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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 (proteinuric kidney disease) ## Adult Dosing Dosing varies by specific ACE inhibitor. Generally, start at a low dose and titrate upwards as tolerated and needed for therapeutic effect. * **Hypertension:** * Benazepril: Initial 10 mg once daily, usual range 20-40 mg once daily. * Captopril: Initial 25 mg twice daily, usual range 50 mg three times daily. * Enalapril: Initial 5 mg once daily, usual range 10-40 mg once or twice daily. * Fosinopril: Initial 10 mg once daily, usual range 20-40 mg once daily. * Lisinopril: Initial 10 mg once daily, usual range 10-40 mg once daily. * Moexipril: Initial 7.5 mg once daily, usual range 15-30 mg once daily. * Perindopril: Initial 5 mg once daily, usual range 5-10 mg once daily. * Quinapril: Initial 10 mg once or twice daily, usual range 20-80 mg once or twice daily. * Ramipril: Initial 2.5 mg once daily, usual range 5-10 mg once daily. * Trandolapril: Initial 1 mg once daily, usual range 2-4 mg once daily. * **Heart Failure:** Dosing typically starts lower and titrates to higher doses than for hypertension, aiming for target doses that have demonstrated mortality benefit in clinical trials. Specific target doses vary by agent and patient tolerance. * **Post-MI/Diabetic Nephropathy:** Dosing generally follows hypertension guidelines, but specific protocols may exist. ## Pediatric Dosing * **Hypertension:** Dosing is weight-based and varies by agent. Consult specific pediatric guidelines or drug monographs. For example: * Enalapril: 0.07 to 0.1 mg/kg/dose orally every 12 to 24 hours. Maximum dose: 0.5 mg/kg/day. * Lisinopril: 0.07 to 0.2 mg/kg/dose orally once daily. Maximum dose: 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary in patients with significant renal impairment (e.g., creatinine clearance < 30 mL/min). Specific reductions depend on the agent and degree of renal dysfunction. * **Hepatic Impairment:** Use with caution. Some agents (e.g., enalapril, perindopril) are prodrugs requiring hepatic activation; hepatic impairment may reduce efficacy. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially in the second and third trimesters). * Known hypersensitivity to the drug. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (including laryngeal edema), hypotension, acute kidney injury, hyperkalemia, rash, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of kidney damage. * **Diuretics (especially thiazides):** Additive hypotensive effect. Initial doses may need to be reduced. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concurrent use, especially in diabetics. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of adverse events including renal impairment, hyperkalemia, and hypotension. Avoid combination. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly assess to ensure adequate control and monitor for hypotension. * **Serum Potassium:** Monitor baseline and periodically thereafter, especially in patients with renal impairment or on potassium-sparing agents. * **Renal Function:** Monitor serum creatinine and BUN at baseline and periodically, particularly in patients with pre-existing renal disease or those at risk for acute kidney injury. * **Angioedema:** Educate patients to report immediately any swelling of the face, lips, tongue, or throat. ## Clinical Pearls * Cough is a common side effect and often necessitates discontinuation. * Initiate at low doses, especially in volume-depleted patients, those with heart failure, or renal impairment, to minimize risk of excessive hypotension. * First-dose hypotension can occur, particularly in patients taking diuretics. Consider withholding diuretic therapy 2-3 days prior to starting ACE inhibitor therapy if possible. * ACE inhibitors are generally safe and effective in diabetic patients, and may offer renal protective benefits in those with proteinuria. *** *This information is intended for healthcare professionals and does not substitute for comprehensive drug information resources. Always consult the most current prescribing information and professional guidelines before making clinical decisions.*