Model Features of a Cardiac lontophoretic Drug Delivery Implant

Pharmaceutical Research -     

Two deaths from intravenous nifedipine abuse

Summary An incident is reported in which 2 intravenous drug abusers died as the result of uncontrolled experimentation with intravenous injection of the common anti-hypertensive and anti-anginal drug Nifedipine (Adalatt.m. Bayer), probably in mistake for the commonly abused short-acting benzodiazepine drug Temazepam. Large quantities of Nifedipine were identified in the blood of both deceased men by gas chromatography. Apart from intense gastric mucosal congestion, pulmonary oedema and general visceral congestion, the autopsy findings were entirely nonspecific. The similarity in colour, shape and texture between capsules of Nifedipine and those of Temazepam is likely to have prompted the mistake.     

药物不良反应国内文献题录检索系统

本文报道了药物不良反应国内文献题录检索系统的设计原理、功能特点,以输入药名及不良反应类别为例,显示了检索系统操作简便,提供信息及时准确的特点。本系统可从药名、不良反应类别及作者等多方面进行检索,可为查询者提供所需的详细资料,弥补了人工查阅文献的不足。并将继续扩大文献资料库,由题录向电报文体文摘形式转化,以贮存更多的信息。     

Effect of Omeprazole on Diazepam Disposition in the Rat: in Vitro and in Vivo Studies

Purpose. The inhibitory effects of omeprazole on diazepam metabolism in vitro and in vivo are compared in the rat. Methods. 3-hydroxylation and N-demethylation of diazepam was investigated in the presence of a range of omeprazole concentrations (2-500µM) in hepatic microsomes and hepatocytes. Zero order infusions together with matched bolus doses of omeprazole were used to achieve a range of steady state plasma concentrations (10-50mg/ L) and to study the diazepam-omeprazole interaction in vivo. Results. The 3-hydroxlation pathway was more prone to inhibition (K_Is 108 ± 30 and 28 ± 11 µM in microsomes and hepatocytes, respectively) than the demethylation pathway (K_Is of 226 ± 76 and 59 ± 27 µM in microsomes and hepatocytes, respectively). In both in vitro systems, the mechanism of inhibition was competitive with Km/K_I ratios larger than 1 for the 3HDZ pathway and smaller than 1 for the NDZ pathway. There was an omeprazole concentration dependent decrease in diazepam clearance in vivo which could be modelled using a simple inhibition equation with a K_I of 57µM (19.8mg/L). In contrast there was no statistically significant change in the steady state volume of distribution for diazepam in the presence of omeprazole. Conclusions. The in vivo K_I for the omeprazole: diazepam inhibition interaction shows closer agreement with the K_I values obtained in hepatocytes than with those observed in microsomes.     

消炎痛对大鼠肾上腺素性肺损伤的影响

本实验采用静脉注射肾上腺素造成大鼠肺损伤模型,观察消炎痛对肾上腺素性肺损伤时,肺血管壁通透性及肺组织形态学影响。结果表明:消炎痛可预防肾上腺素所致的肺血管壁、肺泡壁通透性增高(分别为P<0.025;P<0.01),延长存活时间(P<0.001);形态学检查:肺损伤明显减轻(P<0.005)。提示前列腺素(PG)参与了肾上腺素性肺损伤。     

Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.     

抗生素的合理使用

随着医药工业的发展,新药层出不穷。以抗生素为例,20世纪50年代临床用的抗生素只有青、链、红、氯四大素,现在常用临床的抗生素以有100多种,临床医生长期来忙与医疗任务,如何掌握新药信息,做到合理选药,合理用药,使药物的药理作用转化为治疗效应,已成为临床医生日益关心的问题。1抗生素在临床应用中存在问题1.1常规固定方案长期以来根据以往的经验或资料,正式或非正式采用抗生素治疗方案。如:氨苄西林+庆大霉素、青霉素+庆大霉素、红霉素+氯霉素。由于对致病菌针对性不强,以致延误治疗。1.2抗生素在选择中存在问题随着医药工业的发展,抗生素…     

The effect of quinidine on the analgesic effect of codeine

Summary We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pin-prick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo.After codeine and placebo, the peak plasma concentration of morphine was 6–62 (median 18) nmol·.l^–1. When quinidine pre-treatment was given, no morphine could be detected (<4 nmol·l^–1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds.These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results.     

覆醛氧化淀粉联合硝苯啶治疗老年慢性肾功能衰竭264例

对老年慢性肾功能衰竭264例患者(男148例,女116例;年龄66±7a)用硝苯啶10mg联合覆醛氧化淀粉5-10mg,tid,po。另设相似88例患者(男48例,女40例;年龄66±7a)单服覆醛氧化淀粉与之对照,用法同前。2组均连服16wk。结果:前者有效216例(81.8％),后者有效49例(56％),组间比较P<0.01。2组副作用相似,均可坚持服药。