Drugs
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Several compounds of the chemical class arylethanolamines have been shown to possess combined alpha- or vasodilator and beta-adrenoceptor blocking properties. The first drug was labetalol (AH5158)[5-(1-hydroxy-2)1-methyl-3-phenylpropyl(amino)-ethyl (salicylamide)]. Others include medroxalol, bucindolol and YM-09538, which differ from labetalol either by the nature of the substitution on the primary benzene ring and/or on the terminal nitrogen. ⋯ It is particularly valuable in allowing a reduction in the number of drugs required for adequate blood pressure control. The early theoretical prediction that postural hypotension would occur with high doses is now acknowledged to be labetalol's major dose-limiting side effect. Most of the available pharmacokinetic data on labetalol were derived from studies which utilised a fluorimetric assay.(ABSTRACT TRUNCATED AT 400 WORDS)
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Both beta- and alpha-adrenergic mechanisms are important in the control of blood pressure; alpha-mediated vasoconstriction is responsible for the regulation of vascular tone, and beta-mediated responses stimulate the heart directly and indirectly by liberating renin and affecting vascular smooth muscle tone. beta-Adrenergic blocking drugs have long been established in the treatment of hypertension. The development of drugs which combine this action with an alpha-blocking effect represents an additional mode of action to lower the blood pressure. Numerous studies have demonstrated that labetalol intravenously or orally gives a rapid fall of blood pressure in essential and renal hypertension. ⋯ It has been suggested that the side effects attributable to the beta-blocking component are less obtrusive than those seen with pure beta-blocking drugs without alpha-activity because the alpha-blockade modifies the consequences of beta-blockade. Heart failure has been reported, but for haemodynamic reasons would be expected to be less common; careful patient selection should avoid any risk. Similarly labetalol may worsen asthma even if the risks are probably less than with non-selective beta-blockade alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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The cardinal haemodynamic disturbance in established hypertension is an increased total peripheral resistance and a subnormal blood flow, particularly during exercise. The spontaneously occurring changes in central haemodynamics have been followed in young males with essential hypertension over a 17-year period: a gradual increase in total peripheral resistance and blood pressure, and a gradual fall in cardiac output and stroke volume, have been demonstrated. Labetalol is a unique antihypertensive agent which induces both alpha- and beta-blockade. ⋯ Over the years total peripheral resistance was gradually reduced by 15 to 20% at rest as well as during exercise. Stroke volume gradually increased and after 6 years of treatment was approximately 10% higher than the pretreatment value. This compensated for the reduced heart rate and no significant reduction in cardiac output was seen either during exercise or at rest.(ABSTRACT TRUNCATED AT 400 WORDS)