Effect of deuteration of imipramine on its pharmacokinetic properties in the rat

Imipramine was specifically deuterated in either both aromatic rings or in the N-methyl group, or in both positions, and the pharmacokinetic properties of the products were determined in the rat and compared with those of the non-deuterated analogue. Deuteration of imipramine resulted in a small but significant isotope effect on N-demthylation while aromatic hydroxylation was unaffected. This isotope effect led to a slower rate of systemic clearance, a longer half-life and, when orally administered, enhanced bioavailability. Urinary excretion of didesmethylimipramine-d₄, following oral administration of imipramine-d₇, was significantly lower than the excretion of didesmethylimipramine following administration of unalabelled imipramine, indicating inhibited demethylation. Similarly, the urinary excretion of desmethylimipramine-d₄, didesmethylimipramine-d₄ and 2-hydroxydes-methylimipramine-d₄ were lower than for the corresponding unlabelled or d₇-analogues, indicating the stability of the N-CD₃ group. Deuteration had no effect on the pharmacological properties of imipramine as determined in this study.     

A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium

A single and multiple oral dose administration study of meclofenamate sodium (Meclomen) was conducted in ten healthy male volunteers. An initial 300 mg oral dose on day 1 was followed by a 100 mg every 8 h dosage regimen on study days 4 through 18. Intensive plasma and urine sample collection was carried out over the first three study days, and for 120 h following administration of the final dose on day 18. Plasma and urine specimens were analyzed by a specific HPLC assay for unconjugated meclofenamic acid and metabolites I and II of meclofenamic acid before and after sample incubation with beta-glucuronidase. Meclofenamic acid was rapidly absorbed following oral dose administration. Concentrations of meclofenamic acid existed primarily as unconjugated drug in plasma, with only a small amount present in the conjugated form. Meclofenamic acid was rapidly eliminated, with an elimination half-life of approximately 1.3 h. This resulted in no detectable accumulation upon multiple dose administration. Metabolite I, which is one-fifth as active as meclofenamic acid in in vitro inhibition of cyclooxygenase, was present in unconjugated form at steady state in concentrations approximately 50 per cent of those of meclofenamic acid, as unconjugated drug. The majority of metabolite I in plasma existed as glucuronide conjugate. Metabolite II, which is inactive, was present in very significant concentrations in unconjugated form. Plasma protein binding determinations conducted on meclofenamic acid and metabolite I indicated that the free fraction of metabolite I was 8.7 to 10.9 times higher than that of meclofenamic acid. When the lower activity and lower steady state concentrations, but higher free fraction, are considered, it would appear that metabolite I may contribute significantly to the in vivo inhibition of cyclooxygenase activity seen after administration of meclofenamic acid.     

酒石酸布托啡诺术后镇痛对老年创伤患者芬太尼用量及术后认知功能的影响

目的观察酒石酸布托啡诺术后镇痛对老年创伤患者芬太尼用量及术后认知功能的影响。方法选取112例老年创伤手术患者,随机分为2组,每组56例。对照组用芬太尼术后镇痛,观察组用酒石酸布托啡诺复合芬太尼术后镇痛。用VAS评分法对两组患者术后6、24、48 h的镇痛效果进行评估,同时采用Ramsay镇静评分。两组患者术前1 d(T0)测定认知功能基础值,术后在30 min(T1)、1 h(T2)、2 h(T3)、12 h(T4)、24 h(T5)5个时间点再进行认知功能测定,MMSE满分为30分,术后低于术前2分以上且总分≤24分认定发生术后认知功能障碍。观察两组患者芬太尼的用量及自控给药次数、不良反应发生情况。结果观察组术后6 h、24 h时VAS评分明显低于对照组(P<0.05),术后48 h时,两组患者VAS评分比较差异无统计学意义。观察组、对照组的术后镇静满意率分别为94.64%、80.36%,观察组镇静满意度明显高于对照组(P<0.05)。观察组、对照组在术后分别有2例、9例发生术后认知功能障碍,两组比较差异有统计学意义(P<0.05),且观察组在T1、T2时,4项认知功能测试评分均明显高于对照组(P<0.05)。观察组、对照组的芬太尼用量分别为(564.3±67.5)μg、(867.4±120.2)μg,自控给药次数分别为(6.9±3.1)次、(14.2±4.8)次,观察组均明显低于对照组(P<0.05)。观察组、对照组分别有6例(10.71%)、16例(28.57%)发生不良反应,观察组明显低于对照组(P<0.05)。结论对老年创伤手术患者采用酒石酸托啡诺术后镇痛可减少芬太尼用量,提高镇痛及镇静效果,而且可有效降低术后认知功能的发生及不良反应发生率。     

