WorldWideScience

Sample records for severe carbamazepine overdose

  1. Carbamazepine overdose after exposure to simethicone: a case report

    Directory of Open Access Journals (Sweden)

    Guneysel Ozlem

    2008-07-01

    Full Text Available Abstract Introduction Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine. Case presentation We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twice daily, and experienced carbamazepine overdose after exposure to simethicone. After cessation of simethicone therapy normal drug levels of carbamazepine were obtained again with the standard dose of the drug. The mechanism of interaction is unknown but the risk of overdose should be considered when prescribing simethicone to a patient who is using carbamazepine. Conclusion Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.

  2. Carbamazepine and carbamazepine-10,11-epoxide clearance measurements during continuous venovenous hemofiltration in a massive overdose.

    Science.gov (United States)

    Smollin, Craig Geoffrey; Petrie, Matthew S; Kearney, Thomas

    2016-06-01

    Carbamazepine (CBZ) overdose can result in significant neurologic and cardiovascular toxicity, and is compounded by the presence of an active metabolite, carbamazepine-10,11-epoxide (CBZE). Existing publications describing continuous venovenous hemofiltration (CVVH) in CBZ overdose are limited in their ability to calculate accurate clearances. We report a case of CBZ overdose treated with CVVH with detailed measurement of CBZ, CBZE and their respective clearances calculated utilizing serial effluent measurements. This was coupled with serum level determinations comparing two analytical methodologies, time-of-flight mass spectroscopy and an immunoassay. A 41-year-old woman presented unresponsive after an overdose of CBZ. Initial CBZ serum levels were markedly elevated (57.8 μg/mL) and continued to rise. Due to continued hemodynamic instability, extracorporeal removal was initiated using CVVH. During the first 30 h of CVVH, interval serum samples and all ultrafiltrate bags were collected and analyzed. Serum and effluent levels of CBZ and CBZE were measured using an Agilent 6230 time-of-flight high-resolution mass spectrometer (TOF-MS). CBZ levels were also obtained utilizing the Microgenics CEDIA Carbamazepine Immunoassay (Thermo Fisher, Waltham, MA) for serum and effluent samples. Immunoassay analysis was performed using Siemens ADVIA 1800 instrument. The clearances achieved for CBZE (mean = 25.2, range 17.7-42.6 mL/min) exceeded that for CBZ (mean = 18.1, range 12.7-28.7 mL/min). CVVH removed a total of 1293 and 1261 mg of CBZ and CBZE, respectively. Serum levels of CBZ measured by immunoassay when compared with TOF-MS indicated cross reactivity of CBZE with the immunoassay. CVVH removed CBZE with higher clearances than CBZ. However, CVVH clearance rates for both CBZ and CBZE were lower than published clearances of CBZ and CBZE by intermittent hemodialysis. Our methodology allowed for a precise pharmacokinetic assessment of clearance based on

  3. Carbamazepine

    Science.gov (United States)

    ... Adasuve); certain medications to treat malaria such as chloroquine (Aralen) and mefloquine ; medications for anxiety or mental ... pills, patches, rings, injections, implants, or intrauterine devices). Use another form of birth control while taking carbamazepine. ...

  4. Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

    Directory of Open Access Journals (Sweden)

    Jason L. Russell

    2015-01-01

    Full Text Available Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity.

  5. Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

    Science.gov (United States)

    Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

    2011-01-01

    AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

  6. Severe Hypertension and Bradycardia Secondary to Midodrine Overdose.

    Science.gov (United States)

    Wong, L Y; Wong, A; Robertson, T; Burns, K; Roberts, M; Isbister, G K

    2017-03-01

    The objective of this case is to describe the pharmacokinetics and toxicity of midodrine in overdose. A 20 year old female ingested up to 350 mg midodrine while recovering in hospital from another overdose. She developed vomiting and severe hypertension (blood pressure [BP], 210/100 mmHg). Remarkable findings included a heart rate with a range of 43-60 beats/min, spontaneous respirations (20 breaths/min), and oxygen saturations of >95 % on FiO2 25 %, and a GS of 8. She was admitted to intensive care and had a normal non-contrast CT brain. She was treated with a glyceryl trinitrate patch (5 mg) and observed for 36 h with subsequent BP reduction to 124/81 mmHg and improved in conscious state. Midodrine and desglymidodrine concentrations were measured with liquid chromatography tandem mass spectrometry and were detected with 2-h post-ingestion at concentrations of 158.4 and 169.7 ng/mL, respectively. The parent drug concentrations rapidly decreased with an elimination of half-life of 1.6 h, and the metabolite initially increased and then decreased. The peak in blood pressure appeared to coincide with peak metabolite concentrations. Midodrine in overdose can potentially cause severe hypertension and reflex bradycardia but given its short half-life treatment with vasodilator agents and supportive care is sufficient.

