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  • 1
    Electronic Resource
    Electronic Resource
    Effects of atipamezole — a selective α2-adrenoceptor antagonist — on cardiac parasympathetic regulation in human subjects (2004)
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 24 (2004), S. 0 
    Details
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of α2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml−1 at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15–0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (±SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml−1. 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1474-8673.2004.00318.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of cardiac vagal outflow on complexity and fractal correlation properties of heart rate dynamics (2003)
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 23 (2003), S. 0 
    Details
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 Cardiac vagal outflow is the major factor determining the magnitude of heart rate (HR) variability analysed by traditional time and frequency domain methods. New analysis techniques, such as fractal and complexity methods, have been developed to probe non-linear features in HR behaviour that may not be detectable by traditional methods.2 We investigated the effects of vagal blockade (glycopyrrolate i.v. 5 μg kg−1 h−1 for 2 h, n = 8 vs. unmedicated control group, n = 8) and various breathing patterns (n = 12) on two non-linear measures of HR variability – detrended fluctuation analysis (DFA) and approximate entropy (ApEn) – in healthy male volunteers.3 Glycopyrrolate decreased the mean (±SD) ApEn from 1.46 ± 0.18 to 0.85 ± 0.24 (P = 0.001 in comparison with the control group), and increased the short-term (α1) and intermediate-term (α2) fractal scaling exponents of DFA, α1 from 0.96 ± 0.19 to 1.43 ± 0.29 (P = 0.003) and α2 from 1.13 ± 0.10 to 1.34 ± 0.14 (P 〈 0.001).4 Decrease in fixed respiration rate from 15 to 6 breaths min−1 increased α1 from 0.83 ± 0.25 to 1.18 ± 0.27 (P 〈 0.001), but decreased α2 from 0.88 ± 0.09 to 0.45 ± 0.17 (P 〈 0.001) and ApEn from 1.26 ± 0.12 to 1.10 ± 0.14 (P = 0.028). Rapid breathing (24 min−1) had no influence on these non-linear measures of HR variability. Hyperventilation (15 min−1, tidal volume increased voluntarily by 0.5 l) decreased α1 from 0.83 ± 0.25 to 0.66 ± 0.28 (P = 0.002) but did not affect α2 or ApEn.5 To conclude, vagal blockade alters the fractal scaling properties of R-R intervals (α1, α2) and reduces the complexity (ApEn) of HR behaviour. Both the fractal and complexity measures of HR variability can also be influenced by changes in the breathing pattern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1474-8673.2003.00293.x
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  • 3
    Electronic Resource
    Electronic Resource
    Correlation of EEG spectral entropy with regional cerebral blood flow during sevoflurane and propofol anaesthesia (2005)
    Oxford, UK : Blackwell Science Ltd
    Anaesthesia 60 (2005), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: ENTROPY™ index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.5 and 19.0 μg.ml−1 plasma drug concentrations of propofol. Spectral entropy from the frequency band 0.8–32 Hz was calculated and cerebral blood flow assessed using positron emission tomography and [15O]-labelled water at baseline and at each anaesthesia level. Both drugs induced significant reductions in spectral entropy and cortical and global cerebral blood flow. Midfrontal-central spectral entropy was associated with individual frontal and whole brain blood flow values across all conditions, suggesting that this novel measure of anaesthetic depth can depict global changes in neuronal activity induced by the drugs. The cortical areas of the most significant associations were remarkably similar for both drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.2005.04289.x
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  • 4
    Electronic Resource
    Electronic Resource
    Dexmedetomidine as intramuscular premedication for day-case cataract surgery (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 49 (1994), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of dexmedetomidine 1.0 μg.kg-1, midazolam 20 μg.kg-1 and saline placebo were assessed in a double-blind, randomised study in 90 patients undergoing day-case cataract surgery under regional anaesthesia. The trial drug was injected into the deltoid muscle 45 min before the peri-ocular block. Dexmedetomidine 1.0 μg.kg-1 decreased intra-ocular pressure before, during and after surgery. The maximum reduction in mean (SD) intra-ocular pressure occurred in the dexmedetomine group just before discharge from hospital (17.7 (2.8) mmHg to 11.5 (2.9) mmHg) (p 〈 0.001 compared with midazolam and placebo). In contrast, midazolam did not differ from saline placebo. Dexmedetomidine and midazolam produced a similar sedative effect of short duration. Dexmedetomidine induced a moderate decrease in blood pressure (p 〈 0.001 compared with placebo) and a slight but statistically significant decrease in heart rate throughout the study period (p 〈 0.001 compared with placebo). Dexmedetomidine 1.0 μg.kg-1 intramuscularly, effectively reduced intra-ocular pressure and produced short-acting sedation with marginal cardiovascular effects; it may be a useful premedicant drug for elderly patients undergoing day-case cataract surgery under regional anaesthesia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.1994.tb04257.x
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  • 5
    Electronic Resource
    Electronic Resource
    Dexmedetomidine as intramuscular premedication in outpatient cataract surgery (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 48 (1993), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Alpha2 agonists have been shown to decrease intra-ocular pressure in ophthalmic surgery. We studied the effects of dexmedetomidine, a new a2 agonist, on intra-ocular pressure, haemodynamic parameters, sedation, anxiolysis and dryness of mouth in 35 (Asa physical status 1–3) patients undergoing day-case cataract surgery under peri-ocular anaesthesia. Five different doses of dexmedetomidine (0.25, 0.5, 0.75, 1.0 and 1.5 μg.kg−1) were used in this double-blind, randomised and placebo-controlled study. The trial drug was administered into the deltoid muscle 60 min before surgery. The 1.0 μg.kg−1 dose of dexmedetomidine produced a 32% reduction of intra-ocular pressure (p = 0.002). This dose induced moderate sedation, but was not associated with significant haemodynamic changes. A significant decrease in heart rate and systolic blood pressure was seen only with the highest dose of dexmedetomidine. Our results suggest that dexmedetomidine 1.0 μg.kg−1 produces sedation and a reduction of intra-ocular pressure with minimal haemodynamic side effects when given intramuscularly as premedication before cataract surgery under regional anaesthesia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.1993.tb07066.x
