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# Angiotensin-Converting Enzyme (ACE) Inhibitors
## Overview
ACE inhibitors are a class of drugs that primarily treat hypertension and heart failure by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation and reduced aldosterone secretion.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (for certain agents)
* Diabetic nephropathy (proteinuric kidney disease)
## Adult Dosing
Dosing is agent-specific and typically initiated at a low dose, then titrated upwards based on patient response and tolerability.
* **Benazepril:** Initial 10 mg once daily, usual range 20-40 mg once daily.
* **Captopril:** Initial 25 mg twice daily, usual range 25-150 mg twice or three times daily.
* **Enalapril:** Initial 5 mg once daily (oral), usual range 10-40 mg once daily. For IV: 1.25 mg every 6 hours.
* **Fosinopril:** Initial 10 mg once daily, usual range 20-40 mg once daily.
* **Lisinopril:** Initial 10 mg once daily, usual range 10-40 mg once daily.
* **Moexipril:** Initial 7.5 mg once daily, usual range 15-30 mg once daily.
* **Perindopril:** Initial 2.5-5 mg once daily, usual range 5-10 mg once daily.
* **Quinapril:** Initial 5-10 mg twice daily, usual range 20-80 mg twice daily.
* **Ramipril:** Initial 2.5 mg once daily, usual range 5-10 mg once daily.
* **Trandolapril:** Initial 0.5-1 mg once daily, usual range 1-4 mg once daily.
## Pediatric Dosing
Dosing in children is less standardized and often based on weight. Consult specific pediatric guidelines or drug information resources.
* **Enalapril:** 0.07 mg/kg/day to 0.21 mg/kg/day divided once or twice daily (max 40 mg/day).
* **Lisinopril:** 0.07 mg/kg/day to 0.21 mg/kg/day divided once daily (max 20 mg/day in children <6 years; max 40 mg/day in children ≥6 years).
* **Ramipril:** 0.05 mg/kg/day once daily, may titrate up to 0.1 mg/kg/day (max 10 mg/day).
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary, especially with significant renal dysfunction (creatinine clearance <30 mL/min). Specific recommendations vary by agent.
* **Hepatic Impairment:** Generally less impact, but captopril and enalapril (prodrugs) may have reduced activation. Monitor closely.
## Contraindications
* History of angioedema related to prior ACE inhibitor therapy.
* Concomitant use with aliskiren in patients with diabetes or moderate to severe renal impairment.
* Pregnancy (especially second and third trimesters).
## Adverse Effects
* **Most Common:** Dry cough, dizziness, headache, fatigue.
* **Serious:** Angioedema (rare but life-threatening), hyperkalemia, acute kidney injury (especially in susceptible individuals), hypotension.
* **Other:** Rash, taste disturbances, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of kidney damage, especially in volume-depleted patients.
* **Diuretics (especially loop and thiazide):** Increased risk of symptomatic hypotension, particularly after initiation.
* **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.
* **Sacubitril/Valsartan:** Concomitant use is contraindicated due to increased angioedema risk. If switching from ACE inhibitor to sacubitril/valsartan, allow at least a 36-hour washout period.
## Monitoring
* **Blood Pressure:** Regularly, especially after dose initiation or changes.
* **Renal Function (serum creatinine, BUN):** Baseline and periodically, especially in patients with pre-existing renal disease or risk factors.
* **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment, diabetes, or those on potassium-sparing agents.
* **Angioedema:** Educate patients to report any swelling, especially of the face, lips, tongue, or throat, immediately.
## Clinical Pearls
* The characteristic dry cough is usually dose-dependent and may resolve upon discontinuation.
* Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor.
* ACE inhibitors are generally renoprotective in proteinuric kidney disease, but close monitoring of renal function and potassium is crucial.
* Initiate at low doses and titrate slowly, especially in elderly patients, those on diuretics, or with renal impairment.
* Ensure adequate hydration to minimize the risk of hypotension.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and professional guidelines before making clinical decisions.*
