Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600097 (Sedation)
 1,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that elderly men eliminate alprazolam more slowly than young adults. This study in the elderly was designed to determine whether a change in pharmacokinetics influences the response to alprazolam during multiple dose regimens. In addition, the study was designed to determine alprazolam pharmacokinetics and the degree to which its hydroxymetabolites accumulate, the degree of psychomotor impairment, and whether tolerance to impairment and sedation develops during three different multiple dose regimens. Twenty-six subjects completed this study. The subjects were randomized into one of three treatment groups: 0.25 mg q8h, 0.5 mg q8h, and 2 mg q12h. Subjects remained in the clinic for 8 days (day -2-day 5). Day 0 was used as a drug free testing day to establish baseline scores for sedation, digit symbol substitution (DSS), card sorting (CS) tasks, and two computer tests. Subjects received the drug according to schedule on days 1 through 4, with day 5 as the washout day. Blood samples were assayed for alprazolam, alpha-hydroxyalprazolam and 4-hydroxyalprazolam. Alpha-hydroxyalprazolam concentrations were below assay detection limits in all subjects in the 0.25 and 0.5 mg q8h groups and less than or equal to 2.6 ng/ml in the 2 mg q12h group. When detectable, 4-hydroxyalprazolam concentrations were less than 10% of the corresponding alprazolam concentration. Mean alprazolam oral clearance values in the three treatment groups ranged between 0.54 and 0.62 ml/min/kg and half-lives were in excess of 21 h. Degree of sedation and impairment was dose related. Sedation and impairment was not higher on day 4 despite concentrations 2-3 times as great as on day 1, indicating development of tolerance. Subjects were not, however, back to baseline level of performance on day 4.
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PMID:Alprazolam in the elderly: pharmacokinetics and pharmacodynamics during multiple dosing. 232 Jul 8

The relationships between alprazolam and metabolite concentrations and CNS effects were determined in a double-blind placebo controlled four-way crossover trial in 16 normal male volunteers. Active drug treatments consisted of 4-day regimens of 4 mg alprazolam PO daily as 2 mg bid., 1 mg qid, and 0.25 mg each hour. On days 1 and 4, the kinetics, sedative and psychomotor effects were evaluated. Plasma concentrations of the 4- and alpha-hydroxy metabolites of alprazolam were less than 10% of unchanged alprazolam levels on both days. Accumulation of these metabolites and alprazolam was dependent on alprazolam half-life (11.6 h). Acute and chronic tolerance to the sedative and psychomotor effects was observed with all active drug treatments. All alprazolam treatments resulted in significantly greater sedation than placebo on days 1 and 4. However, on day 4, sedation was 16-36% less than observed on day 1, despite plasma concentrations 1.4-2.76 times the day 1 concentrations. Sedation from alprazolam was reduced in each successive study phase, suggesting a tolerance which was sustained during the 10-day washout between phases. By day 4, psychomotor performance was not different from placebo, indicating more complete development of tolerance than occurred for the sedative effect. Sedation and psychomotor impairment on day 1 were greatest with 2 mg alprazolam bid. During the initiation of therapy, the patient will likely experience less sedation and psychomotor impairment with smaller, more frequent doses. Since tolerance develops to these effects, the advantage of more frequent dosing regimen dissipates by the 4th day.
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PMID:Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. 311 8

Sedation and impairment of psychomotor performance are well known adverse effects of the traditional antihistamines. These effects appear to be caused by different mechanisms, but both may have potentially dangerous consequences. while several of the newer antihistamines, such as terfenadine, have overcome the problem of sedation, it is also important to establish their propensity to cause psychomotor impairment. Many single- and multiple-dose studies (mostly in healthy volunteers) have compared the effects of terfenadine on psychomotor performance with those of placebo, as well as traditional and other nonsedating antihistamines. Over half of the studies employed divided-attention tasks that are considered relevant to everyday activities, such as driving. Like several other nonsedating antihistamines, single doses of terfenadine of up to 120 mg did not impair driving performance and generally had no significant effects on other psychomotor tests compared with placebo. In most of the multiple-dose studies, terfenadine 60 mg twice daily was administered for up to 5 days. Again, the effects of terfenadine on psychomotor performance differed little from those of placebo. Thus, the available evidence suggests that the problem of impaired psychomotor performance associated with the older, traditional antihistamines does not apply to terfenadine.
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PMID:Effects of terfenadine on psychomotor performance. An overview. 848 Dec 18

We have evaluated the perioperative effects of melatonin with those of midazolam in 75 women in a prospective, randomized, double-blind, placebo-controlled study. Patients were given sublingual midazolam 15 mg, melatonin 5 mg or placebo, approximately 100 min before a standard anaesthetic. Sedation, anxiety and orientation were quantified before, and 10, 30, 60 and 90 min after premedication, and 15, 30, 60 and 90 min after admission to the recovery room. Psychomotor performance was evaluated at these times also, using the digit-symbol substitution test (DSST) and the Trieger dot test (TDT). Patients who received premedication with either midazolam or melatonin had a significant decrease in anxiety levels and increase in levels of sedation before operation compared with controls. Midazolam produced the highest scores for sedation at 30 and 60 min after administration and significant psychomotor impairment in the preoperative period compared with melatonin or placebo. After operation, patients who received midazolam or melatonin premedication had increased levels of sedation at 30 min and impairment in performance on the DSST at 15, 30 and 90 min compared with controls. There were no significant differences between the three groups for anxiety levels or TDT performance after operation. Amnesia was notable only in the midazolam group for one preoperative event (entry into the operating room). Patient satisfaction was noted in the midazolam and melatonin groups only. We have demonstrated that melatonin can be used effectively for premedication of adult patients.
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PMID:Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. 1056 82