Sympathetic Blockade in Treatment of Hypertension

Ten years ago, in papers on medical sympathectomy and the clinical use of methonium compounds, early experience in this unit with ganglion-blocking drugs was recorded (Turner, 1950, 1951). Recently the indications for treatment, method of administration, and the problems of tolerance and side-effects were reviewed (Turner, 1959). At an early stage it was decided that to initiate life long treatment with potent and potentially dangerous drugs was a major decision and that it was best first to make a detailed and standardized assessment of each patient in hospital. If treatment was indicated we tried to achieve a steady state with the appropriate drug, and then further treatment was supervised on a long-term basis in a special clinic organized for the purpose. This procedure has helped to ensure the proper and uniform selection of patients suitable for treatment, has facili tated the maintenance of good control over the blood pressure as well as the collection and correlation of data, and has made possible comparative assessments of different drugs. Numerous ganglion-blocking agents have been investigated, all potent in lowering the blood pressure, but none free from difficulties of administra tion, particularly as regards tolerance and side-effects. None, in fact, has been satisfactory. Although the blood-pressure can be reduced to almost any desired level this can rarely be achieved without troublesome side-effects from concomitant parasympa thetic blockade. Some improvement results from combining the ganglion-blocking drug with chloro thiazide or rauwolfia, but in some degree most patients complain of constipation, dryness of the mouth, diffi culty with accommodation, delay in micturition, or impotence. In many individuals these effects are asso ciated with a feeling of general malaise. Because of all this, physicians have looked forward to the day when research workers would be rewarded by the finding of a compound with selective blocking action on the sympathetic nervous system. Recently, in the laboratories of the Wellcome Founda tion in England and the Ciba Foundation in Switzer land, compounds have been isolated which do selectively block the peripheral sympathetic nervous system by accumulating in sympathetic ganglia and post-ganglionic fibres. The first of these has been given the name of bretylium tosylate (" darenthin "), and has the formula N-o-bromobenzyl-N-ethyl : N : N-dimethylammonium p toluenesulphonate. The second substance has been given the name of guanethidine (" ismelin ") and has the formula 2-(octahydro-L-azocinyl-ethyl) guanidine sulphate. This paper is principally concerned with a clinical trial of bretylium, which we have used for 15 months in the treatment of 43 patients with hypertension.