  7. Methamphetamine overdose

    Science.gov (United States)

    ... dialysis (kidney machine) Destruction of muscles, which can lead to amputation An extremely large methamphetamine overdose can cause death. Alternative Names Intoxication - amphetamines; Intoxication - uppers; Amphetamine intoxication; Uppers overdose; Overdose - ...

  8. Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose.

    Science.gov (United States)

    Fitzgibbons, L J; Snoey, E R

    1999-01-01

    Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed.

  9. Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity.

    Science.gov (United States)

    Isbister, Geoffrey K; Heppell, Simon P; Page, Colin B; Ryan, Nicole M

    2017-03-01

    There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults. This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (>200 μg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records. From 133 admissions for clonidine poisoning (1988-2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14-65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100 μg (interquartile range [IQR]: 400-15,000 μg). Median LOS was 21h (IQR: 14-35 h) and there were no deaths. Glasgow coma score [GCS] central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.

  10. Bilateral blindness secondary to optic nerve ischemia from severe amlodipine overdose: a case report.

    Science.gov (United States)

    Kao, Raymond; Landry, Yves; Chick, Genevieve; Leung, Andrew

    2017-08-03

    Calcium channel blockers are commonly prescribed medications; calcium channel blocker overdose is becoming increasingly prevalent. The typical presentation of a calcium channel blocker overdose is hypotension and decreased level of consciousness. We describe a case of a calcium channel blocker overdose that led to bilateral cortical blindness, a presentation that has not previously been reported. A 49-year-old white woman with known bilateral early optic atrophy presented to our hospital with hypotension and obtundation following a known ingestion of 150 mg of amlodipine. She was transferred to our intensive care unit where she was intubated, mechanically ventilated, and required maximal vasopressor support (norepinephrine 40 mcg/minute, epinephrine 40 mcg/minute, and vasopressin 2.4 units/hour) along with intravenously administered crystalloid boluses. Despite these measures, she continued to deteriorate with persistent hypotension and tachycardia, as well as anuria. Intralipid emulsion therapy was subsequently administered to which no initial response was observed. A chest X-ray revealed diffuse pulmonary edema; intravenous diuresis as well as continuous renal replacement therapy was initiated. Following the initiation of continuous renal replacement therapy, her oxygen requirements as well as urine output began to improve, and 3 days later she was liberated from mechanical ventilation. Following extubation, she complained of new onset visual impairment, specifically seeing only red-green colors, but no objects. An ophthalmologic examination revealed that this was due to bilateral optic atrophy from prolonged hypotension during the first 24 hours after the overdose. Persistent hypotension in the setting of a calcium channel blocker overdose can lead to worsening optic atrophy resulting in bilateral cortical blindness.

  11. An Acute Ibuprofen Overdose Masking a Severe Staphylococcus aureus Meningitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Matthew Smetana

    2013-01-01

    Full Text Available Acute bacterial meningitis has a low incidence (3/100,000 in the United States and yet high fatality rate (approximately 14–16% and classically presents as a triad of fever, neck stiffness, and altered mental status. However, less than half of patients with meningitis present with this classic triad. We present the clinical course of a patient who initially presented to the emergency department after overdosing on ibuprofen for what he described as back pain secondary to mechanical injury. However, the patient's condition quickly deteriorated: he developed tachycardia, mental status changes, was intubated due to respiratory distress, and then suffered an 8-minute PEA arrest before return of spontaneous circulation was achieved. After the patient was stabilized, in addition to the nonsteroidal anti-inflammatory drug (NSAID overdose Staphylococcus aureus meningitis, bacteremia, and pneumonia were diagnosed. We report this case to illustrate that the initial presentation of meningitis may be extremely unusual especially in the setting of NSAID overdose and the acutely decompensating patient. As the risk of adverse clinical outcomes increases with delays in appropriate antibiotic therapy, it is therefore crucial to recognize the many signs and symptoms of meningitis, typical and atypical, and quickly begin appropriate treatment.

  12. Carbamazepine (Tegretol) and Pregnancy

    Science.gov (United States)

    ... take. Can taking carbamazepine during pregnancy affect my baby’s development? More studies are needed before we can be ... taking carbamazepine monotherapy does not appear to affect infant growth or development. Some healthcare providers can measure levels of carbamazepine ...

  13. Aspirin overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002542.htm Aspirin overdose To use the sharing features on this page, please enable JavaScript. An overdose of aspirin means you have too much aspirin in your ...

  14. Contac overdose

    Science.gov (United States)

    Symptoms of a Contac overdose include: Blurred vision Depression Delirium Disorientation, nervousness, hallucinations Drowsiness Enlarged pupils Fever Inability to urinate or completely empty the bladder Increased ...

  15. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Niko Bekjarovski

    2013-09-01

    How to cite this article: Bekjarovski NG. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature. Asia Pac J Med Toxicol 2013;2:114-6.

  16. Caffeine overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002579.htm Caffeine overdose To use the sharing features on this page, please enable JavaScript. Caffeine is a substance that exists naturally in certain ...

  17. Piroxicam overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002534.htm Piroxicam overdose To use the sharing features on this page, please enable JavaScript. Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) used ...

