长期的影响的前瞻性研究timolol疗法对α-和beta-adrenoceptor和血管紧张素ⅱ受体介导反应正常的受试者。
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铁,大厅JA,迪克森我棕色的乔丹
长期的影响的前瞻性研究timolol疗法对α-和beta-adrenoceptor和血管紧张素ⅱ受体介导反应正常的受试者。
Br中国新药杂志。1997年3月,43 (3):301 - 8。
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9088585 (在PubMed]
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目的:长期治疗与β1-selective肾上腺素拮抗剂引起cross-sensitisation心脏β2-adrenoceptor反应,没有相应的改变β1-adrenoceptor反应。我们进行了一项前瞻性随机双盲安慰剂对照交叉研究的影响与timolol非选择性beta-blockade和血管紧张素ⅱ受体介导反应者在正常科目。我们也希望研究β1 -和β的时间进程2-adrenergic timolol撤军后的反应。方法:6个健康男性收到timolol每天两次10毫克或安慰剂为14天。11天的治疗,血管α1,α2 -和血管紧张素ⅱ受体反应评估通过测量血压升高静脉注射去甲肾上腺素,分别alpha-methylnoradrenaline和血管紧张素酰胺,一剂后timolol 10毫克(阻止该项苯肾上腺素和alpha-methylnoradrenaline)的影响。收缩压和舒张压增加以应对这些药物,但是这不是不同timolol或安慰剂治疗。timolol或安慰剂治疗停止后,β1 -和β2-adrenoceptor介导反应评估通过测量心率反应跑步机锻炼和静脉注射舒喘灵分别注入。一半的每个对象分别接受了这2天,3天,结束后治疗。结果:运动和salbutamol-induced心动过速不不同的安慰剂后或3天结束后timolol治疗。然而,2天timolol治疗后,两人都是减毒; the reduction in salbutamol-induced tachycardia was significant, whilst the reduction in exercise tachycardia did not reach statistical significance. We also measured metabolic responses to exercise and to salbutamol infusion. Exercise induced a rise in plasma potassium and noradrenaline. Salbutamol produced a fall in plasma potassium, a rise in plasma glucose and insulin and also a rise in plasma noradrenaline. All of these changes were not different following placebo or 3 days after the end of timolol treatment; by contrast, 2 days following timolol treatment, all were significantly attenuated, with the exception of the rise in plasma glucose. In addition, the rise in both plasma glucose and insulin in response to an oral load of 75 g glucose were not different post-placebo, 2 or 3 days post-timolol. CONCLUSIONS: These results show that, following 14 days of nonselective beta-adrenoceptor blockade with timolol, there is evidence of residual beta-adrenoceptor blockade 2 days after drug withdrawal; this finding is in contrast with the known plasma profile of timolol (half-life 3-6 hours), but is consistent with our previous observations of the slow speeds of association and dissociation of timolol with beta-adrenoceptors in vitro. There is no evidence, in this study, of beta-adrenergic sensitisation following timolol withdrawal, nor of cross-regulation of vascular alpha 1-, alpha 2- or angiotensin II receptors in response to nonselective beta-adrenoceptor blockade.