Which alpha-adrenergic antagonist produces an irreversible blockade?

Which alpha-adrenergic antagonist produces an irreversible blockade?

• A. Phentolamine
• B. Prazosin
• C. Yohimbine
• D. Phenoxybenzamine

Answer: (D)

Irreversible blockade happens when an antagonist binds to the receptor in a way that cannot be easily reversed, typically by forming a covalent bond, so the receptor remains inactive until new receptors are made. Among these agents, the one that does this is phenoxybenzamine. It is an irreversible, nonselective alpha-adrenergic blocker that forms a covalent bond with alpha receptors, producing a long-lasting blockade that persists after the drug has cleared. This is why its effects can last far longer than its presence in the blood, requiring careful dosing and monitoring, especially around pheochromocytoma management. Phentolamine, prazosin, and yohimbine are reversible antagonists—phentolamine is a competitive blocker of both alpha-1 and alpha-2, prazosin selectively blocks alpha-1, and yohimbine mainly blocks alpha-2. Their effects diminish as the drug is cleared, unlike the irreversible action of phenoxybenzamine.

Irreversible blockade happens when an antagonist binds to the receptor in a way that cannot be easily reversed, typically by forming a covalent bond, so the receptor remains inactive until new receptors are made. Among these agents, the one that does this is phenoxybenzamine. It is an irreversible, nonselective alpha-adrenergic blocker that forms a covalent bond with alpha receptors, producing a long-lasting blockade that persists after the drug has cleared. This is why its effects can last far longer than its presence in the blood, requiring careful dosing and monitoring, especially around pheochromocytoma management.

Phentolamine, prazosin, and yohimbine are reversible antagonists—phentolamine is a competitive blocker of both alpha-1 and alpha-2, prazosin selectively blocks alpha-1, and yohimbine mainly blocks alpha-2. Their effects diminish as the drug is cleared, unlike the irreversible action of phenoxybenzamine.