in patients with risk factors. * **Serum potassium:** At baseline, periodically, and in patients with risk factors for hyperkalemia. * **Signs/symptoms of angioedema and hypersensitivity.** ## Clinical Pearls * Initiate at low doses, especially in volume-depleted patients, those with heart failure, renal impairment, or the elderly. * First-dose hypotension can occur. Monitor closely after the initial dose. * Angioedema is a rare but serious adverse effect; patients should be educated to seek immediate medical attention if symptoms occur. * Cough is a common side effect, but often reversible. If bothersome, consider switching to an ARB. * Monitor renal function and potassium closely, particularly in vulnerable populations. * Discontinue ACE inhibitors immediately if pregnancy is detected. *** **Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for specific patient management decisions.