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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 play a critical role in managing cardiovascular and renal conditions by promoting vasodilation and reducing tissue remodeling.
## Primary Indications
* Hypertension
* Heart failure (HFrEF)
* Post-myocardial infarction (left ventricular dysfunction)
* Chronic kidney disease (diabetic nephropathy/proteinuria)
## Adult Dosing
*Dosing varies significantly by agent (e.g., lisinopril, enalapril, ramipril). Examples below:*
* **Lisinopril (Hypertension):** Start 10 mg once daily; max 40 mg/day.
* **Enalapril (Heart Failure):** Start 2.5 mg BID; titrate to target 10–20 mg BID.
* **Ramipril (Post-MI/Cardiovascular Risk):** Start 2.5 mg BID; titrate to 5 mg BID; max 10 mg/day.
## Pediatric Dosing
*Dosing is weight-based and specific to the agent; protocols vary by institution/specialty.*
* **Enalapril (Hypertension):** 0.08 mg/kg once daily; max 0.6 mg/kg/day (or 40 mg/day).
* **Lisinopril (Hypertension):** 0.07 mg/kg once daily; max 0.6 mg/kg/day (or 40 mg/day).
* *Note: ACE inhibitors are generally avoided in neonates due to risk of renal failure.*
## Dose Adjustments
* **Renal Impairment:** Reduce starting doses and monitor serum creatinine/potassium closely. Discontinue if creatinine increases >30% from baseline.
* **Hepatic Impairment:** Use with caution; some agents (enalapril, ramipril) require lower starting doses, while others may require conversion to their active metabolite.
## Contraindications
* History of angioedema (hereditary or ACE-inhibitor-induced).
* Concomitant use with aliskiren in patients with diabetes.
* Pregnancy (Category D: fetal toxicity and death).
* Bilateral renal artery stenosis.
## Adverse Effects
* **Common:** Dry, hacking cough (due to bradykinin accumulation), hyperkalemia, headache, dizziness.
* **Serious:** Angioedema (rare but life-threatening), acute renal failure, neutropenia (rare), symptomatic hypotension.
## Key Drug Interactions
* **Potassium-sparing diuretics/Potassium supplements:** High risk of severe hyperkalemia.
* **NSAIDs:** May reduce efficacy; increased risk of acute kidney injury.
* **ARBs/Direct Renin Inhibitors:** Dual RAAS blockade increases risk of hypotension, hyperkalemia, and renal failure.
* **Lithium:** May increase serum lithium levels, leading to toxicity.
## Monitoring
* **Baseline:** Serum creatinine, BUN, potassium, and blood pressure.
* **Post-initiation:** Recheck creatinine/potassium 1–2 weeks after starting or dose increase.
* **Long-term:** Blood pressure and renal function at regular intervals based on patient stability.
## Clinical Pearls
* **Cough:** If a patient develops an intractable cough, switch to an Angiotensin II Receptor Blocker (ARB).
* **First-dose effect:** Hypotension is most likely with the first dose, particularly in volume-depleted or diuretic-treated patients. Consider holding diuretics 2–3 days before initial dose.
* **Renal Protection:** While initial increases in serum creatinine are common (up to 30%), they are usually hemodynamic and indicate improved long-term renal outcomes, provided the rise stabilizes.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice protocols vary. Always verify current prescribing information, laboratory values, and institutional guidelines before administering or prescribing any medication. Consult the most recent FDA-approved package inserts.