  18. Dextromethorphan overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002628.htm Dextromethorphan overdose To use the sharing features on this page, please enable JavaScript. Dextromethorphan is a medicine that helps stop coughing. It ...

  19. Ibuprofen overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002655.htm Ibuprofen overdose To use the sharing features on this page, please enable JavaScript. Ibuprofen is a type of nonsteroidal anti-inflammatory drug ( ...

  20. Extracorporeal treatment for carbamazepine poisoning

    DEFF Research Database (Denmark)

    Ghannoum, Marc; Yates, Christopher; Galvao, Tais F

    2014-01-01

    in carbamazepine poisoning. METHODS: After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness......-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR...... is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D...

  1. Nail changes after carbamazepine

    Directory of Open Access Journals (Sweden)

    Chopra Adarsh

    2000-01-01

    Full Text Available Antiepileptics are known to produce different types of side effects including nail changes. A 20-year-old epileptic man had yellowish discolouration followed by dystrophy and onycholysis of his 15 nails after taking carbamazepine for 3 months which cleared within six months after discontinuation of the drug. This type of change has not been reported earlier with carbamazepine

  2. Radiographic abnormalities in tricyclic acid overdose

    International Nuclear Information System (INIS)

    Varnell, R.M.; Richardson, M.L.; Vincent, J.M.; Godwin, J.D.

    1987-01-01

    Several case reports have described adult respiratory distress syndrome (ARDS) secondary to tricyclic acid (TCA) overdose. During a 1-year period 83 patients requiring intubation secondary to drug overdose were evaluated. Abnormalities on chest radiographs occurred in 26 (50%) of the 54 patients with TCA overdose, compared to six (21%) of the 29 patients overdosed with other drugs. In addition, five (9%) of the patients with TCA overdose subsequently had radiographic and clinical abnormalities meeting the criteria for ARDS. Only one (3%) of the patients with non-TCA overdose subsequently had change suggesting ARDS. TCAs should be added to the list of drugs associated with ARDS, and TCA overdose should be considered a major risk factor in the development of radiographically evident abnormalities

  3. Carbamazepine degradation by gamma irradiation coupled to biological treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shizong [Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084 (China); Wang, Jianlong, E-mail: wangjl@tsinghua.edu.cn [Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory of Radioactive Wastes Treatment, Tsinghua University, Beijing 100084 (China)

    2017-01-05

    Highlights: • Carbamazepine was removed by the combined gamma radiation and biodegradation. • The removal efficiency of carbamazepine increased with dose. • Irradiation could enhance the mineralization of carbamazepine significantly. • The combined irradiation and biodegradation was effective for carbamazepine removal. - Abstract: Carbamazepine is an emerging contaminant and resistant to biodegradation, which cannot be effectively removed by the conventional biological wastewater treatment processes. In this study, the combined gamma irradiation and biodegradation was employed to remove carbamazepine from wastewater. The effect of dose on the removal of carbamazepine was studied at different doses (300, 600 and 800 Gy). The results showed that the removal efficiency of carbamazepine increased with dose increasing during the irradiation process. The maximum removal efficiency was 99.8% at 800 Gy, while the removal efficiency of total organic carbon (TOC) was only 26.5%. The removal efficiency of TOC increased to 79.3% after the sequent biological treatment. In addition, several intermediates and organic acids were detected. The possible degradation pathway of carbamazepine during the integrated irradiation and biodegradation was proposed. Based on the overall analysis, the combined gamma irradiation and biological treatment process can be an alternative for removing the recalcitrant organic pollutants such as carbamazepine from wastewater.

  4. Calcium carbonate overdose

    Science.gov (United States)

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Products that contain calcium carbonate are certain: Antacids (Tums, Chooz) Mineral supplements Hand lotions Vitamin and mineral supplements Other products may also contain ...

  5. Hyponatremia following acute overdose with paroxetine

    DEFF Research Database (Denmark)

    Johnsen, C R; Hoejlyng, N

    1998-01-01

    This case illustrates severe hyponatremia following an acute overdose of paroxetine. An 83-year-old woman was admitted to our hospital after an attempt to commit suicide. She had consumed an overdose of 360 mg paroxetine. The treatment was started 3 days previously with 10 mg/day because of regular...... suffering from obsessive and suicidal thoughts. An initial sign of overdose was excessive vomiting. Five days late she developed hyponatremia (serum sodium 112 mmol/l) with somnolence, confusion, muscle spasms, dehydration of arms and legs and slow reflexes. Ecchymoses and myxoedema were also observed...

