Adverse effects of alpha 1-adrenergic blocking drugs

Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)