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1.
Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma 总被引:6,自引:1,他引:6
Bradykinin, a nonapeptide cleavage product of high molecular weight kininogen, is a potent bronchoconstrictor agonist in asthma; however, its mechanism of action is not known. Since bradykinin has been shown to stimulate mediator release from mast cells and augment the release of prostanoids, we have examined the effect of a selective histamine H1 receptor antagonist, terfenadine and a potent cyclooxygenase inhibitor, flurbiprofen on bronchoconstriction provoked by inhaled bradykinin in asthma. As a bronchial provocation procedure bradykinin challenge was repeatable to within 1 doubling dilution. In nine atopic asthmatic subjects, terfenadine 180 mg, when compared to placebo, increased the geometric mean provocation concentration of inhaled agonist required to reduce FEV1 by 20% of baseline (PC20) from 0.7 to greater than 22.9 mg/ml for histamine (P less than 0.01) and 0.3 to 0.5 mg/ml for bradykinin (P less than 0.01). In a further nine atopic asthmatics, flurbiprofen 150 mg when compared to placebo produced a small but significant protection of the airways against bradykinin, geometric mean PC20 increasing from 0.40 to 0.79 mg/ml (P less than 0.05). We conclude that bradykinin is a potent bronchoconstrictor agonist in asthma, being approximately 9.5 times more potent than histamine in molar terms. Pharmacological intervention with terfenadine and flurbiprofen led to a significant protection of the airways against the constrictor effect of bradykinin but the effect in each case was small. Thus, while histamine and prostanoids may contribute as mediators of bradykinin-induced bronchoconstriction, they are unlikely to account for the majority of the response. 相似文献
2.
John A. Wolfe Bruce E. Stuck Steven T. Schuschereba Leslie P. Fox 《Documenta ophthalmologica. Advances in ophthalmology》1985,59(3):277-299
A moderately severe thermal injury of the central cornea of 48 Dutch-belted rabbit eyes was produced with a carbon (CO2) laser. The lesions were photographed with a slit lamp (SL) camera immediately following the injury and at 1, 2, 4, 7, 14, 21, 30 and 60 days after the exposure. Lesion size, opaqueness, and depth were graded clinically by SL biomicroscopy at the same intervals. No significant differences were found (p 0.05) between groups of eyes treated with flurbiprofen (0.03%), prednisolone acetate (1%), and vehicle control four-times-a-day for three weeks following injury. Additionally, eyes were studied histopathologically at 3 and 60 days following injury by light and transmission electron microscopy, and clinically at 30 and 60 days by endothelial specular microscopy. Important clinical and histopathological findings included coagulative necrosis of the corneal epithelium, epithelial sloughing, fusion of stromal collagen, stromal edema and inflammatory cell infiltration, stromal scar formation, corneal thinning, endothelial hyperplasia and metaplasia, fibrinous anterior chamber reaction with hypopyon, and retrocorneal fibrous membrane formation. 相似文献
3.
Tang-Liu Diane D. -S. Liu Sandra 《Journal of pharmacokinetics and pharmacodynamics》1987,15(4):387-397
The differences in flurbiprofen disposition in the aqueous humor and the plasma were examined after systemic doses. Steady state plasma concentrations of flurbiprofen (20–60 g/mL) were achieved via intravenous infusion to albino rabbits. Flurbiprofen demonstrated linear systemic kinetics throughout the dosing range, with constant body clearance and unbound fraction in plasma. At steady state, aqueous humor drug concentrations depended on the corresponding plasma drug concentration. Two clearance terms—CLso, the systemic clearance to ocular tissues, and CLos, the ocular clearance to systemic circulation—were used. After systemic doses, the drug concentration in the aqueous humor was related to that in the plasma as well as to the ratio of these two clearances. Flurbiprofen was extensively bound to plasma proteins and showed limited ocular distribution; its CLso to CLso tratio was very small. Thus, the concentration of flurbiprofen in the aqueous humor after systemic doses was lower than that obtained after ophthalmic doses. A plasmapheresis technique was utilized to lower the plasma protein concentrations to 60% of normal levels. As a consequence, flurbiprofen demonstrated reduced aqueous humor protein concentrations, increased unbound fractions in the plasma and the aqueous humor, elevated aqueous humor drug concentrations, and elevated total body clearance. The unbound body clearance stayed unchanged. Our study indicated that a drug should present a significant CLso/CLos ratio in order to achieve therapeutic concentrations in the eye via systemic doses. The drug-protein binding kinetics can be different between the plasma and the aqueous humor circulations. Because the ocular compariment is very small compared to the overall systemic distribution of flurbiprofen, it has little effect on the steady state systemic concentrations. 相似文献
4.