  6. Mental disorders induced by carbamazepine.

    Science.gov (United States)

    Mizukami, K; Naito, Y; Yoshida, M; Nakanishi, T; Koizumi, J

    1990-03-01

    We present here a case with various physical and neuropsychiatric symptoms caused by the administration of carbamazepine. The patient suffering from right ophthalmic neuralgia showed fever, eczema, erythema, lymphoadenopathy, eosinophilia, vomiting, headache, dizziness, nystagmus, and various mental disorders which consisted of emotional instability, personality change, delusions of reference and persecution, depressive state, and hyperventilation syndrome during the administration of carbamazepine. The physical symptoms in the present case were conformable to the side effect of carbamazepine. The mental disorders appeared in a few days from the start of carbamazepine administration and disappeared after the discontinuation of the administration of this drug without antipsychotic therapy and have never relapsed until now. The mental disorders and the physical symptoms were in parallel with their clinical course. This kind of mental disorders induced by carbamazepine has not yet been reported.

  7. Paracetamol overdose: the liver unit perspective.

    LENUS (Irish Health Repository)

    Iqbal, M

    2012-09-01

    Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.

  8. Naproxen sodium overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002507.htm Naproxen sodium overdose To use the sharing features on this page, please enable JavaScript. Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) used ...

  9. Adrenergic bronchodilator overdose

    Science.gov (United States)

    Adrenergic bronchodilators are inhaled medicines that help open up the airways. They are used to treat asthma and chronic bronchitis. Adrenergic bronchodilator overdose occurs when someone accidentally or intentionally ...

  10. Sports cream overdose

    Science.gov (United States)

    Sports creams are creams or ointments used to treat aches and pains. Sports cream overdose can occur if someone uses this ... Two ingredients in sports creams that can be poisonous are: Menthol Methyl salicylate

  11. Diclofenac sodium overdose

    Science.gov (United States)

    ... will likely get better. In rare cases, a blood transfusion is needed. Passing a tube through the mouth into the stomach (endoscopy) may be required to stop internal bleeding. Alternative Names Voltaren overdose References Aronson JK. Non-steroidal ...

  12. Acetaminophen and codeine overdose

    Science.gov (United States)

    ... and is not helped by other types of painkillers. Acetaminophen and codeine overdose occurs when someone takes ... a vein) A laxative Medicine to reverse the effects of the poison and treat symptoms Tube through ...

  13. Barbiturate intoxication and overdose

    Science.gov (United States)

    ... users who do not know these combinations can lead to coma or death Experienced users who use them on purpose to alter their consciousness Symptoms Symptoms of barbiturate intoxication and overdose include: Altered level of consciousness Difficulty ...

  14. Fenoprofen calcium overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002649.htm Fenoprofen calcium overdose To use the sharing features on this page, please enable JavaScript. Fenoprofen calcium is a type of medicine called a nonsteroidal ...

  15. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used ...

  16. Birth control pills overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002599.htm Birth control pill overdose To use the sharing features on ... the medicine was prescribed for the person Poison Control Your local poison center can be reached directly ...

  17. Zinc oxide overdose

    Science.gov (United States)

    Zinc oxide is an ingredient in many products. Some of these are certain creams and ointments used ... prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone eats one of ...

  18. Stevens-Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2011-01-01

    Full Text Available Carbamazepine and other anticonvulsants are commoner cause of severe adverse cutaneous drug reactions such as erythema multiforme, toxic epidermal necrolysis (TEN, and Stevens-Johnson syndrome (SJS. We report a case of SJS rapidly progressing to TEN with a combination of haloperidol and carbamazepine in a patient with bipolar affective disorder. The pathophysiological mechanism underlying this reaction is discussed.

  19. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2011-03-24

    Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.

  20. Compound list: carbamazepine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available carbamazepine CBZ 00018 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/carbamazepine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/carbamazepine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/carbamazepine.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc

  1. WITHDRAWN: Carbamazepine for cocaine dependence.

    Science.gov (United States)

    Lima Reisser, Anelise A R L; Silva de Lima, Mauricio; Soares, Bernardo Garcia de Oliveira; Farrell, Michael

    2009-01-21

    Cocaine dependence has become a public health problem, developing a significant number of medical, psychological and social problems. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorders, has been used for treatment of cocaine dependence, although its effectiveness has not been established. To determine whether carbamazepine is effective for the treatment of cocaine dependence. We searched: Cochrane Controlled Trials Register (Cochrane Library issue 1, 1999), MEDLINE (f1966 - October 1997), EMBASE (1980 - October 1997), PsycLIT (1974 - July 1997), Biological Abstracts and LILACS (1982 - 1997); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. The specialised register of trials of Cochrane Group on Drugs and Alcohol until February 2003. All randomised controlled trials focused on the use of carbamazepine versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. The reviewers extracted the data independently, Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. 5 studies were included (455 participants). No differences regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety

  2. Intravenous Carbamazepine for Adults With Seizures.

    Science.gov (United States)

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

    2018-03-01

    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  3. Sassafras oil overdose

    Science.gov (United States)

    Sassafras oil comes from the root bark of the sassafras tree. Sassafras oil overdose occurs when someone swallows more than the ... Safrole is the poisonous ingredient in sassafras oil. It is a clear or ... yellow oily liquid. It can be dangerous in large amounts.

