术前口服依他昔布对妇科手术后病人自控镇痛的影响

目的:观察妇科开腹手术患者术前给予依他昔布120mg对术后自控镇痛(PCA)吗啡用量的影响及其副作用。方法:随机选取全麻下接受妇科开腹全子宫(双附件)切除患者40例,术前分别给予安慰剂或依他昔布120mg口服。在手术后观察24h患者PCA吗啡用量,同时记录患者的疼痛评分和满意度评分,并观察不良反应。结果:术后PCA吗啡24h消耗量在依他昔布组为9.4±7.6mg,显著低于安慰剂组15.7±8.9mg。两组患者24h内对PCA的按压次数依他昔布组也低于安慰剂组(P<0.05)。其中术后3、6、8和12hPCA吗啡消耗量在两组间无显著差异。两组患者术后24h疼痛评分和对镇痛治疗的满意度也无差异。两组患者不良反应的发生率亦无差别。结论:在妇科开腹手术患者术前应用依他昔布120mg可使患者术后PCA吗啡消耗量降低,且在术后12h后下降明显。未发现与依他昔布应用相关的副作用。     

环氧合酶及其抑制剂与肿瘤防治的研究进展

环氧合酶（COX）及其抑制剂是近年肿瘤防治研究的热点之一。目前认为，COX通过多种途径参与肿瘤的发生发展，COX抑制对结肠癌等多种肿瘤有预防作用，也可能增强肿瘤的放化疗疗效，但安全性及有效性均不理想，且可能存在非COX途径。因此，COX作为肿瘤防治靶点的临床价值还有待进一步评价。     

Lumiracoxib: the evidence of its clinical impact on the treatment of osteoarthritis

INTRODUCTION: The symptoms of osteoarthritis (OA) include joint pain, stiffness, and a reduced ability to perform normal daily activities, which result in decreased quality of life. There is currently no known cure or means of preventing the progression of joint damage due to OA. Therefore, treatment focuses on the control of symptoms, including the use of various agents [including nonselective and selective nonsteroidal antiinflammatory drugs (NSAIDs)] to provide pain relief and reduce inflammation. Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of OA. AIMS: To review the evidence for the treatment of OA with lumiracoxib. EVIDENCE REVIEW: There is evidence that lumiracoxib reduces the pain and stiffness associated with OA, and is as effective as nonselective NSAIDs, and the COX-2 inhibitor celecoxib. There is some evidence that lumiracoxib treatment results in a lower incidence of upper gastrointestinal (GI) ulcer complications compared with nonselective NSAIDs. However, evidence suggests that there is no GI benefit in patients receiving concomitant aspirin medication. With the exception of GI ulcers, the evidence indicates that lumiracoxib has a tolerability profile similar to nonselective NSAIDs: low risk of cardiovascular (CV) events and a low incidence of edema. Changes in liver function occur in some patients, largely at doses >100 mg. The cost effectiveness of lumiracoxib compared with nonselective NSAIDs remains to be determined. CLINICAL VALUE: Lumiracoxib is an alternative treatment option for OA which provides effective pain relief without the GI complications associated with nonselective NSAIDs, and with a low risk of CV events. Lumiracoxib is contraindicated in patients with current, previous, or at risk of, hepatic impairment.     

A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis

SUMMARY

Objective: To evaluate and compare the efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis of the knee or hip.

Methods: In this 6-week double-blind, active comparator controlled, parallel-group study eligible osteoarthritis patients were randomised to receive either etoricoxib 60?mg once daily (n?=?256) or diclofenac 50?mg three times daily (n?=?260). The primary study endpoint was the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. Other endpoints included were the WOMAC stiffness and physical function subscales, and the Patient's Global Assessment of Response to Therapy (PGART) questionnaire. Early efficacy was evaluated using WOMAC first question (pain walking on a flat surface) and PGART 4?h after the morning dose of each drug on

days 1 and 2. Rescue medication (paracetamol) used was also recorded. The study was designed to show comparable efficacy between etoricoxib 60?mg once daily and diclofenac 50?mg three times daily with respect to the primary endpoint and was conducted outside the United States at 67 centres in 29 countries.

