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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily to treat hypertension and heart failure. 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) * Post-myocardial infarction (for patients with evidence of left ventricular dysfunction or heart failure) * Diabetic nephropathy (in patients with type 1 diabetes, hypertension, and proteinuria) ## Adult Dosing Dosing varies significantly by agent. Initiation typically starts at a low dose and titrates upwards. * **Hypertension:** * Benazepril: 10-40 mg once daily. Max: 80 mg/day. * Captopril: 25 mg BID-TID. Max: 150 mg TID. * Enalapril: 5 mg once daily, titrate to 10-40 mg once daily or BID. Max: 40 mg/day. * Fosinopril: 10-40 mg once daily. Max: 80 mg/day. * Lisinopril: 10 mg once daily. Max: 40 mg/day. * Moexipril: 7.5-15 mg once daily. Max: 30 mg/day. * Perindopril: 2.5-5 mg once daily. Max: 10 mg/day. * Quinapril: 10-20 mg BID. Max: 80 mg/day. * Ramipril: 2.5-5 mg once daily. Max: 10 mg/day. * Trandolapril: 1-4 mg once daily. Max: 8 mg/day. * **Heart Failure:** * Captopril: 6.25 mg TID, titrate to 50 mg TID. Max: 150 mg TID. * Enalapril: 2.5 mg BID, titrate to 10-20 mg BID. Max: 40 mg/day. * Lisinopril: 5 mg once daily, titrate to 20-40 mg once daily. Max: 40 mg/day. * Ramipril: 2.5 mg BID, titrate to 5 mg BID. Max: 10 mg/day. * **Post-MI:** * Captopril: 6.25 mg TID, titrate as tolerated to 12.5 mg TID, then 25 mg TID. Max: 50 mg TID. * Enalapril: 5 mg BID, titrate to 10 mg BID. Max: 20 mg/day. * Lisinopril: 5 mg once daily, titrate to 10 mg once daily. Max: 40 mg/day. ## Pediatric Dosing * **Hypertension:** Dosing is highly variable and depends on age, weight, and specific agent. Consult pediatric guidelines or specialist literature for exact recommendations. Generally, start low and titrate carefully. * Enalapril: 0.07-0.1 mg/kg/day once daily or BID. Max: 0.61 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/day once daily. Max: 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate more slowly. Specific dose reductions depend on the specific ACE inhibitor and degree of renal impairment (serum creatinine or GFR). * **Hepatic Impairment:** Use with caution. Some agents (e.g., enalapril, lisinopril) are renally cleared and may not require significant adjustment, while others (e.g., captopril, moexipril) are hepatically metabolized and may require dose reduction. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment * Concomitant use with aliskiren in patients with diabetes or renal impairment * Pregnancy (especially second and third trimesters) * Hypersensitivity to the ACE inhibitor or any component of the formulation ## Adverse Effects * **Common:** Dry cough, dizziness, fatigue, headache, hyperkalemia, hypotension, nausea, renal dysfunction. * **Serious:** Angioedema (can be life-threatening, affecting face, lips, tongue, throat, intestines), acute kidney injury, severe hypotension, hepatotoxicity, agranulocytosis/neutropenia (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use, especially in diabetics or those with renal impairment. * **NSAIDs (including COX-2 inhibitors):** May blunt antihypertensive effect and increase risk of renal dysfunction, especially in the elderly, volume-depleted, or renally impaired patients. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension, particularly after the first dose. Consider initiating ACE inhibitor at a lower dose or discontinuing the diuretic temporarily. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. Monitor lithium levels closely. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * Blood pressure * Serum potassium * Renal function (serum creatinine, GFR) - baseline and periodically, especially with dose changes or in patients with risk factors. * Signs and symptoms of angioedema. * Complete blood count (CBC) - baseline and periodically, especially in patients with connective tissue disease or renal impairment. ## Clinical Pearls * Dry cough is a common side effect and is usually dose-dependent; switching to a different ACE inhibitor or an ARB may be necessary. * Angioedema is a serious, rare, but potentially fatal adverse effect. Patients should be counseled to seek immediate medical attention if swelling of the face, lips, tongue, or throat occurs. * First-dose hypotension can occur, especially in patients taking diuretics or those who are volume-depleted. Consider a lower starting dose and close monitoring. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Captopril has a shorter half-life and requires TID dosing, while most others are once or BID daily. --- This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive dosing, administration, and safety information.