NEW APPROACHES IN IMMUNOTHERAPY

In particular, their mode of action has not yet been elucidated. The initial concept that the blood pressure-lowering effect was achieved through a fall in cardiac output has been challenged.1 Other work has been put forward suggesting a possible central mode of action on the one hand and an effectof reducing plasma renin activity on the other," though the latter proposition has also been challenged.3 A recent symposium on the current status of the beta blockers in hypertension was conducted during February, 1976, at the Flinders Medical Centre in Adelaide under the auspices of the International Society of Hypertension. The meeting was chaired by Professor John Chalmers. Dr Roland Gugler from the University of Bonn discussed differences in the pharmacokinetics of the various beta blockers. With the exception of practolol and sotolol, the half-life of beta blockers in the plasma is short. It is variable for drugs such as propranolol and alprenolol which are subject to first-pass elimination through the liver, resulting in the metabolism of a large amount of an. oral dose immediately after absorption and consequent low bioavailability. Disorders which will retard liver perfusion will increase the half-lifeof such drugs. On the other hand there is complete absorption and no first-pass elimination of practolol, prindolol and sotolol. These pharmacokinetic properties explain why a wide dosage range of propranolol, alprenolol and oxprenolol is used to obtain therapeutic effects. Professor de Jong, of the Rudolf Magnus Institute of Pharmacology, Utrecht, examined some of the possible mechanisms of action of the beta-blocking drugs in producing the hypotensive effect. It may be that these drugs exert multiple actions on factors such as cardiac output, renin release, baroreceptors and the release of noradrenaline from peripheral sympathetic neurones. Another possible site of action, however, is the brain, a possibility supported by side effects such as vivid dreams and sleep disturbances. Animal and human data obtained during long-term treatment with propranolol have revealed sufficiently high levelsof this drug in the brain to indicate a central antihypertensive action. Administration of propranolol into cerebral ventricles in several species of animal is capable of producing prolonged hypotension associated with bradycardia. Whatever the mode of action in the brain, it is unlike that of clonidine and methyldopa, the effects of which can be blocked by centrally administered alpha-adrenoreceptor blocking agents. Professor Zanchetti of Milan discussed the reno-endocrine actions of the beta blockers and produced evidence for a direct effect on renal innervation of beta-adrenergic receptors in the juxtaglomerular cells. There is a reflex release of renin with tilting and acute salt depletion which is abolished with betaadrenergic blockade. However, Professor Zanchetti questioned the value of classifying patients into high, low and normal renin hypertensivesand stated that, in general terms, the response to beta-blockers was not related to the plasma renin level. This work, which followed Laragh's hypothesis, has been called in question also by Johnston et alii.4 Professor Peter Sleightdiscussed the clinical application of the beta-blockers in the management of hypertension. At present the thiazides have the least side effects in the short term, but there are some misvigings about the metabolic effects of these drugs in the long term. 5 Trials in the United Kingdom have