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# ACE Inhibitors
## Overview
ACE inhibitors (ACEIs) are a class of medications that block the action of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. This results in decreased blood pressure and reduced cardiac workload.
## Primary Indications
* Hypertension
* Heart failure (reduced ejection fraction)
* Post-myocardial infarction
* Diabetic nephropathy
* Proteinuric chronic kidney disease
## Adult Dosing
Dosing varies significantly by specific agent and indication. Titration is typically guided by blood pressure response, tolerability, and clinical goals.
* **Hypertension:** Initial doses are usually low and titrated upwards every 1-4 weeks. Examples:
* Lisinopril: 10 mg once daily, titrate up to 40 mg once daily.
* Enalapril: 5 mg once or twice daily, titrate up to 10-20 mg twice daily.
* Ramipril: 2.5 mg once daily, titrate up to 10 mg once daily.
* **Heart Failure:** Typically initiated at low doses and titrated to the maximum tolerated dose. Examples:
* Lisinopril: 5 mg once daily, titrate up to 20-40 mg once daily.
* Enalapril: 2.5 mg twice daily, titrate up to 10-20 mg twice daily.
* Ramipril: 1.25 mg once daily, titrate up to 10 mg once daily.
* **Post-MI:** Typically started within 24 hours, with doses similar to or slightly lower than hypertension.
* **Diabetic Nephropathy/Proteinuric CKD:** Doses often titrated to the maximum tolerated dose to achieve optimal blood pressure and proteinuria reduction.
## Pediatric Dosing
Dosing in pediatric patients is weight-based and agent-specific. It requires careful titration and monitoring.
* **Hypertension:**
* Enalapril: 0.07-0.1 mg/kg/dose orally every 12-24 hours. Max 0.58 mg/kg/day.
* Lisinopril: 0.07-0.2 mg/kg/dose orally once daily. Max 10 mg/day for children < 20 kg; max 20 mg/day for children ≥ 20 kg.
* Captopril: 0.3 mg/kg/dose orally every 8-12 hours. Max 1.5 mg/kg/day.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is typically required in patients with impaired renal function (e.g., CrCl < 30 mL/min). Specific guidance depends on the individual agent.
* **Hepatic Impairment:** Caution is advised, and starting with lower doses may be necessary, particularly with prodrugs like enalapril and ramipril.
## Contraindications
* History of angioedema related to previous ACEI therapy.
* Concomitant use of sacubitril/valsartan (within 36 hours of the last dose of sacubitril/valsartan).
* Hereditary or idiopathic angioedema.
* Pregnancy (especially in the second and third trimesters).
* Bilateral renal artery stenosis.
## Adverse Effects
Common adverse effects include cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, and hypotension. Less common but serious adverse effects include angioedema, acute kidney injury, and neutropenia.
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, and salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment.
* **Diuretics (thiazide and loop):** Additive hypotensive effect; risk of severe hypotension with initial doses of ACEI.
* **Lithium:** ACEIs can reduce lithium clearance, increasing lithium toxicity risk.
* **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **Sacubitril/valsartan:** Contraindicated due to increased risk of angioedema.
## Monitoring
* **Baseline:** Serum creatinine, potassium, electrolytes, blood pressure.
* **During therapy:**
* Blood pressure (including orthostatic measurements).
* Serum creatinine and potassium (especially within 1-4 weeks of initiation or dose change, and in patients with risk factors for renal dysfunction).
* Electrolytes.
* Signs and symptoms of angioedema.
* Renal function in patients with pre-existing kidney disease or risk factors.
## Clinical Pearls
* The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB).
* ACEIs can protect kidney function in patients with diabetes and proteinuria.
* Initiate at low doses and titrate slowly, especially in patients who are volume depleted, on diuretics, or have impaired renal function.
* Monitor potassium closely, as ACEIs can cause hyperkalemia.
* Angioedema is a medical emergency; discontinue ACEI immediately and manage airway.
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*This information is intended for healthcare professionals and does not substitute for professional medical advice. Always consult current prescribing information and relevant guidelines for complete and up-to-date details on drug use.*