  4. Concomitant overdosing of other drugs in patients with paracetamol poisoning

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    AIMS: Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome...... of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal...... favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity...

  5. Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature.

    Science.gov (United States)

    Martins, Silvia S; Sampson, Laura; Cerdá, Magdalena; Galea, Sandro

    2015-11-01

    Drug overdose is an important, yet an inadequately understood, public health problem. Global attention to unintentional drug overdose has been limited by comparison with the scope of the problem. There has been a substantial increase in drug overdose incidence and prevalence in several countries worldwide over the past decade, contributing to both increased costs and mortality. The aim of this study was to systematically synthesize the peer-reviewed literature to document the global epidemiological profile of unintentional drug overdoses and the prevalence, time trends, mortality rates, and correlates of drug overdoses. We searched different combinations of Medical Subject Headings (MeSH) terms in PubMed for articles published from 1980 until July 2013, and we organized these results in tabular spreadsheets and compared them. We restricted the search to English-language articles that deal with unintentional overdose, focusing on 1 or more of the following key constructs: prevalence, time trends, mortality rates, and correlates. The term "overdose" as a MeSH major topic yielded 1076 publications. In addition, we searched the following combinations of nonmajor MeSH terms: "street drugs" and "overdose" yielded 180, "death" and "overdose" yielded 114, and "poisoning" and "drug users" yielded 17. There was some overlap among the searches. Based on the search and inclusion and exclusion criteria, we selected a total of 169 relevant articles for this article based on a close review of abstracts. We found wide variability in lifetime prevalence of experiencing a nonfatal overdose or witnessing an overdose, and in mortality rates attributable to overdose. Lifetime prevalence of witnessed overdose among drug users (n = 17 samples) ranged from 50% to 96%, with a mean of 73.3%, a median of 70%, and a standard deviation of 14.1%. Lifetime prevalence of drug users personally experiencing a nonfatal overdose (n = 27 samples), ranged from 16.6% to 68.0% with a mean of 45

  6. Non-recurrence of carbamazepine induced vitiligo after rechallenge with carbamazepine.

    Directory of Open Access Journals (Sweden)

    Masoomeh Saeedloo

    2013-12-01

    Full Text Available Vitiligo is a rare side effect of carbamazepine whose exact mechanism is unknown. The aim of this report is to describe a single case of vitiligo induced by carbamazepine.The case was a patient with Bipolar I disorder whose medications were changed from valproate to carbamazepine and who developed vitiligo after a short while. We followed the case for about four years when he was rechallenged with carbamazepine.When depigmentation occurred, we immediately discontinued carbamazepine after which the depigmented areas improved gradually. About three years later, he received carbamazepine again, but depigmentation did not recur.Carbamazepine-induced vitiligo is not an absolute contraindication for the prescription of carbamazepine if other choices fail to respond or are not tolerated. The case has implications for the mechanism of medication induced vitiligo.

  7. Polyuria following an overdose

    OpenAIRE

    Collins, Angela; White, Nigel A

    2013-01-01

    Case report detailing the occurrence of diabetes insipidus in a 42-year-old man admitted to the intensive treatment unit (ITU) following an overdose. Whilst on ITU, he was sedated with propofol. Cessation of treatment with propofol coincided with resolution of the polyuria. Animal studies suggest a theoretical mechanism for propofol as the causative agent, but this phenomenon is not commonly seen in humans.

  8. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.

    2009-01-01

    Background Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. Objectives To compare efficacy and tolerability of carbamazepine and oxcarbazepine

  9. Comparison of toxicity of acute overdoses with citalopram and escitalopram.

    Science.gov (United States)

    Hayes, Bryan D; Klein-Schwartz, Wendy; Clark, Richard F; Muller, Allison A; Miloradovich, Jane E

    2010-07-01

    Seizures and QTc prolongation are associated with citalopram poisoning; however, overdose experience with escitalopram is more limited. The goals of this study were to compare citalopram's vs. escitalopram's clinical effects in overdose, including the incidence of seizures. A retrospective review was conducted for single-substance acute overdoses with citalopram and escitalopram, managed in hospitals, that were reported to six U.S. poison centers from 2002-2005. There were 374 citalopram and 421 escitalopram overdose cases. Gender and ages were similar between the two, with 68-70% females and a median age of 20 years for citalopram and 18 years for escitalopram. Median dose by history was 310 mg for citalopram and 130 mg for escitalopram. More serious outcomes were associated with citalopram overdoses (p escitalopram were tachycardia, drowsiness, hypertension, and vomiting. Seizures (30 vs. 1, respectively, p escitalopram cases (p = 0.109). There was an association between increasing dose and severity of outcome for citalopram (p escitalopram (p = 0.011). In children escitalopram cases experienced toxicity, such as drowsiness, nausea/vomiting, and tachycardia. There were no seizures in this age group. Escitalopram seems to be less toxic than citalopram after an acute overdose; seizures and tremors were more common with citalopram. Initial management of overdoses should include seizure precautions for citalopram and cardiac monitoring for both drugs. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Interventions for paracetamol (acetaminophen) overdose

    DEFF Research Database (Denmark)

    Chiew, Angela L; Gluud, Christian; Brok, Jesper

    2018-01-01

    BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various...... of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best...... was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol...

