Solid-phase microextraction and GC-ECD of benzophenones for detection of benzodiazepines in urine. (1/1442)

Benzodiazepines are common drugs that cause intoxication. Benzodiazepines and their metabolites can be converted by hydrolysis in acid to the corresponding benzophenones, which are easier to be separated from matrices because of their hydrophobic properties. In this study, a new separation technique called solid-phase microextraction (SPME), which can integrate extraction, concentration, sampling and sample introduction into one single procedure, has been employed to extract the products of benzodiazepines from urine after acid hydrolysis. The extracts were determined by gas chromatography with electron-capture detection (GC-ECD). The hydrolysis conditions were optimized by a statistic orthogonal design. Factors influencing direct-immersion (DI)-SPME process were also checked and chosen experimentally. The method was evaluated with spiked human urine samples. The recoveries of nine benzodiazepines ranged from 1 to 25%, with the highest for oxazolam and the lowest for bromazepam. The calibration curves were linear from 10 to 500 ng/mL for oxazolam, haloxazolam, flunitrazepam, nimetazepam, and clonazepam and from 20 to 1000 ng/mL for the others except bromazepam. The detection limits were 2-20 ng/mL for most drugs tested. The intraday and interday coefficients of variation of the developed method were within 10 and 17%, respectively. In addition, the utility of the method was confirmed by determining two ingested benzodiazepines (flunitrazepam and oxazolam) in a volunteer's urine; urine flunitrazepam was still detectable 32 h after a therapeutic dose (1.2 mg) of the drug. Finally, the DI-SPME was compared with the conventional liquid-liquid extraction with regard to detection limits and extraction efficiency of the analytes. By DI-SPME, more amounts of analytes could be introduced into GC column than by conventional liquid-liquid extraction, and thus lower detection limits of the analytes were reached, although benzophenone recoveries by DI-SPME were rather low.  (+info)

Psychotropic drug use among women. (2/1442)

The consistent 2:1 ratio of women to men in the receipt of prescriptions for psychotropic drugs is reflected in the higher rates for women of neurotic illness, symptoms of both physical and mental discomfort, and help-seeking and drug-taking behaviour. Physicians' perceptions of the problems presented by their male and female patients influence their prescribing of these drugs. Recent statistics in Ontario indicate that greater use of physicians' services by women is an inadequate explanation of the higher rate of prescribing of psychotropic drugs to women. A longitudinal study of a large insured population in Ontario showed that almost twice the proportion of females, compared with males, received a prescription for psychotropic drugs in 1970-71 and in 1973-74, a higher proportion of females received multiple prescriptions for each drug class, and males were more likely than females to have received only one prescription in a year.  (+info)

Benzodiazepine premedication: can it improve outcome in patients undergoing breast biopsy procedures? (3/1442)

BACKGROUND: Women awaiting needle-guided breast biopsy procedures may experience high anxiety levels. A randomized, double-blind, placebo-controlled study was designed to evaluate the ability of midazolam and diazepam (in a lipid emulsion [Dizac]) to improve patient comfort during needle localization and breast biopsy procedures. METHODS: Ninety women received two consecutive doses of a study medication, one before the mammographic needle localization and a second before entering the operating room. Patients were assigned randomly to receive saline, 2.0 ml intravenously, at the two time points; midazolam, 1.0 mg intravenously and 2.0 mg intravenously; or diazepam emulsion, 2.0 mg intravenously and 5.0 mg intravenously, respectively. Patients assessed their anxiety levels before the needle localization, before entering the operating room, and on arrival in the operating room. Patients completed a questionnaire evaluating their perioperative experience at the time of discharge. RESULTS: Patient satisfaction during needle localization was significantly improved in both benzodiazepine treatment groups (vs. saline). The incidence of moderate-to-severe discomfort during needle localization was lower in the midazolam (20%) and diazepam emulsion (6%) groups compared with the saline group (70%) (P<0.05). The preoperative visual analogue scale anxiety scores were similar in all three groups. In the operating room, however, anxiety scores were 55% and 68% lower after midazolam (21+/-19) and diazepam emulsion (15+/-14) compared with saline (46+/-28). Finally, there was no difference in the time to achieve home-readiness or actual discharge time among the three groups. CONCLUSIONS: Premedication with midazolam or diazepam emulsion improved patients' comfort during needle localization procedures and significantly reduced intraoperative anxiety levels before breast biopsy procedures without prolonging discharge times. Use of diazepam emulsion may be an effective alternative to midazolam in this population.  (+info)

