Phenoxybenzamine phaeochromocytoma

Phentolamine and phenoxybenzamine are older O -adrenoceptor antagonists, which may be used occasionally in course of the surgical removal of phaeochromocytoma, with the aim to suppress the vasoconstrictor effects of noradrenaline/adrenaline released from the tumor as a result of surgical manipulation. 

Deficiency of adrenal medullary catecholamines appears to give no ill effects, and replacement therapy is therefore not used, but adrenal medullary tumours, phaeochromocytomas, secrete excess catecholamines often causing hypertension with dramatic episodes of headache, palpitations, pallor, sweating and anxiety. This condition is normally treated surgically, but preoperative preparation is mandatory to avoid catastrophic effects of surges of catecholamine release. A combination of alpha- and beta-adrenergic receptor blockade is normally used, with drugs such as phenoxybenzamine or doxazosin as alpha-blockers, and propranolol as a non-selective beta-blocker. 

Alpha-adrenoceptor antagonists are used as antihypertensives and to reduce afterload in the treatment of heart failure. Urapidil and, to a lesser extent, ketanserin are used in the treatment of essential hypertension and acute perioperative hypertension. In contrast to other vasodilators urapidil does not increase intracranial pressure when given intravenously, making it preferable for use in neurosurgical interventions. The effects of the excessive catecholamine concentrations in patients with phaeochromocytoma can be treated by the non-selective ol- and o2-adrenoceptor antagonists phentolamine or phenoxybenzamine. 

Phenoxybenzamine is an irreversible nonselective a-adrenoceptor blocking drug whose effects may last 2 days or longer. The daily dose must therefore be increased slowly. It is impossible to reverse the circulatory effects by secreting noradrenaline (norepinephrine) or other sympathomimetic drugs because its effects are insurmountable. This makes it the preferred a-blocker for treating phaeochromocytoma (see p. 495). 

Phenoxybenzamine hydrochloride capsules 10 mg. Adult dose 1-2 mg/1 daily for short-term management of phaeochromocytoma. 

The main indication of phentolamine is in the management of phaeochromocytoma but, unlike phenoxybenzamine, its action is reverable It belongs to the imidazoline class of compounds like xylometazoline but functions as an a-receptor antagonist rather than an agonist. It is diffi-cult to rationalise its antagonistic artivity on the basis of its structure. 

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