Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Aug 2013
The neurotoxicity of intrathecal lidocaine is enhanced in postpartum compared to virgin rats.
During the perinatal period, the pharmacokinetics and pharmacodynamics of drugs may be altered. Data about the neurotoxicity of intrathecal local anesthetics in the peripartum period are lacking. So we hypothesized that the neurotoxicity of intrathecal lidocaine during perinatal period may be changed. ⋯ Lidocaine induced a dose-dependent impairment in TF latencies and nerve injury scores. There was no significant interaction between postpartum and the drug. Our results suggest that the neurotoxicity of intrathecal lidocaine is enhanced in rats during the early postpartum period compared with nonpregnant, virgin rats.
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Fundam Clin Pharmacol · Jun 2013
Randomized Controlled TrialParacetamol and opioid pathways: a pilot randomized clinical trial.
Previous studies suggest that the antinociceptive action of paracetamol (acetaminophen, APAP) might involve descending inhibitory pain pathways and the opioidergic system: this study explores this issue in humans with naloxone, the opioid antagonist. After ethical approval, 12 healthy male volunteers were included in this randomized, controlled, double-blind, crossover, four-arm study. They were administered intravenous paracetamol (APAP 1 g) or saline (placebo, pl) followed at 100 min with IV naloxone (Nal 8 mg) or saline, every week for 4 weeks. ⋯ AUC (0-150) of APAP/pl is significantly different from pl/pl (-3452%.min (95%CI -4705 to -2199) vs. -933% min (95%CI -2273 to 407; P = 0.015) but not from APAP/Nal (-1731% min (95%CI -3676 to 214; P = 0.08) and other treatments. AUC (90-150) is not significantly different. This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception, suggesting no significant implication of the opioid system in paracetamol mechanism of action: this needs be confirmed on a larger number of subjects.
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Fundam Clin Pharmacol · Jun 2013
The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia.
Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma-aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro-inflammatory compound carrageenan. ⋯ Local peripheral topiramate (0.03-0.34 mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.05-0.2 mg/paw; i.pl.) but not by local peripheral bicuculline (0.15 mg/paw; i.pl.) or naloxone (0.1 mg/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABAA and opioid receptors and by peripheral and most probably central α2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.
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Fundam Clin Pharmacol · Feb 2013
ReviewVolatile anaesthetics and cardioprotection: lessons from animal studies.
Volatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. ⋯ Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies.
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Fundam Clin Pharmacol · Dec 2012
Randomized Controlled TrialEvaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double-blind placebo-controlled pilot study.
Cardiac surgery and cardiopulmonary bypass (CPB) induce ischemia-reperfusion and subsequent cellular injury with inflammatory reaction. Clinical and experimental studies suggest that recombinant human erythropoietin (EPO) independently of its erythropoietic effect may be used as a cytoprotective agent against ischemic injury. We tested the hypothesis that one large dose of EPO administered shortly before CPB prevents the elevation of cardiac and cerebral ischemic blood markers as well as the systemic inflammatory response induced by cardiac surgery with CBP through this randomized double-blind placebo-controlled pilot trial. ⋯ Compared with the placebo, EPO administration before CPB did not prevent an increase of all these markers following CPB. In conclusion, one large dose of EPO, given shortly before CPB, did not protect against cardiac and cerebral ischemia and inflammatory response occurring during CABG surgery with CPB. Although the long-term clinical implications remain unknown, the findings do not support use of EPO at this dose as a cytoprotective agent in patients undergoing cardiac surgery.