Results: Etoricoxib (60?mg once daily) was comparable in efficacy to diclofenac (150?mg daily) on all the above parameters. The one exception was in the assessment of early efficacy where etoricoxib demonstrated significantly greater benefit within 4?h of taking the first dose on the first day of therapy (p?=?0.007) as evaluated by the percentage of patients with good or excellent (PGART) responses. The treatment effects of both drugs were similar by the time day 2 was reached

and were sustained throughout the 6 weeks of therapy. Both treatments were generally well tolerated.

Conclusions: Etoricoxib is clinically effective in the therapy of osteoarthritis providing a magnitude of effect comparable to that of the maximum recommended daily dose of diclofenac. The onset of clinical benefit with etoricoxib on day one is more rapid than that of diclofenac. Both drugs were generally well tolerated.     

Amlodipine and celecoxib for treatment of hypertension and osteoarthritis pain

ABSTRACT

Introduction: Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved.

Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters.

Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules.     

Characterization of eltenac and novel COX-2 selective thiopheneacetic acid analogues in vitro and in vivo

We assessed the effect of novel selective thiopheneacetic acids on cyclooxygenase isoenzymes in vitro and in vivo. Thiopheneacetic acid Eltenac and derivatives were investigated in this study. In human whole blood experiments these derivatives were potent inhibitors of COX-2 (IC(50)=0.02-0.4 microM) with less pronounced effect on COX-1 (IC(50)=0.15-5.6 microM). With COX-1/COX-2 ratios between 7.5- and 16-fold they are in the range of Celecoxib (13-fold). The parent drug Eltenac demonstrated no selectivity for COX-2. In a rat paw edema model, these compounds showed reduction of edema volume in the range of 36-45% at 10 mg/kg (Eltenac 52%, Diclofenac 51%). However, the compounds were superior to Diclofenac and Eltenac with respect to their ulcerogenic and gastrointestinal properties. Introduction of a nitrate-ester moiety to either Eltenac or a derivative did neither improve selectivity or potency in vitro, nor ulcerogenicity in vivo. Molecular modeling of selective thiopheneacetic acid derivatives to the active site of human COX-2 suggested similar binding properties as Lumiracoxib and Diclofenac. In summary, modification of Eltenac generates moderately selective COX-2 drugs in the range of Celecoxib with respect to potency and selectivity. The drugs showed potent anti-inflammatory properties and significant improvement of animal survival in a sub-chronical experimental set up. Thiopheneacetic derivatives are characterized by low pK(a) values, short microsomal half-lives and binding mode to COX-2 similar to Diclofenac and Lumiracoxib. These properties may also have an impact on the transient inhibition of COX-2-dependent prostacyclin, thereby being less associated with vascular complications.     

The safety of rofecoxib

Like all COX-2 inhibitors, rofecoxib has been developed based on the hypothesis that at comparable therapeutic efficacy, it would have a better safety and tolerability profile than conventional NSAIDs. The Vioxx GI Outcomes Research trial has demonstrated that rofecoxib is indeed safer for the gastrointestinal tract than NSAIDs. However, this study has also raised questions regarding the cardiovascular safety of rofecoxib. Thereafter, several epidemiological and case-control studies have reinforced the association between rofecoxib and a higher risk of cardiovascular events. However, at this time, no prospective controlled study is available to conclude definitively on this issue. Several pathogenic mechanisms are evoked to explain why rofecoxib increases the cardiovascular risk. These include the development of a prothrombotic state, a sodium retention and an increase in systemic blood pressure. Recently, new evidence have become available indicating that rofecoxib indeed increases the number of thrombo-embolic events. These data have resulted in the complete withdrawal of rofecoxib from the market. Was it scientifically reasonable to withdraw rofecoxib rather than to adapt its label? Is the safety profile of rofecoxib really much worse than that of aspirin or other traditional NSAIDs? The main consequence of this withdrawal is a considerable threat on the entire class of selective COX-2 inhibitors without a clear evalua-tion of the balance between the risks and benefits of these com-pounds.     

