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Clinical severity of acute carbamazepine poisonings: CNS depression and cardiotoxicity
S252
Abstracts / Toxicology Letters 189S (2009) S57–S273
Results: Gastro-intestinal topics (aluminium hydroxide gel, antiacids) and sustained released forms (enteric-coated aspirin tablets, slow-release carbamazepine or nifedipine) are found to lead to pharmacobezoars which are formed either due to medicine mechanism (gastro-intestinal topics) or to gelification from cellulose derivatives and insolubility of the carrying vehicle of enteric-coated. Risk factors related to the subject are: morphology of the gastro-intestinal tract (stenosis, . . .), its motility (reduced by morphinic, diabetes, . . .). Discussion and conclusion: Knowledge of individual characteristics of subject and of the mechanism under pharmacobezoars formation and their composition could improve the treatment avoiding surgical management (gastroscopy with bezoards fragmentation). These findings also suggest avoiding gastro-intestinal topics and sustained released forms in pediatric, elderly and patients with modification of gastro-intestinal tract or intestinal motility. doi:10.1016/j.toxlet.2009.06.790
G09 Clinical severity of acute carbamazepine poisonings: CNS depression and cardiotoxicity Gordana Babic ∗ , Jasmina Jovic Stosic, Slavica Vucinic, Veljko Todorovic Military Medical Academy, National Poison Control Centre, Belgrade, Serbia Purpose: The analysis of clinical severity, CNS depression, cardiotoxicity and its relation with plasma concentration in acute carbamazepine poisonings. Methods: The retrospective analysis of patients clinically treated for acute carbamazepine poisoning during 2008. Severity assessed according to the Poisoning Severity Score. Results: In the one-year period, 67 patients were treated for acute carbamazepine poisoning. Mild poisoning was exhibited in 27 (40.3%) patients. The serum carbamazepine concentration in this group ranged from 13.04 mg/l to 32.89 mg/l. Somnolence was the most common sign of poisoning, associated with dysarhtria in almost all patients, tachycardia in 5, hypotension in 3 and nonspecific AV conduction delay in 2 patients. Moderate poisoning was found among 17 (25.4%) patients. The serum carbamazepine concentration ranged from 14.83 mg/l to 37.11 mg/l. Sopor was registered in all patients; with 2 patients fluctuation of consciousness with periods of agitation. Tachycardia was noticed in 4, hypotension in 3, and first degree AV block in 2 patients. As a complication of acute poisoning, three patients developed aspiration bronchopneumonia, and 3 developed mild to moderate rhabdomyolisis. Severe poisoning was displayed in 23 (34.3%) patients. The serum carbamazepine concentration ranged from 15.58 mg/l to 49.92 mg/l. All these patients presented with coma, mostly associated with either tachycardia or hypotension, or both. In one patient ECG showed a prolonged QT interval, in two patients registered sinus bradycardia. The mortality rate was 1.49%. A lethal outcome was registered in one patient who was severe intoxicated, with a plasma carbamazepine concentration 51.87 mg/l. doi:10.1016/j.toxlet.2009.06.791
G10 Psychopharmacological properties of the pyridoindole derivative SMe1EC2 Mojmir Mach ∗ , Eduard Ujhazy, Michal Dubovicky Institute of Experimental Pharmacology & Toxicology, Department Reproductive Toxicology, Bratislava, Slovakia Anxiety and depression are the most common mental illnesses affecting more than 35 million Americans each year. More than 27% of adult Europeans are estimated to experience at least one form of mental illness during any one year. According to the World Health Organization, by the year 2020, depression is expected to be the highest ranking cause of disease in the developed world. Pyridoindole derivatives synthesized in our Institute have excellent antioxidant properties and their application is primarily aimed to decrease oxidative stress in certain pathological processes. Moreover, their very low toxicity (LD50 > 2000 mg), thus they are considered safe substances. In our study we found that these derivatives possess also anxiolytic potency. We used a behavioral battery of tests (open field, elevated plus maze and light/dark exploration) to study the anxiolytic activity of the pyridoindole SMe1EC2 derivative at doses of 5, 10 and 25 mg/kg. Diazepam was used as positive control. The results showed that the highest dose of SMe1EC2 increased the time spent in the open arms and it also increased the time spent in the light box. These results were comparable with the golden standard for these tests, diazepam. Moreover, no changes in motor activity were observed, indicating no inhibition or activation of central nervous system. If we take into account the low toxicity and good antioxidant properties, this compound may have a good potential in alleviating anxiety. This study was supported by the grants VEGA 2/0066/09 & 2/0083/08. doi:10.1016/j.toxlet.2009.06.792
G11 Functional status of synaptic structures in posthypoxic period Vyacheslav Lutov 1 , Salavat Sarmanaev 2 , Albert Gizatullin 1 , Roza Tuktarova 3,∗ 1
Bashkir State Medical University, Physiology, Ufa, Russian Federation, 2 FMBA, Toxicological Center, Moscow, Russian Federation, 3 Hospital 21, Emergency, Ufa, Russian Federation Background: Functional recovery of nervous tissue in posthypoxic period has phase character traceable on hypoxia (H) duration. One of the first reasons is functional heterogeneity nervous tissue, realized in various sensitivity of it elements to H. Purpose: Estimation of recovery electroretinogram (ERG) opportunity after H of various duration. Materials: We carried out experimental research on rabbit isolated perfused retina. Results: The process of recovery ERG after 60-min of H proceeded in 3-phases. There is during of the first phase restoration occurred of b-wave amplitude up to control parameters and then a-wave. In the second phase of recovery ERG was observed significant restoration of b-wave; the latency period reached a minimum, but up to the level of the control did not reach. The subsequently amplitude of the b-wave was reduced, and her latency period grew.
