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By T.J. Cleophas

"Knowledge wants raise - it really is like hearth that first has to be kindled by way of a few exterior agent, yet to be able to continually later on propagate itself". Johnson, Letter to William Drummond August thirteen, 1776 The healing effectiveness and safeguard of beta-adrenergic blocking off medications has been good confirmed in sufferers with crucial high blood pressure and arteriosclerotic heart problems. those medicinal drugs are beneficial in basic defense opposed to cardiovascular morbidity or mortality in sufferers with crucial high blood pressure and secondary safety (mor­ bidity and mortality in sufferers with myocardial infarction). even if there are mass motion results universal to all of beta-adrenergic block­ ing brokers, those brokers fluctuate of their results at the RAS process, beta blockade, norepinephrine liberate, CNS results, peripheral vas­ cular resistance, inotrophic results, vasomotor results, and results on plasma quantity. Dr. Ton J. M. Cleophas has addressed this challenge of alternative com­ kilos and varied suggestions within the use of beta-adrenergic blockers. In bankruptcy 1 of this booklet the writer bargains with the matter of paradoxical pressor responses from non cardioselective beta blockade. bankruptcy 2 bargains with a evaluation of the literature facing those pressor responses that are frequently regarded as light and take place in occasions of elevated sympathetic task (57 references). bankruptcy three offers with the benefi­ cial results of alpha blockade in Raynaud's Syndrome, and the influence of beta blockade in counteracting the alpha blocker unintended effects of fluid retention and tachycardia.

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New York: Raven press, p 67, 1984. Cleophas TJ, Kauw FHW: Pressor responses from noncardio-selective beta-blockers. Angiology 39: 587-596,1988. : Plasma adrenaline and noradrenaline during orthostasis in man: The importance of arterial sampling. Scand J Clin Invest 46: 397-401, 1986. Teichholz LE: Problems in echocardiographic volume determinations: Echocardiographic-angiographic correlations in the presence or absence of asynergy. Am J Cardiol 37: 7-11, 1976. van Herwaarden CLA: Selective and nonselective beta-blockade in hypertension.

This was considered as a wash-out period. After this wash-out a third 8 weeks period followed in which the alternate medication was given. Tablets containing one or both drugs or placebo were identical in appearance. The whole study lasted from October to April. At the start of the trial and after every 4 weeks patients were examined at our outpatient clinic. The examinations consisted of a procedure described below. Drugs were administered in oral doses, which were doubled after 4 weeks in each period: phenoxybenzamine 5 mg twice daily in the first half of the 8 weeks, and 10 mg twice daily in the second half; or the same doses of phenoxybenzamine combined with sotalol 20 mg twice daily in the first half of the 8 weeks, and 40 mg twice daily in the second half.

1. Introduction Beta-adrenergic receptor antagonists have previously been found beneficial in subjects with postural hypotension due to sympathetic denervation. This beneficial effect may be due to intrinsic sympathicomimetic activity (lSA) on the heart [1] or to enhancement of alpha-adrenergic vasoconstriction [2] in these patients, who probably have low receptor occupancy. The present study was originally designed, not to further 34 NONSELECTIVE BETA-BLOCKERS IN DIABETICS 35 test these hypotheses, but simply to study whether these beneficial effects would be found even when tests would be performed in a larger group of patients in a double-blind, placebo-controlled regimen.

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