Lobo, P I; Spyker, D; Surratt, P; Westervelt, F B
A case of meprobamate overdosage successfully treated with hemodialysis is described. The patient was admitted 4 hours after an overdosage of meprobamate (30-40 g) deeply unconscious, hypotensive, in respiratory failure and with a serum meprobamate level of 50 mg/100 ml. Hemodialysis was instituted using a Gambro parallel flow dialyzer and a portable re-circulating dialyzate delivery system (Redy, CCi Life Systems). Meprobamate removal with hemodialysis was 672+/-167 mg/hr with a corresponding clearance of 61.97+/-9.9 ml/min. Drug removal with forced diuresis was 177+/-23.4 mg/hr. Metabolic degradation of the drug was approximately 482 mg/hr with a plasma disappearance rate of 5.2%/hr. No drug could be detected in the dialyzate fluid after its passage through the Redy re-circulating dialyzate system. Because of the rapidity of metabolic degradation of meprobamate, we feel that hemodialysis should be reserved for severe clinical intoxication and either compromised normal excretory routes or progressive clinical deterioration.
James, Alexander Owen; Nicholson, Timothy R; Hill, Robert; Bearn, Jennifer
Meprobamate, a benzodiazepine-like drug, was commonly prescribed for anxiety in the 1960s and 1970s, but fell out of favour, at least in part, due to the risk of dependence, for which there is little published evidence to guide clinical management. We discuss a 70-year-old man with a 45-year history of meprobamate dependency and multiple failed previous withdrawal attempts who was successfully withdrawn from meprobamate using diazepam during a 2-week inpatient stay on a specialist Addictions ward. An appropriate diazepam dose was established using the Clinical Institute Withdrawal Assessment scale for benzodiazepines (CIWA-B). This dose was then slowly reduced over 12 days. Multidisciplinary input, especially psychological therapy tackling his underlying anxiety disorder during his admission, was thought to be particularly helpful. 2016 BMJ Publishing Group Ltd.
Jun 29, 2016 ... medicine classes, especially sedatives and anxiolytics. It is possible that males in this study were prescribed a lower percentage of anxiolytic agents, and that they were using meprobamate-containing analgesics for their anxiolytic, rather than their analgesic, effect and hence the higher frequency of.
... 32 mg caffeine and 150 mg meprobamate. The originator product constituted 3.72% of prescribing frequency (average cost: R30.42) compared with 70.63% for the most popular generic (average cost: R11.65). Conclusions: Prescribers should be conscious of the benefits and risks of the active ingredient combinations.
Delavenne, Xavier; Gay-Montchamp, Jean Pierre; Basset, Thierry
We described the development and full validation of rapid and accurate liquid chromatography method, coupled with tandem mass spectrometry detection, for quantification of meprobamate in human plasma with [(13)C-(2)H(3)]-meprobamate as internal standard. Plasma pretreatment involved a one-step protein precipitation with acetonitrile. Separation was performed by reversed-phase chromatography on a Luna MercuryMS C18 (20 mm×4 mm×3 μm) column using a gradient elution mode. The mobile phase was a mix of distilled water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. The selected reaction monitoring transitions, in electrospray positive ionization, used for quantification were 219.2→158.2 m/z and 223.1→161.1m/z for meprobamate and internal standard, respectively. Qualification transitions were 219.2→97.0 and 223.1→101.1 m/z for meprobamate and internal standard, respectively. The method was linear over the concentration range of 1-300 mg/L. The intra- and inter-day precision values were below 6.4% and accuracy was within 95.3% and 103.6% for all QC levels (5, 75 and 200 mg/L). The lower limit of quantification was 1 mg/L. Total analysis time was reduced to 6 min including sample preparation. The present method is successfully applied to 24/7 clinical toxicology and demonstrated its usefulness to detect meprobamate poisoning. Copyright © 2010 Elsevier B.V. All rights reserved.
Quantification of five compounds with heterogeneous physicochemical properties (morphine, 6-monoacetylmorphine, cyamemazine, meprobamate and caffeine) in 11 fluids and tissues, using automated solid-phase extraction and gas chromatography-tandem mass spectrometry.
