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# ACE Inhibitors
## Overview
ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications used primarily to treat cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure.
## Primary Indications
* Hypertension
* Heart Failure (systolic dysfunction)
* Post-myocardial infarction (to improve survival)
* Diabetic nephropathy (proteinuric)
* Chronic kidney disease (proteinuric)
## Adult Dosing
Dosing varies significantly by agent, indication, and patient response. Initiation is typically at a low dose with gradual titration upwards based on clinical response and tolerability.
* **Hypertension:**
* Benazepril: 10-40 mg once daily
* Captopril: 25-150 mg divided into two or three doses daily
* Enalapril: 10-40 mg once or twice daily
* Fosinopril: 10-40 mg once daily
* Lisinopril: 10-40 mg once daily
* Moexipril: 7.5-30 mg once daily
* Perindopril: 2.5-10 mg once daily
* Quinapril: 10-80 mg divided into two doses daily
* Ramipril: 2.5-20 mg once daily
* Trandolapril: 1-4 mg once daily
* *Maximum doses vary by agent and indication.*
* **Heart Failure:** Doses are generally higher than for hypertension, aiming for maximally tolerated doses. Specific titration schedules are often protocolized.
* **Post-MI/Diabetic Nephropathy:** Dosing varies by agent and indication; specific protocols should be followed.
## Pediatric Dosing
ACE inhibitors are approved for hypertension in pediatric patients. Dosing is weight-based and varies by agent. Consult specific pediatric guidelines or drug monographs for exact dosing.
* **Enalapril:** 0.07 mg/kg to 0.75 mg/kg per day divided into one or two doses.
* **Lisinopril:** 0.07 mg/kg to 0.4 mg/kg per day once daily.
* *For other agents, consult specific pediatric labeling or guidelines.*
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often required, particularly in severe renal impairment. Specific adjustments depend on the agent and the degree of renal dysfunction (creatinine clearance).
* **Hepatic Impairment:** Generally requires caution; dose adjustment may be needed for some agents.
* **Volume Depletion/Hyponatremia:** Initiate at a lower dose or temporarily discontinue due to risk of hypotension.
* **Concomitant Diuretics:** May increase the risk of hypotension; consider withholding diuretic for 2-3 days prior to initiating ACE inhibitor or start ACE inhibitor at a lower dose.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes.
* Concomitant use with sacubitril/valsartan (within 36 hours of the last dose of sacubitril/valsartan).
* Pregnancy (teratogenic).
## Adverse Effects
* **Common:** Dry cough (most frequent, may limit use), dizziness, hypotension, hyperkalemia, fatigue, headache, rash.
* **Serious:** Angioedema (rare but potentially life-threatening), renal impairment/failure (especially in susceptible individuals), hyperkalemia, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Diuretics:** Increased risk of hypotension and renal dysfunction.
* **Potassium-Sparing Diuretics & Potassium Supplements:** Increased risk of hyperkalemia.
* **NSAIDs/COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction.
* **Lithium:** Increased lithium levels and risk of toxicity.
* **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema.
* **NEP Inhibitors (e.g., sacubitril):** Significantly increased risk of angioedema. Do not co-administer.
* **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid use in patients with diabetes.
## Monitoring
* **Blood Pressure:** Regularly monitor to assess efficacy and risk of hypotension.
* **Renal Function (Serum Creatinine, BUN):** Monitor periodically, especially at initiation, dose increases, or in patients with risk factors.
* **Serum Potassium:** Monitor periodically, especially in patients with renal impairment, diabetes, or those taking potassium supplements/sparing diuretics.
* **Angioedema Symptoms:** Educate patients to report immediately.
## Clinical Pearls
* The dry cough is dose-dependent and often reversible upon discontinuation.
* Hypotension is most likely shortly after initiation or dose increase, especially in volume-depleted patients or those on diuretics.
* Angioedema can occur at any time during treatment and is a medical emergency.
* ACE inhibitors are generally renoprotective in patients with proteinuria.
* In patients with heart failure, titration to maximally tolerated doses is crucial for benefit.
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*Please verify current prescribing information for the most up-to-date details.*
