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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 (reduced ejection fraction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is common. * **Hypertension:** Typical starting doses vary by agent (e.g., lisinopril 10 mg once daily, enalapril 5 mg once or twice daily, ramipril 2.5 mg once daily). Maximum doses also vary (e.g., lisinopril up to 40 mg once daily, enalapril up to 40 mg once daily). * **Heart Failure:** Dosing often starts lower and is titrated upwards more slowly than for hypertension (e.g., lisinopril 5 mg once daily, enalapril 2.5 mg twice daily, ramipril 1.25 mg once daily). Target doses are based on patient tolerance and clinical response, often aiming for doses similar to those shown effective in clinical trials. * **Post-MI:** Dosing typically starts within 24 hours of MI in hemodynamically stable patients (e.g., captopril 6.25 mg TID, lisinopril 5 mg QD). Titration to target doses is encouraged. * **Diabetic Nephropathy:** Dosing is similar to hypertension, titrated to achieve optimal blood pressure control and proteinuria reduction. ## Pediatric Dosing * ACE inhibitors are generally not first-line for pediatric hypertension unless specific comorbidities exist (e.g., significant proteinuria, certain renal conditions). * **Hypertension:** Dosing varies by agent and age group. For example: * Enalapril: 0.08 mg/kg/day to 0.58 mg/kg/day divided once or twice daily (max 40 mg/day). * Lisinopril: 0.07 mg/kg/day to 0.4 mg/kg/day once daily (max 40 mg/day). * Dosage recommendations for other indications in pediatrics are less established and often rely on adult data and expert consensus. ## Dose Adjustments * **Renal Impairment:** Dose reductions are typically required, especially in patients with creatinine clearance < 30 mL/min. Consult specific drug guidelines. * **Hepatic Impairment:** No dose adjustment is typically needed for hepatic impairment, but caution is advised. ## Contraindications * History of angioedema related to prior ACE inhibitor use. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters, due to risk of fetal injury or death). * Concomitant use with sacubitril/valsartan (due to increased risk of angioedema; allow a 36-hour washout period when switching). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening, involving face, lips, tongue, glottis, or intestines), acute kidney injury (especially in bilateral renal artery stenosis), hypotension, hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, angiotensin II receptor blockers (ARBs), heparin, trimethoprim/sulfamethoxazole:** Increased risk of hyperkalemia. * **Diuretics (non-potassium-sparing):** Additive hypotensive effect. Risk of profound hypotension, especially after initiation or first dose. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., everolimus, sirolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. ## Monitoring * **Baseline:** Serum creatinine, potassium, blood pressure. * **During therapy:** * Blood pressure (especially after initiation or dose changes). * Serum creatinine and potassium within 1-2 weeks of initiation or dose increase, and periodically thereafter. More frequent monitoring in patients with renal impairment or at risk for hyperkalemia. * Monitor for signs/symptoms of angioedema. * Monitor for cough. ## Clinical Pearls * Cough is a common, dose-limiting side effect, usually reversible upon discontinuation. * First-dose hypotension can occur, particularly in volume-depleted patients or those on diuretics. Consider withholding diuretics temporarily or using a lower initial dose. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Angioedema is a medical emergency; discontinue ACE inhibitor immediately and do not rechallenge. *** *This information is intended for clinical use and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.*