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# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Myocardial infarction (post-MI, in selected patients)
* Diabetic nephropathy (proteinuric kidney disease)
## Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically performed every 1-4 weeks.
* **Hypertension:** Initial doses vary, with typical maintenance doses for common agents including:
* Lisinopril: 10-40 mg once daily (Max: 80 mg/day)
* Enalapril: 10-40 mg once or twice daily (Max: 40 mg/day)
* Ramipril: 2.5-20 mg once daily (Max: 20 mg/day)
* Benazepril: 10-40 mg once daily (Max: 80 mg/day)
* **Heart Failure:** Dosing is initiated at a low dose and gradually increased.
* Lisinopril: Initial 5 mg once daily, titrate up to target dose of 10-40 mg once daily.
* Enalapril: Initial 2.5-5 mg twice daily, titrate up to target dose of 10-20 mg twice daily.
* Captopril: Initial 6.25 mg three times daily, titrate up to target dose of 25-50 mg three times daily.
* **Post-Myocardial Infarction:** Generally initiated within 24 hours in patients with anterior MI or signs of heart failure.
* Captopril: 6.25 mg three times daily, then increase as tolerated to 12.5 mg three times daily, and then to 25 mg three times daily.
* Enalapril: 2.5 mg twice daily, then increase as tolerated to 5 mg twice daily, and then to 10 mg twice daily.
## Pediatric Dosing
ACE inhibitor use in pediatrics is less established and typically reserved for specific indications like hypertension or heart failure when other agents are ineffective. Dosing is based on weight and often requires specialist consultation.
* **Hypertension:**
* Enalapril: 0.07-0.1 mg/kg/dose once daily, up to a maximum of 0.6 mg/kg/day (or 40 mg/day).
* Lisinopril: 0.07-0.2 mg/kg/dose once daily, up to a maximum of 20 mg/day.
## Dose Adjustments
* **Renal Impairment:** Initial doses should be reduced in patients with renal insufficiency. Further dose adjustments are based on serum creatinine and GFR.
* Lisinopril: CrCl < 30 mL/min, initial dose 5 mg once daily.
* Enalapril: CrCl < 30 mL/min, initial dose 2.5 mg once daily.
* **Hepatic Impairment:** No specific dose adjustments are usually required, but caution is advised due to potential for altered drug metabolism.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment.
* Pregnancy (especially second and third trimesters).
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia.
* **Less Common/Serious:** Angioedema (rare but life-threatening), acute kidney injury (especially in bilateral renal artery stenosis), neutropenia, rash, taste disturbances.
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment.
* **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk.
* **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema.
## Monitoring
* **Blood Pressure:** Regularly monitor for hypotension.
* **Renal Function:** Serum creatinine and BUN at baseline and periodically, especially in patients with risk factors for renal impairment.
* **Serum Potassium:** Monitor at baseline and periodically, especially in patients with renal insufficiency or those taking potassium-sparing agents.
* **Signs of Angioedema:** Educate patients on signs and symptoms.
## Clinical Pearls
* The characteristic dry cough is thought to be due to bradykinin accumulation and usually resolves upon discontinuation.
* Angioedema can occur at any time during treatment and requires immediate discontinuation.
* Initiate with low doses and titrate slowly, especially in elderly patients, those with heart failure, or renal impairment.
* Avoid in patients with bilateral renal artery stenosis due to risk of precipitating renal failure.
* Monitor closely for hyperkalemia, particularly in patients with risk factors.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols for complete and up-to-date guidance.*
