6.15 : Adrenergic Antagonists: ɑ and β-Receptor Blockers

Third-generation β-blockers, such as labetalol and carvedilol, represent a significant advancement in managing cardiovascular conditions. Unlike conventional β-blockers, which can induce peripheral vasoconstriction, third-generation drugs block α₁ adrenoceptors. This promotes vasodilation through several mechanisms, such as increased nitric oxide production, inhibition of calcium ion entry, opening of potassium ion channels, and antioxidant action. Labetalol, for instance, is clinically indicated in pheochromocytoma and hypertensive emergencies due to its dual-action mechanism: inhibition of both β₁ and β₂ adrenoceptors along with α₁ blockade. Its racemic mixture, composed of four distinct isomers, provides specific action on adrenoceptor subtypes. This unique profile allows labetalol to lower blood pressure while reducing vascular resistance without significantly affecting heart rate or cardiac output.

Additionally, labetalol's low lipophilicity and minimal placental transfer mean it effectively controls blood pressure without posing risks to the developing fetus. As a result, it proves a valuable therapeutic alternative for gestational hypertension. Carvedilol, another third-generation drug, demonstrates anti-inflammatory effects and reduces lipid peroxidation and vascular wall thickening. It enhances ventricular function in mild to severe congestive heart failure and myocardial infarction. Additionally, carvedilol exhibits antioxidant properties by neutralizing free radicals and inhibiting their production.

To conclude, third-generation β-blockers offer enhanced therapeutic benefits compared to their predecessors. Their vasodilatory properties and additional mechanisms of action make them practical and versatile options for treating various cardiovascular conditions, including those arising during pregnancy.