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# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that primarily relax blood vessels, lowering blood pressure and reducing the workload on the heart. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor.
## Primary Indications
* Hypertension
* Heart failure (reduced ejection fraction)
* 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. Typical starting doses and maximum daily doses for common indications include:
* **Hypertension:**
* Benazepril: Start 10 mg once daily, max 40 mg daily
* Captopril: Start 25 mg twice daily, max 150 mg twice daily
* Enalapril: Start 5 mg once or twice daily, max 40 mg daily
* Lisinopril: Start 10 mg once daily, max 40 mg daily
* Ramipril: Start 2.5 mg once daily, max 20 mg daily
* Trandolapril: Start 1 mg once daily, max 8 mg daily
* **Heart Failure (HFrEF):**
* Enalapril: Start 2.5 mg twice daily, max 10 mg twice daily
* Lisinopril: Start 5 mg once daily, max 40 mg daily
* Ramipril: Start 1.25 mg once daily, max 10 mg once daily
* **Post-MI:**
* Captopril: Start 6.25 mg three times daily, titrate up to 50 mg three times daily
* Enalapril: Start 2.5 mg twice daily, titrate up to 10 mg twice daily
* Lisinopril: Start 5 mg once daily, titrate up to 10 mg once daily
* **Diabetic/CKD Nephropathy:** Doses are often guided by blood pressure targets and tolerability, typically starting at lower doses and titrating to achieve adequate proteinuria reduction.
Titration is usually done every 1-2 weeks based on blood pressure response and tolerability.
## Pediatric Dosing
ACE inhibitors are used in pediatric patients for hypertension and certain cardiac conditions. Dosing is weight-based and varies by agent.
* **Enalapril:**
* Hypertension: 0.07 to 0.1 mg/kg/dose once daily (max 20 mg/day)
* Congenital Heart Disease: 0.1 mg/kg/dose once daily (max 40 mg/day)
* **Lisinopril:**
* Hypertension: 0.07 mg/kg/dose once daily (max 20 mg/day)
Dosing in neonates and infants is less established and requires careful titration and monitoring.
## Dose Adjustments
* **Renal Impairment:** Reduce initial dose and titrate cautiously. Monitor serum creatinine and potassium closely. Dose adjustments depend on the specific agent's renal clearance and the degree of renal impairment (e.g., CrCl < 30 mL/min).
* **Hepatic Impairment:** Captopril and moexipril, which undergo hepatic metabolism, may require dose reduction. Other ACE inhibitors generally do not require significant dose adjustments in mild to moderate hepatic impairment.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use of sacubitril/valsartan (due to increased risk of angioedema; allow 36 hours after stopping sacubitril/valsartan before initiating ACE inhibitor).
* Pregnancy (especially second and third trimesters, associated with fetal injury and death).
* Hypersensitivity to the specific ACE inhibitor.
* Bilateral renal artery stenosis (relative contraindication, risk of acute kidney injury).
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache.
* **Serious:** Angioedema (lips, face, tongue, throat, intestines), acute kidney injury, severe hypotension, hyperkalemia, neutropenia/agranulocytosis (rare, particularly with captopril).
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, ARBs, aliskiren, heparin:** Increased risk of hyperkalemia.
* **NSAIDs (including aspirin > 325 mg/day):** May reduce antihypertensive effect and increase risk of renal impairment, especially in patients with volume depletion or underlying renal disease.
* **Diuretics (especially loop and thiazide):** Additive hypotensive effect; risk of hypovolemia and acute kidney injury.
* **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels.
* **mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema.
* **Racecadotril:** Increased risk of angioedema.
## Monitoring
* **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium).
* **During Therapy:**
* Blood pressure: Within 1-2 weeks of initiation and titration.
* Serum creatinine: Within 1-2 weeks of initiation and titration, and periodically thereafter (frequency depends on renal function and other risk factors).
* Potassium: Within 1-2 weeks of initiation and titration, and periodically thereafter.
* Angioedema symptoms.
* Signs/symptoms of infection (if neutropenia is a concern).
## Clinical Pearls
* Cough is a common and often bothersome side effect, occurring in up to 20% of patients. If cough develops, consider discontinuing and switching to an angiotensin II receptor blocker (ARB).
* Initiate with low doses and titrate slowly, especially in patients who are volume-depleted, have heart failure, renal impairment, or are taking diuretics.
* First-dose hypotension can occur, particularly in patients with high renin levels (e.g., severe heart failure, volume depletion). Consider administering the first dose at bedtime or with a meal.
* ACE inhibitors are generally not recommended in pregnancy due to teratogenicity.
* Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor.
* Monitor renal function and potassium closely, especially in patients with underlying renal disease, heart failure, or those taking other nephrotoxic agents.
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*This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and your healthcare provider for any health concerns or before making any treatment decisions.*