  11. Prescription Painkiller Overdoses PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the July 2013 CDC Vital Signs report. Prescription painkiller overdoses are an under-recognized and growing problem among women. This program includes things that women and health care providers can do to reduce the risk of overdose.

  12. A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012.

    Science.gov (United States)

    Tolou-Ghamari, Zahra; Zare, Mohammad; Habibabadi, Jafar Mehvari; Najafi, Mohammad Reza

    2013-03-01

    Carbamazepine has been used as AEDs since 1965, and is most effective against partial seizures. Two basic mechanisms of action have been proposed: 1) enhancement of sodium channel inactivation by reducing high-frequency repetitive firing of action potentials, 2) and action on synaptic transmission. The aim of this study was to provide a review of carbamazepine pharmacokinetics and its management guidelines in Iranian epileptic population. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO), Web of Science were searched; 1600, 722 and 167 research and review articles relevant to the topics; carbamazepine pharmacokinetics, carbamazepine pharmacokinetics in epilepsy and review on carbamazepine pharmacokinetics in epilepsy were found, respectively. Carbamazepine is highly bound to plasma proteins. In patients the protein-bound fraction ranged from 75-80% of the total plasma concentration. Bioavailability ranges from 75-85%. The rate or extent of absorption was not be affected by food. It is completely metabolized and the main metabolite is carbamazepine-epoxide (CBZ-E). Carbamazepine induces its own metabolism, leading to increased clearance, shortened serum half-life, and progressive decrease in serum levels. Increases in daily dosage are necessary to maintain plasma concentration. Severe liver dysfunction may cause disordered pharmacokinetics. In cardiac failure, congestion of major vital organs, including kidneys, may result in abnormally slow absorption and metabolism. Carbamazepine shows variability due to its narrow therapeutic window. Therefore clinical management in a3n Iranian epileptic population should focus on results derived from therapeutic drug monitoring in order to reduce inter and intra- individual variability in plasma drug concentrations.

  13. Concomitant overdosing of other drugs in patients with paracetamol poisoning

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal...... was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more...... favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity...

  14. Recovering from Opioid Overdose: Resources for Overdose Survivors & Family Members

    Science.gov (United States)

    ... and gratitude, all accompanied by the discomfort of opioid withdrawal. Most need the support of family and friends to take the next steps toward recovery. While many factors can contribute to opioid overdose, it is al most always an accident. ...

  15. Association of HLA-BFNx011502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians

    Directory of Open Access Journals (Sweden)

    Mehta Timir

    2009-01-01

    Full Text Available Background: Stevens-Johnson Syndrome (SJS and toxic epidermal necrolysis are severe cutaneous reactions caused by certain drugs, including antiepileptic carbamazepine. A strong association has been reported between human leucocyte antigen (HLA-BFNx011502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-BFNx011502 is not a universal marker but is ethnicity-specific for Asians. Aim: To study the association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients. Methods: Eight individuals who fulfilled the diagnostic criteria of SJS induced by carbamazepine were identified and HLA-B molecular typing was performed. HLA-B genotyping was carried out by polymerase chain reaction using sequence-specific primers. Results: Out of eight patients studied for genotype, six patients were found to have the HLA-BFNx011502 allele. Conclusion: This study suggests an association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients.

  16. Olanzapine Overdose in a Pin Point Pupil with Altered Sensorium

    Directory of Open Access Journals (Sweden)

    Naresh Midha

    2017-09-01

    Full Text Available Background:Olanzapine is a highly tolerable and easily affordable atypical antipsychotic drug which has been commonly prescribed in both inpatient and outpatient settings for several mental disorders. Olanzapine overdose is commonly seen in psychiatric patients, who attempt suicide by intoxicating themselves with their own prescribed medications. Increased olanzapine use is associated with increased incidence of overdosing. Case Presentation:We are reporting a case of olanzapine overdosage as a cause of pinpoint pupils and altered sensorium with exclusion of other differentials. The mainstay of managementof olanzapine overdose is general supportive and symptomatic measures. Discussion: Pinpoint pupils with altered sensorium and agitation are always an alarming situation for a clinician, because of differentials like organophosphorus poisoning, pontine hemorrhage and opium overdosing. Due to olanzapine overdosage, similar clinical picture can be confusing in the emergency department and early identification of such cases is helpful to decrease the risk of fatality. Conclusion: This case highlights the significance of olanzapine overdosing as a differential diagnosis for patients presented with altered sensorium and pinpoint pupils in the emergency department. Olanzapine overdosage is associated with high morbidity and mortality. Although there is no specific antidote for olanzapine overdose, appropriate history, assessment and early diagnosis are very useful for the better outcome.