Synthesis and COX-2 inhibitory properties of N-phenyl- and N-benzyl-substituted amides of 2-(4-methylsulfonylphenyl)cyclopent-1-ene-1-carboxylic acid and of their pyrazole, thiophene and isoxazole analogs

Some N-phenyl- (7a-10a) and N-benzyl-substituted (7b-10b) amido analogs of cyclooxygenase (COX-2) selective tricyclic non-steroidal anti-inflammatory drugs have been synthesized with the aim to obtain information on the structural requirements for the COX-inhibitory activity. Compounds 7-10 were tested in vitro for their inhibitory properties only towards COX-2 enzyme by measuring prostaglandin E2 (PGE2) production on activated J774.2 macrophages. Some of the new compounds (7a, 8a, 9a and 9b) showed a modest activity, with percentage inhibition values near 30% at a concentration of 10 microM. These data have been tentatively explained by a conformational study which indicates that at least the N-phenyl-substituted amides 7a-9a present steric hindrances which may prevent a good interaction with COX-2 active site.     

Comment and reply on: Atorvastatin: safety and tolerability

In a very short time, COX-2 enzyme inhibitors have gone from the darlings to the pariahs of the pharmaceutical industry. These drugs were developed based on the hypothesis whereby selective inhibition of the COX enzyme would lead to reduction in pain and inflammation without associated gastrointestinal and bleeding risks. However, in September 2004, rofecoxib was voluntarily removed from the market for increased cardiovascular risk and in April 2005, valdecoxib was also withdrawn, at least in part, due to excess cardiovascular risk. Celecoxib was the first COX-2 inhibitor introduced and the only remaining one on the US market. There is consequently a justified concern that cardiovascular toxicity is a class effect of all COX-2 inhibitors. This article systematically reviews the evidence surrounding COX-2 inhibitors and cardiovascular risk. Although the evidence suggests a fairly consistent cardiovascular risk with rofecoxib, the evidence for cardiovascular risk with celecoxib is more equivocal. Although isolated studies have suggested some cardiovascular risk for celecoxib, the totality of the evidence suggests that any risk is likely to be small and comparable to traditional NSAIDs. The cardiovascular risks of COX-2 inhibitors appear heterogeneous, influenced not only by the drug class, but also individual drug, dosage and patient characteristics. Specific modifying factors of the cardiovascular risk of COX-2 inhibitors including dose, concomitant drugs, individual cardiac and genetic risk profiles, will require further study.     

Cyclo-oxygenase isozymes in mucosal ulcerogenic and functional responses following barrier disruption in rat stomachs

1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses.
2. Rat stomachs mounted in ex vivo chambers were perfused with 50 mM HCl and transmucosal potential difference (p.d.), mucosal blood flow (GMBF), luminal acid loss and luminal levels of prostaglandin E₂ (PGE₂) were measured before, during and after exposure to 20 mM TC.
3. Mucosal application of TC in control rats caused a reduction in p.d., followed by an increase of luminal acid loss and GMBF, and produced only minimal damage in the mucosa 2 h later. Pretreatment with indomethacin (10 mg kg⁻¹, s.c.), a nonselective COX-1 and COX-2 inhibitor, attenuated the gastric hyperaemic response caused by TC without affecting p.d. and acid loss, resulting in haemorrhagic lesions in the mucosa. In contrast, selective COX-2 inhibitors, such as NS-398 and nimesulide (10 mg kg⁻¹, s.c.), had no effect on any of the responses induced by TC and did not cause gross damage in the mucosa.
4. Luminal PGE₂ levels were markedly increased during and after exposure to TC and this response was significantly inhibited by indomethacin but not by either NS-398 or nimesulide. The expression of COX-1-mRNA was consistently detected in the gastric mucosa before and after TC treatment, while a faint expression of COX-2-mRNA was detected only 2 h after TC treatment.
5. Both NS-398 and nimesulide significantly suppressed carrageenan-induced rat paw oedema, similar to indomethacin.
6. These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC-induced barrier disruption, and suggest that COX-1 but not COX-2 is a key enzyme in maintaining ‘housekeeping'' functions in the gastric mucosa under both normal and adverse conditions.

