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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, leading to systemic vasodilation, reduction in aldosterone secretion, and inhibition of cardiac/vascular remodeling.
## Primary Indications
* Hypertension
* Heart Failure (HFrEF)
* Post-Myocardial Infarction
* Chronic Kidney Disease (proteinuria attenuation)
* Diabetic Nephropathy
## Adult Dosing
*Dosing varies significantly by agent (e.g., Lisinopril, Ramipril, Enalapril). The following reflects typical titration for Lisinopril:*
* **Hypertension:** Start 10 mg orally once daily. Target 20–40 mg/day. Max 80 mg/day.
* **Heart Failure:** Start 2.5–5 mg once daily. Titrate to target 20–40 mg/day (usually limited by hypotension or renal function).
* **Acute MI:** Start 5 mg within 24 hours, followed by 5 mg at 24h, 10 mg at 48h, then 10 mg daily for 6 weeks.
## Pediatric Dosing
*Generally indicated for hypertension. Dosing based on weight:*
* **Lisinopril:** Start 0.07 mg/kg once daily (max 5 mg). Titrate up to 0.6 mg/kg/day (max 40 mg).
* **Enalapril:** Start 0.08 mg/kg once daily (max 5 mg). Titrate based on BP response.
## Dose Adjustments
* **Renal Impairment:** Reduce starting doses and titrate slowly. Contraindicated in patients with bilateral renal artery stenosis.
* **Hepatic Impairment:** Use cautiously; some agents (e.g., Enalapril) are prodrugs requiring hepatic conversion to active metabolites (Enalaprilat).
## Contraindications
* History of angioedema (hereditary, idiopathic, or ACE-induced).
* Pregnancy (Category D: causes fetal injury/death, especially in 2nd/3rd trimesters).
* Concomitant use with aliskiren in patients with diabetes.
* Concomitant use with sacubitril/valsartan (Entresto); requires a 36-hour washout period.
## Adverse Effects
* **Common:** Dry, hacking cough (due to bradykinin accumulation).
* **Serious:** Angioedema (life-threatening), hyperkalemia, acute kidney injury (AKI), hypotension.
* **Rare:** Neutropenia/agranulocytosis (mostly with Captopril), hepatotoxicity.
## Key Drug Interactions
* **Potassium-sparing diuretics/Potassium supplements:** High risk of severe hyperkalemia.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of acute renal failure.
* **Lithium:** ACE inhibitors can decrease lithium clearance, leading to toxicity.
## Monitoring
* **Baseline/Titration:** Serum creatinine, BUN, and serum potassium (within 1–2 weeks of initiation/dose change).
* **BP:** Monitor for symptomatic hypotension.
* **Physical:** Monitor for signs of angioedema (swelling of face, lips, tongue, or airway).
## Clinical Pearls
* **The Cough:** If a patient develops an intractable dry cough, switch to an Angiotensin II Receptor Blocker (ARB).
* **Renal Function:** A transient increase in serum creatinine (up to 30%) is often acceptable after initiation, but sharp rises suggest intrinsic renal pathology or renal artery stenosis.
* **First-Dose Phenomenon:** Counsel patients on the risk of orthostatic hypotension with the first dose, especially in patients on high-dose diuretics or with severe heart failure.
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**Educational Disclaimer:** This information is for educational purposes only. Always consult the latest manufacturer prescribing information, clinical practice guidelines, and your institution's specific formulary protocols before prescribing or administering medication.