Bévalot, Fabien; Bottinelli, Charline; Cartiser, Nathalie; Fanton, Laurent; Guitton, Jérôme
An automated solid-phase extraction (SPE) protocol followed by gas chromatography coupled with tandem mass spectrometry was developed for quantification of caffeine, cyamemazine, meprobamate, morphine and 6-monoacetylmorphine (6-MAM) in 11 biological matrices [blood, urine, bile, vitreous humor, liver, kidney, lung and skeletal muscle, brain, adipose tissue and bone marrow (BM)]. The assay was validated for linearity, within- and between-day precision and accuracy, limits of quantification, selectivity, extraction recovery (ER), sample dilution and autosampler stability on BM. For the other matrices, partial validation was performed (limits of quantification, linearity, within-day precision, accuracy, selectivity and ER). The lower limits of quantification were 12.5 ng/mL(ng/g) for 6-MAM, morphine and cyamemazine, 100 ng/mL(ng/g) for meprobamate and 50 ng/mL(ng/g) for caffeine. Analysis of real-case samples demonstrated the performance of the assay in forensic toxicology to investigate challenging cases in which, for example, blood is not available or in which analysis in alternative matrices could be relevant. The SPE protocol was also assessed as an extraction procedure that could target other relevant analytes of interest. The extraction procedure was applied to 12 molecules of forensic interest with various physicochemical properties (alimemazine, alprazolam, amitriptyline, citalopram, cocaine, diazepam, levomepromazine, nordazepam, tramadol, venlafaxine, pentobarbital and phenobarbital). All drugs were able to be detected at therapeutic concentrations in blood and in the alternate matrices.
Mirna Fernández Cervera
Full Text Available Se estudió el comportamiento de diferentes variantes tecnológicas de tabletas de liberación inmediata de meprobamato (400 mg, obtenidas por granulación húmeda. El tiempo de desintegración y el porcentaje de fármaco disuelto mostraron dependencia significativa con las proporciones del lauril sulfato de sodio/croscarmelosa sódica en las formulaciones. Se evaluaron las propiedades físicas y químicas de las tabletas durante 6 meses (estabilidad acelerada y 24 meses (de vida útil, respectivamente. Se obtuvieron a partir de las formulaciones seleccionadas granulados y tabletas con propiedades organolépticas, físico-mecánicas y tecnológicas satisfactorias, lo que indicó la factibilidad del proceso de fabricación de este producto. Los resultados demostraron la buena estabilidad de las formulaciones de tabletas de liberación inmediata de meprobamato seleccionadas. La disolución in vitro no mostró diferencias significativas, por lo que ni el tiempo transcurrido ni la composición de la formulación influyeron sobre los porcentajes del fármaco disuelto. La valoración mostró diferencias significativas, sin embargo, las formulaciones evaluadas cumplieron con las especificaciones farmacéuticas oficiales durante 24 meses.The behavior of different technological variants of fast release tablets of Meprobamato (400 mg obtained by wet granulation. The desintegration time and the percentage of the dissolved drug showed a significant dependence of the sodium lauryl sulfate /sodium croscarmelose ratios present in formulae. The physical and chemical properties of tablets were assessed during 6 months (accelerated stability and dring 24 months (useful life, respectively. From the formulae selected it was possible to obtain granulates and tablets with organoleptic, physicomechanical and technological properties, demonstrating the feasibility of the process of fabrication of this product. Results showed the good stability in the immediate release of Meprobamato tablets selected. The in vitro dissolution hasn't significant differences, thus, neither the time elapsed nor the composition of formula inluenced on the percentages of dissolved drug. The assessment demonstrated significant differences, however, assessed formulae fulfilled with official pharmaceutical specifications during 24 months.
Full Text Available DG02007 DGroup Antianxiety, carbamate derivatives ... D00376 ... Meprobamate (JAN/USP/I...NN) ... D07317 ... Emylcamate (INN) D01807 ... Mebutamate (JAN/USAN) Neuropsychiatric agent ... Antianxiety ...
Conclusions: well-tolerated combination analgesics in patients experiencing moderate to severe acute pain. Keywords: acute pain, anxiolytic, codeine, combination analgesics, meprobamate, paracetamol, Stilpane®, Tramacet®, tramadol. Introduction. Acute pain is disabling and common, and while it may be inevitable,. 1.
