New insights into the use of currently available non-steroidal anti-inflammatory drugs.
New insights into the use of currently available non-steroidal anti-inflammatory drugs.
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DOI：
10.2147/jpr.s75160
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发表时间：
2015
影响因子：
2.7
通讯作者：
Patrignani P
中科院分区：
文献类型：
--
作者：
Brune K;Patrignani P
100多年前发现了通过抑制环氧合酶（考克斯）同工酶发挥作用的非甾体抗炎药（NSAID）。它们仍然是急性和慢性疼痛药理学管理的关键组成部分。考克斯-1和考克斯-2同工酶具有不同的生物学功能;镇痛活性主要（但不是唯一地）与考克斯-2的抑制相关，而不同的副作用由考克斯-1和考克斯-2的抑制引起。所有可用的NSAID，包括对乙酰氨基酚和阿司匹林，都与潜在的副作用有关，特别是胃肠道和心血管作用，与它们对考克斯-1和考克斯-2的相对选择性有关。由于所有NSAID都通过抑制考克斯同工酶发挥其治疗活性，因此需要策略来降低与NSAID相关的风险，同时实现充分的疼痛缓解。基于药代动力学和药效学特性（例如，抑制剂量、吸收、血浆与组织分布和消除），更好地了解治疗剂量下NSAID的抑制活性和考克斯-1/考克斯-2选择性，以及对药物耐受性和安全性的影响，可以指导选择适当的NSAID用于疼痛管理。例如，许多对考克斯-2相对于考克斯-1具有中等至高选择性的NSAID可以以使功效最大化（考克斯-2的~80%抑制）同时使考克斯-1抑制和相关副作用如胃肠道毒性最小化的剂量施用。可另外给药具有良好组织分布和短血浆半衰期的酸性NSAID以提供接近恒定的镇痛，同时使血浆浓度最小化以允许在血管壁和其他器官中恢复COX介导的前列腺素产生。在选择适当的NSAID时，应考虑每个患者的临床背景，包括胃肠道和心血管风险因素。新的方法正在出现，以帮助临床医生选择适当的NSAID及其剂量/时间表，如生物标志物，可以预测个体患者对NSAID治疗的反应。
Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively) associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination), and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (~80% inhibition of COX-2) while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while minimizing plasma concentrations to permit recovery of COX-mediated prostaglandin production in the vascular wall and other organs. Each patient’s clinical background, including gastrointestinal and cardiovascular risk factors, should be taken into account when selecting appropriate NSAIDs. New methods are emerging to assist clinicians in the selection of appropriate NSAIDs and their doses/schedules, such as biomarkers that may predict the response to NSAID treatment in individual patients.