护理干预对普外术后患者疼痛的影响

目的探讨护理干预对普外术后患者疼痛的影响。方法选择普外科患者180例随机分为两组,对照组护理措施采用常规的术后护理操作。实验组在常规的术后护理操作基础上进行护理干预,对比两组术后疼痛情况。结果两组术后24h及72h疼痛评分、睡眠评分及住院时间比较,差异有统计学意义(P<0.05),实验组术后24h及72h疼痛评分、睡眠评分及住院时间均优于对照组。两组患者术后72h内镇痛药物使用比率分别为34.74%(31/90)和54.44%(49/90),差异有统计学意义(P<0.05)。结论护理干预可有效的减轻普外科患者术后的疼痛,从而促进患者术后康复,同时提高普外科的整体护理质量。     

护理干预对泌尿外科术后疼痛的效果分析

目的观察并分析护理干预对泌尿外科术后疼痛的效果。方法将泌尿科手术患者100例随机均分两组,对照组采用常规护理;观察组在对照组的基础上,应用特殊护理。比较两组干预前后疼痛程度及干预后使用药物止痛情况。结果干预前疼痛程度无明显差异的两组,在干预后,观察组明显优于对照组（χ2=19.54,P=0.00062）,观察组中有32%的患者使用药物止痛,明显低于对照组的76%（χ2=5.94,P=0.015）。结论对泌尿外科术后疼痛实施有效、科学、合理的护理干预措施,能大大地减轻患者术后疼痛,提高患者生存质量。     

大剂量氨溴索治疗术后急性呼吸衰竭疗效观察

目的观察大剂量氨溴索对术后急性呼吸衰竭的治疗作用。方法选择术后急性呼吸衰竭患者40例,随机分为试验组和对照组,每组20例。2组患者在常规机械通气、抗感染及营养支持等综合治疗的基础上,试验组每天给予氨溴索10mg/kg持续静脉微量泵注射,对照组每天给予等容积生理盐水,均连续7d。比较2组治疗前和治疗后2、5、7d的动脉血气及ICU治疗时间。结果 2组患者治疗后PaO2和PaO2/FiO2水平均有不同程度升高（P〈0.05）,且试验组治疗后2、5、7dPaO2和PaO2/FiO2水平均显著高于对照组（P〈0.05）。试验组患者ICU住院时间为（8.2±5.8）d明显短于对照组的（10.4±6.6）d,差异有统计学意义（P〈0.05）。结论大剂量氨溴索能促进术后急性呼吸衰竭患者氧合状况的改善,缩短ICU治疗时间。     

Influence of naloxone on the postoperative analgesic and respiratory effects of buprenorphine

Summary Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fraction 60%; Group BN) in the early postoperative period by means of the On-Demand Analgesia Computer (ODAC). The duration of patient-controlled analgesia (PCA) was 21.0 h (B) or 23.5 h (BN), during which 12.2 (B) and 18.2 (BN) demands per patient were recorded, representing significantly different consumption of buprenorphine 0.80 (B) and 1.07 (BN) µg·kg^–1·h^–1. Retrospective pain scores were significantly better in Group B, and respiratory rate was significantly higher in Group BN. The analgesia was judged superior by 81% (B) and 88% (BN) of the patients compared to conventional postoperative pain treatment. The minimum effective buprenorphine concentration (MEC) varied greatly in both groups with no significant differences between them (median 0.4 ng·ml^–1, range 0.1–8.6 ng·ml^–1); intra-individual variability was lower (67.9% B, and 58.2% BN) than inter-individual variability (107.3% B and 84.0% BN). Accumulation in plasma and acute tolerance did not occur. Thus, admixture of 60% naloxone decreased both the analgesic and respiratory depressant effects of buprenorphine which were generally independent of plasma concentrations. The analgesia achieved with the buprenorphine/naloxone mixture under patient-controlled conditions was comparable to that of other narcotic analgesics. Accordingly, this drug combination may be expected to give clinically adequate analgesia without notable impairement of spontaneous respiration, whilst withdrawal symptoms would probably arise in drug addicts abusing other opiates.     

心理干预对耳鼻喉科患者手术后疼痛的影响

目的 探讨心理干预对减轻耳鼻喉科手术后疼痛程度的影响.方法 选取2011年2月至2014年9月在我院行耳鼻喉部手术的120例患者作为研究对象,采用随机数字表法将所选患者分为研究组和对照组各60例,研究组给予针对性心理护理干预,对照组给予耳鼻喉科常规护理,使用视觉模拟评分法(VAS)评价疼痛程度,比较两组患者术后疼痛分级、疼痛程度、住院时间和护理满意度.结果 研究组术后总疼痛率为11.7％,显著低于对照组的61.7％(P＜0.05);研究组患者术后24、72 h VAS评分均优于对照组(P＜0.05),住院时间短于对照组(P＜0.05);研究组护理满意度为96.7％,高于对照组的83.3％ (P＜0.05).结论 心理护理干预用于耳鼻喉部手术术后疼痛患者效果确切,可有效减轻术后疼痛,促进患者早日康复.     

