特异性环氧酶-2抑制剂--帕瑞昔布

帕瑞昔布是一种新型的特异性环氧化酶-2(COX-2)抑制剂，临床上用于中度或重度术后急性疼痛的治疗，药物不良反应少，耐受良好。     

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。     

帕瑞昔布钠和曲马多在肛周脓肿术中超前镇痛的效果比较

肛周脓肿是肛肠外科常见病和多发病，手术是主要治疗手段，其手术创面通常较大，间隙较深，术后疼痛常较剧烈，因此短期内常需反复依靠镇痛药缓解疼痛。超前镇痛是指在伤害性刺激作用于机体之前采取一定的措施，防治神经中枢敏化，减少或消除伤害引起的疼痛[1]。目前已越来越多地应用于临床，并显示出较好的术后镇痛效果。本研究对帕瑞昔布钠和盐酸曲马多在肛周脓肿术中超前镇痛的临床疗效和不良反应进行比较，为临床实际问题提供解决方案。     

帕瑞昔布钠对肝癌切除术患者肝功能及术后镇痛药物舒芬太尼用量的影响

目的探讨帕瑞昔布钠对肝癌切除术患者肝功能及术后镇痛药物舒芬太尼用量的影响。方法 36例原发性肝癌患者随机分为超前镇痛组(A组)、术后镇痛组(B组)和对照组(C组)各12例。A组于麻醉诱导前30min和12h后、B组于手术结束时和12h后分别静脉注射帕瑞昔布钠40mg;C组在手术结束时和12h后分别静脉注射生理盐水2mL。3组均采用舒芬太尼自控镇痛(patient controlled intravenous analgesia,PCIA),观察术后3组患者肝功能指标变化、舒芬太尼用量、PCIA总次数和PCIA有效次数以及术后2,4,6,12,24hVAS评分和患者镇痛满意度。结果与C组比较,给药12,24h后A,B组舒芬太尼用量减少,PCIA总次数和PCIA有效次数降低(P<0.05),术后2,4,6,12,24h VAS评分降低,术后24h镇痛满意度明显提高(P<0.01);术后即刻和术后1d3组总蛋白、白蛋白降低,谷丙转氨酶、谷草转氨酶升高,术后2～3d总蛋白、白蛋白逐渐升高,谷丙转氨酶、谷草转氨酶逐渐降低,A,B组与C组比较差异均无统计学意义(P>0.05);3组各时间点肌酐、尿素氮、血小板、凝血酶原时间、活化部分凝血活酶时间等指标无明显变化(P>0.05);A组与B组间在舒芬太尼用量、镇痛效果及术中出血量方面比较差异无统计学意义(P>0.05)。结论肝癌切除术患者使用帕瑞昔布钠可减少术后舒芬太尼用量,提高镇痛质量,且对肝功能无明显影响。     

帕瑞昔布钠预防腹腔镜胆囊切除术后咽喉痛疗效观察

目的观察帕瑞昔布钠预防腹腔镜胆囊切除术后咽喉痛的疗效。方法选取2018年6月至2019年1月在重庆市北碚区中医院择期行腹腔镜胆囊切除术的130例全身麻醉患者作为研究对象,性别不限,年龄21~67岁,美国麻醉医师协会分级为Ⅰ、Ⅱ级,随机分为帕瑞昔布钠组(P组)和生理盐水组(S组)。手术结束前10 min P组患者静脉注射帕瑞昔布钠40 mg,S组患者静脉注射等容量生理盐水。记录两组患者术后拔管即刻,术后2、6、12、24 h咽喉痛的视觉模拟评分(VAS评分)。观察并记录拔管期间出现不良反应情况,随访记录患者术后6 h咽喉部并发症发生率、静脉自控镇痛(PCIA)使用情况,以及术后24、48 h 15项恢复质量量表评分。结果P组患者术后拔管即刻,术后2、6、12 h VAS评分均低于S组,PCIA按压次数均少于S组,拔管期间不良反应发生率、术后6 h咽喉部并发症发生率均明显低于S组,术后24、48 h QoR-15项恢复质量量表评分均明显高于S组,差异均有统计学意义(P<0.05)。结论帕瑞昔布钠能有效减轻腹腔镜胆囊切除术后咽喉痛发生情况。     

