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多培沙明:一种新型多巴胺能激动剂

[Dopexamine: a new dopaminergic agonist].

作者信息

Perrin G, Papazian L, Martin C

机构信息

Département d'Anesthésie-Réanimation, Hôpital Sainte-Marguerite, Marseille.

出版信息

Ann Fr Anesth Reanim. 1993;12(3):308-20. doi: 10.1016/s0750-7658(05)80658-6.

Abstract

Dopexamine hydrochloride is a new synthetic catecholamine for intravenous use in low cardiac output states with co-existing raised systemic or pulmonary vascular resistance. Dopamine has been commonly used since several years in these situations. The drawbacks of dopamine include a vasoconstrictive effect with high infusion rates, and a marked tendency for ventricular ectopy due to the potent beta-1 adrenergic stimulation. Dopexamine hydrochloride has interesting vasodilator properties, with marked intrinsic agonist activity at beta-2 adrenoreceptors and a lesser agonist activity at dopaminergic receptors (DA1 and DA2). Its mild inotropic activity arises primarily from baroreceptor reflex stimulation with a possible contribution from direct stimulation of myocardial beta 2-adrenoreceptors. Dopexamine hydrochloride is responsible for an inhibition of neuronal re-uptake of catecholamines (uptake-1), producing an indirect stimulation of cardiac beta 1-receptors. This catecholamine has no effect at alpha 1 and alpha 2-adrenoreceptors, and only very weak and clinically insignificant beta 1-adrenoreceptor agonist activity. Dopexamine hydrochloride improves cardiac performance by a marked vasodilation and a mild inotropic activity. The specific activity at dopaminergic receptors increases cerebral, myocardial, splanchnic and renal blood flows. These haemodynamic effects are associated with an increase in diuresis and natriuresis. These benefits are achieved without side effects such as an increased myocardial oxygen consumption, although induced tachycardia may be responsible for chest pain/anginae pain in patients with ischaemic heart disease. In clinical practice, dopexamine hydrochloride is easy to use; the short plasma half-life (6 minutes in healthy volunteers and 11 minutes in patients with low cardiac output) allows a rapid return to pretreatment status at discontinuation of the infusion. Preliminary studies have shown that dopexamine hydrochloride can produce beneficial effects in patients with acute heart failure or with compromised left ventricular function following cardiac surgery. The drug has also been assessed in patients with septic shock, most often in association with dopamine or norepinephrine. In these patients, dopexamine produces a dose-related increase in cardiac index, stroke volume, heart rate and a decrease in systemic vascular resistance. Its use in this indication must be cautious, particularly in patients with hypotension or decreased venous return. Comparative therapeutic trials are clearly required to establish the efficiency and tolerance of dopexamine hydrochloride in comparison with dopamine and dobutamine, before its place in therapy can fully be defined.

摘要

盐酸多培沙明是一种新型合成儿茶酚胺,用于心输出量低且伴有体循环或肺循环血管阻力升高的静脉给药。多巴胺多年来一直在这些情况下普遍使用。多巴胺的缺点包括高输注速率时的血管收缩作用,以及由于强效β1肾上腺素能刺激导致的明显室性异位倾向。盐酸多培沙明具有有趣的血管舒张特性,在β2肾上腺素受体处具有显著的内在激动剂活性,在多巴胺能受体(DA1和DA2)处的激动剂活性较低。其轻度正性肌力活性主要源于压力感受器反射刺激,可能还有直接刺激心肌β2肾上腺素受体的作用。盐酸多培沙明可抑制儿茶酚胺的神经元再摄取(摄取-1),间接刺激心脏β1受体。这种儿茶酚胺对α1和α2肾上腺素受体无作用,且仅有非常微弱且临床上无显著意义的β1肾上腺素受体激动剂活性。盐酸多培沙明通过显著的血管舒张和轻度正性肌力活性来改善心脏功能。在多巴胺能受体处的特异性活性可增加脑、心肌、内脏和肾血流量。这些血流动力学效应与利尿和排钠增加有关。在不产生诸如心肌氧消耗增加等副作用的情况下即可实现这些益处,尽管诱发的心动过速可能会导致缺血性心脏病患者出现胸痛/心绞痛。在临床实践中,盐酸多培沙明易于使用;较短的血浆半衰期(健康志愿者为6分钟,低心输出量患者为11分钟)使得在停止输注后能迅速恢复到治疗前状态。初步研究表明,盐酸多培沙明可对急性心力衰竭患者或心脏手术后左心室功能受损的患者产生有益作用。该药物也已在感染性休克患者中进行评估,最常与多巴胺或去甲肾上腺素联合使用。在这些患者中,多培沙明可使心脏指数、每搏量、心率呈剂量相关增加,并使体循环血管阻力降低。在该适应证中的使用必须谨慎,尤其是在低血压或静脉回流减少的患者中。在其在治疗中的地位能完全确定之前,显然需要进行对比治疗试验以确定盐酸多培沙明与多巴胺和多巴酚丁胺相比的疗效和耐受性。

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