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# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily for managing cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Myocardial infarction (post-MI, to improve survival)
* Diabetic nephropathy (proteinuric)
## Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically guided by blood pressure, symptoms, and tolerability.
* **Hypertension:**
* Benazepril: Start 5-10 mg once daily, titrate up to 40 mg/day.
* Captopril: Start 12.5-25 mg BID, titrate up to 50 mg TID.
* Enalapril: Start 5 mg once daily, titrate up to 10-40 mg/day.
* Fosinopril: Start 10 mg once daily, titrate up to 40 mg/day.
* Lisinopril: Start 10 mg once daily, titrate up to 40 mg/day.
* Moexipril: Start 7.5 mg once daily, titrate up to 30 mg/day.
* Perindopril: Start 2.5-5 mg once daily, titrate up to 10 mg/day.
* Quinapril: Start 5-10 mg BID, titrate up to 20 mg BID.
* Ramipril: Start 2.5 mg once daily, titrate up to 10 mg/day.
* Trandolapril: Start 0.5-1 mg once daily, titrate up to 4 mg/day.
* **Heart Failure:**
* Generally started at a lower dose and titrated more slowly than for hypertension.
* Enalapril: Start 2.5 mg BID, titrate up to 10-20 mg BID.
* Lisinopril: Start 5 mg once daily, titrate up to 10-20 mg/day.
* Ramipril: Start 1.25-2.5 mg BID, titrate up to 5 mg BID.
* **Post-MI:**
* Lisinopril: Start 5 mg within 24 hours of MI, followed by 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg once daily. Continue for at least 6 weeks.
* Ramipril: Start 1.25 mg once daily, titrate up to 5 mg BID.
## Pediatric Dosing
ACE inhibitors are used in pediatric patients for hypertension, heart failure, and other conditions. Dosing is typically based on weight and often initiated at lower doses. Specific dosing varies by agent and indication.
* **Hypertension:** Doses are highly variable and often require consultation with pediatric nephrology or cardiology. Example:
* Enalapril: 0.08-0.1 mg/kg/dose PO every 12-24 hours. Max 0.5 mg/kg/day (or 40 mg/day).
* Lisinopril: 0.07-0.2 mg/kg/dose PO once daily. Max 0.61 mg/kg/day (or 20 mg/day).
* **Heart Failure:** Specific guidelines are less established.
## Dose Adjustments
* **Renal Impairment:** Initial doses should be reduced, and titration should be slower. Doses often need to be halved or quartered in severe renal impairment (e.g., CrCl < 30 mL/min). Captopril and Fosinopril may require less adjustment than others.
* **Hepatic Impairment:** Dose adjustments are generally not required, but caution is advised, especially with prodrugs like enalapril and perindopril.
## Contraindications
* History of angioedema related to previous ACE inhibitor therapy.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes mellitus.
* Concomitant use with sacubitril/valsartan (within 36 hours of the last dose of either).
* Pregnancy (teratogenic; generally contraindicated in the 2nd and 3rd trimesters).
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache.
* **Serious:** Angioedema (potentially life-threatening, especially of the airway), acute kidney injury (especially in patients with bilateral renal artery stenosis), neutropenia, hepatotoxicity.
## Key Drug Interactions
* **Potassium-sparing diuretics, Potassium supplements, Salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients.
* **Diuretics:** Increased risk of symptomatic hypotension, particularly with loop diuretics.
* **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk.
* **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **ARBs:** Increased risk of hyperkalemia, renal dysfunction, and hypotension. Avoid concomitant use unless specifically indicated and carefully monitored.
## Monitoring
* **Renal function (serum creatinine, BUN) and electrolytes (serum potassium):** Baseline and periodically, especially after dose increases or in high-risk patients (e.g., renal insufficiency, heart failure).
* **Blood pressure:** Regularly, especially during initiation and titration.
* **Signs/symptoms of angioedema:** Educate patients on recognition and immediate reporting.
* **CBC:** Periodically, especially in patients at risk for neutropenia.
## Clinical Pearls
* The characteristic dry cough is thought to be due to the accumulation of bradykinin and substance P in the respiratory tract. It typically resolves within 1-4 weeks after discontinuation.
* Angioedema can occur at any time during therapy, even after prolonged use. It is a medical emergency.
* ACE inhibitors are generally renoprotective in proteinuric diabetic patients.
* In patients with heart failure, ACE inhibitors are cornerstone therapy and have demonstrated mortality benefit.
* Consider switching to an Angiotensin II Receptor Blocker (ARB) if angioedema occurs, though cross-reactivity is possible.
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**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 clinical guidelines before making any treatment decisions. Dosing and management may vary based on individual patient factors and local protocols.
