British journal of clinical pharmacology
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Br J Clin Pharmacol · Feb 2004
Randomized Controlled Trial Clinical TrialModelling acute tolerance to the EEG effect of two benzodiazepines.
We studied the development of acute tolerance to the EEG effect of midazolam and the new benzodiazepine Ro 48-6791. ⋯ Midzolam and Ro 48-6791 showed acute tolerance to the EEG effect which might be caused by competitive interaction with the metabolite.
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Br J Clin Pharmacol · Feb 2004
Randomized Controlled Trial Comparative Study Clinical TrialComparative population pharmacokinetics of lorazepam and midazolam during long-term continuous infusion in critically ill patients.
It is well established that there is a wide intra- and interindividual variability in dose requirements for lorazepam and midazolam in intensive care patients. The objective of this study was to compare the population pharmacokinetics of lorazepam and midazolam after long-term continuous infusion in mechanically ventilated critically ill patients. ⋯ The pharmacokinetics of both lorazepam and midazolam were well described by a two-compartment model. Inclusion of alcohol abuse and age as covariates improved both models. PEEP was identified as an additional covariate for lorazepam, and the APACHE score for midazolam. For both drugs there is a large interindividual variability in their pharmacokinetics when used for long-term sedation in critically ill patients. However, the intra-individual variability is much lower for lorazepam.
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Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacology of the drug and therefore potentially avoidable. Frail elderly patients appear to be particularly at risk of ADRs and this group is also likely to be receiving several medicines. ⋯ The use of computer-based decision support systems (CDSS) and electronic prescribing should be encouraged, and when problems do occur, health professionals need to be aware of their professional responsibility to report suspected adverse drug events (ADEs) and ADRs. "Rational" or "obligatory" polypharmacy is becoming a legitimate practice as increasing numbers of individuals live longer and the range of available therapeutic options for many medical conditions increases. The clear risk of ADRs in this situation should be considered in the context that dose-related failure of existing therapy to manage the condition adequately may be one of the most important reasons for admission of the elderly to hospital. Thus, age itself should not be used as a reason for withholding adequate doses of effective therapies.