Figure 724

The side effect profile of the peripheral aj-adrenergic antagonists. aj-Adrenergic antagonists are associated with relatively few side effects [6,9]; the most striking is the "first-dose effect" [12]. It occurs 30 to 90 minutes after the first dose and is dose dependent. It is minimized by initiating therapy in the evening and by careful dose titration. The "first-dose effect" is exaggerated by fasting, upright posture, volume contraction, concurrent ^-adrenergic antagonism, or excessive catecholamine activity (eg, pheochromo-cytoma). (From Graham and coworkers [12]; with permission.)

Indicates blockade

Indicates blockade

Moderately selective peripheral «¡-adrenergic antagonists. Phenoxybenzamine is a moderately selective peripheral a ¡-adrenergic antagonist [6,9]. It is 100 times more potent at («¡-adrenergic receptors than at («2-adrenergic receptors. Phenoxybenzamine binds covalently to ( -adrenergic receptors, interfering with the capacity of sympathomimetic amines to initiate action at these sites. Phenoxybenzamine also increases the rate of turnover of norepi-nephrine (NE) owing to increased tyrosine hydroxylase activity, and it increases the amount of norepinephrine released by each nerve impulse owing to blockade of presynaptic («2-adrenergic receptors [11]. The net physiologic effect is a decrease in peripheral resistance and increases in heart rate and cardiac output. Postural hypotension may be prominent, related to blockade of compensatory responses to upright posture and hypovolemia. The degree of vasodilation is dependent on the degree of adrenergic vascular tone.


Generic (trade) name

First dose, mg

Usual daily dose, mg

Maximum of action, mg

Duration of action

Phenoxybenzamine (Dibenzyline)

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