Postoperative behavioral outcomes in children: effects of sedative premedication. (4/1442)

BACKGROUND: Although multiple studies document the effect of sedative premedication on preoperative anxiety in children, there is a paucity of data regarding its effect on postoperative behavioral outcomes. METHODS: After screening for recent stressful life events, children undergoing anesthesia and surgery were assigned randomly to receive either 0.5 mg/kg midazolam in 15 mg/kg acetaminophen orally (n = 43) or 15 mg/kg acetaminophen orally (n = 43). Using validated measures of anxiety, children were evaluated before and after administration of the intervention and during induction of anesthesia. On postoperative days 1, 2, 3, 7, and 14, the behavioral recovery of the children was assessed using the Post Hospitalization Behavior Questionnaire. RESULTS: The intervention group demonstrated significantly lower anxiety levels compared with the placebo group on separation to the operating room and during induction of anesthesia (F[1,77] = 3.95, P = 0.041). Using a multivariate logistic regression model, the authors found that the presence or absence of postoperative behavioral changes was dependent on the group assignment (R = 0.18, P = 0.0001) and days after operation (R = -0.20, P = 0.0001). Post hoc analysis demonstrated that during postoperative days 1-7, a significantly smaller number of children in the midazolam group manifested negative behavioral changes. At week 2 postoperatively, however, there were no significant differences between the midazolam and placebo groups. CONCLUSIONS: Children who are premedicated with midazolam before surgery have fewer negative behavioral changes during the first postoperative week.  (+info)

Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal. (5/1442)

OBJECTIVE: To analyse the evidence for the efficacy and potential harmful effects of benzodiazepines compared with other therapies in the treatment of acute alcohol withdrawal. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1997 that described randomized controlled trials (RCTs) of benzodiazepines in the treatment of acute alcohol withdrawal. Key words included "benzodiazepines" (exploded) and "randomized controlled trial." Bibliographies of relevant articles were reviewed for additional RCTs, and manufacturers of benzodiazepines were asked to submit additional RCT reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were RCTs involving patients experiencing acute alcohol withdrawal and comparing a benzodiazepine available in Canada with placebo or an active control drug. Of the original 23 trials identified, 11 met these criteria, representing a total of 1286 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analysis of benefit (therapeutic success within 2 days) showed that benzodiazepines were superior to placebo (common odds ratio [OR] 3.28, 95% confidence interval [CI] 1.30-8.28). Data on comparisons between benzodiazepines and other drugs, including beta-blockers, carbamazepine and clonidine, could not be pooled, but none of the alternative drugs was found to be clearly more beneficial than the benzodiazepines. The meta-analysis of harm revealed no significant difference between benzodiazepines and alternative drugs in terms of adverse events (common OR 0.67, 95% CI 0.34-1.32) or dropout rates (common OR 0.68, 95% CI 0.47-0.97). INTERPRETATION: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal.  (+info)

Randomised controlled trial of reminders to enhance the impact of audit in general practice on management of patients who use benzodiazepines. (6/1442)

