Beta-adrenergic receptor blocking drugs in angina pectoris.

Abstract

Increased sympathetic activity involves increased oxygen consumption by the heart. β-Adrenergic receptor blocking (β-blocking) drugs generally reduce myocardial oxygen consumption. These drugs, regardless of their associated properties such as membrane stabilising action and intrinsic sympathomimetic effect, have all been found to increase exercise tolerance in angina pectoris. The membrane stabilising action has no relevance in the effect of these drugs in angina. The (+)-isomer of propranolol in clinical doses is devoid of haemodynamic action and is ineffective in angina, and the non-membrane-active β-adrenoceptor blocking drugs are effective antianginal agents. Acute exercise tests have failed to reveal any differences between the various β-blocking drugs, except Inpea which was found ineffective at maximum tolerated doses. However, short-term administration is different from long-term clinical use; certain side-effects are not apparent from single-dose administration. Therapeutic trials of β-blocking drugs have shown them to be effective prophylactics when administered over a long period. Trials that have not given clear results have been defective in design; inadequate ‘run-in’ period, sub-optimum fixed dosage and too short a period of assessment are common sources of error. Aspects of trial design are discussed as the response to β-blocking agents is assessed. Far the greatest experience has been with propranolol and best results have been obtained in trials that have used larger and individualised dosages. A clear dose response relationship has been established. Comparative trials of any two drugs in any condition requires that each should be given in optimum dosage if the assessment is to be meaningful. Studies with propranolol and practolol indicated that the former is more effective, and likewise, propranolol is superior to sotalol. Sotalol, which has minimum membrane stabilising activity, unlike practolol, was superior to a low dose (one eighth) of propranolol. Important contra-indications to β-blocking drugs are asthma (except the cardioselective practolol) and heart failure. If these contra-indications are observed β-blocking drugs are relatively safe. Dosage should be commenced at a low level and then gradually increased (say 25 % increments) until optimum effect is obtained. The greatest change in sympathetic environment of the heart occurs at the commencement of treatment (e.g. propranolol 10 mg 3 times daily) and it is then that heart failure may suddenly occur if patient selection has not been adequate. Subsequently, any small increase in dosage does not produce any sudden change in sympathetic environment and thus is relatively safe. An increase in dosage from say 500 mg three times daily of propranolol to 550 mg three times daily is negligible in pharmacological terms, and by such small percentage changes the dosage can be safely and gradually increased to the desired level.