Phenoxybenzamine

Phenoxybenzamine is a non-selective, irreversible alpha-adrenergic antagonist used primarily in the management of catecholamine-secreting tumors such as pheochromocytoma. It binds covalently to alpha-adrenergic receptors, producing long-lasting receptor blockade even after the drug is cleared from the bloodstream.

Pharmacology and mechanism of action: By blocking both alpha-1 and alpha-2 receptors, phenoxybenzamine prevents norepinephrine- and epinephrine-induced vasoconstriction. The irreversible nature of its binding leads to sustained vasodilation and a reduction in blood pressure that can persist long after administration ceases. The blockade can cause reflex tachycardia and orthostatic hypotension, along with other anticholinergic-like effects such as nasal congestion.

Medical uses: The primary indication is preoperative management of pheochromocytoma to prevent hypertensive crises during tumor manipulation. It may be used to control symptoms of catecholamine excess in some patients, but it is not a first-line treatment for essential hypertension. Historically, it has been explored for other vascular conditions, but its use in those settings is limited.

Administration and pharmacokinetics: Phenoxybenzamine is given orally, with dosing titrated to achieve adequate alpha blockade and hemodynamic stability. Because of its irreversible binding, its effects can last for days after stopping the drug, requiring careful perioperative planning and monitoring.

Adverse effects and interactions: Common adverse effects include orthostatic hypotension, dizziness, fatigue, tachycardia, nasal congestion, and edema. It may amplify hypotension when combined with other antihypertensives or vasodilators and requires caution in patients with cardiovascular disease or dehydration.

History and context: Introduced in the mid-20th century, phenoxybenzamine was among the first irreversible alpha blockers. It is often contrasted with reversible agents such as phentolamine, which are used in different clinical scenarios, including pheochromocytoma crises.