Robertson, M M; Marinetti, L J
Carisoprodol, a commonly prescribed muscle relaxant, has adverse effects on human performance and is gaining recognition as a factor in driver impairment and accident causation. Carisoprodol is a centrally acting skeletal muscle relaxant indicated for the relief of musculoskeletal pain. Carisoprodol and its major metabolite meprobamate have central nervous system (CNS) sedating effects similar to benzodiazepines or alcohol. Following the ingestion of carisoprodol or meprobamate symptoms such as drowsiness, confusion, poor balance, and coordination are well documented in drivers, all of which are detrimental to human performance and driving ability. Although identified as a drug capable of producing decreased human performance, the full extent of carisoprodol and meprobamate's involvement in motor vehicle accidents and effect on driving skills may not be fully appreciated. This is due in part to the common co-administration of other CNS depressants, hypnotics, or narcotic drugs and the lack of routine testing for carisoprodol and meprobamate in the human performance toxicology laboratory. Copyright © 2003 Central Police University.
Simonsen, Kirsten Wiese; Steentoft, Anni; Buck, Maike
. The method was fully validated for salicylic acid, paracetamol, phenobarbital, carisoprodol, meprobamate, topiramate, etodolac, chlorzoxazone, furosemide, ibuprofen, warfarin, and salicylamide. The method also tentatively includes thiopental, theophylline, piroxicam, naproxen, diclophenac, and modafinil......We describe a multi-method for simultaneous identification and quantification of 12 acidic and neutral compounds in whole blood. The method involves a simple liquid-liquid extraction, and the identification and quantification are performed using liquid chromatography-tandem mass spectrometry...
Peña-López, Miguel; Neumann, Helfried; Beller, Matthias
A general study of the iron-catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N-unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamate), without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono- and disubstituted ureas via selective transamidation reaction. These atom-economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis-acidic iron(II) catalyst. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Ana Julia García Milian
Full Text Available Teniendo en cuenta las evidencias de un consumo elevado del meprobamato (10,4 % de los pacientes de la tercera edad lo consumen y es el 4,2 % del total de los medicamentos consumidos por ellos, además de un aumento en el consumo nacional del medicamento expresado en DDD (1996-3,4 a 1999-4,2/1 000 habitantes. Se decidió realizar un estudio de utilización de medicamentos indicación-prescripción que permitiera identificar los diagnósticos más frecuentes que motivaron la prescripción del medicamento y las especialidades que lo prescriben en Ciudad de La Habana en el período de septiembre de 2000 a enero de 2001. Se encuestó el 86,6 % de la muestra y se identificó la indicación del meprobamato en 11 afecciones; la hipertensión arterial constituyó la más frecuente y la Medicina General Integral la especialidad que más lo prescribe. Se recomienda la realización de una intervención sobre hipertensión arterial en Atención Primaria de Salud y educar a la población en el tratamiento de dicha enfermedad, así como los usos y riesgos del meprobamato.Taking into account the evidences of an elevated consumption of meprobamate (10.4 % of the patients at the third age take it, and it accounts for 4.2 % of the total of drugs consumed by them, and an increase in the national consumption of the drug expressed in DDD (from 1996-3.4 to 1999-4.2/1 000 inhabitants, it was decided to carry out a study on the use of indication-prescription drugs that allowed to identify the most frequent diagnoses leading to the prescription of drugs and the specialties of the physicians prescribing it in Havana City, from September, 2000, to January, 2001. 86.6 % of the sample were surveyed and the indication of meprobamate was found in 11 affections. Arterial hypertension was the most common affection and General Comprehensive Medicine was the specialty prescribing it the most. It was recommended to make an intervention on arterial hypertension in Primary Health
Pélissier-Alicot, Anne-Laure; Piercecchi-Marti, Marie-Dominique; Bartoli, Christophe; Kuhlmann, Erika; Coiffait, Philippe-Emmanuel; Sanvoisin, Alain; Giocanti, Dominique; Léonetti, Georges
Because psychostimulants have serious possible side effects and particular potential for abuse, their therapeutic indications are today exclusively limited to disorders such as obesity, narcolepsy, or attention deficit/hyperactivity disorder. We report two cases of abusive prescription of these drugs. The first concerns a woman who was treated for a 3 kg weight gain with fenproporex for 5 years and presented a withdrawal syndrome when this drug was no longer marketed in France. In the second case, a woman who complained of atypical sleep problems was prescribed modafinil, methylphenidate, clobazam, lormetazepam, meprobamate, and aceprometazine, and was found dead in her home a few weeks later in unexplained circumstances. For these two patients, neither the indications, nor the contraindications, nor the prescribing rules for these restricted drugs had been complied with. This case report highlights the extreme danger of these substances and stresses the importance of adhering to the rules of prescription.
