质子泵抑制剂的代谢与细胞色素P450

质子泵抑制剂（PPIs）系苯并咪唑同系物．其通过抑制H^＋-K^＋-ATP酶而发挥作用,抑酸作用极强。已被公认为是治疗胃酸相关性疾病最有效的药物。1988年第一个PPIs——奥美拉唑上市以后,兰索拉唑、潘托拉唑、雷贝拉唑和埃索美拉唑等陆续用于临床．     

质子泵抑制剂对氯吡格雷抗血小板效应的影响

急性冠状动脉综合征(ACS)是一组由于冠状动脉粥样硬化斑块破裂、表面破损或出现裂纹引发血小板激活,进而引起冠状动脉内不同程度血栓形成和远端血管闭塞的一组心血管急症,是目前引起死亡的主要原因之一.近年来逐渐认识到其主要病理基础为不稳定斑块引起的血小板继发性激活从而引起冠状动脉局部血栓形成,因此抗血小板治疗是目前治疗急性冠状动脉综合征的基础.因此,美国心脏病学会(ACC)及美国心脏学会(AHA)推荐氯吡格雷联合阿司匹林的双联抗血小板治疗用于不稳定性心绞痛、非ST段抬高型心肌梗塞及行药物溶栓或经皮冠状动脉介入治疗(PCI)治疗的心肌梗塞患者[1].     

质子泵抑制剂对氯吡格雷抗血小板疗效的影响

2008年美国心脏病学会基金会、美国胃肠病学会和美国心脏协会专家共识文件指出,对于采用阿司匹林和氯吡格雷双重抗血小板的冠心病患者服用质子泵抑制剂(PPI)可预防和治疗药物相关性胃和十二指肠损伤.然而,PPI通过肝细胞色素P450途径竞争性抑制氯吡格雷的抗血小板聚集作用,从而可能增加心血管事件发生率.该文综述近年来PPI...     

不同质子泵抑制剂对急性心肌梗死患者直接经皮冠状动脉介入治疗的影响

目的探讨不同机制的质子泵抑制剂对急性心肌梗死患者直接PCI术后临床效果的影响。方法选择在北京安贞医院抢救中心实施直接PCI、术前术后给予氯吡格雷联合阿司匹林抗血小板治疗的患者354例。随机分为奥美拉唑组(116例)、泮托拉唑组(121例),2组术前分别开始静脉滴注40 mg/d,7 d后持续口服1年(20 mg/d),对照组(117例)未用质子泵抑制剂。观察3组主要不良心血管事件发生率和出血并发症发生情况。结果 3组临床基本资料、冠状动脉造影及PCI比较差异无统计学意义,心源性死亡、非致死性心肌梗死、靶血管血运重建、支架内血栓的发生率奥美拉唑组分别为1.7%、3.4%、9.5%、1.7%,泮托拉唑组分别为1.7%、5.0%、10.7%、2.5%,对照组分别为0.9%、3.4%、12.0%、1.7%。3组主要不良心血管事件发生率相近(P>0.05)。总出血事件发生率与对照组(9.4%)比较,奥美拉唑组(2.6%)和泮托拉唑组(3.3%)明显减少(P<0.01),但奥美拉唑组与泮托拉唑组比较,总出血事件发生率差异无统计学意义(P>0.05)。结论奥美拉唑和泮托拉唑的作用相近,不降低冠状动脉支架置入术后氯吡格雷联合阿司匹林治疗对心血管事件的效果,同时可显著降低出血事件的发生率。     

长期使用质子泵抑制剂(PPI)可产生严重的副作用

长期忍受消化性溃疡折磨的患者可能对PPI有一定的认识,知道是用于治疗消化性溃疡,可快速抑制胃酸分泌和清除幽门螺旋杆菌的药物,但却不一定知道PPI的作用机制是什么,以及它对人体的副作用又是怎样产生的。     

不同的质子泵抑制剂与氯吡格雷相互作用的研究进展

大量研究表明阿司匹林和氯吡格雷联合抗血小板可以降低急性冠状动脉综合征及冠状动脉支架植入术后复发心血管事件的概率。但由于联合抗血小板治疗会增加出血的风险,所以目前临床推荐加用质子泵抑制剂以预防胃肠道溃疡和出血。氯吡格雷和质子泵抑制剂均通过细胞色素P450同工酶系统代谢,质子泵抑制剂通过竞争性抑制细胞色素P450同工酶CYP2C19,而降低氯吡格雷的抗血小板活性,增加复发心血管事件的概率。最近的研究发现不同的质子泵抑制剂影响程度不同,泮托拉唑和埃索美拉唑对氯吡格雷作用影响较小,而奥美拉唑、雷贝拉唑和兰索拉唑对氯吡格雷的抗血小板活性抑制作用较大。     

