European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 1995
ReviewFlucloxacillin associated cholestatic hepatitis. An Australian and Swedish epidemic?
The clinico-pathological entity of flucloxacillin-associated cholestatic hepatitis is described and the recognition and documentation of cholestasis associated with flucloxacillin and with related isoxazolyl-penicillins (cloxacillin, dicloxacillin) is examined on an international basis, with particular reference to Australia. Data were obtained from the literature, from the Australian adverse drug reaction monitoring agency and from the Collaborative Centre for International Drug Monitoring (World Health Organisation) in Sweden. Approximately 600 cases of flucloxacillin-associated cholestatic hepatitis were collected, as well as 164 cases associated with other isoxazolyl penicillins. ⋯ In Australia, the remarkably high rate of reports appears to be the result of sustained publicity for the reaction. There is only a trickle of reports of cholestatic hepatitis in association with the use of cloxacillin and dicloxacillin from the USA and Canada. The high level of awareness of the reaction and consequential regulatory action so far have not resulted in a diminution of its occurrence in Australia.
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According to the World Health Organisation, a country's morphine consumption is an important indicator of progress in cancer pain relief. Due to its very high opioid consumption, Denmark is often pointed out as a country worthy of imitation. The aim of the present study was to analyse Danish opioid consumption in order to elucidate the usage pattern and to identify the consumers. ⋯ The consumption of long acting opioids (sustained release morphine, methadone, buprenorphine) and short acting opioids (others) increased by 1427% and 105%, respectively. Analysis of a sample of 1854 prescriptions for opioids revealed that less than 10% of the prescriptions were issued for cancer pain conditions. It is concluded: that if other countries consider Denmark as worthy of imitation in opioid treatment for cancer pain, attention should be paid to the pattern of the Danish opioid consumption, which is outstanding with respect to quantity but the quality may be questionable.
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Eur. J. Clin. Pharmacol. · Jan 1995
CSF concentrations and clinical effects following intravenous dixyrazine premedication.
Single concurrent plasma and lumbar spinal fluid samples were collected from twenty-two patients given IV dixyrazine 0.15 mg/kg, 10-106 min earlier in an open study. Dixyrazine penetrated rapidly into the spinal fluid; the CSF/P ratio was 0.3 by 10 min after drug administration and persisted at that level during the study period. The uncontrolled sedative and anxiolytic effects assessed by the patients were slight, and were correlated with the CSF drug concentrations only during the first 30 min after medication.
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Eur. J. Clin. Pharmacol. · Jan 1995
Randomized Controlled Trial Comparative Study Clinical TrialThe cognitive and psychomotor effects of opioid analgesics. II. A randomized controlled trial of single doses of morphine, lorazepam and placebo in healthy subjects.
Twelve subjects (8 male) took part in a randomised double blind four way crossover design study comparing four treatments: (i) morphine sulphate 10 mg, (ii) morphine sulphate 15 mg, (iii) lorazepam 1 mg (positive control) and (iv) placebo. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam produced a marked impairment in the tests of attention and memory. ⋯ Morphine 15 mg produced a significant improvement in accuracy on the choice reaction time test at the 2, 4 and 6 h assessments. These results show minimal impairment of cognitive and psychomotor function after single oral doses of morphine and with possible improvement in one test. Further studies are required to examine the effect of repeated doses.
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Eur. J. Clin. Pharmacol. · Jan 1995
Randomized Controlled Trial Clinical TrialInfluence of piroxicam coadministration on pharmacodynamic parameters and the plasma concentration/effect relationship of recombinant hirudin (CGP 39393).
Recombinant hirudins are currently under investigation for use in myocardial infarction and unstable angina. In this study the influence of piroxicam on the pharmacodynamics and pharmacokinetics of a recombinant hirudin preparation (CGP 39393) administered intravenously was determined. Twelve healthy, male volunteers received piroxicam 10 mg and matching placebo once daily for 12 days according to a double-blind, randomised cross-over design. ⋯ No change was observed in the platelet adhesion index. Responsiveness parameters according to a sigmoidal Emax-model were obtained from the hirudin-plasma concentration/effect (i.e. APTT-prolongation)-curves after placebo and piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)