A multicentre study of co-proxamol poisoning suicides based on coroners' records in England

AIMS: To examine in detail a series of coproxamol overdose deaths in order to provide information that will assist in the development of strategies to prevent such fatalities. METHOD: Inquest records in 24 coroners' jurisdictions in England on deaths between January 2000 and December 2001 which received a verdict of either suicide or undetermined cause (with a high or moderate probability of suicide) were examined. RESULTS: One hundred and twenty-three coproxamol poisoning suicides were identified. Alcohol was involved in 58.5% of the overdoses and these individuals generally had lower blood drug levels and consumed fewer tablets. Younger people were more likely to have consumed alcohol and to have lower levels of suicide intent. Nearly half the individuals had a history of self harm, and a third were under psychiatric care. The coproxamol had been prescribed for the individual in 81.5% of cases, although only in 55.0% of those aged 10–34 years. In other cases the source of the coproxamol was nearly always a family member or partner. Some deaths resulted from relatively small overdoses. CONCLUSIONS: Strategies to reduce self poisoning deaths due to coproxamol should take account of the high toxicity of coproxamol in overdose, especially when combined with alcohol, and the fact that risk of death extends beyond the person for whom the drug is prescribed

Amelioration of the Cardiovascular Effects of Cocaine in Rhesus Monkeys by a Long-Acting Mutant Form of Cocaine Esterase

A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5–10 min, and saline-like HR measures restored within 20–40 min of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans