Tolerance and dependence to opiates

In the 19th century, investigators recognized that addiction to opiates involves tolerance and dependence. In the United States, the National Academy of Sciences and the Public Health Service initiated systematic investigations into opiate addiction in 1929. Tolerance and dependence to morphine, the prototype for opiate drugs, were the emphasis of human studies for the next fifty years. This presentation highlights salient features of tolerance and dependence learned in these studies and relates these findings to clinical use in treating pain.     

Prothrombin times and activated partial thromboplastin times in toxicology: a comparison of different blood withdrawal sites for wistar rats

The prothrombin time (PT) and the activated partial thromboplastin time (APTT) for untreated male Wistar rats were determined on the Sysmex CA-5000 Instrument for blood taken from the orbital sinus, tail vein, vena cava and aorta. Boxplot and statistical analysis was performed. Only orbital sinus puncture yields unpredictable and unacceptable variation/prolongation of clotting times.     

How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

泌尿生殖道患者沙眼衣原体和支原体检测及支原体药敏分析

目的　检测皮肤性病门诊泌尿生殖道患者沙眼衣原体 (CT)和支原体感染情况及支原体培养加药敏分析。方法　对5 0 95例泌尿生殖道感染者用金标法检测沙眼衣原体抗原 ,用微量肉汤稀释法检测解脲支原体 (Uu)和人型支原体 (Mh)并进行 8种抗生素的药敏试验。结果　 5 0 95例泌尿生殖道感染者中衣原体阳性 417例 ,总阳性率为 8 2 % ,女性患者阳性率 ( 11 2 % )明显高于男性患者阳性率 ( 6 2 % ) ,有显著性差异 ( χ2 =40 1,P <0 0 1) ;检出支原体 172 8例 ,总阳性率为 3 3 9% ,女性患者阳性率 ( 4 3 0 % )明显高于男性患者阳性率 ( 2 8 0 % ) ,有显著性差异 ( χ2 =114 8,P <0 0 1) ;其中Uu感染 ( 12 5 1例 ,2 4 6% )明显高于Mh感染 ( 71例 ,1 4% )和Uu +Mh混合感染 ( 4 0 6例 ,8 0 % )。Uu对红霉素、罗红霉素、交沙霉素、阿奇霉素、强力霉素、美满霉素、氧氟沙星、环丙沙星的高度敏感率分别为 60 3 %、67 5 %、73 2 %、85 3 %、5 5 7%、40 1%、2 5 6%、2 7%。Uu +Mh混合感染对 8种抗生素均出现不同程度的耐药菌株。结论　湖南地区泌尿生殖道感染患者中 ,衣原体、支原体感染处于国内较高水平。支原体对不同种类抗生素有较高的耐药性 ,特别是Uu +Mh混合感染 ;临床上做支原体培养加药敏试验 ,对指导     

口服Sumatriptan治疗偏头痛的临床评价

本文报告口服Sumatriptan 100mg对偏头痛急性发作119例次的治疗结果。治疗后4h内显效91例次(76.5％),好转16例次(13.4％),无效12例次(10.1％),总有效率为89.9％。对偏头痛伴随症状恶心、呕吐和畏光、畏声的缓解率分别为94.2％、96％和94.3％。     

Effects of food deprivation on cocaine base smoking in rhesus monkeys

Studies have shown that both food deprivation and response cost have important influences on the magnitude of self-administration of a wide variety of psychoactive drugs. In an attempt to extend these findings to the smoked route of drug self-administration, the effects of food allotment and fixed-ratio (FR) value were evaluated in four male rhesus monkeys trained to smoke cocaine base. In the first phase of the experiment, monkeys were trained to self-administer smoked cocaine base under a chained progressive-ratio (PR), fixed-ratio (FR) schedule during daily experimental sessions. Monkeys were required to make 20 lever-press responses and then five inhalations on a smoking spout to obtain the first smoke delivery. The lever ratio then increased to 60, 140, 300, 620, 1260, 2540, and 4940 for each successive smoke delivery. The initial lever ratio value was reset to 20 at the beginning of each daily session. The body weights of three monkeys were determined under free-feeding conditions. Monkeys were then restricted to 100 g food and, when body weights had stabilized, the daily food allotment was increased to 150 g, approximately 210 g, or greater than 400 g (satiation). As the daily food allotment and body weight increased, the mean number of smoke deliveries decreased in two of three monkeys. In the second phase of the experiment, three monkeys were maintained under either food-satiated or food-restricted conditions. Body weights were maintained at approximately 90% of their free-feeding weights under food-restricted conditions. The cost of the drug (lever FR value) was constant within each experimental session, but was increased after 3 consecutive days of stable responding. Fixed-ratio values were increased from 128 to 256, 512, 1024, and 2048. Monkeys were required to complete the lever FR value and then to make five inhalations on the smoking spout to gain access to 1.0 mg/kg per delivery cocaine base. The mean number of smoke deliveries increased at FR 256, 512, and 1024 when monkeys were food-restricted as opposed to food-satiated. Correspondingly, the mean number of responses increased under food-restricted conditions. Responding continued to increase over a wider range of FR values, and the peak number of responses was higher under food-restricted, as opposed to food-satiated conditions. These results, using the smoking route of administration, are consistent with the hypothesis that food deprivation increases the self-administration of reinforcing drugs.     

