Losartan (DB00678): A Comprehensive Monograph on the Archetypal Angiotensin II Receptor Blocker

Executive Summary

Losartan stands as a landmark therapeutic agent in cardiovascular medicine, distinguished as the first orally active, nonpeptide Angiotensin II Receptor Blocker (ARB) to be developed and approved for clinical use.[1] Its introduction fundamentally altered the therapeutic landscape for hypertension and related cardiovascular disorders, offering a novel mechanism of action with a distinct tolerability profile compared to its predecessors. As a small molecule drug identified by DrugBank ID DB00678 and CAS Number 114798-26-4, Losartan represents the progenitor of the "sartan" class of medications.[2]

The core mechanism of Losartan involves its function as a selective and competitive antagonist of the Angiotensin II Type 1 (AT1) receptor.[4] By blocking this receptor, Losartan effectively prevents the potent vasoconstrictive and aldosterone-secreting effects of angiotensin II, the primary effector hormone of the Renin-Angiotensin System (RAS).[6] This blockade results in vasodilation, a reduction in total peripheral resistance, and consequently, a lowering of systemic blood pressure, establishing it as a cornerstone therapy for hypertension.[3]

The United States Food and Drug Administration (FDA) has approved Losartan for several key indications. Its primary use is in the management of hypertension in both adult and pediatric populations (aged 6 years and older).[3] Beyond simple blood pressure control, it is also indicated for the reduction of stroke risk in patients with hypertension and associated left ventricular hypertrophy (LVH), a benefit that clinical evidence suggests may not be applicable to patients of African heritage.[3] Furthermore, Losartan is approved for the treatment of diabetic nephropathy in patients with type 2 diabetes and a history of hypertension, where it serves to delay the progression of renal disease.[3]