[慢性阻塞性肺疾病中的选择性磷酸二酯酶-4(PDE-4)抑制剂]

[Selective phosphodiesterase-4 (PDE-4) inhibitors in COPD].

作者信息

Tatlicioğlu Türkan

机构信息

Department of Chest Diseases, Faculty of Medicine, Gazi University, Ankara, Turkey.

出版信息

Tuberk Toraks. 2008;56(4):472-84.

DOI:
Abstract

Chronic obstructive pulmonary disease (COPD) is a worldwide health problem resulting in significant morbidity and mortality; however, it could not be understood totally so far. Treatment options for the disease are quite limited and there is an urgent need for new treatment strategies. Among new therapeutic agents that are under development, a group of significant importance is phosphodiesterase-4 (PDE-4) inhibitors shown to have antiinflammatory actions. Phosphodiesterases are the enzymes responsible from the breakdown and inactivation of cyclic adenosine monophosphate (cAMP) which is an intracellular second messenger molecule. They are present in several structural and inflammatory cells, in these cells the inactivation of cAMP results in a proinflammatory cascade. So, in COPD which goes together with chronic inflammation, prevention of cAMP inactivation via phosphodiesterase enzyme inhibition made phosphodiesterase enzymes potential targets. Main phosphodiesterase playing a part in COPD is PDE-4 which is predominantly present in inflammatory cells and airway smooth muscle cells. The studies therefore focused on inhibitors selective to PDE-4 subtype. The two selective PDE-4 inhibitors that are at Phase III clinical trial stage are cilomilast and roflumilast. The studies have demonstrated that antiinflammatory effects of cilomilast and roflumilast positively contribute to the respiratory function, frequency of exacerbations and quality of life of COPD patients. Despite we need new studies to evaluate the influence of these agents on the natural course of COPD as well as their long-term safety; we can certainly comment that cilomilast and roflumilast are promising hope in COPD treatment by their clinical and antiinflammatory effects.

摘要

慢性阻塞性肺疾病(COPD)是一个全球性的健康问题,会导致严重的发病率和死亡率;然而,到目前为止人们还不能完全了解它。该疾病的治疗选择非常有限,迫切需要新的治疗策略。在正在研发的新型治疗药物中,一类具有重要意义的是已显示具有抗炎作用的磷酸二酯酶-4(PDE-4)抑制剂。磷酸二酯酶是负责分解和失活环磷酸腺苷(cAMP)的酶,cAMP是一种细胞内第二信使分子。它们存在于多种结构细胞和炎症细胞中,在这些细胞中cAMP的失活会导致促炎级联反应。因此,在伴有慢性炎症的COPD中,通过抑制磷酸二酯酶来防止cAMP失活使磷酸二酯酶成为潜在的治疗靶点。在COPD中起作用的主要磷酸二酯酶是PDE-4,它主要存在于炎症细胞和气道平滑肌细胞中。因此,研究集中在对PDE-4亚型具有选择性的抑制剂上。处于III期临床试验阶段的两种选择性PDE-4抑制剂是西洛司特和罗氟司特。研究表明,西洛司特和罗氟司特的抗炎作用对COPD患者的呼吸功能、急性加重频率和生活质量有积极贡献。尽管我们需要新的研究来评估这些药物对COPD自然病程的影响及其长期安全性;但我们可以肯定地说,西洛司特和罗氟司特因其临床和抗炎作用,在COPD治疗中是充满希望的。

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