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β-adrenoreceptors and the risk of Parkinson's disease
The Lancet Neurology ( IF 48.0 ) Pub Date : 2020-03-01 , DOI: 10.1016/s1474-4422(19)30400-4
Franziska Hopfner 1 , Günter U Höglinger 2 , Gregor Kuhlenbäumer 3 , Anton Pottegård 4 , Mette Wod 5 , Kaare Christensen 6 , Caroline M Tanner 7 , Günther Deuschl 3
Affiliation  

BACKGROUND β-adrenoceptors are widely expressed in different human organs, mediate important body functions and are targeted by medications for various diseases (such as coronary heart disease and heart attack) and many β-adrenoceptor acting drugs are listed on the WHO Model List of Essential Medicines. β-adrenoceptor antagonists are used by billions of patients with neurological disorders, primarily for the treatment of migraine and action tremor (mainly essential tremor), worldwide. RECENT DEVELOPMENTS An observational study reported a link between the chronic use of the β-adrenoceptor antagonist propranolol and an increased risk of Parkinson's disease, while the chronic use of the β-adrenoceptor agonists was associated with a decreased risk. Further support of this association was provided by a dose-dependent decrease in the risk of Parkinson's disease with chronic β-adrenoceptor agonist (eg, salbutamol) use, and by functional data indicating a possible underlying molecular mechanism. Five additional epidemiological studies have examined the modulation of the risk of Parkinson's disease as a result of the use of β-adrenoceptor-acting drugs in different populations. Overall, similar estimates but different interpretations of the associations were provided. Several findings suggest that the increase in risk of Parkinson's disease associated with β-adrenoceptor antagonists use can be explained by reverse causation because prodromal Parkinson's disease is often associated with non-specific action tremor, which is usually treated with propranolol. The lower risk of Parkinson's disease seen in patients receiving β-adrenoceptor agonists is likely to be indirectly mediated by smoking because smoking has a strong inverse association with Parkinson's disease (people that smoke have a reduced risk of developing Parkinson's disease). Smoking also causes chronic obstructive pulmonary disease, which is treated with β-adrenoceptor-agonist medications. Even if causal, the effect of β-adrenoceptor antagonists on the risk of Parkinson's disease would be small compared with other Parkinson's disease risk factors and would be similar to the risk evoked by pesticide exposure. The estimated risk of Parkinson's disease because of β-adrenoceptor antagonists use corresponds to one case in 10 000 patients after 5 years of propranolol use, and would be considered a very rare adverse effect. Thus, not using β-adrenoceptor antagonists would severely harm patients with recommended indications, such as heart disease or migraine. Similarly, 50 000 people would have to be treated for 5 years with salbutamol to prevent Parkinson's disease in one patient, suggesting that primary preventive therapy studies on disease modification are not warranted. WHERE NEXT?: Epidemiological evidence for a causal relationship between use of β2-adrenoceptor antagonists and the increased risk of Parkinson's disease is weak, with other explanations for the association being more probable. Future observational studies are warranted to clarify this association. However, given the very low risk associated with propranolol, most clinicians are unlikely to change their treatment approach.

中文翻译:

β-肾上腺素能受体与帕金森病的风险

背景β-肾上腺素能受体在人体不同器官中广泛表达,介导重要的身体机能,是治疗各种疾病(如冠心病和心脏病)的药物靶向药物,许多β-肾上腺素能受体作用药物被列入世界卫生组织基本药物标准清单。药物。β-肾上腺素能受体拮抗剂被全球数十亿患有神经系统疾病的患者使用,主要用于治疗偏头痛和动作性震颤(主要是特发性震颤)。最近的发展 一项观察性研究报告了长期使用 β-肾上腺素能受体拮抗剂普萘洛尔与帕金森病风险增加之间的联系,而长期使用 β-肾上腺素能受体激动剂与风险降低有关。长期使用β-肾上腺素能受体激动剂(如沙丁胺醇)可降低帕金森病风险的剂量依赖性,以及表明可能潜在分子机制的功能数据,进一步支持了这种关联。另外五项流行病学研究检查了在不同人群中使用β-肾上腺素能受体作用药物对帕金森病风险的调节。总体而言,提供了相似的估计但对关联的不同解释。一些研究结果表明,与使用 β-肾上腺素能受体拮抗剂相关的帕金森病风险增加可以用反向因果关系来解释,因为前驱帕金森病通常与非特异性动作性震颤有关,通常用普萘洛尔治疗。接受 β-肾上腺素能受体激动剂治疗的患者患帕金森病的风险较低可能是由吸烟间接介导的,因为吸烟与帕金森病有很强的负相关(吸烟的人患帕金森病的风险较低)。吸烟还会导致慢性阻塞性肺疾病,这种疾病可以用 β-肾上腺素能受体激动剂药物治疗。即使是因果关系,与其他帕金森病风险因素相比,β-肾上腺素能受体拮抗剂对帕金森病风险的影响也很小,并且与农药暴露引起的风险相似。由于使用 β-肾上腺素能受体拮抗剂,估计的帕金森病风险相当于使用普萘洛尔 5 年后每 10 000 名患者中就有 1 例,并且会被认为是非常罕见的不良反应。因此,不使用 β-肾上腺素能受体拮抗剂会严重伤害具有推荐适应症的患者,例如心脏病或偏头痛。同样,50 000 人必须接受沙丁胺醇治疗 5 年才能预防一名患者的帕金森病,这表明没有必要对疾病改变进行初级预防性治疗研究。下一步在哪里?:关于使用 β2-肾上腺素能受体拮抗剂与帕金森病风险增加之间因果关系的流行病学证据很弱,对这种关联的其他解释更有可能。未来的观察性研究有必要澄清这种关联。然而,鉴于与普萘洛尔相关的风险非常低,大多数临床医生不太可能改变他们的治疗方法。不使用β-肾上腺素能受体拮抗剂会严重伤害有推荐适应症的患者,如心脏病或偏头痛。同样,50 000 人必须接受沙丁胺醇治疗 5 年才能预防一名患者的帕金森病,这表明没有必要对疾病改变进行初级预防性治疗研究。下一步在哪里?:关于使用 β2-肾上腺素能受体拮抗剂与帕金森病风险增加之间因果关系的流行病学证据很弱,对这种关联的其他解释更有可能。未来的观察性研究有必要澄清这种关联。然而,鉴于与普萘洛尔相关的风险非常低,大多数临床医生不太可能改变他们的治疗方法。不使用β-肾上腺素能受体拮抗剂会严重伤害有推荐适应症的患者,如心脏病或偏头痛。同样,50 000 人必须接受沙丁胺醇治疗 5 年才能预防一名患者的帕金森病,这表明没有必要对疾病改变进行初级预防性治疗研究。下一步在哪里?:关于使用 β2-肾上腺素能受体拮抗剂与帕金森病风险增加之间因果关系的流行病学证据很弱,对这种关联的其他解释更有可能。未来的观察性研究有必要澄清这种关联。然而,鉴于与普萘洛尔相关的风险非常低,大多数临床医生不太可能改变他们的治疗方法。
更新日期:2020-03-01
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