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尼古丁的心血管作用

Author
Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
Section Editor
Neal L Benowitz, MD
Deputy Editor
Gordon M Saperia, MD, FACC
Translators
张韶冈, 主任医师

引言

尼古丁是一种天然存在的生物碱，主要存在于烟草中。它最常从香烟烟雾中被吸收。一支香烟含10-15mg尼古丁，其中平均1mg尼古丁进入吸烟者体内。尼古丁也可从无烟烟草(鼻烟、咀嚼烟草)，斗烟和雪茄，水烟，以及多种戒烟药物中获得。尼古丁也存在于一些杀虫剂中，这可能是意外或故意中毒的一种来源。

药代动力学

吸烟过程中尼古丁的血浆浓度峰值为10-50ng/mL，其中约5%与蛋白结合。半衰期平均为2小时。约80%-90%的尼古丁在肺、肝脏和肾脏代谢；主要代谢物为可替宁，其血浆浓度是尼古丁的10倍。可替宁的半衰期为15-20个小时，被用作尼古丁暴露的生物标志物[1]。

约17%的尼古丁以原型经尿液排出。其尿排泄率与pH值相关，在碱性尿液中排泄率降低。哺乳女性的乳汁中发现有尼古丁，其浓度与血浆浓度平行。

烟草相关疾病的种族差异不能完全用吸烟行为解释。尽管黑人每日吸烟更少，但血清可替宁浓度更高。一项研究比较了黑人和白人吸烟者中尼古丁的每日摄入量和代谢率，结果发现黑人每支香烟的烟草烟雾和尼古丁摄入比白人高30%，而黑人中可替宁总清除率和非肾脏清除率明显更低(低10%-15%)[2]。因此，尼古丁摄入量更高且可替宁代谢率更慢导致黑人血清可替宁浓度更高。

遗传因素

CYP2A6基因 — 吸烟过程中血浆尼古丁和可替宁浓度的个体差异相当大，即使在尼古丁摄入剂量相近的个体中也如此。尼古丁主要通过肝酶CYP2A6代谢。已经报道了许多CYP2A6基因变异型，其中几种与尼古丁代谢较慢有关。已报道一些个体有CYP2A6基因缺失，这些个体代谢尼古丁的速度异常缓慢，几乎不生成可替宁。在亚洲人和黑人中，与慢代谢相关的基因变异型更普遍。遗传学上的慢代谢者相比于快代谢者往往每日吸更少的香烟，并且能够更容易地戒烟[3]。

                       

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Literature review current through: 2017-06 . | This topic last updated: 2015-11-05.
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