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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of drugs primarily used for managing hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure and workload on the heart.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (MI) to improve survival
* Diabetic nephropathy (proteinuria reduction)
* Chronic kidney disease (CKD) with proteinuria
## Adult Dosing
Dosing varies by specific agent. Titration is typically guided by blood pressure response and tolerability.
* **Benazepril:** Start at 5-10 mg once daily. Max: 40 mg daily.
* **Captopril:** Start at 12.5-25 mg twice daily. Max: 150 mg twice daily. (More frequent dosing due to shorter half-life).
* **Enalapril:** Start at 5 mg once daily. Max: 40 mg daily. (Can be given IV: 1.25 mg every 6 hours).
* **Fosinopril:** Start at 10 mg once daily. Max: 40 mg daily.
* **Lisinopril:** Start at 10 mg once daily. Max: 40 mg daily.
* **Moexipril:** Start at 7.5 mg once daily. Max: 30 mg daily.
* **Perindopril:** Start at 2.5-5 mg once daily. Max: 10 mg daily.
* **Quinapril:** Start at 5-10 mg twice daily. Max: 40 mg twice daily.
* **Ramipril:** Start at 2.5-5 mg once daily. Max: 10 mg daily.
* **Trandolapril:** Start at 1 mg once daily. Max: 4 mg daily.
## Pediatric Dosing
Established pediatric dosing is available for some ACE inhibitors, but often requires specialist consultation and careful titration.
* **Captopril:** Oral: 0.3 mg/kg/dose every 8 hours initially. Max: 1 mg/kg/dose every 8 hours.
* **Enalapril:** Oral: 0.07 mg/kg/dose once daily. Max: 0.57 mg/kg/dose once daily. IV: 0.01 mg/kg/dose every 6 hours.
* **Lisinopril:** Oral: 0.07 mg/kg/dose once daily. Max: 0.61 mg/kg/dose once daily or 20 mg daily.
## Dose Adjustments
* **Renal Impairment:** For most ACE inhibitors, starting doses should be reduced and titration slowed in patients with significant renal impairment (CrCl < 30 mL/min). Specific recommendations vary by agent.
* **Hepatic Impairment:** Cautious use is recommended; no specific dose adjustments are typically listed, but titrate slowly.
* **Volume Depletion:** Correct volume or salt depletion before initiating therapy or use a lower starting dose.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes or renal impairment.
* Pregnancy (especially second and third trimesters).
## Adverse Effects
* **Dry cough:** Common and often dose-limiting.
* **Hyperkalemia:** Especially in renal impairment or with potassium-sparing diuretics.
* **Hypotension:** Particularly with the first dose or in volume-depleted patients.
* **Angioedema:** Rare but potentially life-threatening; can occur at any time.
* **Renal dysfunction:** Can occur, especially in patients with bilateral renal artery stenosis.
* **Dizziness, fatigue.**
* **Rash.**
## Key Drug Interactions
* **Potassium supplements, potassium-sparing diuretics (e.g., spironolactone, amiloride), other drugs that increase potassium:** Increased risk of hyperkalemia.
* **Diuretics:** Additive hypotensive effect. Risk of severe hypotension, especially with loop diuretics.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment.
* **Lithium:** ACE inhibitors can increase lithium levels; monitor lithium levels closely.
* **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Contraindicated in diabetics and those with renal impairment.
* **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema.
## Monitoring
* **Blood pressure:** Before and regularly after initiation and titration.
* **Serum potassium:** Before initiation and periodically, especially in patients with renal impairment or on other potassium-altering medications.
* **Renal function (serum creatinine, BUN):** Before initiation and periodically.
* **Angioedema:** Patients should be educated on signs and symptoms and instructed to discontinue immediately if they occur.
## Clinical Pearls
* Start low and go slow, especially in elderly, volume-depleted, or renally impaired patients.
* The dry cough is usually reversible upon discontinuation.
* Angioedema is a medical emergency and necessitates immediate cessation of the ACE inhibitor and careful monitoring.
* ACE inhibitors are renoprotective in patients with diabetes and proteinuria.
* Captopril has a shorter half-life and may require more frequent dosing than other ACE inhibitors.
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*This information is intended for healthcare professionals. Always consult the current prescribing information and relevant clinical guidelines for complete details and to ensure appropriate patient care.*
