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# ACE Inhibitors
## Overview
ACE inhibitors (ACEIs) are a class of medications that block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and also stimulates aldosterone release, leading to sodium and water retention. By inhibiting ACE, these drugs lead to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Myocardial infarction (post-MI management)
* Diabetic nephropathy
* Chronic kidney disease (proteinuric)
## Adult Dosing
Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is usually required.
* **Hypertension:** Initial doses are typically low (e.g., captopril 12.5-25 mg BID, enalapril 2.5-5 mg QD, lisinopril 5-10 mg QD). Usual maintenance doses vary, with maximum daily doses often around:
* Captopril: 150 mg/day
* Enalapril: 40 mg/day
* Lisinopril: 40 mg/day
* Ramipril: 10 mg/day
* **Heart Failure:** Initial doses are low to avoid hypotension and worsening renal function (e.g., enalapril 2.5-5 mg BID, lisinopril 5 mg QD, ramipril 2.5 mg BID). Doses are gradually increased as tolerated to target doses:
* Enalapril: 10-20 mg BID
* Lisinopril: 20-40 mg QD
* Ramipril: 5 mg BID
* **Post-Myocardial Infarction:** Typically initiated within 24 hours if no contraindications. Doses aim for those used in hypertension or heart failure, depending on clinical status (e.g., ramipril 5 mg BID, lisinopril 5-10 mg QD).
* **Diabetic Nephropathy/CKD:** Doses are titrated to the maximum tolerated dose to achieve blood pressure goals and reduce proteinuria.
## Pediatric Dosing
ACE inhibitors are used in pediatric patients for hypertension and heart failure. Dosing varies by age and indication and should be guided by institutional protocols or specialized pediatric resources.
* **Hypertension:**
* Enalapril: 0.08 mg/kg/day divided BID, max 40 mg/day.
* Lisinopril: 0.07-0.2 mg/kg/day QD, max 40 mg/day.
* **Heart Failure:** Similar initial doses to hypertension, titrated upwards.
## Dose Adjustments
* **Renal Impairment:** Reduce dose and titrate cautiously, especially in patients with significant renal dysfunction. Creatinine may increase by up to 30% and is generally acceptable if stable and the patient is asymptomatic.
* **Hepatic Impairment:** Cautious initiation and titration; no specific dose adjustments are usually mandated due to hepatic metabolism, but effects may be prolonged.
* **Volume Depletion/Hyponatremia:** Risk of symptomatic hypotension. Correct volume status and/or sodium levels before initiating or increasing dose.
* **Concomitant Diuretics:** Start with a lower dose of ACEI and consider discontinuing the diuretic temporarily or 2-3 days prior to initiating ACEI to minimize risk of first-dose hypotension.
## Contraindications
* History of angioedema related to prior ACEI therapy.
* Hereditary or idiopathic angioedema.
* Concomitant use of neprilysin inhibitors (e.g., sacubitril) within 36 hours.
* Pregnancy (especially in the second and third trimesters).
* Known hypersensitivity to the drug.
* Severe aortic stenosis or hypertrophic cardiomyopathy (relative contraindication, risk of worsening obstruction).
## Adverse Effects
* **Common:** Cough (dry, persistent), hyperkalemia, dizziness, headache, fatigue, hypotension (especially first dose).
* **Serious:** Angioedema (can be fatal, involves larynx, tongue, lips, face), renal failure (especially in patients with bilateral renal artery stenosis), severe hypotension, neutropenia/agranulocytosis (rare).
* **Other:** Rash, dysgeusia, nausea, diarrhea.
## Key Drug Interactions
* **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride), Potassium Supplements, Trimethoprim:** Increased risk of hyperkalemia. Monitor potassium closely.
* **NSAIDs (including COX-2 inhibitors):** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients or those with pre-existing renal disease.
* **Lithium:** ACEIs can decrease lithium clearance, increasing lithium toxicity risk. Monitor lithium levels.
* **Sacubitril/Valsartan:** Contraindicated within 36 hours of each other due to increased risk of angioedema.
* **Diuretics:** Increased risk of symptomatic hypotension, especially with thiazide diuretics.
## Monitoring
* **Blood Pressure:** Regularly, especially after dose initiation or titration.
* **Renal Function (Serum Creatinine, BUN):** Before initiating therapy, and periodically thereafter (e.g., within 1-2 weeks of initiation/dose change, and then every 6-12 months).
* **Serum Potassium:** Before initiating therapy, within 1-2 weeks of initiation/dose change, and then periodically.
* **Signs/Symptoms of Angioedema:** Counsel patients to seek immediate medical attention if swelling of the face, lips, tongue, or throat occurs.
* **Hemoglobin/Hematocrit:** Baseline and periodically, especially if concerns for anemia.
* **White Blood Cell Count:** If neutropenia is suspected (fever, infection).
## Clinical Pearls
* The characteristic dry cough is dose-dependent and reversible upon discontinuation.
* First-dose hypotension is a risk, especially in volume-depleted patients or those on diuretics. Administer first dose with caution, monitor closely.
* Angioedema is a medical emergency and can occur at any time during therapy. Discontinue immediately if suspected.
* ACEIs are generally considered renoprotective in proteinuric kidney disease.
* Avoid in pregnancy due to risk of fetal harm.
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*This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the current prescribing information and relevant clinical guidelines for the most up-to-date and comprehensive details before making any treatment decisions.*
