Beta Adrenoceptor Antagonists

Peter J. Tyrer

Department of Psychological Medicine, Imperial College, London, UK

Synonyms

Beta-adrenoceptor blocking drugs; Beta-blockers Definition

Beta-adrenoceptor antagonists (b-blockers), created by Sir James Black after research in the 1950s and 1960s, are well-known drugs in cardiology and circulatory diseases, and their role in psychiatry is limited. As their name implies, they inhibit the effects of adrenaline and ► nor-adrenaline on b-receptors, but the members of the drug class vary in their affinity for the two main types of b-receptor and in the extent to which they have stimulant (i.e., partial agonist) effects on these receptors. Stimulation of ^-receptors by adrenaline has its main effects on the heart with increased speed of cardiac conduction velocity and cardiac output, with a lesser effect on the kidney in stimulating the release of renin. Stimulation of b2-receptors induces tremor in striated muscle but relaxation in smooth muscle, and by increasing glycogenolysis in both liver and striated muscles, it promotes the production of glucose for increased pumping action. There are also b3-receptors involved in the breakdown of fat (lipolysis), which may also have a role in smooth muscle and cardiac function, but their effects are minor compared with the other b receptors.

Pharmacological Properties

^-Adrenoceptor antagonists act on the receptors in heart and kidney and their blockade reduces the demands on cardiac muscle, and by concomitant reduction of renin secretion in the kidney, blood pressure is lowered. They also act on ^-receptors in the eye and may be used to reduce glaucoma. b2-blocking drugs act on receptors in skeletal muscle, smooth muscle in the gastrointestinal tract, liver, uterus, and lungs, and thereby reduce tremor in voluntary musculature, reduce the opening of bronchi in the respiratory tract, and lessen the breakdown of glycogen. It has also been suggested that b-adrenoceptor antagonists may block ► serotonin autoreceptors, and thereby have a role in the augmentation of antidepressant therapy with selective serotonin reuptake inhibitors, and one b-blocking drug, pindolol, has been used specifically for this purpose. However, this pharmacological action is far from being confirmed and remains a speculative suggestion. In general, the b1-blocking effects are regarded as therapeutically valuable and b2-blockade as unhelpful with a tendency to create adverse effects, of which reduced bronchial dilation, provoking asthma in susceptible subjects, is one of the most prominent. In higher doses, b-adrenoceptor antagonists have some central nervous system effects including drowsiness, insomnia, and impairment of reaction time, but it seems unlikely that these are due to b-blockade. As some drugs (e.g., sotalol, aten-olol) are water soluble and do not penetrate the central nervous system easily, they may reduce the incidence of such effects. As some of the more peripheral indications for b-adrenoceptor antagonists (e.g., reduction of aggression) are likely, if confirmed, to be due to central nervous system action, this is relevant to the choice of drug. One of the well-documented adverse effects of b-adrenoceptor antagonists in general medicine is depression; it is not clear how this is generated.

Mechanisms of Action

There are many b-adrenoceptor antagonists; the main ones and their indications are summarized in Table 1. It is noted that very few of them are used for psychiatric purposes. The possible action of pindolol in promoting the effect of ► SSRI antidepressants mentioned earlier has not been tested with other drugs in this group; its value remains to be determined.

The b1-blocking effects that are so helpful in cardiology have a potential use in the treatment of various forms of anxiety. There has been considerable argument over the mechanism whereby such effects are mediated. Most available data support the hypothesis that the action is a direct consequence of peripheral ► P-blockade, not of any central effects. This is based on several lines of reasoning: the fact that water-soluble b-blocking drugs are as effective as lipid-soluble ones in anxiety, the evidence that the specific somatic symptoms of tremor and palpitations are helped most by treatment, the lack of efficacy of the d-isomer of ► propranolol, which has no b-blocking activity, and the relatively low doses of drug necessary to reduce anxiety symptoms when compared with the higher doses normally associated with central nervous system effects.

Some studies have suggested that many other symptoms found in ► generalized anxiety, completely

Beta-Adrenoceptor Antagonists. Table 1. Beta-adrenoceptor antagonists in common use.

Type of receptor blockade

Intrinsic sympathomimetic activity present

Approved name

Main therapeutic use in medicine

Main therapeutic use in psychiatry

Nonselective (i.e., mixed blockade)

No

Propranolol

Hypertension, angina prophylaxis of myocardial infarction

Generalized anxiety, specific social anxiety disorders. Tremor (all causes)

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