Is Olmesartan an ACE Inhibitor or ARB?

Olmesartan is a medication prescribed for high blood pressure, but there is often confusion about whether it belongs to the class of ACE inhibitors or angiotensin II receptor blockers (ARBs). Understanding its classification is essential for selecting the right treatment and managing potential side effects.

To clarify Olmesartan’s role in blood pressure regulation, it’s important to examine its interaction with the renin-angiotensin-aldosterone system (RAAS) and compare it to ACE inhibitors.

Classification In The Renin Angiotensin Aldosterone System

Olmesartan targets the renin-angiotensin-aldosterone system (RAAS), a hormonal network that regulates blood pressure and fluid balance. Renin, an enzyme secreted by the kidneys in response to low blood pressure or sodium levels, converts angiotensinogen into angiotensin I. The angiotensin-converting enzyme (ACE) then transforms angiotensin I into angiotensin II, which binds to angiotensin II type 1 (AT₁) receptors to increase vascular resistance and sodium retention, raising blood pressure.

Olmesartan is classified as an angiotensin II receptor blocker (ARB), meaning it prevents angiotensin II from binding to AT₁ receptors. Unlike ACE inhibitors, which stop the formation of angiotensin II by inhibiting ACE, ARBs allow its production but block its effects. This distinction is important because ARBs do not interfere with bradykinin metabolism, avoiding side effects like persistent cough and angioedema that are associated with ACE inhibitors.

Olmesartan has a high binding affinity for AT₁ receptors, providing prolonged action that allows for once-daily dosing. This sustained blockade ensures consistent blood pressure reduction, making it a preferred option for long-term therapy. Additionally, Olmesartan offers organ-protective benefits, particularly for the kidneys and cardiovascular system, by reducing proteinuria and improving endothelial function. These effects are especially relevant for patients with hypertension-related complications such as diabetic nephropathy or left ventricular hypertrophy.

Mechanism Of Action In Blocking Angiotensin II Receptors

Olmesartan works by selectively binding to AT₁ receptors, preventing angiotensin II from triggering vasoconstriction and aldosterone release. This results in reduced vascular resistance and lower blood pressure. Its targeted action ensures effective inhibition of the RAAS without significantly affecting other physiological pathways.

Olmesartan’s strong receptor affinity surpasses that of endogenous angiotensin II, leading to prolonged inhibition even as angiotensin II levels fluctuate. This sustained receptor occupancy provides consistent blood pressure control, reducing the risk of variability-related cardiovascular complications. Unlike some antihypertensive drugs, Olmesartan does not interfere with AT₂ receptors, which contribute to vasodilation and antifibrotic effects, potentially offering additional vascular benefits.

Administered as the prodrug Olmesartan medoxomil, it undergoes rapid hydrolysis in the gastrointestinal tract to become active, ensuring high bioavailability. It reaches peak plasma concentrations within one to two hours, initiating its antihypertensive effects efficiently. Primarily eliminated through biliary excretion with minimal renal metabolism, Olmesartan is suitable for patients with mild to moderate renal impairment. Its pharmacokinetics allow for consistent receptor blockade with once-daily dosing.

How It Differs From An ACE Inhibitor

Olmesartan and ACE inhibitors both target the RAAS but through different mechanisms. ACE inhibitors, such as lisinopril and enalapril, prevent the conversion of angiotensin I to angiotensin II by inhibiting ACE, while Olmesartan directly blocks AT₁ receptors, stopping angiotensin II from exerting its effects. This difference influences both their efficacy and side effect profiles.

A key distinction is the impact on bradykinin. ACE inhibitors reduce angiotensin II levels but also cause bradykinin accumulation, which can lead to a persistent dry cough in 5-20% of users and, in rare cases, angioedema. Olmesartan does not affect bradykinin metabolism, eliminating these side effects, making it a preferred option for patients intolerant to ACE inhibitors.

Both drug classes offer renal protection by lowering intraglomerular pressure and reducing proteinuria, particularly in patients with diabetes or chronic kidney disease. However, ACE inhibitors may cause a transient decline in kidney function due to their effect on efferent arteriolar dilation, which can sometimes lead to acute kidney injury. Olmesartan, by selectively blocking AT₁ receptors without directly altering angiotensin II synthesis, provides similar renal benefits with a lower risk of acute kidney-related complications. Additionally, ARBs tend to have a lower likelihood of causing significant potassium imbalances compared to ACE inhibitors, making them a safer option for patients at risk of hyperkalemia.