海洛因依赖伴发意识障碍与苯二氮滥用关系

目的了解海洛因依赖者脱毒时伴发意识障碍与苯二氮     

Psychopharmacology and Cardiovascular Disease

This review discusses common mental health disorders and their associations with cardiovascular disease risks. Commonly found mental health disorders include depression, anxiety, and personality types. The link between depression and cardiovascular disease mortality has been established. Depression is also common in patients with heart failure. In addition to discussing psychological disorders, a review of psychotropic drugs is also included. Drugs are described for therapy for depression and anxiety, as well as associations with cardiovascular drug-drug interactions. Drug-drug interactions are more common and potentially dangerous in elderly patients, in whom the conditions often coexist. The most common drug-drug interactions involve the P450 system of enzymes.     

Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats

Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P < 0.05) without altering minute volume (V_E). In combination to DZP, BUP/NLX significantly increased expiratory time (P < 0.01) and decreased f (P < 0.01), tidal volume (V_T, P < 0.001), and V_E (P < 0.001) while BUP only decreased V_T (P < 0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P < 0.001) and decreased f (P < 0.01) and V_E (P < 0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined.     

Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic drugs including the involvement of group I metabotropic glutamate (mGlu) receptors. Given the recent discovery of a selective and brain penetrable mGlu5 receptor antagonists, the effect of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP), i.e. the most potent mGlu5 antagonist, was evaluated in established models of anxiety after single or repeated administration. We also studied if the anxiolytic effect of MTEP is mediated by mechanism involving the GABA-benzodiazepine (BZD) receptor complex. Experiments were performed on male Wistar rats or male Albino Swiss mice. The anxiolytic-like effects of MTEP were tested in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. MTEP (0.3-3.0 mg/kg) induced anxiolytic-like effects in the conflict drinking test (after single and repeated administration) and in the elevated plus-maze test in rats. In the four-plate test in mice, it exerted anxiolytic activity at a dose of 20 mg/kg. MTEP had no effect on the locomotor activity of animals. The anxiolytic-like effect of MTEP was not changed by BZD antagonist flumazenil. Moreover, a synergistic interaction between non-effective doses of MTEP and diazepam was observed in the conflict drinking test. These data suggest that selective mGlu5 receptor antagonists mediated anxiolysis is not dependent on GABA-ergic system and that these agents may play a role in the therapy of anxiety.     

Effects of combined alcohol and benzodiazepine: a review

Both human and animal studies relating to the combined effects of alcohol and benzodiazepine (BZD) are reviewed. Although the combination of alcohol and BZD is sometimes associated with drug-induced deaths, drug overdoses and traffic accidents or fatalities, epidemiological information is lacking on the true extent of the combined abuse and on the patterns and prevalence of use of these two drugs. Since BZD are widely used for the short- and long-term treatment of alcoholics, these patients are deemed more at risk of developing BZD or alcohol/BZD dependence than the general population. There is a dire need for large-scale controlled studies concerning the efficacy of BZD in the long-term treatment of alcoholics. Compared to men, women are at a higher risk as far as the potential for BZD addiction is concerned, since they tend to use BZD more often. Epidemiologic studies on the patterns of use of BZD, alcohol or alcohol/BZD in pregnant women are called for. Animal models are also needed to ascertain whether prenatal exposure to both alcohol and BZD can impart long-lasting behavioral changes in the progeny. It is possible that BZD can exacerbate the damaging prenatal effects of alcohol.     

Action of suriclone in naturally and allyglycine-induced photosensitive baboons, Papio papio

Suriclone (SC) is a new anxiolytic compound with a chemical structure different from that of benzodiazepines (BZD) but SC possesses a high affinity for the so-called BZD receptors. SC was tested in the naturally or the allylglycine-treated photosensitive baboon Papio papio. As active BZD administered by the intramuscular or oral route, this new compound possesses a marked protective effect against the excessive photosensitivity of the baboons, it blocks myoclonus following EEG spike and waves discharges induced by intermittent light stimulation; as BZD again, SC can induce spontaneous myoclonus not accompanied by EEG spike and wave discharges.     

