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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, leading to decreased systemic vascular resistance and reduced aldosterone secretion. They provide renoprotective and cardioprotective benefits in chronic kidney disease and heart failure.
## Primary Indications
* Hypertension
* Heart Failure with reduced ejection fraction (HFrEF)
* Post-myocardial infarction
* Diabetic nephropathy (proteinuria reduction)
* Chronic Kidney Disease (CKD)
## Adult Dosing
*Note: Dosages vary by specific agent (e.g., Lisinopril, Ramipril, Enalapril). Local protocols may prioritize specific agents based on formulary.*
* **Lisinopril (HTN):** Start 10 mg daily; maintenance 20–40 mg daily. Max 80 mg/day.
* **Lisinopril (HFrEF):** Start 2.5–5 mg daily; target dose 20–40 mg daily.
* **Enalapril (HTN):** Start 5 mg daily; maintenance 10–40 mg daily in 1–2 divided doses. Max 40 mg/day.
* **Ramipril (HTN):** Start 2.5 mg daily; maintenance 2.5–20 mg daily. Max 20 mg/day.
## Pediatric Dosing
*Dosing is weight-based and typically requires adjustment by specialized pediatric pharmacy guidelines.*
* **Enalapril (HTN):** Start 0.08 mg/kg once daily (max 5 mg). Titrate based on response/tolerability.
* **Lisinopril (HTN, ≥6 years):** Start 0.07 mg/kg once daily (max 5 mg). Max dose 0.61 mg/kg/day (or 40 mg total).
## Dose Adjustments
* **Renal Impairment:** Requires dose reduction or longer dosing intervals for most agents if CrCl < 30 mL/min.
* **Hepatic Impairment:** Generally safe, but monitor closely for prodrugs (e.g., Enalapril) that require hepatic conversion to active metabolites.
* **Volume Depletion:** Start at the lower end of the dosing range if the patient is on a diuretic or volume-depleted.
## Contraindications
* History of angioedema.
* Concomitant use with aliskiren in patients with diabetes.
* Pregnancy (Category D: fetal toxicity and renal failure in second/third trimesters).
* Bilateral renal artery stenosis.
## Adverse Effects
* **Common:** Dry, persistent cough (due to bradykinin accumulation).
* **Serious:** Angioedema (life-threatening, higher incidence in Black patients), hyperkalemia, acute kidney injury (AKI), hypotension.
## Key Drug Interactions
* **Potassium-sparing diuretics/K-supplements:** Increased risk of severe hyperkalemia.
* **NSAIDs:** Increased risk of acute renal failure and loss of antihypertensive efficacy.
* **Lithium:** ACE inhibitors decrease renal clearance, increasing lithium concentrations and toxicity risk.
* **ARBs/Direct Renin Inhibitors:** Dual blockade of the RAAS is generally not recommended due to increased risk of hyperkalemia and AKI.
## Monitoring
* **Baseline:** Serum creatinine (SCr), blood urea nitrogen (BUN), and potassium.
* **Post-Initiation:** Recheck renal function and potassium within 1–2 weeks of initiation or dose increase.
* **Acceptable change:** A rise in SCr up to 30% from baseline is generally acceptable; increases >30% require investigation (possible renal artery stenosis).
## Clinical Pearls
* **Cough Management:** If a dry, persistent cough develops, switch to an Angiotensin II Receptor Blocker (ARB).
* **Washout Period:** If switching from an ACE inhibitor to Entresto (Sacubitril/valsartan), a 36-hour washout period is required to prevent angioedema.
* **Renal protection:** ACE inhibitors are the preferred agents for patients with albuminuria/proteinuria.
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**Disclaimer:** This information is for educational purposes only. Always consult current, institution-specific clinical guidelines, drug monographs (e.g., Lexicomp, UpToDate), and local prescribing protocols before initiating or adjusting therapy.
