Although both epinephrine and norepinephrine activate α- and β-receptors, they differ in their affinities:

• Norepinephrine has a higher affinity for α₁-receptors, producing potent vasoconstriction and sustained elevations in blood pressure.

• Epinephrine, which acts on both α and β receptors, predominantly stimulates β1 and β₂-receptors at low concentrations (causingincreased heart rate, vasodilation and bronchodilation), while at higher levels it shifts toward α₁-mediated vasoconstriction, leading to variable blood pressure effects.
  

Illustration: Affinity of Norerpinephrine and Epinephrine on adrenergic receptor subtypes

Since most pheochromocytomas predominantly secrete norepinephrine, the result is sustained α-adrenergic vasoconstriction and hypertension.

Therefore, preoperative adrenergic blockade is initiated to prevent catecholamine-induced hypertensive crises during surgery. However, β-blockade before α-blockade is contraindicated, as it can precipitate a dangerous hypertensive crisis by leaving unopposed α-adrenergic stimulation.

This paradoxical rise in blood pressure occurs because circulating catecholamines, especially norepinephrine, continue to activate α-receptors, while β-receptors (including β₂-mediated vasodilatory pathways) are pharmacologically blocked.

Thus, α-adrenergic blockade is always initiated first (typically with phenoxybenzamine or doxazosin) to control hypertension and prevent catecholamine-induced vasoconstriction. β-blockade is added only after adequate α-blockade has been achieved to manage tachycardia or arrhythmias.

Illustration: unopposed α-adrenergic vasoconstriction in β-blockade therapy before α-blockade therapy in catecholamine excess

Important note:
Preoperative preparation for pheochromocytoma involves more than just adrenergic blockade and is typically performed under inpatient supervision. For detailed guidance, refer to the cited literature on perioperative management of pheochromocytomas.

References

All Illustrations were created in https://BioRender.com

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