OBJECTIVE: To determine whether reminder cards in medical records enhance the effectiveness of audit with feedback in improving the care of patients taking long term benzodiazepine drugs. DESIGN: Randomised trial, practices receiving feedback only in one group and practices receiving feedback plus reminder cards in the other group. SETTING: 18 general practices in Leicestershire. SUBJECTS: Random samples of patients who had been taking a benzodiazepine anxiolytic or hypnotic drug for four weeks or longer. MAIN OUTCOME MEASURES: Entries in medical records indicating compliance with five criteria of care: assessment of suitability for withdrawal; being told about dependency; withdrawal being recommended; withdrawal or continuing medication; and a consultation with the general practitioner in the past year. Data were collected before and after feedback or feedback plus reminders. RESULTS: Of a total population of 125,846 registered with the 18 practices, 2409 (1.9%) had been taking a benzodiazepine for four weeks or longer. Of the 742 in the first samples, 543 (73.2%) were women, the mean (SD) age was 68.7 (14.9) years, and they had been taking a benzodiazepine for 10.1 (6.7) years. The number of patients whose care complied with the criteria rose after the interventions to implement change. The increase was greater in practices receiving feedback plus reminders for only two of the five criteria "told about dependency" increasing from 52 (11.1%) to 118 (25.8%) in the feedback only group, and from 27 (10.5%) to 184 (43.0%) in the feedback plus reminders group; odds ratio (OR) 1.46 (95% confidence interval (95% CI) 1.32 to 5.21); and "consulted in the past year" increasing from 434 (93.1%) to 411 (95.8%) in the feedback only group and 255 (96.6%) to 400 (99.8%) in the feedback plus reminders group, OR (95% CI) 13.5 (2.01 to 330.3). CONCLUSIONS: Reminder cards had only a limited effect and cannot be recommended for routine use. There were improvements in the care of patients of both groups of practices and further studies are indicated to determine the impact of both systematically developed criteria and reminders embedded into restructured medical records.  (+info)

Outpatient antidepressant utilization in a Dutch sick fund. (7/1442)

OBJECTIVE: To identify quality improvement opportunities in the management of depression by evaluating patterns of antidepressant use and concurrent use of anxiolytics or sedative/hypnotics among patients who initiated therapy with amitriptyline, fluoxetine, fluvoxamine, or paroxetine. DESIGN: A longitudinal, retrospective study using electronic prescription data from a Dutch sick fund, ZAO Zorgverzekeringen. PATIENTS AND METHODS: The study patients (n = 2,554) initiated therapy between October 1, 1994 and December 31, 1995. Follow-up periods were 6 months (antidepressant use) and 60 days (concurrent anxiolytic and sedative/hypnotic use). RESULTS: The three key findings were as follows: (1) the majority of patients received less than 4 months of therapy (more common for patients receiving amitriptyline); (2) the average daily doses for initial prescriptions for all four study drugs were below the recommended therapeutic minimums for depression (overall and final amitriptyline doses also were consistently low); and (3) the incidence of concurrent anxiolytic and sedative/hypnotic use during days 2-60 after antidepressant therapy initiation was 18.2%. CONCLUSION: The study suggests that patients in this Dutch sick fund were not likely to receive either adequate antidepressant doses or adequate durations of therapy relative to Dutch guidelines for the treatment of depression. These findings are consistent with findings in other Dutch, European, and US studies and may present opportunities for quality improvement.  (+info)

Supraspinal neurotensin-induced antianalgesia in mice is mediated by spinal cholecystokinin. (8/1442)

Intracerebral injection of neurotensin into specific brain loci in rats produces hyperalgesia due to the release of cholecystokinin (CCK) in the spinal cord. The present purpose was to show in another species that neurotensin can antagonize the antinociceptive action of morphine through the spinal CCK mechanism in mice. Neurotensin given intracerebroventricularly (i.c.v.) at doses higher than 100 ng produced antinociception in the tail flick test. However, at lower doses between 1 pg to 25 ng, neurotensin antagonized the antinociceptive action of morphine given intrathecally (i.t.), thus demonstrating the antianalgesic activity of neurotensin. The rightward shift in the morphine dose-response curve produced by i.c.v. neurotensin was eliminated by an i.t. pretreatment with CCK8 antibody (5 microl of antiserum solution diluted 1:1000). I.t. administration of lorglumide, a CCK(A)-receptor antagonist (10-1000 ng), and PD135,158, a CCK(B)-receptor antagonist (250-500 ng), also eliminated the antianalgesic action of neurotensin. Thus, the mechanism of the antianalgesic action of neurotensin given i.c.v. involved spinal CCK. This mode of action is similar to that for the antianalgesic action of supraspinal pentobarbital which also involves spinal CCK.  (+info)