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  • Title: Review of the use of alpha-adrenoceptor antagonists in hypertension.
    Author: Stokes GS, Marwood JF.
    Journal: Methods Find Exp Clin Pharmacol; 1984 Apr; 6(4):197-204. PubMed ID: 6146746.
    Abstract:
    The discovery of alpha-adrenoceptor antagonists with selectivity for the post-synaptic alpha 1-adrenoceptor has yielded a group of antihypertensive agents of high specificity in blocking sympathetic impulses to resistance and capacitance vessels. This group differs from the previously-developed alpha-adrenoceptor blockers, phentolamine and phenoxybenzamine, in that they do not block the pre-synaptic alpha 2-adrenoceptors which modulate the release of neurotransmitter, and therefore do not cause as much reflex activation of the sympathetic nervous system. These differences have important clinical implications in regard to the antihypertensive efficacy of prazosin and its congeners, and to their use in combination with beta-blockers. Evidence that there are structural similarities between alpha-adrenoceptors and serotonin receptors is supported by the finding that ketanserin, developed for its 5HT2-receptor blocking property, exerts at least part of its antihypertensive action through alpha 1-adrenoceptor blockade. The most important limiting factor in the clinical application of prazosin is the postural hypotension and tachycardia associated with initial dosing. It is of some academic interest that these first-dose effects may be utilized to predict the long-term efficacy of the drug in individual patients. From a practical viewpoint, they may be largely avoided by starting therapy with small doses and recognising factors, such as a contracted plasma volume, which can sensitize the patient to sudden withdrawal of sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)
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