  17. Allegheny County Fatal Accidental Overdoses

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Fatal accidental overdose incidents in Allegheny County, denoting age, gender, race, drugs present, zip code of incident and zip code of residence. Zip code of...

  18. Overdose Deaths Among Homeless Persons

    Science.gov (United States)

    ... Twitter Overdose Deaths Among Homeless Persons January 2013 Homelessness is a persistent problem—nearly 690,000 people ... will ultimately help address the tragic problem of homelessness too, as many homeless people cite drug or ...

  19. Characterization of Carbamazepine-Loaded Solid Lipid ...

    African Journals Online (AJOL)

    loaded solid lipid nanoparticles by RESS as well as their characterization has been achieved in this study. Keywords: Rapid expansion of supercritical fluid, Stearic acid, Solid lipid nanoparticles, Carbamazepine, Co-precipitation ...

  20. Prescription Painkiller Overdoses PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-07-02

    This 60 second public service announcement is based on the July 2013 CDC Vital Signs report. Prescription painkiller overdoses are an under-recognized and growing problem among women. This program includes things that women and health care providers can do to reduce the risk of overdose.  Created: 7/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/2/2013.

  1. Carbamazepine - hematologic effects of the use

    Directory of Open Access Journals (Sweden)

    Kamil Leis

    2018-06-01

    Full Text Available Carbamazepine is an antiepileptic drug which exhibits a number of side effects, namely including a headache, abdominal pain, increased blood pressure, but also hematologic disorders. Thrombocytopenia, hypogammaglobulinemia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, pure red cell aplasia, leukemia or eosinophilia with DRESS syndrome belong to the latter. There is a low incidence of carbamazepine pharmacotherapy related symptoms and their exact mechanisms of action are still unknown.

  2. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity

    Science.gov (United States)

    Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

    2012-01-01

    AIMS Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P = 0.025), although this overdose pattern did not independently predict death. The King's College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P = 0.009). CONCLUSIONS Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres. PMID:22106945

  3. Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?

    Directory of Open Access Journals (Sweden)

    Kalsi SS

    2011-10-01

    Full Text Available Sarbjeet S Kalsi1,2, David M Wood2–4, W Stephen Waring5, Paul I Dargan2–4 1Emergency Department, 2Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London; 3King's Health Partners, 4King's College London, London; 5York Teaching Hospital NHS Foundation Trust, York, UK Abstract: Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI. In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as “high-risk” after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John's wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose. Keywords

  4. A Systematic Review on Insulin Overdose Cases

    DEFF Research Database (Denmark)

    Johansen, Nicklas Järvelä; Christensen, Mikkel Bring

    2018-01-01

    A large overdose of insulin is a serious health matter. Information concerning administration and duration of intravenous (IV) glucose, other treatment options or complications beside hypoglycaemia following large insulin overdoses is not readily apparent from the literature. This article...

  5. Characterization and Management of Patients with Heroin versus Nonheroin Opioid Overdoses: Experience at an Academic Medical Center.

    Science.gov (United States)

    Morizio, Kate M; Baum, Regan A; Dugan, Adam; Martin, Julia E; Bailey, Abby M

    2017-07-01

    To characterize the differences between patients who had heroin and nonheroin opioid overdoses and to determine whether there were any significant differences in their management with regard to the naloxone use. Retrospective cohort study. Large academic medical center. A total of 923 patients admitted to the medical center who were identified for overdose by heroin or other opiate-related narcotics between January 2010 and September 2015; 480 patients experienced a nonheroin opioid overdose event, and 443 patients experienced a heroin overdose event. Patients presenting with heroin overdose tended to be younger and male, with higher rates of hepatitis C virus (HCV) infection compared with those presenting with nonheroin opioid overdose (pevent, history of injection drug use, and history of prescription opioid abuse compared with the nonheroin group (pevent with the same drug. The proportion of patients presenting with a heroin overdose steadily increased from 2010-2015; the number of patients presenting to the emergency department with nonheroin opioid overdoses steadily decreased. As rates of heroin overdose increased each year, the incidence of HCV infection increased dramatically. This study indicates that the incidence of heroin overdoses has significantly increased over the last several years, and the rates of HCV infection 4-fold since the start of the study period. Patients admitted for nonheroin opioid overdose were more likely to be admitted to the hospital and intensive care unit compared with those admitted for heroin overdose. The rise in overdose events only further illustrates a gap in our understanding of the cycle of addiction, drug abuse, and overdose events. © 2017 Pharmacotherapy Publications, Inc.

