Perindopril: Mechanism of Action
Perindopril is an ACE inhibitor that lowers blood pressure, reduces cardiac workload, and provides kidney protection in hypertension, heart failure, and diabetic nephropathy.
ACE inhibitors block the conversion of angiotensin I to angiotensin II, reducing blood pressure and cardiac afterload.
How It Works
Angiotensin-converting enzyme (ACE) inhibitors competitively inhibit ACE (peptidyl-dipeptidase A), a zinc-dependent metalloprotease responsible for converting angiotensin I to angiotensin II (Ang II). By blocking Ang II formation, ACE inhibitors prevent vasoconstriction, reduce aldosterone secretion (decreasing sodium/water retention), and lower sympathetic activation. Additionally, ACE inhibitors prevent breakdown of bradykinin, which contributes to vasodilation but also causes the characteristic dry cough (15–20% incidence) and, rarely, angioedema.
Receptor / Target Profile
- •ACE (angiotensin-converting enzyme) — primary target; zinc-dependent metalloprotease
- •AT1 receptor (angiotensin II type 1) — indirect reduction in AT1 activation
- •Bradykinin B2 receptor — bradykinin accumulation causes cough and vasodilatory effect
- •eNOS (endothelial nitric oxide synthase) — upregulated, contributing to vasoprotection
Pharmacokinetics
Onset of Action
BP reduction within 1–4 hours of first dose; maximal therapeutic effect 2–6 weeks
Half-Life (t½)
Varies: enalaprilat (active form) ~11 hours; lisinopril ~12 hours; ramiprilat (active) ~9–18 hours; perindoprilat ~3–10 hours
Most ACE inhibitors are prodrugs converted to active diacid forms by hepatic esterases. Lisinopril is not a prodrug. Primarily eliminated renally — dose adjustment required for eGFR <30. Minimal CYP metabolism — fewer pharmacokinetic drug interactions than many other antihypertensives.
Conditions Treated with Perindopril
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