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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used 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 (HFrEF) * Post-Myocardial Infarction (MI) * Diabetic Nephropathy * Proteinuric Kidney Disease ## Adult Dosing Dosing varies significantly by agent. Typical starting doses are low and titrated upwards based on clinical response and tolerability. * **Benazepril:** Start 10 mg daily, titrate to 40 mg daily. * **Captopril:** Start 25 mg BID, titrate to 50 mg TID. * **Enalapril:** Start 5 mg daily (or 2.5 mg BID for heart failure), titrate to 10-40 mg daily (or 20 mg BID for heart failure). * **Fosinopril:** Start 10 mg daily, titrate to 40 mg daily. * **Lisinopril:** Start 10 mg daily, titrate to 40 mg daily. * **Moexipril:** Start 7.5 mg daily, titrate to 30 mg daily. * **Perindopril:** Start 2.5-5 mg daily, titrate to 10 mg daily. * **Ramipril:** Start 2.5 mg daily, titrate to 10 mg daily. * **Trandolapril:** Start 1 mg daily, titrate to 4 mg daily. ## Pediatric Dosing Pediatric dosing is established for some agents and often weight-based. Consult specific product labeling or pediatric pharmacotherapy resources. * **Enalapril:** 0.07-0.1 mg/kg/dose IV every 6 hours or 0.1-0.5 mg/kg/day PO divided BID (max 20 mg/day). * **Lisinopril:** 0.07-0.2 mg/kg/day PO divided daily (max 20 mg/day for <6 years or 40 mg/day for >6 years). * **Ramipril:** 0.03-0.06 mg/kg/day PO divided daily. ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary, especially with lower glomerular filtration rates (GFR). Specific guidelines vary by agent and severity of renal dysfunction. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Caution is advised, though specific dose adjustments are not always clearly defined. Enalapril and lisinopril are generally preferred in mild to moderate hepatic impairment due to less extensive hepatic metabolism. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters, Category C in 1st trimester). ACE inhibitors can cause fetal injury or death. * Known hypersensitivity to the drug. ## Adverse Effects * **Common:** Cough (dry, persistent), hyperkalemia, dizziness, hypotension, fatigue, headache. * **Serious:** Angioedema (including laryngeal edema, potentially fatal), acute kidney injury, severe hypotension, hyperkalemia, hepatic dysfunction. ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in volume-depleted patients. * **Diuretics (Thiazide, Loop):** Increased risk of hypotension, especially with initial doses. Consider withholding diuretic or starting ACE inhibitor at a lower dose. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. ACE inhibitors should not be co-administered with sacubitril/valsartan; allow at least 36 hours between stopping one and starting the other. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, serum potassium, GFR. * **During therapy:** Blood pressure, serum creatinine, serum potassium, particularly after initiating therapy, dose increases, or in patients with risk factors for renal dysfunction. Monitor for signs/symptoms of angioedema and cough. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * Start at low doses and titrate slowly, especially in the elderly, volume-depleted patients, or those with heart failure or renal impairment, to minimize risk of profound hypotension and acute kidney injury. * ACE inhibitors are generally renoprotective in diabetic nephropathy and proteinuric kidney disease. * First-dose hypotension can occur, especially in patients taking diuretics. Administer the first dose at bedtime or advise patients to lie down for a few hours after taking it. * Angioedema can occur at any time during therapy and is a medical emergency. Patients should be instructed to seek immediate medical attention if swelling of the face, lips, tongue, or throat occurs. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making therapeutic decisions.