Third-Generation Beta-Blockers

Introduction & definition

• Third-generation (vasodilating) β-blockers are β-adrenergic antagonists that, in addition to β-receptor blockade, possess intrinsic vasodilating properties mediated by mechanisms largely unrelated to β-blockade — the defining feature that separates them from the first and second generations.
• Prototypes — carvedilol and labetalol (non-selective β + α₁-block) and nebivolol and celiprolol (β₁-selective + vasodilation); carteolol, bucindolol, betaxolol, bevantolol & nipradilol are other (mostly non-US) members.
• Rationale — the added peripheral vasodilation counteracts the acute rise in peripheral vascular resistance seen with classical β-blockade (unopposed vascular α-tone + loss of β₂-vasodilation), giving a more favourable haemodynamic and metabolic profile.
• Clinical relevance — they are the preferred β-blocker subclass when vasodilation, metabolic neutrality or favourable central haemodynamics are wanted — chiefly in HFrEF, hypertension with metabolic syndrome/diabetes, and hypertensive emergency/pregnancy.