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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications 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 with reduced ejection fraction (HFrEF) * Post-myocardial infarction (MI) for individuals with clinical signs of HFrEF * Diabetic nephropathy (in patients with type 2 diabetes and hypertension or proteinuria) ## Adult Dosing Dosing is highly individualized and dependent on the specific ACE inhibitor used, the indication, and patient response. Titration is typically performed every 1-4 weeks. * **Hypertension:** Starting doses vary, e.g., lisinopril 5 mg PO daily, enalapril 5 mg PO BID, ramipril 2.5 mg PO daily. Usual maintenance doses range from 10-40 mg daily for lisinopril, 10-40 mg daily for enalapril, and 5-10 mg daily for ramipril. Maximum doses vary by agent but are generally limited by adverse effects. * **Heart Failure (HFrEF):** Starting doses are typically lower than for hypertension to minimize the risk of hypotension and renal dysfunction. E.g., enalapril 2.5 mg PO BID, lisinopril 2.5-5 mg PO daily, ramipril 1.25 mg PO daily. Doses are titrated upwards as tolerated to target goals. * **Post-MI:** Dosing often follows guidelines and may start within 24 hours of MI. E.g., captopril 6.25 mg PO TID, ramipril 1.25 mg PO BID. * **Diabetic Nephropathy:** Dosing is similar to hypertension regimens. ## Pediatric Dosing Dosing in pediatric patients is less well-established and should be guided by specific product labeling and clinical expertise. Doses are typically based on weight. * **Hypertension:** E.g., Enalapril: 0.07-0.1 mg/kg/dose PO q12-24h; maximum 0.6 mg/kg/day. Lisinopril: 0.07-0.2 mg/kg/dose PO q24h; maximum 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary in patients with renal insufficiency. Specific adjustments depend on the degree of renal impairment and the individual ACE inhibitor. Serum creatinine and potassium should be monitored closely. * **Hepatic Impairment:** Generally, no dose adjustment is needed for mild to moderate hepatic impairment, but caution is advised. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Concomitant use of aliskiren in patients with diabetes or renal impairment. * Known hypersensitivity to ACE inhibitors. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Dry cough, dizziness, hyperkalemia, hypotension, fatigue, headache, renal dysfunction. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, severe hypotension, hyperkalemia. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, angiotensin II receptor blockers (ARBs):** Increased risk of hyperkalemia. * **NSAIDs:** May reduce the antihypertensive effect and increase the risk of renal impairment, especially in volume-depleted patients. * **Diuretics:** Additive hypotensive effect. Hypokalemia from diuretics can be masked. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. ## Monitoring * Blood pressure (before and during treatment). * Serum potassium and creatinine (baseline and periodically, especially in patients with renal impairment or those taking potassium-sparing agents). * Signs and symptoms of angioedema. * Renal function (especially in patients with pre-existing renal disease or those on concomitant nephrotoxic medications). ## Clinical Pearls * The characteristic dry cough is often dose-limiting and may necessitate discontinuation. * Angioedema can occur at any time during therapy and requires immediate discontinuation and medical attention. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, elderly, or have renal impairment, to minimize risk of hypotension and renal dysfunction. * Avoid combination therapy with ACE inhibitors and ARBs or aliskiren unless under specific expert guidance for select patient populations due to increased risk of adverse events without clear benefit. *** *This information is intended for healthcare professionals and does not replace comprehensive drug information resources. Always verify current prescribing information with the official product labeling and consult relevant clinical guidelines.*