Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths.

Present study evaluated the relationship between estrogenic hormones concentrations (17ethinylestradiol and 17β-estradiol) in surface waters in the Metropolitan Region of São Paulo (Brazil) and environmental variables. Four sampling stations were monitored ranging from a protected area to streams discharging human effluent in and around Billings Reservoir. Four sampling campaigns were carried out in each seasonal period: DRY and WET. Samples for hormone analysis (in ng L -1 ) were concentrated (1000X) using solid phase extraction C 18 cartridges and analysed by liquid chromatography coupled to quadrupole mass spectrometry detection, with 100 ng L -1 limit of quantification. Water temperature, pH, electrical conductivity (EC) and total dissolved solids were determined in situ; total phosphorus and Sinapis alba bioassays were performed subsequently. Reservoir active capacity (AC) and precipitation were also obtained. Estrogenic hormones concentrations were always below limit of quantification at pristine site; at the other sampling stations, 17β-estradiol concentrations varied from below limit of quantification to 1,720 ng L -1 and 17ethinylestradiol from below limit of quantification to 1,200 ng L -1 , with the highest concentrations found in the streams discharging into the reservoir. These streams showed higher Pearson's correlation between 17-ethinylestradiol, total phosphorus, and electrical conductivity when compared with reservoir stations. Germination index and EC presented negative correlation (Pearson's r = -0.61), denoting a phytotoxicity increase with EC increment. AC influenced the dilution of pollutants and showed negative correlations with total phosphorus (Pearson's r = -0.56). These results highlight the relevance of including streams in water monitoring programs, since they are important pollutants loads into watersheds.

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A newly available dataset on pharmaceuticals used in Scottish hospitals enabled an environmental risk assessment that includes hospital consumption of pharmaceuticals, as previous United Kingdom rankings have been based on community prescriptions only. Although health and the environment are devolved issues for the Scottish government, it is merited to consider a Scottish ranking separately; regional differentiation is particularly relevant in the spatial context of the European Commission's Water Framework Directive. Nine pharmaceuticals are identified as having a risk quotient greater than 1. Four of these, the antibacterials piperacillin, tazobactam, flucloxacillin, and ciprofloxacin, had high hospital contributions and had not been highlighted previously in rankings based on community prescriptions. Some drugs with a risk quotient < 0.1 are used almost exclusively in hospitals and could be more concentrated near effluents carrying hospital wastewater, where they may be of local concern. Although treating hospital effluents separately is a policy option, specifically including hospital consumption is important. Continually increasing the availability of ecotoxicological data and trends in consumption further contributes to a substantially different prioritization than in previous rankings. This leads the authors to conclude that regular review of risk is necessary.

In recent years, there is a growing concern about the alarming spread of antimicrobial resistance (AMR) in different environments. Increasingly, many species of bacteria, fungi and viruses are becoming immune to the most commonly used pharmaceuticals. One of the causes of the development of the resistance is the persistence of these drugs, excreted by humans, in municipal and hospital wastewater (WW). Consequently, wastewater treatment plants (WWTPs) are a primary source of antimicrobial resistance genes as novel pollutants. This systematic review sought to examine the relevant literature on pharmaceutical residues (PRs) responsible for AMR in municipal and hospital WW in order to propose a classification of the PRs of greatest concern and provide an updated source for AMR management in WWTPs. Among 546 studies collected from four databases, 18 were included in the present review. The internal and external validity of each study was assessed, and the risk of bias was evaluated on a 20-parameter basis. Results were combined in a narrative synthesis discussing influent and effluent PR concentrations at 88 WWTPs, seasonal variations, differences between hospital and municipal WW, environmental risk assessment values of antimicrobial substances and treatment facilities removal efficiencies. Among the 45 PRs responsible for AMR evaluated in this study, the antibiotics ciprofloxacin, clarithromycin, erythromycin, metronidazole, ofloxacin, sulfamethoxazole and trimethoprim constitute a considerable risk in terms of ubiquitous distribution, worrying concentrations, risk quotient values and resistance to removal treatments. Gaps in knowledge, data and information reported in this review will provide a valuable source for managing AMR in WWTPs.