The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into “rogues,” regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional “cop” agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions. PMID:18343498
The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into "rogues," regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional "cop" agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions.
Matthews, R T; McMillen, B A; Speciale, S G; Jarrah, H; Shore, P A; Sanghera, M K; Shepard, P D; German, D C
The effects of zoxazolamine (ZOX) and related centrally acting muscle relaxants on striatal dopamine (DA) metabolism and turnover, and substantia nigra zona compacta DA neuronal impulse flow were studied in rats. ZOX, chlorzoxazone and mephenesin, but not meprobamate, chloral hydrate, diazepam, pentobarbital, ethanol or dantrolene, decreased striatal DA metabolism without affecting striatal DA concentrations. More specifically, ZOX, as a representative muscle relaxant, was shown to decrease striatal DA turnover without directly affecting DA synthesis, catabolism, reuptake, or release. ZOX decreased nigral DA neuronal firing rates and dramatically decreased firing rate variability (normally many of the cells fire with bursting firing patterns but after ZOX the cells often fired with a very regular pacemaker-like firing pattern). ZOX and related centrally acting muscle relaxants appear to decrease striatal DA turnover by decreasing both neuronal firing rate and firing rate variability. The possible relationships between DA neuronal activity and muscle tone are discussed.
Fisher, Irene; Phillips, Patrick; Colella, Kaitlyn; Fisher, Shawn C.; Tagliaferri, Tristen N.; Foreman, William T.; Furlong, Edward T.
Coastal onsite wastewater disposal systems (OWDS) were inundated by Hurricane Sandy's storm tide. This study compares the shallow groundwater quality (nutrients, pharmaceuticals, and hormones) downgradient of OWDS before and after Hurricane Sandy, where available, and establishes a baseline for wastewater influence on groundwater in coastal communities inundated by Hurricane Sandy. Nutrients and contaminants of emerging concern (CECs) were detected in shallow groundwater downgradient of OWDS in two settings along the New Jersey and New York coastlines: 1) a single, centralized OWDS in a park; and 2) multiple OWDS (cesspools) in low-density residential and mixed-use/medium density residential areas. The most frequently detected pharmaceuticals were lidocaine (40%), carbamazepine (36%), and fexofenadine, bupropion, desvenlafaxine, meprobamate, and tramadol (24–32%). Increases in the number and total concentration of pharmaceuticals after Hurricane Sandy may reflect other factors (seasonality, usage) besides inundation, and demonstrate the importance of analyzing for a wide variety of CECs in regional studies.
Anaí García Fariñas
Full Text Available Se caracterizó a la población hipertensa que consumía meprobamato como parte del tratamiento de la hipertensión arterial y se calculó el efecto económico para el individuo y la sociedad de esta inadecuada terapia. El universo estuvo compuesto por 27 pacientes mayores de 15 años de edad que consumían meprobamato como parte del tratamiento de la hipertensión. El 40,7 % de los pacientes que consumen meprobamato para la hipertensión, refirió propiedades terapéuticas no adecuadas como hipotensor. La imposibilidad de acceder al medicamento repercutió en la calidad de vida de los pacientes. El 51,8 % manifestó sentirse descontrolado cuando no tenía el medicamento. El costo de bolsillo mensual por pacientes osciló entre $ 1.60 y $ 40.00, en dependencia de la forma de adquisición. Como resultado de la investigación se pudo concluir que el uso inadecuado del meprobamato como hipotensor, ocasiona una fármaco-dependencia innecesaria y que unida a un aumento de la demanda productiva del medicamento en el ámbito industrial provoca que se destinen recursos hacia su producción que se le resta a otras opciones.The hypertensive population taking meprobamate as part of the arterial hypertension treatment was characterized and the economic effect of this inadequate therapy for the individual and for the society was calculated. 27 patients over 15 that were treated with this drug were studied. 40.7 % of these patients referred to unappropriated therapeutic properties of this drug as hypotensive. The impossibility to have the drug influenced on the quality of life of the patients. 51.8 % felt uncontrolled when they could not take the drug. Every patient spent between $1.60 and $40.00 a month, depending on the way of acquisition. As a result of the research, it was concluded that the inadequate administration of meprobamate as a hypotensive agent brings about an unnecessary drug dependance that together with the increase of the production demand
