Adrenoceptors can be divided into α-receptors, whose stimulation results in excitatory responses, and β-receptors which are mainly responsible for inhibitory responses plus cardiac stimulation. β-Receptors can be further subdivided into β1-receptors in the heart and β2-receptors elsewhere. Drugs are now available which selectively antagonise responses mediated by both α-and β-adrenoceptors. α-Adrenoceptor blocking drugs have been known for many years. Some are competitive inhibitors (e.g. tolazoline and thymoxamine); others (such as phenoxybenzamine) produce non-equilibrium blockade once their effect is established; still others (prazosin) appear to block post-junctional α-receptors selectively and consequently exert an antihypertensive effect without tachycardia. The effects of α-adrenoceptor antagonists in therapeutic doses are seen chiefly in the cardiovascular system: if the patient changes from the supine to the standing position or if there is a marked reduction in plasma volume, a marked fall in blood pressure occurs with reflex tachycardia. α-Adrenoceptor blocking drugs have additional potent pharmacological properties, some of which profoundly impair their usefulness and increase toxicity. The principal usefulness of α-adrenoceptor antagonists is in the management of phaeochromocytoma — preoperative preparation, prevention of paroxysmal hypertension during surgery and prolonged treatment of cases not amenable to surgery. Occasionally, combined α-and β-adrenoceptor blockade may be required, but the α-blockade must always be established first. α-Adrenoceptor blocking drugs have never been widely used in the management of essential hypertension due to reflex tachycardia and a tendency for their hypotensive effect to wear off. However, the newer drugs prazosin and indoramin do not appear to share these disadvantages and may establish a greater therapeutic role. α-Adrenoceptor antagonists are also used in the treatment of shock and peripheral vascular insuffïciency, although evidence for their efficacy in the latter is sparse except where decreased blood flow is due to spasm of the vessels (e.g. Raynaud’s phenomenon). Recently, phentolamine and prazosin have been shown to be useful in some patients with refractory congestive cardiac failure. β-Adrenoceptor blocking drugs are competitive antagonists which have enjoyed increasingly widespread clinical usage during their 10 year history. There are now a number of drugs of this type available, all of which competitively block β-receptors. They differ in terms of their additional properties, such as membrane stabilising activity, partial agonist activity and cardioselectivity, but it would appear that of these, only the latter is of clinical importance. Cardioselectivity refers to the ability to block cardiac β1-receptors selectively without blocking β2-receptors in the bronchi and blood vessels. Atenolol and metoprolol have been shown to be cardioselective drugs and these drugs should be prescribed in patients with obstructive airways disease and insulin-dependent diabetes in preference to the other non-selective drugs. However, all β-adrenoceptor antagonists should be used cautiously in these patients and in those with a previous history of or evidence of incipient congestive heart failure, as potentially they may cause serious adverse reactions. The maximum danger period exists during administration of the initial low doses in these patients because this represents the maximum interference with the sympathetic environment. If harm does not ensue in this period, further increases in dose are less likely to cause problems. β-Adrenoceptor antagonists were originally prescribed for angina pectoris, cardiac dysrhythmias and phaeochromocytoma. Subsequently, they have been found to be of use in hypertension, following myocardial infarction, in hyperthyroidism, anxiety states, migraine, hypertrophic obstructive cardiomyopathy and drug addiction withdrawal syndromes. Their use is also being investigated in a number of other conditions. β-Adrenoceptor blockade does not appear to explain satisfactorily their efficacy in all of these circumstances. The role of β-adrenoceptor antagonists prophylactically in angina pectoris is clearly established and is an effective alternative to coronary artery bypass surgery in many patients. Recently, it has also been suggested that these drugs may reduce mortality in patients following an acute anterior myocardial infarction. β-Adrenoceptor blocking drugs are amongst the drugs of first choice, if not the drugs of first choice, in the treatment of hypertension, as they combine satisfactory efficacy with low toxicity. In addition, they can be used to good effect in combination with diuretics, vasodilators or other antihypertensive drugs. Various cardiac dysrhythmias can be successfully treated with β-adrenoceptor antagonists. In hyperthyroidism, these drugs ameliorate the peripheral manifestations of the disease: they can be life-saving in hyperthyroid crisis, and can be used instead of conventional antithyroid drugs in the preoperative preparation of patients for thyroideciomy or following radioiodine therapy. The somatic symptoms and signs of anxiety neurosis are improved by β-adrenoceptor blockade and the frequency of occurrence of migraine headache has been found to be reduced by the prophylactic use of propranolol. Thus β-adrenoceptor blockade has a much wider role in the management of disease in man than has α-adrenoceptor blockade. The former have achieved great importance in a short time. © 1979, ADIS Press Australasia Pty Ltd. All rights reserved.
