Adverse effects of COX-2 inhibitors.
Adverse effects of COX-2 inhibitors.
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DOI：
10.1100/tsw.2005.82
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发表时间：
2005-08-18
影响因子：
--
通讯作者：
Jawad NM
中科院分区：
文献类型：
--
作者：
Sharma JN;Jawad NM
环氧合酶 2 选择性抑制剂 (COXIB) 的主要目的是最大限度地减少使用传统非甾体抗炎药 (NSAID) 时出现的胃肠道不良反应。它们的长期使用受到很大一部分患者出现高血压、水肿和充血性心力衰竭的限制。 NSAIDs 阻断 COX 同工酶 COX-1 和 COX-2 的活性，后者介导花生四烯酸酶促转化为前列腺素 H2 (PGH2) 和其他前列腺素 (PG) 代谢物。众所周知，COX-2 抑制剂的心血管特征可以通过抑制 COX 依赖性 PG 合成来解释。在 COX 介导的花生四烯酸合成 PGH2 后，PGH2 代谢为至少五种生物活性 PG 之一，包括 PGE2、PGI2、PGF2、PGD2 或血栓素 A2 (TXA2)。这些前列腺素具有多效性心血管作用，改变血小板功能和肾功能，并且它们可以充当血管扩张剂或血管收缩剂。尽管COX-1和COX-2在体外将花生四烯酸转化为PGH2方面表现出相似的生化活性，但由于COX-1和COX-2的不同调节、组织分布和前列腺素合酶的可用性，它们在体内产生的最终前列腺素可能不同。 PGs已被证实在缓解高血压、帮助维持髓质血流（MBF）、促进尿盐排泄以及维持血栓形成的正常稳态方面发挥着重要作用，研究人员发现，使用COX-2抑制剂会导致许多严重的并发症，从而改变正常的身体稳态。本研究的目的是简要解释COX-2抑制剂对肾脏和心血管系统的副作用。
Cyclooxygenase-2 selective inhibitors (COXIBs) were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2) and other prostaglandin (PG) metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2). These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF), promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.
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