Aminot, Yann; Fuster, Laura; Pardon, Patrick; Le Menach, Karyn; Budzinski, Hélène
This study focuses on the fate of pharmaceuticals discharged into an estuarine environment, particularly into the Turbidity Maximum Zone (TMZ). Batch experiments were set up to investigate the factors regulating the degradation of 53 selected pharmaceuticals. Treated effluents from Bordeaux city (France) were mixed with water from the estuarine Garonne River during 4weeks under 6 characterized conditions in order to assess the influence of suspended particulates, sterilization, untreated wastewater input and dilution on the degradation kinetics. Of the 53 pharmaceuticals monitored, 43 were quantified at the initial time. Only 7 exhibited a persistent behavior (e.g. carbamazepine, meprobamate) while biotic degradation was shown to be the main attenuation process for 38 molecules (e.g. abacavir, ibuprofen highly degradable). Degradation was significantly enhanced by increasing concentrations of suspended solids. A persistence index based on the half-lives of the compounds has been calculated for each of the 43 pharmaceuticals to provide a practical estimate of their relative stability. The stability of pharmaceuticals in estuarine environments is likely to be highly variable and attenuated primarily by changes in suspended solid concentration. Copyright © 2017 Elsevier B.V. All rights reserved.
Delayed and sometimes total lack of communications, lower standards of medical care, low physician: population ratio, absence of monitoring systems affect all phases of drug consumption in developing countries--from procedures for introducing a new drug to its marketing on a broad scale, and ultimate decline. The number of prescriptions and the choice of drug are determined only partly by physicians. Such other factors as medicaments furnished by the government either free or at a small charge, the type of health service, accessibility to paramedical and nonmedical advice, as well as hard-sell marketing practices, often through the mass media, tend to set the pattern of drug usage. The practice of drug storming in "home pharmacies", a phenomenon surveyed by the author, is described and the reasons for it analyzed. In general, the categories of drugs (e.g., antibiotics, cardiovascular, analgesics) consumed are the same in the rest of Europe, the United States, and Latin America. Among the minor tranquilizers, the consumption of meprobamate has risen by about a third, chlordiazepoxide markedly, while phenobarbital consumption has remained about the same from 1969 to 1973. This is said to illustrate the pattern of an upward curve in consumption of a new drug, and the displacement of an old one. The overall rise of these drugs during this period was 72.1% in Hungary. Similar surveys are reported for oral hypoglycemic and antiarrhythmic drugs. Of hypotensive drugs, rauwolfia usage has declined and methyldopa has increased by over 200%.
Kim, M; Guerra, P; Shah, A; Parsa, M; Alaee, M; Smyth, S A
Ninety-nine pharmaceuticals and personal care products (PPCPs) were analyzed in influent, final effluent, and biosolids samples from a wastewater treatment plant employing a membrane bioreactor (MBR). High concentrations in influent were found for acetaminophen, caffeine, metformin, 2-hydroxy-ibuprofen, paraxanthine, ibuprofen, and naproxen (10(4)-10(5) ng/L). Final effluents contained clarithromycin, metformin, atenolol, carbamazepine, and trimethoprim (>500 ng/L) at the highest concentrations, while triclosan, ciprofloxacin, norfloxacin, triclocarban, metformin, caffeine, ofloxacin, and paraxanthine were found at high concentrations in biosolids (>10(3) ng/g dry weight). PPCP removals varied from -34% to >99% and 23 PPCPs had ≥90% removal. Of the studied PPCPs, 26 compounds have been rarely or never studied in previous membrane bioreactor (MBR) investigations. The removal pathway showed that acetaminophen, 2-hydroxy-ibuprofen, naproxen, ibuprofen, codeine, metformin, enalapril, atorvastatin, caffeine, paraxanthine, and cotinine exhibited high degradation/transformation. PPCPs showing strong sorption to solids included triclocarban, triclosan, miconazole, tetracycline, 4-epitetracycline, norfloxacin, ciprofloxacin, doxycycline, paroxetine, and ofloxacin. Trimethoprim, oxycodone, clarithromycin, thiabendazole, hydrochlorothiazide, erythromycin-H2O, carbamazepine, meprobamate, and propranolol were not removed during treatment, and clarithromycin was even formed during treatment. This investigation extended our understanding of the occurrence and fate of PPCPs in an MBR process through the analysis of the largest number of compounds in an MBR study to date.
