Lubiński Wojciech
Wojskowy Instytut Medyczny, Klinika Chorób Wewnetrznych, Pneumonologii i Alergologii CSK MON w Warszawie.
Pol Merkur Lekarski. 2004 May;16 Suppl 1:75-6, 78.
Cholinergic nerve fibres arise in the nucleus ambiguus and the dorsal motor nucleus of the vagus nerve in the brainstem. They travel down as the vagus nerve to parasympathetic ganglia placed in the walls of the airways. From these ganglia, short postganglionic fibres innervate airway smooth muscle and the submucosal glands in the lung. Activation of vagal nerve releases acetylcholine at the neuroeffector junctions, where it binds to postsynaptic receptors, resulting in bronchoconstrictions. The resting bronchomotor tone in normal airways has a cholinergic component mediated via muscarinic cholinergic receptors. The human airways have five subtypes of muscarinic cholinergic receptors: the M1 and M3 mediate bronchoconstriction and stimulation of mucus secretion, while M2 control the release of acetylcholine from M1 and M3 receptors through a negative-feedback mechanism. Anticholinergic bronchodilators act by blocking muscarinic receptors. Tiotropium bromide is cutting age anticholinergic bronchodilator. It dissociates more slowly from M1 and M3 than from M2 receptors and subsequently has a long and safety duration of action. In COPD patients tiotropium comparing to placebo, ipratropium and long acting beta agonists significantly improves lung function. It is an effective bronchodilator that reduces dyspnea, COPD exacerbations frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic pulmonary disease therapy.
胆碱能神经纤维起源于脑干的疑核和迷走神经背运动核。它们作为迷走神经下行至位于气道壁内的副交感神经节。从这些神经节发出的节后短纤维支配气道平滑肌和肺内的黏膜下腺。迷走神经激活后在神经效应器接头处释放乙酰胆碱,乙酰胆碱与突触后受体结合,导致支气管收缩。正常气道的静息支气管运动张力有一个通过毒蕈碱胆碱能受体介导的胆碱能成分。人类气道有五种毒蕈碱胆碱能受体亚型:M1和M3介导支气管收缩和黏液分泌的刺激,而M2通过负反馈机制控制乙酰胆碱从M1和M3受体的释放。抗胆碱能支气管扩张剂通过阻断毒蕈碱受体起作用。噻托溴铵是一种新型抗胆碱能支气管扩张剂。它从M1和M3受体解离的速度比从M2受体解离的速度慢,因此作用持续时间长且安全。在慢性阻塞性肺疾病(COPD)患者中,与安慰剂、异丙托溴铵和长效β受体激动剂相比,噻托溴铵能显著改善肺功能。它是一种有效的支气管扩张剂,可减轻呼吸困难、降低COPD急性加重频率并改善健康状况。这表明噻托溴铵将对慢性肺病治疗做出重要贡献。