β-ADRENOCEPTOR ANTAGONISTS

2010

β-ADRENOCEPTOR ANTAGONISTS (also known as β-adrenergic receptor blocking drugs, β-adrenoceptor blocking drugs or beta-blockers) are drugs that inhibit certain actions of the sympathetic nervous system by blocking the action of adrenaline and noradrenaline (catecholamine mediators acting predominantly as hormone or neurotransmitter respectively). Among other actions, β-adrenoceptors have cardiac stimulant actions, they dilate certain blood vessels, suppress motility within the gastrointestinal tract, stimulate certain aspects of metabolism causing an increase in glucose and free fatty acids in the blood. These actions, in concert with those of the α-adrenoceptors, help prepare the body for emergency action. However, in disease, some of these effects may be inappropriate, exaggerated and detrimental to health, so β-blockers may be used to restore the balance. Thus β-blockers are used to lower blood pressure when it is abnormally raised in cardiovascular disease (see ANTIHYPERTENSIVE AGENTS): to correct certain heartbeat irregularities and tachycardias (see ANTIARRHYTHMICS); to prevent the pain of angina pectoris during exercise by limiting cardiac stimulation (see ANTIANGINALS)’, to treat myocardial infarction, as prophylaxis to reduce the incidence of migraine attacks (see antimigraine agents) ; to reduce anxiety, particularly its manifestations, such as muscular tremor (see anxiolytics) ; as short-term treatment prior to surgical correction of thyrotoxicosis (see ANTITHYROID AGENTS); and as eye-drops to lower raised intraocular pressure in glaucoma treatment (see ANTIGLAUCOMA TREATMENT).

However, there is usually a price to pay for extensive alteration in autonomic processes in the body. For instance, adverse effects include precipitation of asthma attacks. Similarly, the blood flow in the extremities will often be reduced, so patients may well complain of cold feet or hands. It may be possible to gain some selectivity of drug action, with consequent minimization of side-effects, by using receptor-subtype-selective β-blockers. Thus, β1-adrenoceptor antagonists have a higher affinity for the β1-adrenoceptor of the heart, and thus they may have some preferential action there, since β2-adrenoceptors are found at most other sites in the body, including the airways and blood vessels. Antagonists with similar affinity for β1-adrenoceptor and β2-adrenoceptors include nadolol, oxprenolol, propranolol and timolol; whereas acebutolol, atenolol, esmolol and metoprolol show some β1-adrenoceptor selectivity; and butoxamine is β2-adrenoceptor preferring. Labetolol, in the racemic form used in medicine, acts as both a β-adrenoceptor and an a-adrenoceptor antagonist, though these activities reside in different isomers. Further factors determining the uses of individual agents include variations in half-life, lipid-solubility and membrane-stabilizing actions on the heart (in high doses; e.g. sotalol). In the treatment of glaucoma, some β-blockers can be used topically as eye-drops when they are not suitable for systemic use (e.g. carteolol). See β- ADRENOCEPTOR AGONISTS.