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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications that 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)
* Myocardial infarction (acute and post-MI for prevention of ventricular remodeling)
* Diabetic nephropathy (in patients with diabetes and hypertension or proteinuria)
## Adult Dosing
* **Hypertension:** Dosing is highly variable by agent.
* Benazepril: 10-40 mg once daily.
* Captopril: 25-150 mg divided into two or three doses daily.
* Enalapril: 5-40 mg once or twice daily.
* Fosinopril: 10-40 mg once daily.
* Lisinopril: 10-40 mg once daily.
* Moexipril: 7.5-30 mg divided into two doses daily.
* Perindopril: 2-8 mg once daily.
* Quinapril: 10-80 mg divided into two doses daily.
* Ramipril: 2.5-20 mg once daily.
* Trandolapril: 0.5-4 mg once daily.
* Maximum doses vary by agent and indication.
* **Heart Failure:** Dosing is typically initiated at a lower dose and titrated up.
* Captopril: 6.25-12.5 mg three times daily, titrated to 50 mg three times daily.
* Enalapril: 2.5-5 mg once or twice daily, titrated to 10-20 mg twice daily.
* Lisinopril: 5 mg once daily, titrated to 20-40 mg once daily.
* Ramipril: 1.25-2.5 mg once daily, titrated to 10 mg once daily.
* **Post-Myocardial Infarction:**
* Lisinopril: 5 mg initiated within 24 hours, then 5 mg at 24 hours, followed by 10 mg daily for at least 6 weeks.
* Ramipril: 1.25 mg, then 2.5 mg twice daily, then 5 mg twice daily for 1 week, then 10 mg twice daily for 1 year.
## Pediatric Dosing
* **Hypertension:** Dosing varies by agent and is often based on body surface area or weight.
* Enalapril: 0.07-0.1 mg/kg/day once daily (maximum 40 mg/day).
* Lisinopril: 0.07-0.2 mg/kg/day once daily (maximum 40 mg/day).
* Captopril: 0.3 mg/kg/dose every 8 hours (maximum 30 mg/dose or 0.9 mg/kg/day).
* *Note: Pediatric dosing is less standardized and may require consultation with a specialist.*
## Dose Adjustments
* **Renal Impairment:** Dose reduction is generally required. Specific reductions depend on the agent and the degree of renal impairment (e.g., CrCl < 30 mL/min).
* **Hepatic Impairment:** Enalapril and Benazepril may require dose reduction due to decreased metabolism.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Concomitant use of aliskiren in patients with diabetes.
* Pregnancy (especially second and third trimesters).
* Known hypersensitivity to ACE inhibitors.
## Adverse Effects
* **Common:** Dry cough (most common), dizziness, fatigue, headache, hyperkalemia, hypotension.
* **Serious:** Angioedema (potentially life-threatening), acute kidney injury, severe hypotension, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia.
* **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction.
* **Aliskiren:** Increased risk of hyperkalemia and hypotension; avoid in patients with diabetes.
* **ARBs (Angiotensin II Receptor Blockers):** Increased risk of hyperkalemia, hypotension, and renal dysfunction; generally avoid concomitant use unless closely monitored for specific indications.
* **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity.
* **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
## Monitoring
* Blood pressure.
* Serum potassium.
* Renal function (serum creatinine and BUN) at baseline and periodically, especially in patients with renal insufficiency or at risk.
* Signs and symptoms of angioedema.
## Clinical Pearls
* The characteristic dry cough is thought to be due to increased bradykinin levels and is usually reversible upon discontinuation.
* First-dose hypotension is a risk, especially in patients who are volume-depleted or on diuretics. Consider initiating at a lower dose or withholding diuretics temporarily.
* ACE inhibitors are generally renoprotective in patients with diabetic nephropathy.
* Angioedema can occur at any time during treatment and requires immediate discontinuation of the ACE inhibitor.
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*This information is intended for healthcare professionals. Always verify current prescribing information and consult with the latest drug compendia before initiating or modifying therapy.*
