Please check your internet connection and try again.
# ACE Inhibitors
## Overview
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used for cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity. This results in lower blood pressure and reduced cardiac workload.
## Primary Indications
* Hypertension
* Heart failure (reduced ejection fraction)
* Myocardial infarction (post-MI management, especially with reduced ejection fraction or signs of heart failure)
* Diabetic nephropathy (to slow progression)
* Proteinuric kidney disease
## Adult Dosing
Dosing is highly individualized and titratable based on patient response and tolerability. Starting doses are typically low and gradually increased.
* **Hypertension:**
* Benazepril: 10-40 mg once daily. Max: 80 mg/day.
* Captopril: 25 mg 2-3 times daily. Max: 150 mg 3 times daily.
* Enalapril: 10-40 mg once or twice daily. Max: 40 mg/day.
* Fosinopril: 10-40 mg once daily. Max: 80 mg/day.
* Lisinopril: 10-40 mg once daily. Max: 80 mg/day.
* Moexipril: 7.5-30 mg once or twice daily. Max: 60 mg/day.
* Perindopril: 5-10 mg once daily. Max: 20 mg/day.
* Quinapril: 10-40 mg once or twice daily. Max: 80 mg/day.
* Ramipril: 2.5-20 mg once daily. Max: 20 mg/day.
* Trandolapril: 1-4 mg once daily. Max: 16 mg/day.
* **Heart Failure:**
* Generally start low and titrate to target doses or maximum tolerated dose. Target doses vary by agent but are often higher than for hypertension.
* Enalapril: 2.5-20 mg twice daily. Target: 10-20 mg twice daily.
* Lisinopril: 5-10 mg once daily. Target: 20 mg once daily.
* Ramipril: 2.5-5 mg once daily. Target: 10 mg once daily.
* Captopril: 6.25-12.5 mg 3 times daily. Target: 50 mg 3 times daily.
* **Post-MI:**
* Enalapril: Start 5 mg within 24 hours of MI, then 10 mg 12 hours later, then 20 mg daily or 10 mg twice daily. Continue for at least 6 weeks.
* Lisinopril: Start 5 mg within 24 hours of MI, then 5 mg after 24 hours, then 10 mg daily. Continue for at least 6 weeks.
* Ramipril: Start 1.25 mg once daily, increasing to 2.5 mg twice daily after 2 days, then 5 mg twice daily after 4 weeks.
## Pediatric Dosing
ACE inhibitors are used in pediatric patients, but dosing is less standardized and often based on weight. Consultation with pediatric specialists or specific pediatric guidelines is recommended.
* **Hypertension:**
* Enalapril: 0.07-0.1 mg/kg/dose orally once or twice daily. Max: 0.61 mg/kg/day or 40 mg/day.
* Lisinopril: 0.07-0.2 mg/kg/dose orally once daily. Max: 20 mg/day.
* Captopril: 0.3-0.5 mg/kg/dose orally 3 times daily. Max: 150 mg/day.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary. Specific guidance varies by agent and degree of renal impairment (eGFR).
* For example, lisinopril: If eGFR < 30 mL/min/1.73 m², start at 5 mg daily. If eGFR 30-60 mL/min/1.73 m², start at 10 mg daily.
* **Hepatic Impairment:** Use with caution. Enalapril is a prodrug that requires hepatic activation; caution may be warranted in severe hepatic impairment. Captopril may be used cautiously.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment
* Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment
* Pregnancy (Category D in 2nd and 3rd trimesters, Category C in 1st trimester)
* Known hypersensitivity to ACE inhibitors
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache.
* **Serious:** Angioedema (facial, lip, tongue, throat, intestinal), acute kidney injury (especially in bilateral renal artery stenosis), hyperkalemia, severe hypotension, hepatic dysfunction.
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in elderly or volume-depleted patients.
* **Diuretics:** Increased risk of hypotension, especially with loop diuretics.
* **Lithium:** ACE inhibitors can decrease lithium clearance, leading to increased lithium levels and toxicity.
* **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **Sacubitril/valsartan:** Avoid concomitant use with ACE inhibitors due to increased risk of angioedema. Separate administration by at least 36 hours.
* **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid in diabetic patients.
## Monitoring
* **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), renal function (eGFR).
* **During Therapy:**
* Blood pressure (especially with initiation and dose titration).
* Serum creatinine and electrolytes (especially potassium) within 1-2 weeks of initiation or dose change, and periodically thereafter. Monitor more frequently in patients with renal impairment, heart failure, or at risk of hyperkalemia.
* Signs and symptoms of angioedema.
## Clinical Pearls
* Cough is a common and often dose-limiting side effect, occurring in 5-20% of patients. It is typically dry and persistent and resolves after discontinuation.
* Angioedema is a rare but life-threatening side effect. Patients should be educated to seek immediate medical attention if swelling of the face, lips, tongue, or throat occurs.
* ACE inhibitors should be initiated at low doses and titrated slowly to assess tolerability and efficacy, especially in patients who are elderly, volume-depleted, or have heart failure.
* Consider an ARB (angiotensin II receptor blocker) as an alternative in patients who develop a cough or angioedema with ACE inhibitors.
* ACE inhibitors are generally safe and effective in patients with diabetes and chronic kidney disease to reduce proteinuria and slow disease progression.
***
**Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any decisions about patient care. Dosing may vary based on individual patient factors, local protocols, and specific product labeling.