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  • 6
    Electronic Resource
    Electronic Resource
    A medication database – a tool for detecting drug interactions in hospital (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 13-17 
    Details
    ISSN: 1432-1041
    Keywords: Key words Drug Interactions ; Hospital
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Drug interactions may lead to life-threatening injuries. More often, however, they lead to slow recovery, induce slight symptoms or result only in potential injury. Therefore, clinicians are not always aware of using potentially interacting drug combinations. An on-line alarming system of potential drug interactions was developed in Turku University Central Hospital. In the present study, we utilised the system to find out the incidence and nature of potential drug interactions occurring in a representative hospital patient population. Methods: Computerised anatomical therapeutic chemical (ATC)-coded patient medication data of 2547 patients, treated in two internal medicine wards, were combined with an ATC-coded rule base of drug interactions. All potential drug interactions in the study population were searched for. Results: A total of 326 potentially serious drug interactions were detected in the study population. The number of patients in this group was 173, i.e. 6.8% of all patients had one or several drug combinations which might have led to serious clinical consequences. Concomitant use of calcium and fluoroquinolones (decreased absorption) was the most common mistake (66 prescriptions). Conclusions: Potentially inappropriate drug combinations seem to occur frequently. Structured and coded medication data can be utilised efficiently to detect potential drug interactions in hospital. Computerised on-line monitoring and automatic alarming of potentially hazardous drug combinations might help clinicians to prescribe more safely, but further development of the system is needed to avoid unnecessary alarms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050330
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of dexmedetomidine and midazolam on human performance and mood (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 217-223 
    Details
    ISSN: 1432-1041
    Keywords: Dexmedetomidine ; Midazolam ; Human performance ; α2-adrenoceptor agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of dexmedetomidine (DXM), a novel α2-adrenoceptor agonist, on human performance and mood were studied in a double-blind randomized crossover study in 12 healthy student volunteers. Single IM doses of dexmedetomidine, 0.6 μg/kg (DXM1) and 1.2 μg/kg (DXM2), 80 μg/kg midazolam (MID) and saline placebo, were given at one-week intervals. Performance was measured objectively and mood was assessed subjectively with visual analogue scales (VAS) at baseline and 40 min, 2 h, 4 h and 6 h after each injection. Blood pressure and heart rate in the sitting position were measured and venous blood was sampled during each testing round. DXM1 did not significantly impair cognitive (digit symbol substitution), coordinative (tracking) or reactive skills, and at 6 h it shortened reaction time and reduced errors in complex tracking. It produced exophoria, increased body sway with the eyes open and impaired subjective performance on VAS. The higher dose dexmedetomidine also caused impaired cognitive, coordinative and reactive skills (although a trend towards improved coordination was found at 6 h), reduced attention, produced exophoria, increased body sway with the eyes open and caused drowsiness, clumsiness, passiveness and mental slowness on the appropriate VAS scales. MID resembled DXM2 in impaired objective and subjective measures of skilled performance, although the objective effects of MID were of speedier onset and shorter duration. In contrast to MID, DXM caused a significant and dose-dependent decrease in systolic and diastolic blood pressure still detectable 6 h after injection. It is concluded that IM DXM produces dose related impairment of skilled performance and produces subjective sedation, the effects of 1.2 μg/kg being comparable to those produced by 80 μg/kg MID, although the latter lasted for a shorter period and were not associated with haemodynamic changes. Since the effect of DXM on performance waned earlier than its haemodynamic actions, DXM may constitute a suitable preanaesthetic medication, particularly in hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315433
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  • 8
    Electronic Resource
    Electronic Resource
    A double-blind study of MPV-2213ad, a novel aromatase inhibitor, in healthy male subjects (1999)
    Springer
    European journal of clinical pharmacology 55 (1999), S. 27-34 
    Details
    ISSN: 1432-1041
    Keywords: Key words Aromatase inhibitor ; MPV-2213ad ; Phase I study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Novel aromatase inhibitors are developed with requirements of high potency and selectivity for the aromatase enzyme. The hormonal effects of a new, non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were investigated in this study. Methods: The study was conducted as a double-blind, placebo controlled phase I study, where 32 healthy male volunteers were randomized to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad or placebo. Serum concentrations of estradiol (E2), testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone were determined from samples taken 0, 4, 8 h and 12 h during the day of drug administration and 1, 2, 4 and 7 days after drug intake. The individual diurnal variation of circulating hormone concentrations was determined in all participants at 0, 4, 8 h and 12 h on the day before drug intake. Specimens for hematological and biochemical analyses were also collected. Results: A dose-dependent and statistically significant (P 〈 0.001) decrease in serum E2 concentrations was induced by MPV-2213ad. Lowest mean values were observed 8–12 h after drug administration and at 24 h the reductions were 10%, 34% and 69% from baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18% increase in the placebo group. Serum E2 concentrations returned to baseline within 4 days in all study subjects. A significant increase was observed in the serum concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P 〈 0.001) after administration of MPV-2213ad. Serum concentrations of cortisol and aldosterone were unaffected by MPV-2213ad. The drug was well tolerated. Conclusion: Single oral doses of MPV-2213ad, given to healthy male subjects, induced hormonal effects typical for a specific and selective inhibitor of the aromatase enzyme. Importantly, this study design with the determination of the diurnal rhythm in the levels of the corresponding hormones gives additional validity on the results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050588
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