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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors interrupt the renin-angiotensin-aldosterone system (RAAS) by preventing the conversion of angiotensin I to angiotensin II, leading to vasodilation and decreased aldosterone secretion.
## Primary Indications
* Hypertension
* Heart Failure (HFrEF)
* Post-Myocardial Infarction
* Diabetic Nephropathy / Proteinuric Chronic Kidney Disease
## Adult Dosing
*Dosing varies significantly by agent (e.g., Lisinopril, Enalapril, Ramipril). Reference specific agent monographs.*
* **Lisinopril (Hypertension):** Start 10 mg once daily; max 40 mg/day.
* **Lisinopril (Heart Failure):** Start 2.5–5 mg once daily; target 20–40 mg/day.
* **Enalapril (Heart Failure):** Start 2.5 mg twice daily; target 10–20 mg twice daily.
* **Ramipril (Hypertension):** Start 2.5 mg once daily; max 20 mg/day.
## Pediatric Dosing
*Pediatric dosing is highly agent-specific and often weight-based or calculated per institutional protocol.*
* **Lisinopril (≥6 years):** 0.07 mg/kg once daily (max 5 mg initially); titrate up to 0.6 mg/kg/day (max 40 mg).
* **Enalapril (≥1 month):** 0.08 mg/kg once daily; titrate as needed.
## Dose Adjustments
* **Renal Impairment:** Reduce initial doses and titrate slowly for patients with CrCl <30 mL/min.
* **Hepatic Impairment:** Dose adjustments may be required for prodrugs (e.g., Enalapril) that require hepatic conversion to active metabolites.
## Contraindications
* History of angioedema (hereditary or ACE-inhibitor induced).
* Pregnancy (Category D: fetal toxicity/teratogenicity).
* Concomitant use with aliskiren in patients with diabetes.
* Concomitant use with or within 36 hours of sacubitril/valsartan (Entresto).
## Adverse Effects
* **Common:** Dry, persistent cough (due to bradykinin accumulation).
* **Serious:** Angioedema (rare but emergent), hyperkalemia, acute kidney injury (in patients with bilateral renal artery stenosis), symptomatic hypotension (especially with initial dose).
## Key Drug Interactions
* **Potassium-sparing diuretics/K+ supplements:** Risk of hyperkalemia.
* **NSAIDs:** Increased risk of renal impairment (reduced afferent arteriole perfusion).
* **Lithium:** May increase lithium levels/toxicity.
* **ARBs/Direct Renin Inhibitors:** Dual RAAS blockade increases risk of hyperkalemia and renal failure.
## Monitoring
* **Renal Function (SCr/BUN) and Potassium:** Baseline, within 1–2 weeks of initiation, and after dose increases.
* **Blood Pressure:** Monitor for orthostasis, especially in volume-depleted patients.
## Clinical Pearls
* The "first-dose effect" is common in patients who are volume-depleted or on diuretics; consider holding diuretics 2–3 days prior to starting.
* If a dry, persistent cough occurs, switch the patient to an Angiotensin II Receptor Blocker (ARB), which does not inhibit bradykinin degradation.
* In Black patients, ACE inhibitors may be less effective for monotherapy hypertension and carry a higher risk of angioedema.
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**Educational Disclaimer:** This information is for educational purposes only. Always consult current clinical guidelines, institutional protocols, and official package inserts before prescribing or administering any medication.
