Alpha- and beta-blockade in angina pectoris.
Angina pectoris encompasses a clinically diverse group of syndromes in which the common factor is myocardial ischaemia resulting from an imbalance between oxygen requirement and delivery. Anginal pain is most frequently precipitated by exercise, but may occur without any apparent cause at rest. Fixed obstructions in the coronary vessels, often attended by thickening of the overlying coronary artery media, are the most frequent cause of ischaemic cardiac pain. The resulting myocardial fibrosis impairs efficient filling and emptying of the ventricles, further aggravating the functional embarrassment resulting from the reduced coronary blood flow. In stable coronary heart disease the increased energy demands during exercise are associated with the rapid development of a haemodynamic profile characteristic of acute left ventricular failure. This results in further substantial increases in pressure work, wall stress and oxygen consumption of the left ventricle. The reflex sympathoadrenal consequences of these primary haemodynamic changes lead to further mechanical and electrical embarrassment of the ischaemic heart. Increased stimulation of beta 1- and beta 2-receptors in the heart increases heart rate and contractility and thereby myocardial oxygen demand. Increased stimulation of alpha-receptors in the peripheral veins and arteries indirectly increases left ventricular oxygen demand still further by increasing preload and afterload, respectively. The reduced blood flow to the endocardium enhances its sensitivity to increased sympathoadrenal stimulation and facilitates initiation of arrhythmias. Blockade of all adrenergic activity, particularly in the myocardium, coronary arteries and peripheral blood vessels should, therefore, help alleviate the myocardial ischaemia. There is a rational argument for the use of alpha-blockade in coronary heart disease, particularly in conjunction with beta-blockade. Attenuation of the risk of coronary spasm and ventricular arrhythmias and reduction of pressure work and left ventricular afterload are amongst the potential attributes of alpha-blockade. Alone, however, their utility is severely limited by the risks of hypotension and reduction in coronary perfusion pressure and reflex oxygen-wasting tachycardia. Alone, alpha-adrenoceptor antagonists have no place in the treatment of angina pectoris. beta-Adrenoceptor blocking drugs competitively inhibit catecholamines at both cardiac and peripheral vascular beta-adrenergic receptors. Their main advantage is that they reduce many of the important determinants of myocardial oxygen consumption, particularly by reducing the heart rate during exercise.(ABSTRACT TRUNCATED AT 400 WORDS)
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects; D050260:Carbohydrate Metabolism; D003327:Coronary Disease / Q000188:drug therapy; D004562:Electrocardiography; D011464:Epoprostenol / Q000378:metabolism; D004983:Ethanolamines / Q000627:therapeutic use*; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007741:Labetalol / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D008074:Lipoproteins; D011464:Epoprostenol; D007741:Labetalol