     

Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor

1. DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone) was identified as a novel orally active and highly selective cyclo-oxygenase-2 (COX-2) inhibitor.
2. In CHO cells stably transfected with human COX isozymes, DFU inhibited the arachidonic acid-dependent production of prostaglandin E₂ (PGE₂) with at least a 1,000 fold selectivity for COX-2 (IC₅₀=41±14 nM) over COX-1 (IC₅₀>50 μM). Indomethacin was a potent inhibitor of both COX-1 (IC₅₀=18±3 nM) and COX-2 (IC₅₀=26±6 nM) under the same assay conditions. The large increase in selectivity of DFU over indomethacin was also observed in COX-1 mediated production of thromboxane B₂ (TXB₂) by Ca²⁺ ionophore-challenged human platelets (IC₅₀>50 μM and 4.1±1.7 nM, respectively).
3. DFU caused a time-dependent inhibition of purified recombinant human COX-2 with a K_i value of 140±68 μM for the initial reversible binding to enzyme and a k₂ value of 0.11±0.06 s⁻¹ for the first order rate constant for formation of a tightly bound enzyme-inhibitor complex. Comparable values of 62±26 μM and 0.06±0.01 s⁻¹, respectively, were obtained for indomethacin. The enzyme-inhibitor complex was found to have a 1 : 1 stoichiometry and to dissociate only very slowly (t_1/2=1–3 h) with recovery of intact inhibitor and active enzyme. The time-dependent inhibition by DFU was decreased by co-incubation with arachidonic acid under non-turnover conditions, consistent with reversible competitive inhibition at the COX active site.
4. Inhibition of purified recombinant human COX-1 by DFU was very weak and observed only at low concentrations of substrate (IC₅₀=63±5 μM at 0.1 μM arachidonic acid). In contrast to COX-2, inhibition was time-independent and rapidly reversible. These data are consistent with a reversible competitive inhibition of COX-1.
5. DFU inhibited lipopolysaccharide (LPS)-induced PGE₂ production (COX-2) in a human whole blood assay with a potency (IC₅₀=0.28±0.04 μM) similar to indomethacin (IC₅₀=0.68±0.17 μM). In contrast, DFU was at least 500 times less potent (IC₅₀>97 μM) than indomethacin at inhibiting coagulation-induced TXB₂ production (COX-1) (IC₅₀=0.19±0.02 μM).
6. In a sensitive assay with U937 cell microsomes at a low arachidonic acid concentration (0.1 μM), DFU inhibited COX-1 with an IC₅₀ value of 13±2 μM as compared to 20±1 nM for indomethacin. CGP 28238, etodolac and SC-58125 were about 10 times more potent inhibitors of COX-1 than DFU. The order of potency of various inhibitors was diclofenac>indomethacin∼naproxen>nimesulide∼ meloxicam∼piroxicam>NS-398∼SC-57666>SC-58125>CGP 28238∼etodolac>L-745,337>DFU.
7. DFU inhibited dose-dependently both the carrageenan-induced rat paw oedema (ED₅₀ of 1.1 mg kg⁻¹ vs 2.0 mg kg⁻¹ for indomethacin) and hyperalgesia (ED₅₀ of 0.95 mg kg⁻¹ vs 1.5 mg kg⁻¹ for indomethacin). The compound was also effective at reversing LPS-induced pyrexia in rats (ED₅₀=0.76 mg kg⁻¹ vs 1.1 mg kg⁻¹ for indomethacin).
8. In a sensitive model in which ⁵¹Cr faecal excretion was used to assess the integrity of the gastrointestinal tract in rats, no significant effect was detected after oral administration of DFU (100 mg kg⁻¹, b.i.d.) for 5 days, whereas chromium leakage was observed with lower doses of diclofenac (3 mg kg⁻¹), meloxicam (3 mg kg⁻¹) or etodolac (10–30 mg kg⁻¹). A 5 day administration of DFU in squirrel monkeys (100 mg kg⁻¹) did not affect chromium leakage in contrast to diclofenac (1 mg kg⁻¹) or naproxen (5 mg kg⁻¹).
9. The results indicate that COX-1 inhibitory effects can be detected for all selective COX-2 inhibitors tested by use of a sensitive assay at low substrate concentration. The novel inhibitor DFU shows the lowest inhibitory potency against COX-1, a consistent high selectivity of inhibition of COX-2 over COX-1 (>300 fold) with enzyme, whole cell and whole blood assays, with no detectable loss of integrity of the gastrointestinal tract at doses >200 fold higher than efficacious doses in models of inflammation, pyresis and hyperalgesia. These results provide further evidence that prostanoids derived from COX-1 activity are not important in acute inflammatory responses and that a high therapeutic index of anti-inflammatory effect to gastropathy can be achieved with a selective COX-2 inhibitor.

