Beta-blocking agents with vasodilator activity.

Abstract

Use of non-selective beta-blockers: Non-selective beta-blockers reduce blood pressure by reducing cardiac output. They have a proven record of efficacy, alone or in combination with other drug classes, in the treatment of hypertension, ischemic heart disease and some tachyarrhythmias. They have also proved effective in the primary and secondary prevention of myocardial infarction. However, adverse effects include increased peripheral resistance, limitation of exercise tolerance, and bradyarrhythmia, cold extremities and bronchoconstriction in susceptible patients. Effects of beta 1-selective blockers: beta 1-Selective antagonists cause less vasoconstriction and less bronchoconstriction than non-selective beta-blockers, but the reduction in cardiac output may still activate a sympathetically mediated increase in peripheral resistance. beta 1-blockers with beta 2 agonist activity are vasodilatory because they activate postsynaptic beta 2 receptors on vascular smooth muscle cell membranes, via the formation of cyclic AMP. Non-selective beta-blockers with alpha 2-adrenoceptor blocking activity: Non-selective beta-adrenoceptor blockers with alpha 1-adrenoceptor blocking activity, such as carvedilol, labetalol, medroxalol and bucindolol, combine the advantages of beta- and alpha 1-blockade, including peripheral vasodilation. As an example of this class of agent, carvedilol has been shown to be effective in the treatment of hypertension by reducing peripheral resistance. There are some indications, still to be confirmed, that it improves left ventricular diastolic function and causes regression of left ventricular hypertrophy, and that it may be useful in the treatment of some patients with congestive heart failure or arrhythmia. In animal models of myocardial ischemia, carvedilol has proved to be cardioprotective.