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# ACE Inhibitors ## Overview ACE inhibitors are a class of medications that block the action of angiotensin-converting enzyme (ACE). This enzyme plays a role in regulating blood pressure. By inhibiting ACE, these drugs reduce the production of angiotensin II, a potent vasoconstrictor, leading to vasodilation and decreased blood pressure. They also reduce aldosterone secretion, which can decrease sodium and water retention. ## 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 specific agent and indication. Initial doses are typically low and titrated upwards based on patient response and tolerability. * **Hypertension:** Common starting doses include benazepril 10 mg daily, captopril 25 mg twice daily, enalapril 5 mg daily, lisinopril 10 mg daily, ramipril 2.5 mg daily. Maximum doses vary but commonly range from 40 mg daily for enalapril/lisinopril, 50 mg twice daily for captopril, and 20 mg daily for ramipril. * **Heart Failure:** Common starting doses include captopril 6.25 mg three times daily, enalapril 2.5 mg twice daily, lisinopril 5 mg daily, ramipril 1.25-2.5 mg twice daily. Titration to target doses is crucial, often aiming for captopril 50 mg three times daily, enalapril 10-20 mg twice daily, lisinopril 20-40 mg daily, ramipril 5 mg twice daily. * **Post-MI:** Dosing is typically initiated within 24 hours if hemodynamically stable. Common starting doses include captopril 6.25 mg three times daily, ramipril 1.25 mg twice daily. Titration is aimed at improving survival and can vary. * **Diabetic/Chronic Kidney Disease:** Dosing is similar to hypertension, aiming for blood pressure control and proteinuria reduction. ## Pediatric Dosing Dosing in pediatric patients is weight-based and agent-specific. Refer to specific product monographs or pediatric dosing guidelines. * **Hypertension:** For example, enalapril: 0.07-0.1 mg/kg/dose orally every 12-24 hours; max 0.5 mg/kg/day. Lisinopril: 0.07-0.2 mg/kg/dose orally once daily; max 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally required, especially for agents renally cleared. In severe renal impairment (CrCl < 30 mL/min), initial doses should be halved, and titration should be cautious. * **Hepatic Impairment:** Cautious use and potential dose reduction may be necessary, particularly for prodrugs like enalapril and ramipril. ## Contraindications * History of angioedema related to ACE inhibitor therapy * Concomitant use with aliskiren in patients with diabetes mellitus * Pregnancy (Category D in 2nd and 3rd trimesters) * Known hypersensitivity to the specific ACE inhibitor ## Adverse Effects * **Common:** Dry cough (non-productive), dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening), hypotension, acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), rash, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive efficacy and increase risk of renal dysfunction. * **Lithium:** Increased lithium levels and risk of toxicity. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Avoid concomitant use; increased risk of angioedema. A 36-hour washout period is recommended after stopping an ACE inhibitor before starting sacubitril/valsartan. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), CBC. * **During therapy:** Blood pressure (regular intervals), serum creatinine and potassium (1-2 weeks after initiation or dose increase, then periodically, more frequently in high-risk patients). Monitor for cough and signs of angioedema. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is problematic, consider switching to an angiotensin II receptor blocker (ARB). * Angioedema can occur at any time during therapy and is a medical emergency. * Use with caution in patients with bilateral renal artery stenosis, as it can precipitate acute renal failure. * First-dose hypotension can occur, particularly in volume-depleted patients or those on diuretics. Consider a lower starting dose and administer the first dose at bedtime. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. *** **Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for definitive dosing, indications, and safety information before making any treatment decisions.