3H-胸苷酸掺入法对选择前列腺癌化疗方案的价值

目的为临床选择激素难治性前列腺癌(HRPC)的化疗方案提供参考.方法采用3H-胸苷酸(3H-TdR)掺入法检测了20例HRPC细胞对常用化疗药物的敏感性.结果HRPC对单药的体外敏感性依次为足叶乙苷(VP16)＞阿霉素(ADM)、5-氟尿嘧啶(5-FU)、雌二醇氮芥(EMP)＞长春花碱(VLB)＞顺铂(DDP);二药联合可使敏感性进一步提高,依次为EMP加VP1 6、5-FU加ADM＞EMP加VLB＞5-FU加DDP三药联用抑瘤作用更强,EMP加VLB加APM、5 FU加ADM加DDP＞EMP加VLB加DDP.结论3H-TdR掺入法有助于化疗方案的选择,对HRPC以联合化疗效果较好.     

两种靶控方法输注异丙酚和瑞芬太尼的安全性和有效性比较

目的 比较靶控血浆浓度和效应室浓度输注异丙酚和瑞芬太尼的安全性及有效性。方法 选择44例腹腔镜胆囊切除的病人,年龄18～65岁,ASA Ⅰ～Ⅱ级,随机分为靶控血浆浓度组(P组)和效应室浓度组(E组)。设定异丙酚和瑞芬太尼的靶浓度分别为4 μg/ml和2 ng/ml。观察给药后意识消失时间、血液动力学变化以及听觉诱发电位指数(AAIs)的变化。术中调整两药靶浓度保持AAIS低于20。记录术毕停药后自主呼吸恢复和睁眼时间和AAIs的恢复。结果 E组意识消失的时间[(0.45±0.10)min]明显短于P组;此时两药的用量也明显高于P组。两组均能引起明显的低血压,但降低程度相似,且均未见严重的心血管副作用。AAIs在意识消失时P组为41±22;E组49±16:但插管时均在20以下。术中血液动力学保持较低水平(P<0.01)。两组的插管评分、麻醉质量评分相似。术后自主呼吸恢复时间和睁眼时间两组均无统计学差异。Aldrate评分及手术结束时疼痛评分差异均无显著性。结论靶控血浆和效应室浓度输注均可达到满意的麻醉效果,但靶控效应室诱导时间更短,且无明显心血管副作用。     

腹腔镜手术病人咪达唑仑-芬太尼-异丙酚麻醉诱导的优化配伍方案

目的 采用权重配方法探讨腹腔镜手术病人咪达唑仑、芬太尼、异丙酚复合麻醉诱导的优化配伍方案。方法选择ASAⅠ或Ⅱ级择期腹腔镜手术病人60例，男34例，女26例，年龄31～55岁。诱导药物的低效量和足量分别确定为咪达唑仑0．02、0．06mg／kg，芬太尼2、6μg／kg，异丙酚0．5、1．5mg／kg。根据权重配方法，将病人随机分配至3种药物不同剂量组合的6个配伍组（n=10）。连续监测脑电双频谱指数（BIS）、心率（HR）、平均动脉压（MAP）、脉搏血氧饱和度（SpO2）。各组依次静脉注射相应剂量咪达唑仑、芬太尼、异丙酚和罗库溴铵0．6mg／kg行麻醉诱导和气管插管。记录诱导前即刻、异丙酚注入后1、2min、插管即刻、插管后1、3、5、7min的BIS、MAP及HR。按权重配方法的剂量优化原则评判复合药效，分析各组份药的重要程度及相互作用的性质。结果以BIS为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg／ks、异丙酚1．0mg／kg配伍时，异丙酚为主药，异丙酚与咪达唑仑和芬太。尼具有相加性作用；以MAP为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg，kg、异丙酚1．5mg／kg配伍时，异丙酚为主药，异丙酚与咪达唑仑具有协同性作用，异丙酚与芬太尼具有相加性作用；以HR为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg／kg、异丙酚1．0mg／kg配伍时，芬太尼为主药，异丙酚与咪达唑仑和芬太尼具有协同性作用。结论腹腔镜手术病人咪达唑仑、芬太尼、异丙酚复合麻醉诱导在维持镇静方面为相加作用，在维持血液动力学稳定方面为协同作用；优化配伍方案为咪达唑仑0．06mg／kg、芬太尼5μg／kg、异丙酚1．5mg／kg。     

四类抗感染药物不良反应相关因素的探讨与分析

目的：使输液疗法中药物不良反应降到最低限度，使患者获得安全、有效的治疗，同时，也是对有限药物资源的维护。方法：对用四类抗感染药物出现不良反应91例患者行减慢输液速度、平卧、松解领扣、按合谷穴、心理护理、保暖、进饮食等处置。结果：91例药物不良反应，有89例顺利完成输液治疗，2例无效，更换药物。结论：有责任感，加强观察护理及时发现患者反应前驱症状，迅速采取有效措施，会取得满意效果。