Protective effects of minocycline, doxycycline and tetracycline on seizure and lethality in a mice cocaine toxicity model.

INTRODUCTION: Acute cocaine intoxication is one of the important causes of admission to emergency department, especially in western countries. We aimed to compare the efficacies of tetracycline, minocycline, doxycycline in the prevention of seizures and deaths in mice due to cocaine intoxication. METHODS: In the study, a total of 120 balb-c male mice weighing 25-30 g were randomized into 4 groups as tetracycline 255 mg/kg, minocycline 170 mg/kg, doxycycline 157 mg/kg, 0.5 ml saline (placebo). The doses of tetracycline, minocycline and doxycycline are the calculated ED50 values. The mice in the groups received 93 mg/kg cocaine intraperitoneally 10 min after drug administration. The dose of cocaine is 50% of the lethal dose. After cocaine injection, all mice were observed for 30 min in terms of cocaine toxicity findings. Mortality rates, death times, seizure activities, and seizure onset times of the mice were clinically evaluated in an observational way. RESULTS: There were significant differences among all the groups in terms of seizure and lethality (p < 0.001). The ratio of animals with seizures was significantly lower in the minocycline (73.3%), and doxycycline (73.3%) groups (all p = 0.040). The ratio of animals with lethality was significantly lower in the minocycline (23.3%) group compared with vehicle (p < 0.001). CONCLUSION: In our acute cocaine intoxication model, minocycline was effective in terms of lethality and preventing seizures, doxycycline was effective in preventing seizures.

A Comparison of Dexmedetomidine, Moxonidine and Alpha-Methyldopa Effects on Acute, Lethal Cocaine Toxicity.

BACKGROUND: The treatment of cocaine toxicity is an important subject for emergency physicians. We investigated the effects of dexmedetomidine, moxonidine and alpha-methyldopa on acute cocaine toxicity in mice. OBJECTIVES: The aim of this study was to evaluate the effects of dexmedetomidine, moxonidine and alpha-methyldopa in a mouse model of acute cocaine toxicity. MATERIALS AND METHODS: We performed an experiment consisting of four groups (n = 25 each). The first group received normal saline solution, the second group received 40 µg/kg of dexmedetomidine, the third group received 0.1 mg/kg of moxonidine and the fourth group received 200 mg/kg of alpha-methyldopa, all of which were intraperitoneally administered 10 minutes before cocaine hydrochloride (105 mg/kg). All animals were observed for seizures (popcorn jumping, tonic-clonic activity, or a loss of the righting reflex) and lethality over the 30 minutes following cocaine treatment. RESULTS: The ratio of animals with convulsions was lower in all treated groups when compared to the control (P < 0.001). Furthermore, 68% (n = 17) of animals in the dexmedetomidine group, 84% (n = 21) of the alpha-methyldopa group, 92% (n = 23) of the moxonidine group and 100% (n = 25) of the control group showed evidence of seizure activity (P = 0.009). Cocaine-induced lethality was observed in 12% (n = 3) of the dexmedetomidine group, 48% (n = 12) of the alpha-methyldopa group, 52% (n = 13) of the moxonidine group, and 72% (n = 18) of the control group (P < 0.001). All treatments prolonged the time to seizure, which was longest in the dexmedetomidine group (P > 0.05). In addition, the time to lethality was also longer in the same group (P < 0.001). CONCLUSIONS: The present study provides the first experimental evidence in support of dexmedetomidine treatment for cocaine-induced seizures. Premedication with dexmedetomidine reduces seizure activity in a mouse model of acute cocaine toxicity. In addition, while dexmedetomidine may be effective, moxonidine and alpha-methyldopa did not effectively prevent cocaine-induced lethality.

Assessment of the relation of violence and burnout among physicians working in the emergency departments in Turkey.

BACKGROUND: Violence and burnout are frequently seen among medical doctors; however, the relation is not clear. This study aimed to assess the violence and its possible effects on burnout in physicians working in emergency units. METHODS: This cross-sectional study targeted all physicians working in the emergency units of Pamukkale University Hospital, County and City Hospitals, 112 Emergency Services, and Private Hospitals in Denizli. Data were obtained by means of a self-administered questionnaire that consisted of questions on the demographics of the participants, Turkish version of the Maslach Burnout Inventory, and of the perpetrators of violence. What was also documented on the questionnaire was whether participants had been subjected to or had witnessed any verbal or physical violence during the previous one month of emergency physicians' certification program. RESULTS: A total of one hundred and seventy-four physicians were included into the study (85% of the targeted group). Many of the participants were between 24 and 59 years of age, with a mean age of 36.8±5.8 years. Married male doctors working in the City Hospital made up the majority. There were significant associations between emotional exhaustion and total violence (p=0.012) and verbal violence (p=0.016); depersonalization and total violence (p=0.021) and verbal violence (p=0.012). CONCLUSION: The results presented here indicated that there was a strong relation between burnout and violence experienced by physicians working in emergency units. Violence in the emergency department has a substantial effect on the physicians' well-being.