肝硬化患者长期使用质子泵抑制剂风险分析

目的探讨长期使用质子泵抑制剂(PPI)(3个月)对肝硬化患者的影响。方法选取2015年1月至2018年12月在江阴市中医院消化科、肝病科、心内科就诊的长期使用PPI的患者97例,分为三组,其中A组为非肝硬化患者31例;B组为肝硬化代偿期患者30例;C组为肝硬化失代偿期患者28例。统计各组患者腹痛、腹泻、腹胀、便秘、自发性腹膜炎、肝性脑病的发生率。结果在A、B、C三组患者之间,长期使用PPI出现腹痛、腹泻、腹胀、便秘、自发性腹膜炎、肝性脑病的发生率C组显著高于A组和B组;经停用PPI同时补充益生菌治疗后症状缓解率,A组和B组显著高于C组,差异均有统计学意义(P0.05)。结论肝硬化失代偿期患者长期使用质子泵抑制剂出现腹痛、腹泻、腹胀、自发性腹膜炎、肝性脑病的风险较高,临床应予以重视。     

细胞色素P450 2C19基因多态性对以质子泵抑制剂为基础的三联疗法根除幽门螺杆菌疗效的影响

目的 研究以质子泵抑制剂(PPI)、左氧氟沙星、羟氨苄青霉素作为一线疗法对幽门螺杆菌(Hp)根除的影响,以及Hp根除率与CYP2C19基因多态性的相关性.方法 205例Hp阳性的患者被分为4组:埃索美拉唑20 mg 2次/d(E_(20)组),埃索美拉唑40 mg 2次/d(E_(40)组),雷贝拉唑10 mg 2次/d(R组),兰索拉唑30 mg 2次/d(L组),4组均加左氧氟沙星500 mg 1次/d和羟氨苄青霉素1000 mg 2次/d,疗程1周.其中有161例患者进行了CYP2C19基因型的检测,对Hp根除率分别按意愿治疗(intention-to-treat,ITT)分析和按方案(per protocol,PP)分析进行评估.结果 Hp总根除率为83.4%(PP)和79.0%(ITT).各组的根除率为:E_(20)组86.7%,E_(40)组88.5%,R组73.5%,L组78.1%.其中完成基因型检测的161例患者中,各基因型的根除率分别为:纯合子弱代谢型(PM)90%,杂合子强代谢型(HetEM)81.5%,纯合子强代谢型(HomEM)82.1%.CYP2C19各基因型间Hp根除率、各治疗方案间的根除率及各方案内各基因型间的根除率差异均无统计学意义(P>0.05).结论 以PPI为基础包含左氧氟沙星的三联疗法是目前根除Hp的有效方案,且该方案对Hp的根除率不受CYP2C19基因多态性的影响.     

CYP2C19与质子泵抑制剂

随着对肝脏微粒体细胞色素P450(CYP)基因变异研究的不断深入，人们发现CYP2C19基因多态性与质子泵抑制剂的药动学、药效学等方面密切相关，并影响临床治疗，此文对两者之间的关系作一综述。     

CYP2C19基因多态性对亚洲人群中含质子泵抑制剂三联疗法幽门螺杆菌根除率影响的荟萃分析

以质子泵抑制剂（PPI）为基础的三联疗法的幽门螺杆菌（H．pylori）根除率不尽相同，可能与细胞色素P450（CYP）2C19基因多态性有部分关联。目的：研究CYP2C19基因多态性对亚洲人群中以PPI为基础的三联疗法H．pylori根除率的影响。方法：在PubMed、EMBASE、CNKI和万方数据中进行系统文献检索，以RevMan4．2．8软件行荟萃分析。结果：共17篇文献纳入荟萃分析。不考虑PPI类型，CYP2C19弱代谢型（PM）与杂合子强代谢型（HetEM）之间、PM与纯合子强代谢型（HomEM）之间、HetEM与HomEM之间H．pylori根除率均有显著差异（PM对HetEM：OR=1．75，95％CI1．24—2．47．舟0．002；PM对HomEM：OR=2．82，95％CI1．73～4．60，P〈0．0001；HetEM对HomEM：OR=1．84，95％CI1．33-2．57，P=-0．0003）。在以奥美拉唑或兰索拉唑为基础的三联疗法中，PM与HomEM之间、HetEM与HomEM之间且pylori根除率均有显著差异（含奥美拉唑方案PM对HomEM：OR=4．37，95％CI1．86—10．26．P=0．0007，HetEM对HomEM：OR=3．15,95％CI1．75—5．66，P=0．0001；含兰索拉唑方案PM对HomEM：OR=3．06．95％CI1．56-6．00。P=0．001。HetEM对HomEM：OR=1．95，95％CI1．03～3．70，P=0．04）。在以雷贝拉唑为基础的三联疗法中，PM、HetEM、HomEM三组间H．pylori根除率均无明显差异。结论：在亚洲人群中，以奥美拉唑和兰索拉唑为基础的三联疗法．其H．pylori根除率受CYP2C19基因多态性影响，以雷贝拉唑为基础的三联疗法则否。     

