Antihypertensive activity can be induced by the following types of drugs: α-adrenoceptor antagonists; β-adrenoceptor antagonists (β-blockers); and α2-adrenoceptor agonists (in the central nervous system).
After a general survey of peripheral and central α-and β-adrenoceptors, including their modern classification and subdivision, attention was paid to the various drugs with antihypertensive activity based upon interaction with various α- and β-adrenoceptors. Of the peripheral α-adrenoceptor blockers, only those selective for α1adrenoceptors are useful antihypertensives. Prazosin and its successors (doxazosin, terazosin, trimazosin) are the best-known examples of such drugs. Their mode of action, and the low incidence and degree of reflex tachycardia, can be satisfactorily explained on the basis of α1-adrenoceptor blockade in the periphery and possibly also in the CNS. Urapidil is a selective α1adrenoceptor blocker with an additional central component not based upon interaction with α-adrenoceptors. With respect to centrally acting α2-adrenoceptor agonists, clonidine, guanfacine and α-methyldopa are the prototypes. Their antihypertensive activity is triggered by the stimulation of central α2-adrenoceptors in the brain stem, causing reduced peripheral sympathetic activity and hence a fall in blood pressure and heart rate. Sedation, a common side effect of these drugs, is assumed to be mediated by αa2-adrenoceptors at cortical sites.
Although β-adrenoceptor blocking agents (β-blockers) are widely and successfully used as antihypertensives, their mode of action is still poorly understood, only hypotheses being available at present. However, their side effects can be rationally explained on the basis of β-adrenoceptor blockade.
Clonidine Antihypertensive Drug Prazosin Doxazosin Urapidil
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