     

从复旦大学附属华山医院用药情况浅谈非甾体类抗炎药使用特点和趋势

目的:从复旦大学附属华山医院门诊用药情况分析各类非甾体类抗炎药(NSAIDs)的用药特点和趋势。方法:根据2000~2004年华山医院门诊药房所用的NSAIDs的品种、数量和金额,回顾性地分析比较DDDs、日均费用(DDDc)和金额。结果:5年中NSAIDs年处方总金额在80~120万元间波动上升,DDDc逐年上升。DDDs排位较前的为美洛昔康、双氯芬酸钠缓释制剂和布洛芬缓释制剂。2000年后品种数增加,新一代NSAIDs环氧化酶-2选择性抑制剂被引入临床使用。结论:NSAIDs长期使用都存在一定风险,传统NSAIDs的改良剂型以及安全性更可靠的NSAIDs是研究方向。     

选择性COX-2抑制剂的用药风险与新功用

综述近年来国内外有关选择性COX-2抑制剂的潜在用药风险及新功用的报道，为探讨该类药物的发展方向提供参考。选择性COX-2抑制剂是一类新型非甾体抗炎药，由于其胃肠毒性低而倍受关注，但潜在的心血管风险限制了其临床上的应用，此类药物的去留引起了极大争议。     

An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors

Introduction: Oral antidiabetic medications are important in many type 2 diabetes care plans

Areas covered: The article summarizes the cardiovascular and renal safety data for DPP-4 inhibitors and SGLT-2 inhibitors and specific safety data particular to each class.

Expert opinion: DPP-4 and SGLT-2 inhibitors provide unique anti-hyperglycemic mechanisms. The cardiovascular safety profiles of DPP-4 inhibitors are promising, but do not show the strong CV risk reduction of empagliflozin and canagliflozin. The heart failure signal associated with DPP-4 inhibitor use is unclear with differing agents, demonstrating increased risk or maybe even protective effects. The risk reduction in cardiovascular disease associated with SGLT-2 inhibitors has translated to recommendations to consider these therapies early in the treatment pathway. Both classes have potential safety concerns that necessitate appropriate patient selection and thorough education on potential side-effects. DPP-4 inhibitors are considered to have neutral or in some studies beneficial renoprotective effects. SGLT-2 inhibitor safety effects on the kidney are more complex. There are reports of acute kidney injury occurring soon after initiating SGLT-2 inhibitor therapy. However, there are large recent studies that have demonstrated the beneficial effect of SGLT-2 inhibitors in slowing the progression of established chronic kidney disease.     