目的:研究川芎挥发油的体外促透作用及机制。方法:超临界萃取川芎挥发油,气相色谱-质谱法分析成分,以大鼠皮肤为渗透屏障,氟比洛济为模型药物,Franz扩散池法考察透皮特性,HPLC法测定大鼠皮肤中药物含量。结果:苯酞(91.15%)和萜烯(5.19%)组成的川芎挥发油具有显著的促透作用,但其强度低于同浓度的油酸;3%的挥发油具有最强的促透作用,随着挥发油浓度的增加,促透作用反而下降;透皮流量和皮肤滞留药量之间具有相关性。结论:川芎挥发油能显著增强氟比洛芬的透皮吸收,其作用机制可能是通过破坏角质层的结构,增加皮肤中的药物分配。其促透的物质基础可能是苯酞化合物。 相似文献
5.
目的探究氟比洛芬酯注射液对食管癌术后患者止痛效果、止痛泵用量及不良反应情况的影响。方法选取2014年2月~2015年8月在该院就诊的食管癌患者98例,将患者随机均分为治疗组及对照组,每组49例,对照组给予常规术后自控止痛泵进行止痛处理并辅以常规术后治疗护理措施;治疗组在此基础上加用小剂量氟比洛芬酯注射液。观察比较2组患者术后即刻及术后36h的各项指数及镇痛效果总满意度。结果术前2组患者的心率(HR)、收缩压(SAP)、血氧饱和度(SaO2)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、血小板计数(PLT)、呼吸抑制、恶心、腹痛及大便潜血阳性例数比较,差异无统计学意义(P>0.05);术后36h治疗组患者的HR、SAP及SaO2明显高于对照组,治疗组患者的呼吸抑制及恶心例数明显少于对照组(P<0.05);治疗组患者术后治疗过程中的主动镇痛次数7.85±1.47次、用药量107.53±12.72mL、ICU留观时间18.54±2.67h及咳痰不畅例数(3,6.12%)明显低于对照组9.31±2.89次、115.37±15.29mL、20.47±3.53h、11(22.45%)(P<0.05);治疗组患者镇痛总满意度(47,95.92%)明显高于对照组(41,83.67%)(P<0.05)。结论小剂量应用氟比洛芬酯注射液可明显促进患者术后呼吸系统功能恢复,降低镇痛泵用药量及不良反应发生率,且无明显凝血指标异常等不良反应。 相似文献
6.