帕瑞昔布钠与氟比洛芬酯在多节段腰椎融合术后的镇痛效果比较

目的比较两种非甾体类抗炎药物(nonsteroidal anti-inflammatory drugs,NSAIDs)氟比洛芬酯与帕瑞昔布钠在多节段腰椎融合术后的镇痛效果。方法选取2013年6月-2014年2月本院脊柱外科58例多节段腰椎融合术病例,随机分为3组,术后1 h、4 h、10 h、20 h分别给予氟比洛芬酯、帕瑞昔布钠及0.9%氯化钠注射液,术后3 h、6 h、12 h、24 h使用视觉模拟评分(visual analogue scale,VAS)评估疼痛,并记录患者并发症发生情况。结果氟比洛芬酯组术后3 h、6 h、12 h、24h的VAS评分为1.95、2.60、2.00、1.65;帕瑞昔布钠组术后3 h、6 h、12 h、24 h的VAS评分为2.85、2.55、1.85、1.60;0.9%氯化钠注射液组术后3 h、6 h、12 h、24 h的VAS评分为3.00、3.83、2.70、2.44。3组术后3 h的VAS评分间差异有统计学意义;其他时间氟比洛芬酯与帕瑞昔布钠镇痛效果差异无统计学意义,但均优于0.9%氯化钠注射液组。3组并发症的发生情况无统计学差异。结论氟比洛芬酯与帕瑞昔布钠均应用于多节段腰椎融合术后的镇痛,氟比洛芬酯镇痛起效比帕瑞昔布钠更快。     

Prostaglandin-mediated control of rat brain kynurenic acid synthesis – opposite actions by COX-1 and COX-2 isoforms

Summary. Kynurenic acid (KYNA), an endogenous glutamate-receptor antagonist preferentially blocking NMDA-receptors, has analgesic properties and has also been implicated in the pathophysiology of schizophrenia. Recently, the non-steroid anti-inflammatory drug (NSAID) diclofenac was found to increase rat brain KYNA. Here, we analyze whether cyclooxygenase (COX)-1 or COX-2 modulate the levels of rat brain KYNA. The non-selective COX-inhibitor diclofenac (50mg/kg, i.p.) or indomethacin (50mg/kg, i.p.), a non-selective inhibitor with a preferential selectivity for COX-1, produced an elevation in brain KYNA. In contrast, the COX-2 selective inhibitors parecoxib (25mg/kg, i.p.) or meloxicam (5mg/kg, i.p.) decreased brain KYNA. Both elevation and lowering of brain KYNA by indomethacin or parecoxib, respectively, were prevented by the prostaglandin E₁/E₂ agonist misoprostol (1mg/kg, s.c.). It is proposed that increased brain KYNA formation induced by NSAIDs displaying an inhibitory action on COX-1 contribute to their analgesic efficacy as well as to their psychiatric side effects.     

Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects

BACKGROUND: Opioids are associated with numerous adverse effects. It is unclear if reduced postoperative opioid consumption lowers the incidence and severity of opioid-related adverse effects. This analysis -- from a multicenter, randomized, double-blind trial -- tested if the reduction of opioid consumption among patients who received intravenous preoperative parecoxib 40 mg, followed by oral valdecoxib 40 mg qd postoperatively, in Days 1-4 after outpatient laparoscopic cholecystectomy surgery, reduced opioid-related symptoms. METHODS: Patients received intravenous fentanyl for pain before discharge, and oral acetaminophen 500 mg hydrocodone 5 mg q 4-6 h prn postdischarge for up to 7 days postsurgery. Patients also received intravenous parecoxib 40 mg administered 30-45 min preoperatively, and valdecoxib 40 mg qd up to Day 4 and prn Days 5-7 postsurgery, or placebo. Patients completed an opioid-related Symptoms Distress Scale (SDS) questionnaire every 24 h for 7 days. Opioid use was converted to morphine-equivalent doses (MEDs). Clinically meaningful events (CMEs) for 12 opioid-related symptoms were assessed by three ordinal measures: frequency, severity, and bothersomeness. Reduction of CMEs on Day 1 and number of patient-days with CMEs on Days 1-4 were examined. RESULTS: Cumulative MEDs on Day 0, Day 1, and Days 1-4 were significantly lower in the parecoxib/valdecoxib group compared with the placebo group (P < 0.001). At the end of Day 1, parecoxib/valdecoxib-treated patients had significantly lower SDS scores (P < 0.02), a significantly reduced incidence of CMEs (P < 0.05), and significantly fewer patient-days with CMEs in Days 1-4 than placebo patients (P < 0.05). Patients in the parecoxib/valdecoxib group were less likely to have CMEs for multiple symptoms than those in the placebo group (P < 0.001). CONCLUSIONS: Treatment with parecoxib and valdecoxib significantly reduced the cumulative MED requirements, the incidence of opioid-related adverse effects, and patient-days with CMEs.     

Comparison of the effects of parecoxib and diclofenac in preemptive analgesia: A prospective, randomized, assessor-blind, single-dose, parallel-group study in patients undergoing elective general surgery

Background:

Preoperative administration of analgesics may prevent or reducehyperalgesia, inhibit inflammation, and reduce pain by reducing the synthesis of prostaglandins in response to tissue damage caused by surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potent, widely used class of analgesic agents; however, they may not be as effective as selective cyclooxygenase (COX)-2 inhibitors.

Objective:

The aim of this study was to compare the efficacy and tolerabilityof the COX-2 inhibitor parecoxib sodium and the NSAID diclofenac sodium as preemptive analgesics in patients undergoing elective general surgery.

Methods:

This was a prospective, randomized, assessor-blind, single-dose,parallel-group, comparative trial. Patients aged 18 to 65 years undergoing elective general surgery were enrolled. A single IM injection of parecoxib 40 mg or diclofenac 75 mg was administered 30 to 45 minutes before the induction of anesthesia. Surgery was performed as per standard protocol. The primary measures of efficacy were pain intensity score (measured on a visual analog scale [VAS]), pain relief score, duration of analgesia, and platelet aggregation response to adenosine diphosphate. Tolerability assessment included monitoring of treatment-emergent adverse events (AEs), physical examination, laboratory analysis, electrocardiography, and chest radiography.

Results:

Eighty patients (56 men, 24 women; mean [SD] age, 45.96 [12.83] years) were enrolled in the study (40 patients per treatment group). All patients completed the trial. No pain was reported by any patient in the parecoxib group up to 12 hours; in the diclofenac group, no pain was reported up to 6 hours. At 12 hours, the mean (SD) VAS score was 2.33 (1.39) (moderate pain) in the diclofenac group and 0 (no pain) in the parecoxib group (P < 0.05). At 12 hours, total pain relief was reported by all 40 patients (100.0%) in the parecoxib group but by none (0.0%) in the diclofenac group, and 2 patients in the diclofenac group (5.0%) reported good pain relief (between-group difference for total + good pain relief, P < 0.05). Mean (SD) duration of analgesia was significantly longer in the parecoxib group than in the diclofenac group (19.48 [5.61] hours vs 8.32 [4.11 ] hours; P < 0.05). Platelet aggregation was significantly inhibited in the diclofenac group (change from baseline, 64.0%) but not in the parecoxib group (change from baseline, 12.0%) (P < 0.05). Both regimens were well tolerated, and no AEs were reported.

Conclusions:

In this study of patients undergoing elective general surgery,patients treated with the COX-2 specific inhibitor parecoxib experienced no pain at 12 hours, and the treatment was well tolerated. The results of this study suggest that good postoperative analgesia and minimal interference with platelet function may make parecoxib an alternative to the nonselective NSAID diclofenac in providing preemptive analgesia in patients undergoing general surgery.