护理质量控制对外科患者术后疼痛的影响

目的观察护理质量控制对外科患者术后疼痛的影响。方法将2011年7月～2012年7月本院外科收治的外科术后患者120例分成对照组和实验组,对照组患者接受常规护理,实验组患者在常规护理的基础上．从健康教育、基础护理、情绪控制、合理用药等几方面进行护理质量控制,根据疼痛的级别对两组护理效果进行评估。结果实验组诉无痛12例、轻微疼痛35例、中等疼痛12例、剧烈疼痛1例,对照组诉无痛3例、轻微疼痛16例、中等疼痛31例、剧烈疼痛10例,实验组明显优于对照组（P〈0.01）。结论采取护理质量控制能提高患者对术后疼痛的耐受性,进而提高患者的生活质量,促进手术康复。     

Consensus statement on the anticipation and prevention of acute postoperative pain: multidisciplinary RADAR approach

Abstract

Background:

There has been considerable investment in efforts to improve postoperative pain management, including the introduction of acute pain teams. There have also been a number of guidelines published on postoperative pain management and there is widespread agreement on how pain should be practically managed. Despite these advances, there is no apparent improvement in the number of patients experiencing moderately severe or extreme pain after surgery. This highlights significant scope for improvement in acute postoperative pain management.     

The pharmacokinetic properties of yohimbine in the conscious rat

Summary We used high performance liquid chromatography with fluorescence detection to measure the concentration of yohimbine in serum and brain of conscious Sprague-Dawley rats at various times after the i.v. injection of 1 mg/kg of yohimbine. The serum concentration-time profile of yohimbine was biphasic with a rapid distribution phase (t _1/2 = 0.048 h) followed by a very slow elimination phase (t _1/2 = 16.3 h). The clearance of yohimbine was 11 ml/h·kg^–1, and the volume of distribution was 259 ml/ kg. Increasing doses (0.3, 1 and 3 mg/kg, i.v.) of yohimbine produced non-linear increases in serum yohimbine concentration. Yohimbine entered the brain rapidly (5,000 ng/g at 5 min after 1 mg/kg, i.v.) and disappeared from brain with a t _1/2 of 7.7 h. In contrast to serum yohimbine concentration, increasing doses of yohimbine (0.3, 1 and 3 mg/kg) produced linear increases in brain yohimbine concentration, a phenomenon which is consistent with concentration-dependent binding of yohimbine to plasma proteins. The rapid entry of yohimbine into the brain, the slow rate of elimination of yohimbine from serum and brain and the linear relationship of brain yohimbine concentration as a function of dose should be taken into consideration whenever yohimbine is to be used as a probe of ₂-adrenoceptor function in vivo. Send offprint requests to T. Kent Keeton at the above address     

优质护理对剖宫产术及术后疼痛的影响

目的研究优质护理对剖宫产术后疼痛的影响。方法选取在本院进行剖宫产手术的产妇120例,按照产妇及其家属意愿,分为对照组和实验组,其中对照组60例,治疗期间采用一般护理措施;实验组60例,治疗期间采用优质护理措施,比较两组的手术时间、切皮至胎儿娩出时间、术后排气时间及术后疼痛评分。结果实验组的手术时间、切皮至胎儿娩出时间、术后排气时间均短于对照组,差异有统计学意义（P〈0.05）;实验组的术后疼痛评分低于对照组,差异有统计学意义（P〈0.05）。结论采取优质护理措施有助于缩减剖宫产手术时间、降低产妇疼痛感。     

综合性护理干预对鼻内镜术后患者疼痛及满意度的影响

目的：探讨综合性护理干预对鼻内镜术后疼痛及满意度的影响。方法选取2012年10月~2014年8月在本院行鼻内镜术的84例患者作为研究对象,随机分为两组,各42例。对照组采用常规护理,观察组在对照组的基础上给予综合性护理干预,比较两组的术后疼痛程度及满意度。结果观察组的疼痛程度显著低于对照组,差异有统计学意义(P<0.05)。观察组的满意率为85.71%,显著高于对照组的64.29%,差异有统计学意义(P<0.05)。结论综合性护理干预能够有效减轻鼻内镜术后疼痛,提高患者满意度,值得临床推广应用。     

