British journal of anaesthesia
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Post-ischaemic benzodiazepine administration is neuroprotective, but chronic administration of benzodiazepines can induce tolerance, such that the neuroprotective effect may be reduced. This study investigated whether benzodiazepine tolerance can worsen ischaemic injury and whether neuroprotection by post-ischaemic benzodiazepine administration is affected by benzodiazepine tolerance. We also investigated whether antagonism of benzodiazepine receptors by flumazenil was able to restore neuroprotection during benzodiazepine tolerance. ⋯ Benzodiazepine tolerance can worsen ischaemic neuronal injury and abolish the neuroprotection provided by post-ischaemic diazepam. Pre-treatment with flumazenil treatment reversed benzodiazepine tolerance and restored neuroprotection by post-ischaemic diazepam. These findings may suggest that management of patient's risk of developing cerebral ischaemia may need to take into account current use.
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Carbamazepine and pregabalin have proven effects against neuropathic pain. Carbamazepine blocks voltage-dependent Na(+) channels, whereas pregabalin blocks voltage-dependent Ca(2+) channels. The authors hypothesized that the co-administration of these drugs would synergistically reduce neuropathic pain. ⋯ Carbamazepine and pregabalin ameliorate neuropathic pain synergistically at higher doses.