Review of case reports of inadvertent intrathecal administration of vincristine: Recommendations to reduce occurrence

Vincristine has been in clinical use for over 40 years with initial publication of the results from successful trials in 1962. Catastrophic neurotoxicity has been associated with the administration of vincristine directly into the cerebrospinal fluid (CSF). Since the first case in 1968 there have been numerous other instances, of which 23 have been reported in the literature. Of these cases 18 resulted in death. The most prominent damage on autopsy was generally in the spinal cord, brain stem and cerebellum, with severity tending to be greater in the neurons adjacent to the CSF. Fatalities appeared due to a progressive ascending myeloencephalopathy. Early recognition and immediate treatment with CSF drainage and intrathecal exchange appears to be the only intervention that has improved patient survival. The volume of injection, dose and time from the incident until the ventriculo‐lumbar washout appear critical, as these factors might contribute to the extent of drug distribution in the CNS. Although several antidotes for vincristine have been suggested, including folinic acid and glutamic acid, supportive evidence for their effectiveness is scant. Several recommendations regarding prevention of this catastrophic event have been proposed.     

培朵普利与博安霉素联用对肝癌H22移植瘤生长的影响

目的观察培朵普利(PER)与抗肿瘤抗生素博安霉素(BAM)联合给药对肿瘤生长的影响。方法采用小鼠肝癌H22移植瘤模型观察二者联合给药的作用。结果PER 2 mg.kg-1每天灌胃给药,直到实验结束;BAM 1 mg.kg-1腹腔给药×3,设计了以下二个实验:(1)在肿瘤接种后第1天给药,合用组肿瘤生长速度比单用组的慢,在第19天,PER抑瘤率为59.3%,BAM抑瘤率为39.1%,二者联合的抑瘤率为76.0%,CDI为0.96;(2)在肿瘤接种后延迟给药,合用组肿瘤生长速度也比单用组的慢,在第19天,PER抑瘤率为42.9%,BAM抑瘤率为37.9%,二者联合的抑瘤率为76.6%,CDI为0.66。结论PER与BAM联合抗肿瘤有协同作用。     

新型经皮渗透促进剂的研究进展

介绍国内外近年来报道的新型经皮渗透促进剂的研究与开发进展,重点介绍若干具代表性的新合成的化合物以及新发现的天然产物,包括内酰胺类、糖苷类、氨基酸衍生物、聚合物、挥发油和酶类等,为合成和发现更加安全、高效的促渗剂提供线索.     

优化结构提高效率实现医院可持续发展

随着我国医疗保险的大范围实施，医院只有优化结构、提高效率，才能实现可持续发展。以财务管理为出发点，分析了目前大型医院所面临的现行国家医疗政策、外部环境以及内部约束等条件，提出强化医疗业务管理．建立科学合理的医疗业绩考核指标体系：平均住院天数、出院人数、手术量、门诊预约率，促进医疗业绩的提高：强化财务管理，建立现代医院财务考核指标体系：结余率、人均结余、病人人均费用，对各个科室的经济效益进行考核，促进医院经济效益的提高。     

剖宫产孕妇硬膜外给局麻药的药代动力学

为了解孕妇硬膜外给局麻药的药代动力学，选择２０名实施剖宫产手术的健康临产妇，随机分成硬膜外腔给予了哌卡因组（Ｂ１组）和给予利多卡因组（Ｌ组）。另外， ６例非妊娠患者硬膜外腔给予了哌卡因（Ｂ２组）。Ｂ１和Ｂ２组均给予０．７５％丁哌卡因１～１．５ｍｇ·ｋｇ－１，Ｌ组给予２％利多卡因４～４．５ｍｇ·ｋｇ－１。采用高效液相色谱（ＨＰＬＣ）测定硬膜外给药后血浆药物浓度。结果表明三组病例血药浓度均在安全范围内。Ｂ１组的血药浓度达高峰时间（Ｔｐｅａｋ）和脐静脉与母体血药浓度比（ＵＶ／ＭＶ）值均小于Ｌ组，表明丁哌卡因在硬膜外腔的吸收比利多卡因快，且透过胎盘屏障的药量小于利多卡因，新生儿Ａｐｇａｒ评分在娩出后５分钟均为１０分。Ｂ１组的药代动力学参数与Ｂ２组基本相似。结论：剖宫产手术硬膜外腔给予临床剂量的局麻药是安全的。     

Intravenous or rectal administration of sedatives in outpatient oral surgery

A number of cross-over studies on sedation in outpatient oral surgery investigated the quality of sedation produced by intravenous or rectal administration of diazepam. The sedation methods were equally efficient with a mean dose of 0.24 mg/kg (range 0.1–0.4) for i.v. administration and 0.53 mg/kg (range 0.5–0.6) for rectal administration. Eighty-five percent of the patients preferred surgery under sedation and local anaesthesia to local anaesthesia alone. The patients preferred the session in which they experienced stronger sedation, regardless of the route of administration.     

Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.     

Oral administration of methylergometrine shows a late and unpredictable effect on the non-pregnant human menstruating uterus

Objective: To study the pharmacodynamic and pharmacokinetic properties of oral and intravenous methylergometrine upon uterine motility during menstruation. Study-design: Intra-uterine pressure was measured in six volunteers with a fluid-filled sponge-tipped catheter during menstruation. Methylergometrine was given orally (0.5 mg) or intravenously (0.2 mg) in a cross-over design. Results: After intravenous administration, a fast increase of the frequency of uterine contractions and basal tone occurred with a decrease of amplitude, lasting at least 30 min. Oral administration had a late and less marked effect on uterine motility. An intravenous dose administered 24 h after an oral dose had no effect on uterine motility. Pharmacokinetic data, such as the maximum plasma concentration (C_max), the time at which C_max is reached (t_max) and the half-life of absorption (t_1/2abs) also demonstrated large individual variations after oral administration. Conclusion: Oral administration of methylergometrine had an unpredictable and late effect on uterine motility on the menstruating uterus, probably due to an unpredictable bioavailability, in contrast with the fast and predictable effect after intravenous administration.     

健康志愿者口服青蒿琥酯片剂的生物利用度

本文报道用放射免疫测定法研究口服青蒿琥酯片剂的生物利用度,结果为静脉注射青蒿琥酯后的血药时程为二房室模型,T1/2β为33.96±4.73分钟;口服青蒿琥酯片剂后的血药时程为一房室模型,其达峰时间为53.07±20.58分钟,峰浓度为1.94±1.05mg/L(1.94±1.05μg/ml),T1/2k为41.35±17.89分钟,绝对生物利用度为40.39±14.99％。结果提示口服青蒿琥酯片剂后,在人体内的吸收速度较快,而吸收程度较差。     

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.