Cohen, Sabine; Manat, Aurélie; Dumont, Benoit; Bévalot, Fabien; Manchon, Monique; Berny, Claudette
In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.
Park, Minkyu; Anumol, Tarun; Daniels, Kevin D; Wu, Shimin; Ziska, Austin D; Snyder, Shane A
Ozone oxidation has been demonstrated to be an effective treatment process for the attenuation of trace organic compounds (TOrCs); however, predicting TOrC attenuation by ozone processes is challenging in wastewaters. Since ozone is rapidly consumed, determining the exposure times of ozone and hydroxyl radical proves to be difficult. As direct potable reuse schemes continue to gain traction, there is an increasing need for the development of real-time monitoring strategies for TOrC abatement in ozone oxidation processes. Hence, this study is primarily aimed at developing indicator and surrogate models for the prediction of TOrC attenuation by ozone oxidation. To this end, the second-order kinetic equations with a second-phase R ct value (ratio of hydroxyl radical exposure to molecular ozone exposure) were used to calculate comparative kinetics of TOrC attenuation and the reduction of indicator and spectroscopic surrogate parameters, including UV absorbance at 254 nm (UVA 254 ) and total fluorescence (TF). The developed indicator model using meprobamate as an indicator compound and the surrogate models with UVA 254 and TF exhibited good predictive power for the attenuation of 13 kinetically distinct TOrCs in five filtered and unfiltered wastewater effluents (R 2 values > 0.8). This study is intended to help provide a guideline for the implementation of indicator/surrogate models for real-time monitoring of TOrC abatement with ozone processes and integrate them into a regulatory framework in water reuse. Copyright © 2017 Elsevier Ltd. All rights reserved.
Wu, Xiaoqin; Fu, Qiuguo; Gan, Jay
With the increasing use of treated wastewater and biosolids in agriculture, residues of pharmaceutical and personal care products (PPCPs) in these reused resources may contaminate food produce via plant uptake, constituting a route for human exposure. Although various PPCPs have been reported to be taken up by plants in laboratories or under field conditions, at present little information is available on their metabolism in plants. In this study, we applied carrot cell cultures to investigate the plant metabolism of PPCPs. Five phase I metabolites of carbamazepine were identified and the potential metabolism pathways of carbamazepine were proposed. We also used the carrot cell cultures as a rapid screening tool to initially assess the metabolism potentials of 18 PPCPs. Eleven PPCPs, including acetaminophen, caffeine, meprobamate, primidone, atenolol, trimethoprim, DEET, carbamazepine, dilantin, diazepam, and triclocarban, were found to be recalcitrant to metabolism. The other 7 PPCPs, including triclosan, naproxen, diclofenac, ibuprofen, gemfibrozil, sulfamethoxazole, and atorvastatin, displayed rapid metabolism, with 0.4-47.3% remaining in the culture at the end of the experiment. Further investigation using glycosidase hydrolysis showed that 1.3-20.6% of initially spiked naproxen, diclofenac, ibuprofen, and gemfibrozil were transformed into glycoside conjugates. Results from this study showed that plant cell cultures may be a useful tool for initially exploring the potential metabolites of PPCPs in plants as well as for rapidly screening the metabolism potentials of a variety of PPCPs or other emerging contaminants, and therefore may be used for prioritizing compounds for further comprehensive evaluations. Copyright © 2015 Elsevier Ltd. All rights reserved.
