Pharmacology · Adrenergic Pharmacology

Alpha-Adrenergic Antagonists

Phenoxybenzamine, phentolamine, selective alpha-1 blockers, and pheochromocytoma protocol

Phenoxybenzamine is an irreversible, non-selective alpha-1/2 blocker — covalent binding means the block cannot be overcome by agonist, and recovery requires synthesis of new receptors over 24–48 hours; by also blocking alpha-2 autoreceptors, it removes the feedback brake on norepinephrine release, causing pronounced reflex tachycardia that must be managed with a beta-blocker (added only after alpha blockade is established).
Selective alpha-1 blockers (prazosin, terazosin, doxazosin) preserve alpha-2 autoreceptor feedback, producing less reflex tachycardia than non-selective agents; they treat both hypertension and benign prostatic hyperplasia, but the ALLHAT trial showed doxazosin causes more heart failure than chlorthalidone, removing it from first-line antihypertensive therapy.
Uroselective alpha-1A blockers (tamsulosin, silodosin) have dominant affinity for the alpha-1A subtype in the prostate and urethra over the alpha-1B subtype in vasculature — this selectivity reduces orthostatic hypotension, eliminating the need for a bedtime first-dose rule; however, tamsulosin and silodosin carry a permanent risk of intraoperative floppy iris syndrome during cataract surgery, even years after stopping the drug.
Prazosin has an important non-hypertension indication: it reduces nightmare frequency and sleep disruption in post-traumatic stress disorder (PTSD) by blocking alpha-1 receptors in the brain regions mediating fear arousal during sleep; the PTSD indication requires nightly dosing, often lower than antihypertensive doses.
The pheochromocytoma preoperative rule is absolute — alpha blockade must be established before any beta-blocker is given; if beta-blockers are given first, they eliminate the vasodilatory beta-2 escape valve, leaving unopposed alpha-1 vasoconstriction from tumor-released catecholamines, precipitating hypertensive crisis and potentially death during surgery.

Suggested References

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