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## Angiotensin-Converting Enzyme (ACE) Inhibitors ### Overview ACE inhibitors are a class of medications that primarily block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ### Primary Indications * Hypertension * Heart Failure (reduced ejection fraction) * Post-Myocardial Infarction (in select patients) * Diabetic Nephropathy (proteinuria reduction) ### Adult Dosing Dosages vary significantly by specific ACE inhibitor. Titration is common, starting at a low dose and gradually increasing as tolerated and indicated. * **Hypertension:** Starting doses are typically low, with typical maintenance doses varying widely. For example: * Lisinopril: Start 10 mg PO daily, titrate up to 20-40 mg PO daily. Maximum 80 mg daily. * Enalapril: Start 5 mg PO daily or BID, titrate up to 10-40 mg PO daily. Maximum 40 mg daily. * Ramipril: Start 2.5-5 mg PO daily, titrate up to 10 mg PO daily. Maximum 10 mg daily. * **Heart Failure:** Dosing often starts lower and is titrated more cautiously due to the risk of hypotension and worsening renal function. Specific target doses are often established in guidelines. * **Post-MI/Diabetic Nephropathy:** Dosing regimens are specific to the indication and individual patient response. ### Pediatric Dosing Dosing in pediatric patients is weight-based and requires careful titration. Specific dosing varies by agent and indication, and local institutional protocols should be consulted. Examples include: * **Hypertension:** * Enalapril: 0.07 mg/kg/dose PO every 12-24 hours. Maximum 0.5 mg/kg/day (or 40 mg/day, whichever is less). * Lisinopril: 0.07 mg/kg/dose PO every 24 hours. Maximum 0.61 mg/kg/day (or 40 mg/day, whichever is less). ### Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially with significant renal dysfunction. Monitor potassium levels closely. * **Hepatic Impairment:** While generally less impacted than with some other drug classes, caution and dose adjustment may be needed in severe hepatic impairment. ### Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (Category D). * Hereditary or idiopathic angioedema. ### Adverse Effects * **Most Common:** Cough (dry, persistent), hyperkalemia, dizziness, fatigue, headache, hypotension. * **Serious:** Angioedema (can be life-threatening, affecting face, lips, tongue, throat, intestines), acute kidney injury (especially in patients with bilateral renal artery stenosis), neutropenia, agranulocytosis. ### Key Drug Interactions * **Potassium-Sparing Diuretics & Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Lithium:** ACE inhibitors can increase lithium levels. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Contraindicated in patients with diabetes or renal impairment. * **ARBs:** Increased risk of hyperkalemia and angioedema. Generally avoided unless specific indication and careful monitoring. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ### Monitoring * **Blood Pressure:** Regular assessment to guide titration and assess efficacy. * **Renal Function:** Baseline and periodic monitoring of serum creatinine and BUN. * **Potassium:** Baseline and periodic monitoring, especially in patients with renal impairment, diabetes, or those on potassium-sparing diuretics. * **Signs/Symptoms of Angioedema:** Patient education is critical. ### Clinical Pearls * The characteristic dry cough is often dose-limiting and occurs in 5-20% of patients. Switching to an Angiotensin II Receptor Blocker (ARB) is typically the management strategy. * Hypotension is more likely with the first dose, especially in volume-depleted patients or those on diuretics. Consider a lower starting dose or withholding diuretics prior to initiation. * Angioedema can occur at any time during therapy, even years after initiation. Prompt recognition and discontinuation are crucial. * ACE inhibitors are generally renoprotective in diabetic nephropathy, but close monitoring for worsening renal function and hyperkalemia is essential. *** **Disclaimer:** This information is intended for educational purposes and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for definitive dosing, safety, and indication details before making any treatment decisions. Local institutional protocols may also apply.