British journal of clinical pharmacology
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Br J Clin Pharmacol · Jan 2011
The use of antidepressants and the risk of haemorrhagic stroke: a nested case control study.
Selective serotonin re-uptake inhibitors (SSRI) are associated with an increased risk of bleeding disorders at a number of sites. It is currently unclear whether they increase the risk of haemorrhagic stroke, with conflicting results reported. ⋯ We found no evidence that SSRIs are associated with an increased risk of haemorrhagic stroke, regardless of prior history of cerebrovascular events.
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Br J Clin Pharmacol · Jan 2011
Tobramycin disposition in ICU patients receiving a once daily regimen: population approach and dosage simulations.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? It is well known that tobramycin given as an once daily dose according to the usual recommendations needs therapeutic drug monitoring by measurement of peak and trough concentrations. In the literature, there are only few published studies on the population pharmacokinetics of once daily tobramycin in critically ill patients. Glomerular filtration rate and bodyweight were identified as covariates contributing to the inter-individual variability in the disposition of aminoglycosides. The study, by Peris-Marti et al. [24], only evaluated the pharmacodynamic effectiveness of a 4 mg kg(-1) dose of tobramycin given once daily in critically ill patients. The authors concluded with a simulation showing that for a theoretical MIC of 1 or 2 mg l(-1) , a 7 mg kg(-1) dose was required. ⋯ Even after taking into account COCK and height, for strains with an MIC ≤ 1 mg l(-1) , MCS doses evidenced that peak and AUC pharmacodynamic targets could not be reached simultaneously in more than 45% of the ICU patient population. Combination therapy in addition to drug monitoring are required to manage efficacy and toxicity.
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Br J Clin Pharmacol · Jan 2011
Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.
Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. ⋯ In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure.
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Br J Clin Pharmacol · Jan 2011
Evaluation of a morphine maturation model for the prediction of morphine clearance in children: how accurate is the predictive performance of the model?
The pharmacokinetics of morphine are well known in pre-term and term neonates, infants, younger and older children, as well as in adults. There are circumstances when a pharmacokinetic study may not be possible in children (especially neonates and infants), and as a result one would like to predict drug clearance in children. Several methods, such as allometric scaling and prediction based on incorporation of physiological parameters, have been suggested. Recently a morphine maturation model has been proposed to predict morphine clearance in the paediatric population. ⋯ The morphine maturation model has a poor predictive power of morphine clearance in preterm and term neonates, infants and very young children and may not be of any practical value for the prediction of morphine clearance in this age group.
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Br J Clin Pharmacol · Dec 2010
Evaluation of a QT nomogram for risk assessment after antidepressant overdose.
A QT-heart rate nomogram has recently been proposed as a means of identifying patients at risk of torsades de pointes after antidepressant overdose, based on published cases of drug-induced torsades de pointes. The present study sought to examine the performance of the nomogram in patients who ingest an antidepressant overdose but do not develop arrhythmia. ⋯ The QT nomogram was associated with a lower false positive rate than widely accepted QT(c) criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QT(c) criteria and merits further investigation in a clinical setting.