Wu, Xiaoqin; Fu, Qiuguo; Gan, Jay
With the increasing use of treated wastewater and biosolids in agriculture, residues of pharmaceutical and personal care products (PPCPs) in these reused resources may contaminate food produce via plant uptake, constituting a route for human exposure. Although various PPCPs have been reported to be taken up by plants in laboratories or under field conditions, at present little information is available on their metabolism in plants. In this study, we applied carrot cell cultures to investigate the plant metabolism of PPCPs. Five phase I metabolites of carbamazepine were identified and the potential metabolism pathways of carbamazepine were proposed. We also used the carrot cell cultures as a rapid screening tool to initially assess the metabolism potentials of 18 PPCPs. Eleven PPCPs, including acetaminophen, caffeine, meprobamate, primidone, atenolol, trimethoprim, DEET, carbamazepine, dilantin, diazepam, and triclocarban, were found to be recalcitrant to metabolism. The other 7 PPCPs, including triclosan, naproxen, diclofenac, ibuprofen, gemfibrozil, sulfamethoxazole, and atorvastatin, displayed rapid metabolism, with 0.4–47.3% remaining in the culture at the end of the experiment. Further investigation using glycosidase hydrolysis showed that 1.3–20.6% of initially spiked naproxen, diclofenac, ibuprofen, and gemfibrozil were transformed into glycoside conjugates. Results from this study showed that plant cell cultures may be a useful tool for initially exploring the potential metabolites of PPCPs in plants as well as for rapidly screening the metabolism potentials of a variety of PPCPs or other emerging contaminants, and therefore may be used for prioritizing compounds for further comprehensive evaluations. - Highlights: • Five phase I metabolites of carbamazepine were identified in carrot cell cultures. • The metabolism potentials of 18 PPCPs were evaluated using carrot cell cultures. • Four PPCPs may partially form glycoside conjugates as phase II
Estrada-Arriaga, Edson Baltazar; Cortés-Muñoz, Juana Enriqueta; González-Herrera, Arturo; Calderón-Mólgora, César Guillermo; de Lourdes Rivera-Huerta, Ma; Ramírez-Camperos, Esperanza; Montellano-Palacios, Leticia; Gelover-Santiago, Silvia Lucila; Pérez-Castrejón, Sara; Cardoso-Vigueros, Lina; Martín-Domínguez, Alejandra; García-Sánchez, Liliana
Two full-scale biological nutrient removal systems upgraded with three physico-chemical processes (coagulation, chemical precipitation, and neutral Fenton) were evaluated in order to determine the removal of emerging pollutants (EPs) present in municipal wastewater from Mexico. Between 41 and 55 EPs were detected in the influents of two wastewater treatment plants (WWTPs), including personal care products (PPCPs), antibiotics, analgesics, antiepileptics, antilipidemics, antihypertensives, antiseptics, stimulants, and hormones. Emerging pollutants were detected at concentrations ranging from 0.69ng/L to 94,600ng/L. High concentrations of emerging pollutants were found during dry season. WWTP 1, integrated by oxidation ditches and UV light lamps, showed removal efficiencies of EPs between 20% and 22%. On the other hand, WWTP 2 consisted of anaerobic/anoxic/aerobic tanks coupled with two disinfection processes; chlorine dioxide and UV light lamps, for which the removal of EPs was significant (up to 80%). The concentrations of emerging pollutants in WWTP 1 effluent was found within a rangeremovals, compared to those of WWTP 1, due to a greater activity of the simultaneous nitrification-denitrification processes, hydraulic retention time, and solids retention time. The compounds that were more persistent with removals below 50% in both effluents were: carbamazepine, dehydronifedipine, meprobamate, sertraline, propranolol, propoxyphene, norverapamil, diazepam, alprazolam, sulfamethoxazole, metoprolol, ofloxacin, norfloxacin, fluoxetine, erythromycin-H2O, diphenhydramine, dehydronifedipine, clarithromycin, hydrochlorothiazide, and albuterol. The application of neutral Fenton reaction as post-treatment for the two effluents from the WWTPs is promising for the removal of emerging pollutants (up to 100%) and for assuring high quality of treated water. Copyright © 2016 Elsevier B.V. All rights reserved.
Rhalimi, Mounir; Helou, Rafik; Jaecker, Pierre
Falls in the elderly are common and often serious. Several drugs have been associated with increased fall risk. Older adults often take numerous medications for multiple chronic conditions, so are at increased risk for drugs that potentially cause falls. We studied the association between drug use and falls in recently hospitalized older people in order to identify medications that may increase the risk of falls in this population. A retrospective case control study was performed in the geriatric department of Bertinot Juel Hospital, Chaumont en Vexin, Picardy, France. We assessed the incidence of patient falls during hospitalization in 2004 and 2005 in an acute geriatric ward. We compared medications taken by all patients who fell (134 cases) with those taken by patients who did not fall (126 controls). The 260 participants were all aged >or=65 years. 50% of falls occurred in the first week after admission. In 16% of cases, falls were classified as severe. The characteristics of the two groups (patients who fell and those who did not) were similar: no significant differences were observed in terms of age, sex, number of medicines or prevalence of hypertension or Parkinson's disease. The probability of falls increased when the patients used zolpidem (adjusted odds ratio [AOR] 2.59; 95% CI 1.16, 5.81; p = 0.02), meprobamate (AOR 3.01; 95% CI 1.36, 6.64; p = 0.01) or calcium channel antagonists (AOR 2.45; 95% CI 1.16, 4.74; p = 0.02). Some drugs are associated with an increased risk of falls in the elderly and, when alternatives exist, should be avoided until cohort studies are conducted to confirm or refute these possible increased risks.
Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists.
animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning. Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenytoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies. Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance. In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.
Young, M.; Green, R. L.; Devitt, D.; McCullough, M.; Wright, L.; Vanderford, B. J.; Snyder, S. A.
In arid and semi-arid regions, the use of treated wastewater for landscape irrigation is becoming common practice and a significant asset to conserve potable water supplies. Public interest and lack of field-scale data are leading to a concern that compounds found in reuse water could persist in the environment and contaminate groundwater. As part of a larger study, 2-yr experiments were conducted in CA and NV, where reuse water was the primary source of non-ambient water input. A total of 13 compounds were studied, all originating in irrigation water applied to soil covered in turf or left bare. The target compounds included atenolol, atorvastatin, carbamazepine, diazepam, diclofenac, fluoxetine, gemfibrozil, ibuprofen, meprobamate, naproxen, primidone, sulfamethoxazole, triclosan, and trimethoprim. Analytical protocols for all compounds (detection at ng/L range) were established before the study commenced. The goals of the research were to increase available data on the fate and transport of these target compounds in turfgrass/soil systems, and to use these data to assess long-term risk from using water containing these compounds. Experiments conducted at two scales are discussed here: lysimeter-scale and field-scale. At the lysimeter-scale, 24 drainage lysimeters (120 cm thick) were exposed to treated wastewater as an irrigation source. Lysimeters varied by soil type (two types), soil cover (bare- versus turf-covered) and leaching fraction (5% and 25%). Upper and lower boundary conditions were monitored throughout the study. Water samples were collected periodically after water breakthrough. After the study, soil samples were analyzed for compound mass, allowing compound mass balance and removal to be assessed. At the field-scale, passive drain gages (Decagon Devices) were installed in triplicate in fairways at four operational golf courses, one in NV and three in CA, all with histories of using treated wastewater. The gages measure water fluxes through the 60
Janković Slavko M.
Full Text Available The perplexing and tantalizing disease of rapid eye movement (REM sleep behavior disorder (RBD is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats . In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication , and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse . However, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986 [4-7]. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia . To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al  in 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. . The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep" . Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene
Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J
The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs
In DSM-III (1980), depressive states of neurosis and those of manic-depressive illness (melancholia or endogenous depression) were combined into the single category "major depression," which is the progenitor of "major depressive disorder" in DSM-IV-TR (2000). According to Hamilton, the word "depression" is used in three different ways. In common speech, it is used to describe the state of sadness that all persons experience when they lose something of importance to them. In psychiatry, the word is used to signify an abnormal mood, analogous to the sadness, unhappiness, and misery of everyday experiences. Moreover, the depression discussed in psychiatry often has another quality that makes it distinctive, and this quality appears to be related to an inability to experience any pleasure (anhedonia) regardless of experience. Accordingly, we classify these three uses of the term "depression" into sadness, depression, and melancholia in order of appearance within this paper. According to DSM-IV-TR criteria for major depressive disorder, depression corresponds closely to A1 "depressed mood", while melancholia is roughly compatible with A2 "markedly diminished interest or pleasure." Depression and melancholia differ in terms of origin, psychopathology, and therapy. Before DSM-III, depression had not been considered as a diagnosis, but was a ubiquitous symptom that was seen in such conditions as neurasthenia, psychasthenia, nervousness, and neurosis. Melancholia has a history that reaches back to Hippocratic times. Its modern meaning was established based on Kraepelin's manic-depressive illness. Depression is a deepened or prolonged sadness in everyday life, but melancholia has a distinct quality of mood that cannot be interpreted as severe depression. In modern times, depression has been treated with a diverse range of methods, including rest, talk therapy, amphetamines (1930s), meprobamate (1950s), and benzodiazepines (1970s). Melancholia has primarily been treated with