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## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications that primarily 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, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival and prevent remodeling) * Diabetic nephropathy (to slow progression) * Proteinuric chronic kidney disease ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is typically guided by blood pressure response and tolerability. * **Hypertension:** * Benazepril: 10-40 mg once daily * Captopril: 25-150 mg twice daily (may require TID dosing) * Enalapril: 5-40 mg once or twice daily * Fosinopril: 10-40 mg once daily * Lisinopril: 10-40 mg once daily * Moexipril: 7.5-30 mg once daily * Perindopril: 2-10 mg once daily * Quinapril: 10-80 mg once or twice daily * Ramipril: 2.5-20 mg once daily * Trandolapril: 1-4 mg once daily * *Maximum doses vary by agent and indication.* * **Heart Failure:** Doses are often lower initially and titrated upwards. Consult specific guidelines (e.g., ACC/AHA) for target doses, which may differ from maximum antihypertensive doses. * **Post-MI:** Similar to heart failure, titration to target doses as tolerated is key. ## Pediatric Dosing * **Hypertension:** Dosing varies significantly by agent and age. * Enalapril: 0.07 mg/kg/day once daily (range 0.05-0.4 mg/kg/day). Max 40 mg/day. * Lisinopril: 0.07 mg/kg/day once daily (range 0.07-0.2 mg/kg/day). Max 20 mg/day. * *Specific dosing for other ACE inhibitors and for younger infants may be less established and require careful consideration.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in moderate to severe impairment. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Captopril and enalapril generally do not require dose adjustment in mild to moderate hepatic impairment. Use with caution in severe impairment. * **Volume Depletion/Hyponatremia:** Initiate at a lower dose and titrate cautiously. ## Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Dry cough (most frequent), dizziness, fatigue, headache, hypotension, hyperkalemia. * **Serious:** Angioedema (can be life-threatening, involve face, lips, tongue, larynx), acute kidney injury (especially in patients with bilateral renal artery stenosis), hyperkalemia, neutropenia/agranulocytosis (rare, more common with captopril). ## Key Drug Interactions * **Potassium-sparing diuretics, Potassium supplements, Aldosterone antagonists, Angiotensin II Receptor Blockers (ARBs), Heparin, Trimethoprim:** Increased risk of hyperkalemia. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid in patients with diabetes. * **NSAIDs (including COX-2 inhibitors):** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially thiazides):** Increased risk of hypotension, particularly with initial doses. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium levels and toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During therapy:** * Blood pressure (especially after dose initiation or titration). * Serum creatinine and potassium within 1-2 weeks of initiation or dose increase, and periodically thereafter, especially in patients with risk factors for renal dysfunction or hyperkalemia. * Monitor for signs/symptoms of angioedema and cough. ## Clinical Pearls * The characteristic dry cough is often dose-related and may resolve upon discontinuation. If cough is bothersome and other options are limited, switching to an ARB may be considered. * Angioedema is a medical emergency; discontinue immediately and manage airway. * Initiate therapy at a low dose and titrate slowly, especially in patients who are volume-depleted, salt-depleted, or have heart failure. * First-dose hypotension is a risk, particularly in patients taking diuretics. Consider withholding diuretic temporarily before initiating ACE inhibitor. * Use with caution in patients with bilateral renal artery stenosis due to risk of severe renal failure. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details.*