Benzodiazepine receptors in rat cerebral cortex and hippocampus undergo rapid and reversible changes after acute stress

Rats were submitted to forced swimming and were killed 15 min after initiation of the stress and at 1 h, 1 day and 4 days thereafter. Immediately after the stress there was a decrease of 30% in the density of [³H]flunitrazepam binding sites in the cerebral cortex and of 27% in the hippocampal formation, with no changes in all the other brain areas studied. These changes in the number of benzodiazepine receptors were also corroborated by the binding of [³H]ethyl-β-carboline carboxylate. For both ligands there were no changes in affinity. These effects were selective for the benzodiazepine receptors and no changes in α₁, α₂ and β adrenoceptors and in dopaminergic receptors were observed. One hour after the stress, the number of benzodiazepine receptors had recovered in the cerebral cortex (8% above the control) and had increased greatly in the hippocampal formation ( + 53%). One day after the stress, the [³H]flunitrazepam binding in the cerebral cortex reached the normal level but it was still slightly elevated ( + 16%) in the hippocampus.These results are discussed in relation to some contradictory findings in the literature and to the fact that the hippocampal formation is related to neural mechanisms underlying behavior and neuroendocrine regulation.     

Benzodiazepine Dependence in Singapore

The study, conducted in 2003–2005, was aimed at investigating the pattern of benzodiazepine (BZD) use and the attitudes and perceptions of doctors' prescribing practices by a hundred BZD-dependent patients in Singapore. Data on patients' demographic characteristics, psychiatric profiles, patterns of BZD use, and perceptions about doctors' prescribing practices were collected. A benzodiazepine dependence self-report questionnaire (Bendep-SRQ) was also administered. The mean age of the study participants was 39.4 years (SD = 9.7); 88% were Chinese, 58% were males, 46% were married, 48% had received secondary school education, and 48% were unemployed. BZD abuse in Singapore is contributed to by both doctor-shopping behavior and doctors' prescribing practices. Doctors need training on the assessment and management of BZD dependence. The study's limitations were noted. This project was supported by an institutional block grant received from the National Medical Research Council, Singapore.     

无锡地区老年失眠患者苯二氮类药物使用情况分析

目的:调查了解无锡地区老年失眠患者苯二氮类(BZD)药物使用情况。方法:采用自编调查表调查江苏省荣军医院及无锡市第四人民医院2009年11月～2010年3月因失眠而在门诊就诊的老年患者1 224例,根据限定日剂量(DDD)和药物利用指数(DUI)对BZD等药物的临床使用进行分析。结果:因失眠而就诊的老年人BZD使用频率高达91.83%;BZD合并抗精神病药物及抗抑郁药物占64.22%;两种以上BZD合并使用者占26.72%;艾司唑仑、阿普唑仑、氯硝西泮、硝西泮、地西泮的DUI>1。结论:无锡地区老年人BZD临床使用不尽合理,老年人BZD依赖情况严重,合并用药较多,改变BZD使用模式迫在眉睫。     

门诊精神病患者应用BZD类药物的调查

目的 了解我院门诊复诊精神病人BZD类药品的使用情况和疗效评定。方法 采用“一日统计学”对门诊复诊精神病人使用BZD类药品用量、药品使用频度等项目进行统计,对使用BZD类药品的复诊452例精神病患者．按照联合使用BZD类药品或未使用BZD类药品的使用标准随机分成两组,比较BZD类药品的疗效。结果 门诊复诊使用APD类和BZD类药品联合用药的精神病患者,使用BZD类药品的用量明显降低;两组疗效比较,联合使用药品治疗的疗效与单独使用APD类药品疗效无显著性差异;且使用BZD类药品维持治疗的时间过长。结论 精神病患者并非必须使用BZD类药品。