Mechanism of action
Alpha blockers are substances that antagonize alpha receptors which are located primarily in smooth muscle. This acts to vasodilate in the arterial system and, thus, these agents are used to treat hypertension and urinary symptoms related to prostate enlargement.
Alpha blockers are considered second line therapy in the treatment of hypertension, and thus are only used if first line therapy fails. Alpha blockers are also used to treat the urinary symptoms of benign prostatic hypertrophy (BPH) since they relax the urinary sphincter.
First-dose hypotension frequently occurs and can result in syncope. This is due to the sudden inhibition of the alpha receptors causing intense arterial vasodilation. Once alpha blockade has been present for 48 to 72 hours, the alpha receptor number increases, lessening this effect. Due to first-dose hypotension, these drugs are usually taken at night to lessen the side-effects.
Tamsulosin and alfuzosin are less selective towards arterial alpha receptors and thus have less of a first dose-hypotension effect.
Phenoxybenzamine and phentolamine are irreversible alpha blockers frequently used to treat hypertension in the setting of a pheochromocytoma.
The ALLHAT trial (Antihypertensive and Lipid Lowering Treatment to Prevent Heart ATtack) had an arm comparing chorthalidone (thiazide diuretic) to doxazosin (alpha blocker). The doxazosin arm was stopped early due to a 25% higher rate of combined cardiovascular events compared with chlorthalidone. This lead to the recommendation that alpha blockers be used second line for hypertension.