Assessment of propofol, midazolam and ziprasidone, or the combinations for the prevention of acute cocaine toxicity in a mouse model.

STUDY OBJECTIVE: To evaluate the effects of pretreatment, midazolam (M), propofol (P), ziprasidone (Z), and two combinations of [(midazolam plus propofol (MP); midazolam plus ziprasidone (MZ)] in mice models in the prevention of seizures, and death due to acute cocaine toxicity. METHODS: 180 male CF-1 mice were randomized to 6 groups (30/group) in this experimental study. The animals were administered intraperitoneal injections of M (2mg/kg), P (25mg/kg), Z (4mg/kg), MP (2mg/kg and 25mg/kg) and MZ (2mg/kg and 4mg/kg) or saline (S) as a pretreatment. 10min later, the mice were administered intraperitoneal injections of 105mg/kg cocaine. The groups were observed for cocaine-induced seizure and lethality. RESULTS: The MP and MZ combinations showed the highest protective effect in terms of seizure and lethality relative to P and S (p<0.001). M and Z were found effective compared to P and S (p<0.001). There were no significant differences among MP and MZ, however there were significant differences between MP and Z in terms of lethality (p=0.05). There were no significant differences among MP, MZ, M and Z groups in terms of seizure (p>0.05). No death was observed in the MP combination group. Seizure rate was observed o be least in the MZ group with respect to the other groups. CONCLUSION: According to our particular mouse model, this study suggests that MP and MZ combinations may be more effective than M or Z only for the prevention of cocaine-induced seizure and lethality. However, P alone does not prevent cocaine-induced seizure and lethality.

Effects of pretreatment with etomidate, ketamine, phenytoin, and phenytoin/midazolam on acute, lethal cocaine toxicity.

OBJECTIVE: To evaluate the effects of etomidate, ketamine, phenytoin, and phenytoin/midazolam in a mouse model of acute cocaine toxicity. METHODS: We performed a randomized controlled study consisting of five groups (n = 25 each) of rats that received intraperitoneal injections of normal saline solution, 5 mg/kg ketamine, 7.5 mg/kg etomidate, 40 mg/kg phenytoin, and 40 mg/kg phenytoin and 2 mg/kg midazolam 10 minutes before cocaine hydrochloride (105 mg/kg). Following cocaine administration, a blinded observer watched the animals for 30 minutes to assess seizures (popcorn jumping, tonic-clonic activity, or loss of righting reflex), and lethality for 30 minutes. RESULTS: The number of animals with seizures was lower in the etomidate (60%), phenytoin (40%), and phenytoin/midazolam (40%) groups (P<0.001). The etomidate (24%) and phenytoin/midazolam (16%) treatments were most effective in preventing lethality (P<0.001). Conversely, compared to the vehicle group (72%), cocaine-induced lethality was higher in the ketamine (84%) and phenytoin (92%) groups. All treatments prolonged the time to seizure, but this effect was most pronounced in the etomidate and phenytoin/midazolam groups, which also had the longest average time to lethality. DISCUSSION: The present study provides the first experimental evidence supporting the use of etomidate to treat cocaine-induced seizures. Notably, ketamine and phenytoin were ineffective. Our findings suggest that premedication with etomidate, phenytoin, and phenytoin/midazolam reduced seizure activity in an acute cocaine toxicity mouse model.

Severe metformin intoxication treated with prolonged haemodialyses and plasma exchange.

BACKGROUND: Biguanides pose a significant risk of morbidity, mortality and permanent sequelae secondary to prolonged periods of hypoglycaemia. OBJECTIVES: To investigate the treatment of massive metformin overdose associated with lactic acidosis. CASE REPORT: We present the case of a 30-year-old woman, who attempted to commit suicide by ingesting an 85-g massive metformin overdose associated with severe lactic acidosis, which we treated by performing prolonged haemodialysis with bicarbonate and plasma exchange. CONCLUSION: For the maximum elimination of metformin, extended haemodialysis is required and the treatment of the accompanying metabolic acidosis with bicarbonate is important for the effectiveness of the treatment. Patients benefit much more from the treatment of combined haemodialysis with plasma exchange.