目的评价氟比洛芬酯或芬太尼复合丙泊酚静脉全麻用于无痛胃镜检查的临床疗效及安全性。方法 63例ASAⅠ或Ⅱ级接受胃镜检查的患者随机均分为三组,A组:静脉给予氟比洛芬酯1 mg/kg,5 min后持续泵注丙泊酚1.5~2.5 mg/kg;B组:静注芬太尼1μg/kg,5 min后持续泵注丙泊酚1.5~2.5 mg/kg;C组:持续泵注丙泊酚1.5~2.5 mg/kg,三组丙泊酚泵注速度均为100 mg/min。待患者入睡,睫毛反射消失后即行胃镜检查。观察并记录3组麻醉前、睫毛反射消失时、术中、术毕时的平均动脉压、心率、呼吸频率,手术时间,苏醒时间,丙泊酚总用药量,体动反应,术中麻醉效果以及术毕清醒后1、5、15、30 min视觉模拟评分(VAS)值,并进行组间与组内比较。结果与C组比较,A、B两组术中、术后各时点的MAP降低、HR减慢;A组和B组镜检中体动反应和丙泊酚总用药量均显著低于C组(P<0.05);A、B两组在术毕清醒后各时点的VAS均显著低于C组(P<0.05)。结论氟比洛芬酯或芬太尼复合丙泊酚静脉全麻用于胃镜检查术镇痛效果好,且氟比洛芬酯复合丙泊酚静脉全麻不良反应发生率更低,可安全应于临床。 相似文献
7.
目的评价帕瑞昔布钠用于重症肌无力患者胸腺切除术后镇痛的效果。方法选择行胸腺切除术的重症肌无力患者157例,分为曲马朵组(51例,术后给予肌肉注射曲马朵1.02.0 mg·kg-1)、氟比洛芬酯组(53例,术后予以静脉缓慢滴注0.82.0 mg·kg-1)、氟比洛芬酯组(53例,术后予以静脉缓慢滴注0.81.0 mg·kg-1氟比洛芬酯)和帕瑞昔布钠组(53例,术后予以静脉缓慢滴注0.61.0 mg·kg-1氟比洛芬酯)和帕瑞昔布钠组(53例,术后予以静脉缓慢滴注0.61.0 mg·kg-1帕瑞昔布钠),对3组患者术后1、2、6、12、24 h的静息及运动视觉模拟评分(VAS)、平均动脉压(MAP)、心率(HR)、呼吸频率(RR)、血氧饱和度(SpO2)及不良反应发生率进行比较分析。结果氟比洛芬酯组及帕瑞昔布钠组术后1、2、6、12、24 h的静息及运动VAS评分、MAP、HR、RR显著低于曲马朵组,差异有统计学意义(P<0.05)。帕瑞昔布钠组患者术后1、2、6、12、24 h的静息及运动VAS评分均显著低于氟比洛芬酯组(P<0.05)。氟比洛芬酯组及帕瑞昔布钠组的不良反应发生率均显著低于曲马朵组(P<0.05),且帕瑞昔布钠组的不良反应发生率显著低于氟比洛芬酯组(P<0.05)。结论重症肌无力患者胸腺切除术后采用帕瑞昔布钠进行镇痛,其镇痛时效显著优于氟比洛芬酯及曲马朵,且镇痛药物剂量小,术后不良反应率低。 相似文献
8.
张维清 《辽宁中医药大学学报》2009,(7)
目的:观察氟比洛芬酯注射液(凯纷)对择期子宫次全切手术患者术后疼痛的镇痛效果。方法:60例择期行子宫次全切患者,随机分为A组和B组,每组30例。A组于切皮后静脉注射加入凯纷50mg的生理盐水15mL(共20mL);B组于切皮后静脉注射生理盐水20mL。分别记录术后1、2、4、6、8、12、24h的视觉模拟评分(VAS)、24h镇痛药(扶他捷)服用量和不良反应,并统计患者对24h镇痛治疗的总体满意度。结果:术后1、2、4、6hVAS评分A组均低于B组(P<0.05);术后24h镇痛药扶他捷服用量A组(45±5)mg低于B组(75±6)mg(P<0.05);两组的不良反应(恶心)发生率A组低于B组,差异有显著性(P<0.05);患者对24h镇痛治疗总体满意度方面,A组好于B组,有显著性差异(P<0.05)。结论:凯纷用于择期子宫次全切除术患者,能减少术后镇痛药物服用量、减轻不良反应的发生并能提高镇痛质量。 相似文献
9.
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。 相似文献
10.
《Journal of microencapsulation》2013,30(7):701-708
AbstractNovel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients. 相似文献