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# ACE Inhibitors
## Overview
ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications primarily used to treat cardiovascular conditions like hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (MI) (to improve survival)
* Diabetic nephropathy (to slow progression)
* Proteinuric chronic kidney disease
## Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is key.
* **Hypertension:**
* **Benazepril:** Start at 5-10 mg once daily. Titrate up to 20-40 mg once daily.
* **Captopril:** Start at 12.5-25 mg twice daily. Titrate up to 50 mg three times daily.
* **Enalapril:** Start at 5 mg once daily. Titrate up to 10-40 mg once daily.
* **Fosinopril:** Start at 10 mg once daily. Titrate up to 40 mg once daily.
* **Lisinopril:** Start at 10 mg once daily. Titrate up to 40 mg once daily.
* **Moexipril:** Start at 7.5 mg once daily. Titrate up to 30 mg once daily.
* **Perindopril:** Start at 2.5-5 mg once daily. Titrate up to 10 mg once daily.
* **Quinapril:** Start at 5-10 mg twice daily. Titrate up to 20-80 mg daily, divided into two doses.
* **Ramipril:** Start at 2.5 mg once daily. Titrate up to 10 mg once daily.
* **Trandolapril:** Start at 1 mg once daily. Titrate up to 4 mg once daily.
* **Heart Failure:**
* **Benazepril:** Start at 5 mg once daily. Target 20-40 mg once daily.
* **Captopril:** Start at 6.25 mg three times daily. Target 50 mg three times daily.
* **Enalapril:** Start at 2.5 mg twice daily. Target 10-20 mg twice daily.
* **Lisinopril:** Start at 5 mg once daily. Target 10-40 mg once daily.
* **Ramipril:** Start at 1.25 mg once daily. Target 5-10 mg once daily.
* **Post-MI:**
* **Enalapril:** Start at 2.5 mg twice daily. Target 5-10 mg twice daily.
* **Lisinopril:** Start at 5 mg once daily. Target 10 mg once daily.
* **Ramipril:** Start at 1.25 mg once daily. Target 5 mg twice daily.
* **Diabetic Nephropathy / Proteinuric CKD:**
* Dosing typically starts at the lower end and is titrated to achieve blood pressure goals or reduce proteinuria. Specific targets depend on the agent.
## Pediatric Dosing
ACE inhibitors are used in pediatric patients for hypertension and sometimes heart failure, but dosing is less standardized and often based on body surface area or weight. Specific protocols should be followed.
* **Enalapril:** Hypertension: 0.07-0.1 mg/kg/dose once daily (max 40 mg/day).
* **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/dose once daily (max 40 mg/day).
* **Ramipril:** Hypertension: 0.05 mg/kg/day once daily, may increase to 0.1 mg/kg/day (max 10 mg/day).
## Dose Adjustments
* **Renal Impairment:** Dose reductions are often necessary, particularly for renally cleared ACE inhibitors like enalapril and lisinopril. Consult specific drug guidelines. Captopril and fosinopril are less affected by renal impairment.
* **Hepatic Impairment:** Generally no dose adjustment needed, but caution is advised.
* **Volume Depletion/Hyponatremia:** Start with lower doses due to increased risk of hypotension.
## Contraindications
* History of angioedema related to previous 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:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia.
* **Serious:** Angioedema (potentially life-threatening), hypotension, acute kidney injury (especially in those with bilateral renal artery stenosis), hyperkalemia, rash, dysgeusia.
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, especially in elderly or volume-depleted patients.
* **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid co-administration.
* **ARBs (Angiotensin II Receptor Blockers):** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid co-administration.
* **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. Monitor lithium levels closely.
* **Diuretics (especially thiazides):** Additive hypotensive effect. Risk of severe hypotension upon initiation, especially if volume-depleted.
## Monitoring
* **Before initiation:** Baseline serum creatinine, potassium, and blood pressure.
* **During treatment:**
* Blood pressure regularly.
* Serum creatinine and potassium within 1-2 weeks of initiation or dose increase, and periodically thereafter.
* Monitor for signs/symptoms of angioedema or hypotension.
* For heart failure patients, monitor for worsening symptoms or signs of hyperkalemia.
## Clinical Pearls
* The characteristic dry cough is dose-dependent and often resolves upon discontinuation.
* Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor.
* Initiate at low doses and titrate slowly, especially in patients who are elderly, volume-depleted, or have renal impairment, to minimize the risk of hypotension and renal dysfunction.
* ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria.
* Consider alternative antihypertensives if angioedema occurs, as cross-reactivity with ARBs is low but possible.
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*This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the latest prescribing information and relevant guidelines for complete and up-to-date details.*