Cardiovascular side effects of long-term therapy with tricyclic antidepressants in the aged.

In a study to determine the nature and frequency of cardiac side effects during long-term administration of tricyclic antidepressant drugs in usual dosages in the aged, 32 geriatric patients were followed for an average of 36.6 weeks. Ten of them received amitriptyline in a daily dosage of 20-75 mg for 53 weeks (average); in 2, electrocardiographic side effects developed, viz, inversion of the T waves or evidence of acute coronary insufficiency. Imipramine was administered to 21 patients in a daily dosage of 20-100 mg (average, 66 mg) over a period of 40 weeks; in 3 instances major side effects developed--intermittent left bundle-branch block, acute coronary insufficiency with node dysfunction, or T-wave inversion with sinus tachycardia; in 1 instance there was a minor side effect, viz, tachycardia only. In 1 patient, acute myocardial infarction developed after two 10-mg doses of nortriptyline. Five of the 7 patients with cardiac side effects had prior organic heart disease. It was concluded that the incidence of cardiac side effects in aged persons given tricyclic antidepressant drugs in the usual therapeutic dosages for a prolonged period is great enough to warrant frequent careful monitoring of cardiac status during therapy.     

Polymyalgia rheumatica and giant cell arteritis; diagnosis and side effects of low-dose long-term glucocorticoid therapy]

Due to good therapeutic results and few side-effects so-called "low-dose glucocorticoid therapy" (ldgc) with daily glucosteroid dosage below 10 mg prednisolone-equivalent has recently been recommended in managing polymyalgia rheumatica and giant cell arteritis. This fact is of important interest, since mean therapy time is often over a period of five years. An open-prospective study with 75 patients in a rheumatological unit was done in which different clinical histories were examined and glucosteroid side effects of 47 patients who had received therapy over six months were analyzed. Main side-effect shown was osteoporosis (n = 7), other known steroid-side effects were quite seldom (less than 5%). Dosage regimens and therapy monitoring criteria are proposed.     

No metabolic side effects of long-term treatment with verapamil in hypertension

In a prospective, open study 45 patients (mean age fifty-three years) with essential hypertension were treated with verapamil for four to eight years (mean 5.3 years). Blood pressure was satisfactorily controlled (from 160/104 to 145/91) and the side effects were infrequent, mild, and often transient. Verapamil did not exert any unfavorable metabolic or hematologic effects over the years. HDL-cholesterol was moderately increased (mean 24%) and the other plasma lipids were unaffected. These data suggest that the calcium channel blocker verapamil is a metabolically safe drug to use as monotherapy in essential hypertension.     

Pain therapy of urologic tumors -- prophylaxis and therapy of side effects

Pain is a cardinal symptom in 70 % of cancer patients. Even in developed countries, 30 to 80 % of these patients are inadequately treated. The main cause for this lack of care is not pain refractory to treatment but inadequate or incorrect use of analgesic drugs. A sufficient treatment of pain requires knowledge of the pathomechanism of pain and of the basics of pain management in cancer patients. The choice of analgesic drugs follows the WHO-recommended increase based on need. As long as possible, analgesic drugs should be given orally following a strict schedule and pre-emptively prior to renewed pain. The non-opioids are a heterogeneous group of drugs with different actions and side effects. Maximum doses exist for this group and weak opioids. A change to strong opioids is indicated when weak opioids fail to achieve sufficient pain control despite titration to the maximum dose. No upper limit exists for strong opioids and their use is limited by the side effects. The most frequent side effects are initial emesis and vomiting as well as long-lasting constipation. For this reason, most patients should be prescribed a temporary antiemetic and a laxative on a permanent basis.