胃酸常用药质子泵抑制剂可增加心脏病患病风险
2013/07/12
美国休斯顿卫理公会医院的科学家研究发现,长期服用酸反流药物如质子泵抑制剂类药物可抑制体内DDAH酶的活性,使化学信使ADMA的血药浓度增加,从而增加患心脏病的风险。

美国知名医院休斯顿卫理公会医院的研究人员发现酸反流药物会抑制血管放松,并干扰血管内NO的产生,从而导致心脏病风险增加。这是科学家首次详细展示了质子泵抑制剂类药物(一类常用的抑制胃酸反流的药物,PPls)是如何引发心脏疾病的。该研究已发表在美国《循环》杂志上。


质子泵抑制剂的前世

质子泵抑制剂(proton pump inhibitors,PPls)是目前治疗消化性溃疡最先进的一类药物,它通过高效快速抑制胃酸分泌和清除幽门螺旋杆菌达到快速治愈溃疡的目的。

常用的酸反流类药物主要是兰索拉唑和奥美拉唑,在美国各大药店柜台即可购买到该类药的品牌药或仿制药。美国食品与药品监督管理局(FDA)调查显示,每十四个美国人中就有一个人在服用兰索拉唑和奥美拉唑。2009年质子泵抑制剂药物(PPls)是全美第三大畅销药物,销售额达130亿美元。该类药物可用于治疗许多常见疾病,如幽门螺旋杆菌感染引起的胃溃疡、卓艾综合征等。

质子泵抑制剂的今生

研究人员发现PPls类药物在人体组织内和小鼠模型中均会引起血管的收缩。如果长期服用该类药物将导致高血压和心肌功能减弱。为此研究人员做了一项大规模的研究以证明该结论。

该项研究的首席研究员、医学博士兼哲学博士John Cooke称,服用PPls类药物可增加急性冠脉综合征患者的二次心脏病复发风险。患有心脏病的病人治疗胃酸反流病时,应当服用另外一种药物替代PPls类药物,以降低心脏病复发风险。质子泵抑制剂药物(PPls)起初性质较稳定,口服进入胃中后,被胃内特殊的细胞激活,一旦被激活药物分子便可抑制质子进入肠道内,从而中和和减少胃酸的分泌。

Yohannes Ghepamariam博士和Cooke博士通过研究小鼠模型及人体内皮细胞培养基发现,PPls类药物可抑制二甲基精氨酸二甲胺水解酶DDAH的活性,从而导致化学信使ADMA(非对称二甲基精氨酸)的血药浓度的增加,而ADMA可抑制另外一种化学信使NO的产生。小鼠模型的定量研究表明,服食PPls类药物的组相对对照组血管更易收缩。

Ghepemariam博士发现PPls类药物可干扰血管的放松能力,PPls类药物通过干扰人体血管生成NO的能力,产生这种不利影响。人体血管内产生的这种NO可放松及保护动脉、静脉组织。研究人员发现,质子泵抑制剂(PPls)药物可使血管组织内的ADMA含量平均增加25%,而血管放松能力则降低30%。

质子泵抑制剂的副作用

腹泻:胃酸可以杀灭胃部的多数病原微生物,是消化道重要的保护屏障。质子泵抑制剂抑制胃酸的分泌,减少了烧心的症状,但也破坏了这个防御机制,造成胃部的细菌繁殖,使胃肠道感染的可能性增加。

呼吸道感染:长期用质子泵抑制剂还会削弱呼吸道的非特异性免疫力。此时若患者再出现烧心症状,含有细菌的胃液会反流到咽部,甚至误吸进入呼吸道,肺部感染的风险也会增大。

骨质疏松:长期应用或高剂量使用质子泵抑制剂可增大患者骨折的风险。这类药的强力抑酸作用破坏了胃和十二指肠上段的酸性环境,影响了钙的吸收,可能引起骨质疏松。服用时间越长,剂量越大,骨折风险越高。

未来,研发人员应尽量开发相关替代药物,同时医疗工作者也应减少病人对该类药物的服用量,合理适量的使用质子泵抑制剂。

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  • Use of proton pump inhibitors and risk of osteoporosis-related fractures

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