Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Sep 2013
Intravenous lipid emulsion entraps amitriptyline into plasma and can lower its brain concentration--an experimental intoxication study in pigs.
Intravenous lipid emulsion has been suggested as treatment for severe intoxications caused by lipophilic drugs, including tricyclic antidepressants. We investigated the effect of lipid infusion on plasma and tissue concentrations of amitriptyline and haemodynamic recovery, when lipid was given after amitriptyline distribution into well-perfused organs. Twenty anaesthetized pigs received amitriptyline intravenously 10 mg/kg for 15 min. ⋯ Two pigs developed severe hypotension during the lipid infusion and were given adrenaline. In conclusion, lipid infusion, given not earlier than after an initial amitriptyline tissue distribution, was able to entrap amitriptyline back into plasma from brain and possibly from other highly perfused, lipid-rich tissues. In spite of the entrapment, there was no difference in haemodynamics between the groups.
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Basic Clin. Pharmacol. Toxicol. · Aug 2013
Observational StudySex difference in formation of propofol metabolites: a replication study.
Women recover faster from propofol anaesthesia and have been described to have a higher incidence of awareness during surgery, compared to men - an effect that may be inherent in sex differences in propofol metabolism. In an observational study, 98 ASA I-II patients treated with continuous propofol infusion were recruited. ⋯ There was, however, no significant impact of gene polymorphisms on propofol biotransformation. The results, which are supported by a previous pilot study using a propofol bolus dose, suggest that, compared to men, more rapid propofol metabolism may occur in women - a factor that may contribute to the mentioned differences in the efficacy of propofol anaesthesia between male and female patients.
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Basic Clin. Pharmacol. Toxicol. · Apr 2013
Review Case ReportsAcute poisoning with neonicotinoid insecticides: a case report and literature review.
Neonicotinoids are a new class of insecticides widely applied for crop protection. These insecticides act as agonists at nicotinic acetylcholine receptors, which cause insect paralysis and death. The high specificity for receptors in insects was considered to possess highly selective toxicity to insects and relative sparing of mammals. ⋯ A detailed literature review found that respiratory, cardiovascular and certain neurological presentations are warning signs of severe neonicotinoid intoxication. The amounts of ingested neonicotinoid insecticide and the plasma neonicotinoid concentration are not useful guides for the management of intoxicated patients. Supportive treatment and decontamination are the practical methods for the management of all neonicotinoid-poisoned patients.
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Basic Clin. Pharmacol. Toxicol. · Mar 2013
Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.
Facilitation of spinal GABAergic inhibition with benzodiazepines (BZDs) reverses pain sensitization in animals; however, the use of BZDs in man is limited by their sedative effect. The antihyperalgesic effects of GABA(A) agonists are mediated by GABA(A) receptors containing α2 subunits, whereas sedation is linked to α1 subunit-containing receptors. α2 and α3 selective GABA(A) receptor modulators have been tested in animals but are not yet available for use in human beings. Clobazam is a 1,5-BZD, which exhibits less cognitive side effects than other benzodiazepines. ⋯ Clobazam blood concentrations decreased rapidly, falling below the limit of detection at 120 min. after drug application. Its main metabolite, N-desmethyl-clobazam, showed more delayed and prolonged pharmacokinetics, partly explaining why antihyperalgesia persisted when clobazam was no longer detectable in the blood. Considering its therapeutic margin and its pharmacokinetic properties, clobazam would be a valuable compound to assess the role of the GABAergic pathway in pain transmission in human beings.
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Basic Clin. Pharmacol. Toxicol. · Mar 2013
Randomized Controlled TrialThe effects of lidocaine used in sciatic nerve on the pharmacodynamics and pharmacokinetics of ropivacaine in sciatic nerve combined with lumbar plexus blockade: a double-blind, randomized study.
In this controlled, randomized, double-blind study, we compared the pharmacodynamics and pharmacokinetics of ropivacaine and staged injection of lidocaine and ropivacaine in a combined lumbar plexus-sciatic nerve block. The experiment was performed in two parts: pharmacodynamics study (Group r, n = 20; Group lr, n = 20) and pharmacokinetics study (Group R, n = 10; Group LR, n = 10). The sciatic nerve blockade was performed using either (1) 10 mL of 2% lidocaine and then 10 mL of 0.75% ropivacaine (Group lr and Group LR) or (2) 10 mL of normal saline (N. ⋯ C(max) of ropivacaine in Group LR was significantly higher than that in Group R. A significant increase in AUC((0-t)) and AUC((0-∞)) was observed in Group LR compared with Group R. When 2% lidocaine and 0.75% ropivacaine are used for a combined sciatic nerve-lumbar plexus block by 'staged' injection, lidocaine induced faster onset times, decreased the block duration and increased the AUC and C(max) of ropivacaine.