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# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart failure by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (left ventricular dysfunction)
* Diabetic nephropathy
* Proteinuric kidney disease
## Adult Dosing
Dosing is highly variable by agent and indication. Initiation typically starts at a low dose with titration based on response and tolerability.
* **Hypertension:** Common starting doses include:
* Lisinopril: 10 mg once daily
* Enalapril: 5 mg once or twice daily
* Ramipril: 2.5 mg once daily
* Benzapril: 10 mg once daily
* Captopril: 25 mg twice daily
* *Maximum doses vary by agent (e.g., Lisinopril 40 mg daily, Enalapril 20 mg twice daily).*
* **Heart Failure:**
* Lisinopril: Starting 5 mg daily, titrate up to 40 mg daily
* Enalapril: Starting 2.5 mg twice daily, titrate up to 10-20 mg twice daily
* Ramipril: Starting 2.5 mg twice daily, titrate up to 10 mg twice daily
* **Post-MI:**
* Lisinopril: Starting 5 mg daily, with subsequent doses of 5 mg, 10 mg, and 20 mg daily (administered at 24-hour, 48-hour, and 6-week intervals post-MI, respectively, in eligible patients).
* Captopril: Starting 6.25 mg three times daily, titrate up to 50 mg three times daily.
* **Diabetic Nephropathy/Proteinuric Kidney Disease:**
* Lisinopril: 10-20 mg daily
* Ramipril: 5 mg daily
## Pediatric Dosing
* **Hypertension:** Dosing is weight-based and varies by agent.
* Enalapril: 0.07-0.1 mg/kg/dose (max 5 mg) orally once or twice daily, increased as needed.
* Lisinopril: 0.07-0.2 mg/kg/day (max 10 mg) orally once daily.
* *Consult specific pediatric guidelines for detailed dosing by age and weight.*
## Dose Adjustments
* **Renal Impairment:** Dose reduction is typically required for agents cleared renally. Initial doses should be reduced, and titration should be more cautious. Specific recommendations vary by agent and degree of renal impairment (e.g., CrCl <30 mL/min).
* **Hepatic Impairment:** Use with caution. No specific dose adjustments are usually recommended, but monitoring for adverse effects is important.
## Contraindications
* History of angioedema related to prior ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment.
* Pregnancy (especially second and third trimesters).
## Adverse Effects
* **Common:** Dry cough (most frequent), dizziness, headache, fatigue, hypotension.
* **Serious:** Angioedema (can be life-threatening, especially involving the airway), hyperkalemia, acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), rash, taste disturbances, elevated liver enzymes.
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in patients with pre-existing renal disease.
* **Diuretics (especially thiazides):** Increased risk of hypotension, especially with initiation of ACE inhibitor.
* **Lithium:** ACE inhibitors can decrease lithium clearance, leading to increased serum lithium levels and toxicity.
* **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema.
## Monitoring
* **Baseline:** Blood pressure, serum potassium, serum creatinine/eGFR.
* **During therapy:**
* Blood pressure: To assess efficacy and risk of hypotension.
* Serum potassium: Especially in patients with renal impairment, hyperkalemia risk factors, or concomitant use of potassium-retaining drugs.
* Renal function (serum creatinine/eGFR): Particularly in patients with pre-existing renal disease, heart failure, or bilateral renal artery stenosis. Monitor within 1-2 weeks of initiation or dose increase, and then periodically.
* Signs/symptoms of angioedema or cough.
## Clinical Pearls
* The characteristic dry cough is thought to be due to increased bradykinin levels. Discontinuation of the ACE inhibitor will resolve the cough.
* Angioedema is a rare but potentially fatal side effect and requires immediate discontinuation of the ACE inhibitor and emergency management.
* ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria.
* Initiation in patients with significant volume depletion or diuretic use may lead to symptomatic hypotension. Consider discontinuing diuretics or initiating with a lower dose.
* Avoid in pregnancy due to risk of fetal harm.
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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 or a qualified healthcare provider for specific drug information and treatment decisions.*