腰痛宁胶囊联合依托考昔改善老年腰椎骨性关节炎痛感、炎症状态的临床效果

目的 观察腰痛宁胶囊联合依托考昔改善老年腰椎骨性关节炎痛感、炎症状态的临床效果。方法 将2016年1月至2018年6月就诊于战略支援部队特勤疗养中心的120例老年腰椎骨性关节炎患者,随机分为对照组和观察组各60例。对照组患者给予依托考昔治疗,观察组患者则在对照组基础上加服腰痛宁胶囊,两组患者均连续治疗2周。观察两组患者脊柱疼痛、生活质量评分变化;监测血清中炎症因子肿瘤坏死因子-α（TNF-α）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、环氧合酶（COX-2）、骨形态发生蛋白-2（BMP-2）水平,对比两组治疗的有效率,评价用药的安全性。结果 对照组与观察组患者的有效率分别为78.33%和91.67%,观察组显著优于对照组 (P<0.05);治疗后,观察组患者的疼痛视觉模拟评分（VAS）较对照组明显降低（P<0.05）,生活质量SF-36评分则明显升高（P<0.05）,血清中TNF-α、GM-CSF、COX-2水平均较对照组明显降低（P<0.05）,BMP-2水平则明显升高（P<0.05）。结论 腰痛宁胶囊联合依托考昔治疗老年腰椎骨性关节炎疗效确切,能显著减轻腰痛感,改善生活质量,抑制炎性反应,具有较高的用药安全性,值得临床深入探究。     

A clinical audit of the prescribing of celecoxib and rofecoxib in Australian rural general practice

AIMS: The new cyclooxygenase-2 (COX-2) selective inhibitors, celecoxib (Celebrex) and rofecoxib (Vioxx), have been widely prescribed since their launch. No reviews currently appear in the literature of prescribing patterns in Australia. This paper describes a self-audit of the clinical use of selective COX-2 inhibitor therapy undertaken with rural general practitioners (GPs) in Australia. METHODS: A structured audit form was developed and distributed to interested GPs. The form was self-administered and focused on issues about COX-2 inhibitors and the types of patients who were receiving them, e.g. indications, patient demographics, risk factors and drug interactions. RESULTS: A total of 627 patients were recruited (569 celecoxib and 58 rofecoxib). A range of doses was prescribed. Osteoarthritis was the most common indication (68.1%). Risk factors known for the nonselective nonsteroidal anti-inflammatory drugs were identified in 65.1% of patients, with the most common being advanced age, hypertension and previous peptic ulcer disease. Potential drug interactions were common. A variety of reasons for initiation of therapy was identified; these included perceived increased efficacy, safety and failure of other treatment. CONCLUSIONS: These results show that COX-2 inhibitors are being prescribed for patients with multiple risk factors that may place the patient at increased risk of adverse drug reactions to a COX-2 inhibitor. The perception of improved safety and efficacy was common and is of concern. Limitations of the study include the reliance on self-reporting.     

Selectivity of NSAIDs for COX-2 and cardiovascular outcome

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) with increased selectivity for the cyclooxygenase-2 (COX-2) isoform reduce gastrotoxicity but may increase adverse cardiovascular events. METHODS: We searched the literature for studies that reported the odds ratio (OR) for such events following exposure to NSAIDs. RESULTS: For studies comparing NSAID use with no use, increased COX-2 selectivity was significantly related to cardiovascular risk (log OR) amongst observational studies (R = -0.34, P < 0.001) and randomized controlled trials (RCTs) (R = -0.56, P < 0.001). For studies comparing NSAIDs, difference in selectivity was related to risk for observational studies (R = -0.28, P = 0.005) but not for RCTs (R = -0.23, P = 0.15). CONCLUSIONS: Although increased COX-2 selectivity may reduce gastrotoxicity, this may be at the cost of increasing cardiovascular risk.     

第二代环氧酶-2特异性抑制剂的研究进展

为降低NSAIDs类药物的典型胃肠道不良反应，人们开发了选择性更高的第二代环氧酶-2(COX-2)特异性抑制剂。已开发的代表性化合物有戊地昔布、帕瑞昔布、依地昔布和氯美昔布等。临床试验证实，这些药物具有可靠的抗炎和止痛作用，其中帕瑞昔布作为第一个注射用NSAIDs类药物，可用于治疗手术后疼痛。本文综述该领域的研究进展。