Abstracts / Toxicology Letters 189S (2009) S57–S273
Results: Gastro-intestinal topics (aluminium hydroxide gel, antiacids) and sustained released forms (enteric-coated aspirin tablets, slow-release carbamazepine or nifedipine) are found to lead to pharmacobezoars which are formed either due to medicine mechanism (gastro-intestinal topics) or to gelification from cellulose derivatives and insolubility of the carrying vehicle of enteric-coated. Risk factors related to the subject are: morphology of the gastro-intestinal tract (stenosis, . . .), its motility (reduced by morphinic, diabetes, . . .). Discussion and conclusion: Knowledge of individual characteristics of subject and of the mechanism under pharmacobezoars formation and their composition could improve the treatment avoiding surgical management (gastroscopy with bezoards fragmentation). These findings also suggest avoiding gastro-intestinal topics and sustained released forms in pediatric, elderly and patients with modification of gastro-intestinal tract or intestinal motility. doi:10.1016/j.toxlet.2009.06.790
G09 Clinical severity of acute carbamazepine poisonings: CNS depression and cardiotoxicity Gordana Babic ∗ , Jasmina Jovic Stosic, Slavica Vucinic, Veljko Todorovic Military Medical Academy, National Poison Control Centre, Belgrade, Serbia Purpose: The analysis of clinical severity, CNS depression, cardiotoxicity and its relation with plasma concentration in acute carbamazepine poisonings. Methods: The retrospective analysis of patients clinically treated for acute carbamazepine poisoning during 2008. Severity assessed according to the Poisoning Severity Score. Results: In the one-year period, 67 patients were treated for acute carbamazepine poisoning. Mild poisoning was exhibited in 27 (40.3%) patients. The serum carbamazepine concentration in this group ranged from 13.04 mg/l to 32.89 mg/l. Somnolence was the most common sign of poisoning, associated with dysarhtria in almost all patients, tachycardia in 5, hypotension in 3 and nonspecific AV conduction delay in 2 patients. Moderate poisoning was found among 17 (25.4%) patients. The serum carbamazepine concentration ranged from 14.83 mg/l to 37.11 mg/l. Sopor was registered in all patients; with 2 patients fluctuation of consciousness with periods of agitation. Tachycardia was noticed in 4, hypotension in 3, and first degree AV block in 2 patients. As a complication of acute poisoning, three patients developed aspiration bronchopneumonia, and 3 developed mild to moderate rhabdomyolisis. Severe poisoning was displayed in 23 (34.3%) patients. The serum carbamazepine concentration ranged from 15.58 mg/l to 49.92 mg/l. All these patients presented with coma, mostly associated with either tachycardia or hypotension, or both. In one patient ECG showed a prolonged QT interval, in two patients registered sinus bradycardia. The mortality rate was 1.49%. A lethal outcome was registered in one patient who was severe intoxicated, with a plasma carbamazepine concentration 51.87 mg/l. doi:10.1016/j.toxlet.2009.06.791
G10 Psychopharmacological properties of the pyridoindole derivative SMe1EC2 Mojmir Mach ∗ , Eduard Ujhazy, Michal Dubovicky Institute of Experimental Pharmacology & Toxicology, Department Reproductive Toxicology, Bratislava, Slovakia Anxiety and depression are the most common mental illnesses affecting more than 35 million Americans each year. More than 27% of adult Europeans are estimated to experience at least one form of mental illness during any one year. According to the World Health Organization, by the year 2020, depression is expected to be the highest ranking cause of disease in the developed world. Pyridoindole derivatives synthesized in our Institute have excellent antioxidant properties and their application is primarily aimed to decrease oxidative stress in certain pathological processes. Moreover, their very low toxicity (LD50 > 2000 mg), thus they are considered safe substances. In our study we found that these derivatives possess also anxiolytic potency. We used a behavioral battery of tests (open field, elevated plus maze and light/dark exploration) to study the anxiolytic activity of the pyridoindole SMe1EC2 derivative at doses of 5, 10 and 25 mg/kg. Diazepam was used as positive control. The results showed that the highest dose of SMe1EC2 increased the time spent in the open arms and it also increased the time spent in the light box. These results were comparable with the golden standard for these tests, diazepam. Moreover, no changes in motor activity were observed, indicating no inhibition or activation of central nervous system. If we take into account the low toxicity and good antioxidant properties, this compound may have a good potential in alleviating anxiety. This study was supported by the grants VEGA 2/0066/09 & 2/0083/08. doi:10.1016/j.toxlet.2009.06.792
G11 Functional status of synaptic structures in posthypoxic period Vyacheslav Lutov 1 , Salavat Sarmanaev 2 , Albert Gizatullin 1 , Roza Tuktarova 3,∗ 1
Bashkir State Medical University, Physiology, Ufa, Russian Federation, 2 FMBA, Toxicological Center, Moscow, Russian Federation, 3 Hospital 21, Emergency, Ufa, Russian Federation Background: Functional recovery of nervous tissue in posthypoxic period has phase character traceable on hypoxia (H) duration. One of the first reasons is functional heterogeneity nervous tissue, realized in various sensitivity of it elements to H. Purpose: Estimation of recovery electroretinogram (ERG) opportunity after H of various duration. Materials: We carried out experimental research on rabbit isolated perfused retina. Results: The process of recovery ERG after 60-min of H proceeded in 3-phases. There is during of the first phase restoration occurred of b-wave amplitude up to control parameters and then a-wave. In the second phase of recovery ERG was observed significant restoration of b-wave; the latency period reached a minimum, but up to the level of the control did not reach. The subsequently amplitude of the b-wave was reduced, and her latency period grew.