Enalapril: Mechanism of Action
Enalapril is an ACE inhibitor that lowers blood pressure, reduces cardiac workload, and provides kidney protection in hypertension, heart failure, and diabetic nephropathy.
Enalapril is a prodrug ACE inhibitor converted to enalaprilat, establishing landmark evidence in heart failure and defining the ACE inhibitor drug class.
How It Works
Enalapril is an ethyl ester prodrug converted by hepatic de-esterification to enalaprilat (active diacid). Enalaprilat is a potent competitive ACE inhibitor (Ki ~0.2 nM). As the first ACE inhibitor to demonstrate mortality reduction in heart failure (CONSENSUS trial, 1987), enalapril established ACE inhibitors as foundational HF therapy. Unlike captopril's thiol group (causing taste disturbances and agranulocytosis risk), enalapril's carboxyl pharmacophore provides a cleaner tolerability profile. Like all ACE inhibitors, enalapril accumulates bradykinin — causing the class-effect dry cough (15–20%) and, rarely, angioedema.
Receptor / Target Profile
- •ACE (angiotensin-converting enzyme) — enalaprilat Ki ≈ 0.2 nM; competitive inhibition
- •AT1 receptor — indirect reduction in Ang II-mediated vasoconstriction and aldosterone
- •Bradykinin B2 receptor — bradykinin accumulation; vasodilation and cough
- •Non-CYP esterases — enalapril converted to enalaprilat by esterases (not CYP); fewer CYP drug interactions
Pharmacokinetics
Onset of Action
BP reduction within 1–4 hours; enalaprilat IV within 15 minutes; maximal HF remodelling benefit at 2–6 weeks
Half-Life (t½)
Enalaprilat effective accumulation t½ ~11 hours; enalapril (prodrug) ~1 hour
Enalapril oral bioavailability ~60%. Converted to enalaprilat by non-CYP esterases in liver. Renal elimination — dose reduction required for eGFR <30. IV enalaprilat available for hypertensive urgencies.
Conditions Treated with Enalapril
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