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Combined alpha- and beta-receptor inhibition in the treatment of hypertension.

Drugs 1984
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 also been used intravenously in phaeochromocytoma, tetanus, clonidine withdrawal, and as an adjunct to halothane to produce hypotensive anaesthesia. Intravenously, labetalol is probably best given as a graded infusion or as repeated small bolus injections to assure a smooth fall of blood pressure. Many long term studies have shown it to be effective orally in prolonged treatment of hypertension with studies of over 5 years, showing that tolerance does not develop. Labetalol can be used in combination with diuretics and other drugs when necessary. It can be employed to control the blood pressure in all grades of hypertension. A dosage of 100mg twice daily will often be adequate to control mild hypertension and the use of even lower doses has been reported. However, the dosage can be markedly increased in severe hypertension and while such doses are relatively exceptional, several trials have employed over 2 g per day for the more resistant cases. Studies have demonstrated that blood pressure control with labetalol is equivalent to that with beta-adrenoceptor blocking drugs plus vasodilators, or methyldopa. Labetalol has been used in patients with severe renal impairment and a number of studies suggest that it may now be the drug of choice in raised blood pressure of pregnancy. Side effects can be divided into those related to beta-blockade, those related to alpha-blockade and those not clearly related to either effect. 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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