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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, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart Failure (with reduced ejection fraction) * Post-Myocardial Infarction (to improve survival) * Diabetic Nephropathy (to slow progression) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Doses are typically started low and titrated upwards. * **Hypertension:** * **Benazepril:** Starting dose 10 mg once daily, titrate up to 40 mg once daily. * **Captopril:** Starting dose 25 mg twice daily, titrate up to 50 mg three times daily. * **Enalapril:** Starting dose 5 mg once daily, titrate up to 40 mg once daily (may be divided into twice daily). * **Fosinopril:** Starting dose 10 mg once daily, titrate up to 40 mg once daily. * **Lisinopril:** Starting dose 10 mg once daily, titrate up to 40 mg once daily. * **Moexipril:** Starting dose 7.5 mg once daily, titrate up to 30 mg once daily. * **Perindopril:** Starting dose 5 mg once daily, titrate up to 10 mg once daily. * **Quinapril:** Starting dose 10 mg twice daily, titrate up to 80 mg once or twice daily. * **Ramipril:** Starting dose 2.5 mg once daily, titrate up to 10 mg once daily. * **Trandolapril:** Starting dose 1 mg once daily, titrate up to 8 mg once daily. * **Heart Failure:** Dosing often starts lower and is titrated more cautiously due to risk of hypotension and worsening renal function. Refer to specific guidelines for initiation and titration. * **Post-MI:** Dosing varies by agent and timing post-MI. ## Pediatric Dosing ACE inhibitor use in pediatrics is less common and should be guided by specialist consultation and available evidence. Dosing is based on weight. * **Hypertension:** * **Enalapril:** 0.07 to 0.1 mg/kg/dose orally once or twice daily. Maximum dose typically 0.61 mg/kg/day (e.g., 40 mg/day). * **Lisinopril:** 0.07 to 0.2 mg/kg/dose orally once daily. Maximum dose typically 0.61 mg/kg/day (e.g., 40 mg/day). * **Note:** Pediatric dosing may vary. Consult specific pediatric formularies or guidelines. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially for patients with CrCl < 30 mL/min. Initial doses should be conservative, and renal function monitored closely. * **Hepatic Impairment:** Generally no dose adjustment needed for most ACE inhibitors, but caution is advised, especially with captopril which undergoes hepatic metabolism. ## Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (contraindicated due to fetal toxicity, especially in the second and third trimesters). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (can be life-threatening, especially involving the airway), acute kidney injury (particularly in patients with bilateral renal artery stenosis or severe volume depletion), rash, elevated liver enzymes. ## Key Drug Interactions * **Potassium-Sparing Diuretics, Aldosterone Antagonists, Potassium Supplements, Trimethoprim:** Increased risk of hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of hypotension and volume depletion. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid combination. ## Monitoring * **Blood Pressure:** Regularly monitor BP at home and in clinic. * **Renal Function:** Monitor serum creatinine and BUN, especially after initiation or dose increases, and in patients with renal insufficiency. * **Electrolytes:** Monitor serum potassium, especially in patients with renal impairment, diabetes, or those on potassium-sparing agents. * **Angioedema:** Educate patients to report any swelling, particularly of the face, lips, tongue, or throat. ## Clinical Pearls * Cough is a common dose-limiting side effect, occurring in up to 20% of patients. If cough is bothersome, consider discontinuation and switching to an ARB. * Initiate at low doses and titrate slowly, particularly in patients who are volume-depleted, salt-depleted, or have heart failure. * First-dose hypotension can occur; monitor closely after initial administration. * ACE inhibitors are generally considered safe and effective in patients with diabetes, as they can provide renal protection. * In patients with bilateral renal artery stenosis, ACE inhibitors can precipitate acute renal failure. *** **Disclaimer:** This information is for educational purposes only and does not constitute medical advice. Always consult the most current prescribing information and guidelines for specific patient management.