可吸收聚乳酸医用膜预防妇科术后盆腔粘连

目的 探讨可吸收聚乳酸医用膜对妇科术后盆腔粘连的预防作用和机制.方法 将50只雌性新西兰大白兔随机分为两组,均在子宫、输卵管浆膜面人为制造创伤.实验组以可吸收聚乳酸医用膜敷贴创面;对照组不予处理.分别于术后2、4、6、8和12周肉眼观察两组粘连情况,并进行病理学形态的观察.结果 术后第2、4、8和12周实验组粘连等级显著低于对照组(P＜0.05).光镜下实验组炎症反应轻微,成纤维细胞增生不明显;电镜下实验组成纤维细胞较小,细胞器不发达.结论 可吸收聚乳酸医用膜可有效屏蔽炎细胞和成纤维细胞在创面的积聚,抑制成纤维细胞的增生,有效地降低大白兔术后盆、腹腔粘连的发生,减轻粘连程度.     

Effects of medial raphe and raphe magnus lesions on the analgesic activity of morphine and methadone

The effects of lesions of the raphe nuclei on opiate-induced antinociception and brain serotonin (5-HT) levels were investigated. Lesions of the medial raphe nucleus effectively antagonized the analgesic effects of morphine, but not methadone, and lowered brain 5-HT. The decrement in analgesic activity of morphine was reversed by pretreatment with 5-hydroxytryptophan. Lesions of the raphe magnus, a descending 5-HT system, antagonized the analgesic potency of both morphine and methadone. These experiments indicate a differential effect of 5-HT manipulation on opiate-induced analgesia, suggesting a different mechanism of analgesic action for morphine and methadone.     

非成瘾性镇痛剂丙帕他莫与盐酸哌替啶治疗中等手术后疼痛的双盲对比研究

目的 评价非成瘾性镇痛剂丙帕他莫与度冷丁治疗中等手术后疼痛的效果。方法 120名（年龄18-75岁）接受腹部外科，妇科及矫形外科手术后疼痛达到中度或重度的病人参加本研究。研究组用盐酸丙帕他莫（propacetamol HCL)2g溶解稀释静脉滴注，在静脉滴注时肌注生理盐水1.0mL；对照组用甘露醇（用作安慰剂，dummy drug）1.6g溶解稀释静脉滴注，左静脉滴注开始时肌注盐酸哌替啶（dolantin用作对照）50mg(1.0ml）。按随机双盲原则进行治疗，每个病例的用药观察期为6小时。结果与结论 研究期间均未出现明显不良反应。也无皮疹发生。按盲后显示盐酸丙帕他莫和盐酸哌替啶具有相似的安全性和有效性。但盐酸丙帕他莫不具有成瘾性，作为中等手术后镇痛药有广泛的应用前景。     

自制颈椎固定枕在颈椎术后患者康复中的应用效果

目的：探讨自制颈椎固定枕在颈椎术后患者康复中的应用效果。方法选取28例颈椎手术患者,根据术后颈椎固定方法不同分为颈椎固定枕制动组（简称研究组）15例和沙袋固定颈椎两侧制动组（简称对照组）13例。比较两组疼痛情况和并发症。结果研究组无疼痛3例、轻度疼痛6例、中度疼痛5例、重度疼痛1例、无法忍受疼痛0例,对照组无疼痛1例、轻度疼痛3例、中度疼痛6例、重度疼痛2例、无法忍受疼痛1例。两组疼痛等级比较差异有统计学意义（U＝6．098,P＜0．01）。研究组无1例发生压疮,呼吸道并发症少,而对照组有2例发生压疮,3例发生肺不张。结论用颈椎固定枕患者依从性好,从而减轻术后患者疼痛、提高舒适感、减少并发症、临床效果较好。     

Multiple-dose propranolol administration does not influence the single dose pharmacokinetics of quinapril and its active metabolite (quinaprilat)

To evaluate the influence of multiple dose propranolol administration on the single dose pharmacokinetics of quinapril and its active metabolite, quinaprilat, a drug-drug interaction study was performed in ten healthy volunteers. Each subject received a single 20 mg quinapril oral dose on Days 1 and 16 of the study. Oral propranolol doses of 40 mg BID were initiated on Day 3, titrated gradually to 80 mg TID by Day 10, and continued at 80 mg TID through Day 17. Comparable mean quinapril pharmacokinetic parameter values as well as comparable mean quinaprilat pharmacokinetic parameter values determined following quinapril administered alone and following quinapril administered with propranolol, indicate that propranolol does not alter the single dose pharmacokinetics of quinapril or quinaprilat.