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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications that block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and stimulates aldosterone release, which promotes sodium and water retention. By inhibiting its formation, ACE inhibitors lead to vasodilation, decreased aldosterone secretion, and reduced blood volume, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Post-myocardial Infarction (to improve survival) * Diabetic Nephropathy (proteinuria reduction) * Chronic Kidney Disease (proteinuria reduction) ## Adult Dosing Dosing varies significantly by agent. Initiation is typically at a low dose, titrated upwards every 1-4 weeks based on clinical response and tolerability. * **Hypertension:** Common starting doses include: * Lisinopril: 10 mg once daily. Max: 40 mg once daily. * Enalapril: 5 mg once or twice daily. Max: 40 mg once or twice daily. * Ramipril: 2.5 mg once daily. Max: 10 mg once daily. * **Heart Failure:** * Lisinopril: 5 mg once daily, increase to 10-40 mg once daily. * Enalapril: 2.5 mg twice daily, increase to 10-20 mg twice daily. * Ramipril: 1.25-2.5 mg twice daily, increase to 5-10 mg twice daily. * **Post-MI:** * Lisinopril: 5 mg within 24 hours of stabilization, then 5-10 mg once daily. * Ramipril: 1.25 mg once daily, increase to 2.5-5 mg twice daily. * **Diabetic Nephropathy/CKD:** Dosing is individualized based on blood pressure and proteinuria goals. Generally follows hypertension dosing but titration may be slower. ## Pediatric Dosing Dosing varies by agent and indication. Specific recommendations are often found in pediatric guidelines. * **Hypertension:** * Enalapril: 0.08 mg/kg/day to 0.5 mg/kg/day divided once or twice daily. Max: 40 mg/day. * Lisinopril: 0.07 mg/kg/day to 0.6 mg/kg/day once daily. Max: 40 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific guidelines depend on the agent and the degree of renal impairment (creatinine clearance). Generally, start with a lower dose and titrate cautiously. * **Hepatic Impairment:** Caution is advised, particularly with enalapril. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Most Common:** Dry cough (due to bradykinin accumulation), dizziness, headache, fatigue. * **Serious:** Angioedema (potentially life-threatening), hyperkalemia, acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), hypotension, neutropenia/agranulocytosis (rare). * **Other:** Rash, dysgeusia, elevated liver enzymes. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride), Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs (including Aspirin > 325 mg/day):** May reduce antihypertensive effect and increase risk of renal dysfunction, especially in elderly or volume-depleted patients. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. * **Antihypertensives (other classes):** Additive hypotensive effect. * **mTOR Inhibitors (e.g., sirolimus, everolimus), DPP-4 Inhibitors (e.g., sitagliptin):** Increased risk of angioedema. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction; contraindicated in patients with diabetes or moderate-to-severe renal impairment. ## Monitoring * **Baseline:** Serum creatinine, potassium, and electrolytes. Blood pressure. * **During Therapy:** * Blood pressure: To assess efficacy and identify hypotension. * Serum creatinine and potassium: Typically 1-2 weeks after initiation or dose increase, and then periodically (e.g., annually or as clinically indicated). Monitor more closely in patients with renal impairment or heart failure. * Symptoms of angioedema or cough. ## Clinical Pearls * The dry cough is thought to be due to bradykinin accumulation and may occur weeks to months after starting therapy. It is usually reversible upon discontinuation. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * First-dose hypotension can occur, especially in volume-depleted patients or those on diuretics. Consider withholding diuretics prior to starting ACE inhibitors. * Avoid use in pregnancy due to risk of fetal harm. *** *Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete details, including contraindications, warnings, precautions, and drug interactions, before making any treatment decisions.*