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1.
非甾体抗炎药及其心血管风险   总被引:3,自引:1,他引:2  
非甾体抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)是通过抑制环氧合酶(cyclooxygenase,COX),阻断花生四烯酸(arachidonic acid,Aa)转化为前列腺素(prostaglandins,PGs)而发挥抗炎、镇痛和解热作用的一类药物。特异性COX-2抑制药因避免了传统NSAIDs的常见胃肠道副作用而被广泛应用,但近年来发现该类药物可产生严重的心血管不良反应;而某些非选择性COX抑制药也有可能增加心血管危险性。本文就与NSAIDs心血管风险有关的重要问题进行综述。  相似文献   

2.
COX-2抑制剂与心血管疾病   总被引:6,自引:0,他引:6  
20世纪70年代初,Vane发现,阿司匹林类非甾体抗炎药物(NSAIDs)是通过抑制环氧化酶(COX)并阻断花生四烯酸代谢而发挥药理作用的。90年代初,研究发现COX有2种同功酶,即COX-1和COX-2。普遍认为,COX-1主要在胃肠、肾和血小板表达,产生的前列腺素(PG)参与机体正常生理过程和保护功能,如维持胃肠粘膜完整性,调节肾血流和血小板功能,而COX-2主要在巨噬、软骨和内皮等细胞表达,在基础状况水平极低,一旦受细胞因子或骨毒素刺激而成倍增长时,产生的PG参与炎症反应。在此假设基础上推测,NSAIDs的胃肠不良反应与抑制COX-1有关,而其抗炎止痛作用则因抑制  相似文献   

3.
研究表明环氧合酶-2(COX-2)在胃癌中呈过表达,而非甾体抗炎药(NSAIDs)可以抑制COX-2表达,阻断胃癌细胞增殖,但是NSAIDs拮抗肿瘤的作用机制并不只局限于COX-2通路,其机制尚不清楚。本研究旨在观察选择性COX-2抑制剂NS-398对胃癌细胞增殖与凋亡的影响,探讨选择性COX-2抑制剂抗胃癌的作用机制。  相似文献   

4.
环氧化酶-2及其抑制剂在疼痛治疗中的作用   总被引:1,自引:0,他引:1  
非甾体抗炎药(nonsteroidal anti—inflammatory drugs,NSAIDs)通过抑制前列腺素合成中的环氧化酶(cyclooxygenase,COX)、从而阻断花生四烯酸生成前列腺素,发挥镇痛抗炎的作用。但因其胃肠道、肾功能、心血管和血小板等方面的副作用,限制了它的广泛使用。COX存在两种同分异构体,其中环氧化酶-2(COX-2)主要在损伤或炎症部位表达,并合成前列腺素类物质,由此推动了选择性COX-2抑制剂的研制。普遍认为它与传统的NSAIDs的镇痛抗炎性能相当,但副作用减少。目前,这种学说得到了广泛的认同,然而,COX-2抑制剂的应用还有待深入认识。  相似文献   

5.
环氧合酶-2与大肠癌研究进展   总被引:3,自引:0,他引:3  
熊兵红  程勇 《消化外科》2005,4(6):451-456
环氧合酶(cyclooxgenase,COX)又称前列腺素合酶(PGs),是花生四烯酸(arachidonic acid,AA)代谢的关键限速酶。目前已发现至少存在两种亚型:结构型(consititutive)COX-1和诱导型(inducible)COX-2。近年来研究发现,COX-2不仅在肿瘤组织中有较高表达,并可能参与肿瘤的增殖、转移及分化。传统的非甾体类消炎药(NSAIDs)和选择性COX-2抑制剂已被证实可防治大肠癌、胃癌和家族性结肠息肉病(FAP)。随着COX-2与肿瘤关系的深入研究必将为肿瘤防治提供又一新途径。我们就COX-2的生物学特性、与大肠癌的关系及其可能的机制予以综述。  相似文献   

6.
环加氧酶-2(COX-2)特异性抑制药是一类新的非甾体抗炎药(NSAIDs),比传统的NSAIDs副作用少.本文综述了这类药和结构特点、作用机制和临床应用.  相似文献   

7.
环氧化酶-2及其抑制剂在疼痛治疗中的作用   总被引:1,自引:0,他引:1  
非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)通过抑制前列腺素合成中的环氧化酶(cyclooxygenase,COX)、从而阻断花生四烯酸生成前列腺素,发挥镇痛抗炎的作用.但因其胃肠道、肾功能、心血管和血小板等方面的副作用,限制了它的广泛使用.COX存在两种同分异构体,其中环氧化酶-2(COX-2)主要在损伤或炎症部位表达,并合成前列腺素类物质,由此推动了选择性COX-2抑制剂的研制.普遍认为它与传统的NSAIDs的镇痛抗炎性能相当,但副作用减少.目前,这种学说得到了广泛的认同,然而,COX-2抑制剂的应用还有待深入认识.  相似文献   

8.
早在1988年一项流行病学研究报告发现,长期使用非甾体类抗炎药(nonsteroidal anti-inflammatory drugs, NSAIDs)可以抑制结肠癌的发生、发展[1];新近的研究证据表明环氧化酶2(COX-2)参与了肿瘤发生、发展中的许多生物学进程[2].不同于以往的以核苷酸代谢为抗癌核心的理念,COX-2成为了肿瘤防治的新靶点.大量的流行病学和临床研究结果证实,COX-2及其催化产生的前列腺素产物与肿瘤的演变密切相关,选择性COX-2抑制剂可能阻碍着恶性肿瘤的发展[2].  相似文献   

9.
环加氧酶-2(COX-2)特异性抑制药是一类新的非甾体抗炎药(NSAIDs),比传统的NSAIDs副作用少。本文综述了这类药和结构特点,作用机制和临床应用。  相似文献   

10.
非甾体抗炎药(NSAIDs,包括COX-2抑制剂)在骨关节炎(OA)的疾病管理中起着非常重要的作用,作为一种较新的COX-2抑制剂,依托考昔具有比传统NSAIDs更好的胃肠道安全性,其血药浓度达峰时间短、半衰期长等药理学特性,决定了其起效快和药效长。本文就依托考昔近些年发表的OA治疗相关随机对照研究、系统回顾研究和NNT研究等多个国内外文献进行回顾,并与其他NSAIDs的疗效和安全性进行比较分析,希望较全面总结依托考昔在OA疾病管理中的研究进展,为临床用药提供循证参考。  相似文献   

11.
Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.  相似文献   

12.
Don Dame 《Artificial organs》1996,20(5):613-617
Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.  相似文献   

13.
Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.  相似文献   

14.
Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.  相似文献   

15.
Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H2O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg−1 followed by 0.15 mg · kg−1 · h−1, n=8) or verapamil (0.1 mg · kg−1 followed by 0.3 mg · kg−1 · h−1, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.  相似文献   

16.
Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.  相似文献   

17.
Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.  相似文献   

18.
Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg?1 i. v. and 32 μg · kg?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg?1. The mean ED50s, calculated from dose-response curves, were 5.4 mg · kg?1, 3.9 μg · kg?1 and 0.4 mg · kg?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg?1 and 8 μg · kg?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.  相似文献   

19.
Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg?1 · min?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min?1 · m?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416±91 to 717±110 ml/m2 · m2; VO2I: from 98±25 to 157±22 ml/m2 · m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.  相似文献   

20.
A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.  相似文献   

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