  6. Interventions for paracetamol (acetaminophen) overdose.

    Science.gov (United States)

    Chiew, Angela L; Gluud, Christian; Brok, Jesper; Buckley, Nick A

    2018-02-23

    Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites. To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews. Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens. Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of

  7. Fate of Carbamazepine during Water Treatment

    DEFF Research Database (Denmark)

    Kosjek, T.; Andersen, Henrik Rasmus; Kompare, Boris

    2009-01-01

    of acridone, hydroxy-(9H,10H)-acridine-9-carbaldehyde, acridone-N-carbaldehyde, and 1-(2-benzaldehyde)-(1H,3H-quinazoline-2,4-dione, while biological breakdown of acridine yielded acridone. In parallel, the transformation product iminostilbene was observed during sample analysis. In addition,this study...... compared the treatment technologies according to the removal of carbamazepine and the production and decay of its transformation products. The most successful method for the removal of carbamazepine was UV treatment, while acridine and acridone were more susceptible to biological treatment. Therefore...

  8. Stevens-Johnson Syndrome Induced by Carbamazepine Treatment in a Patient Who Previously Had Carbamazepine Induced Pruritus - A Case Report -

    OpenAIRE

    Bae, Hyun Min; Park, Yoo Jung; Kim, Young Hoon; Moon, Dong Eon

    2013-01-01

    Stevens-Johnson syndrome (SJS) is a rare but life-threatening skin reaction disease and carbamazepine is one of its most common causes. We report a case of SJS secondary to carbamazepine in a patient with previous pruritus due to carbamazepine which was given for treatment of trigeminal neuralgia. We would like to caution all providers that carbamazepine readministration should be avoided in the patient with a previous history of SJS or adverse skin reaction. In addition, we strongly recommen...

  9. Drug overdose resulting in quadriplegia.

    Science.gov (United States)

    Wang, Teresa S; Grunch, Betsy H; Moreno, Jessica R; Bagley, Carlos A; Gottfried, Oren N

    2012-06-01

    To describe a case of cervical flexion myelopathy resulting from a drug overdose. A 56-year-old male presented to the emergency department unable to move his extremities following drug overdose. Neurological examination revealed him to be at C6 ASIA A spinal cord injury. The CT of his cervical spine revealed no fracture; however, an MRI revealed cord edema extending from C3 to C6 as well as posterior paraspinal signal abnormalities suggestive of ligamentous injury. The patient underwent a posterior cervical laminectomy and fusion from C3 to C7. Neurologically he regained 3/5 bilateral tricep function and 2/5 grip; otherwise, he remained at ASIA A spinal cord injury at 6 months. Our patient suffered a spinal cord injury likely due to existing cervical stenosis, and in addition to an overdose of sedating medications, he likely sat in flexed neck position for prolonged period of time with the inability to modify his position. This likely resulted in cervical spine vascular and/or neurological compromise producing an irreversible spinal cord injury. Spinal cord injury is a rare finding in patients presenting with drug overdose. The lack of physical exam findings suggestive of trauma may delay prompt diagnosis and treatment, and thus clinicians must have a high index of suspicion when evaluating patients in this setting.

  10. Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

    Science.gov (United States)

    Mixcoatl-Zecuatl, Teresa; Quinonez-Bastidas, Geovanna N; Caram-Salas, Nadia L; Ambriz-Tututi, Monica; Araiza-Saldana, Claudia I; Rocha-Gonzalez, Hector I; Medina-Santillan, Roberto; Reyes-Garcia, Gerardo; Granados-Soto, Vinicio

    2008-01-01

    Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

  11. Management of lercanidipine overdose with hyperinsulinaemic euglycaemia therapy: case report

    Directory of Open Access Journals (Sweden)

    Messer Ben

    2011-01-01

    Full Text Available Abstract This case report describes the first reported overdose of the dihydropyridine calcium channel blocker (CCB lercanidipine. A 49 yr old male presented to the Emergency Department 3 hrs after the ingestion of 560 mg of lercanidipine. In the department he had a witnessed seizure within 15 minutes of arrival attributed to the overdose. Following immediate recovery of consciousness after the seizure, he had refractory hypotension and bradycardia which failed to respond to fluid resuscitation, glucagon therapy, and intravenous calcium. He went on to require vasopressor support with noradrenaline and was treated with high dose insulin therapy which was successful in achieving cardiovascular stability. Vasopressor therapy was no longer required within one half life of lercanidipine, and the total stay on intensive care was one day before transfer to a ward. Calcium channel blocker overdose is an uncommon but life-threatening overdose. Treatment for severe toxicity is similar to b-blocker overdose. Hypotension is treated with intravenous fluid therapy, intravenous calcium and possibly glucagon with vasopressor or inotropic support as required. Atropine is used to attempt reversal of bradycardia. High doses of intravenous insulin with intravenous dextrose as required (hyperinsulinaemic euglycaemia or HIET, has also been successfully reported. Experimental animal data suggests that HIET is of benefit and potentially superior to fluid therapy, calcium, glucagon and potentially vasopressor therapy. HIET effectively and sustainably reverses hypotension, bradycardia and improves myocardial contractility and metabolism. Current advice in calcium channel blocker overdose is to begin therapy early in toxicity, starting with a 1.0 IU/kg insulin bolus followed by an infusion of 0.5 IU/kg/hr of insulin and dextrose as required titrated to clinical response.

  12. The relationship between US heroin market dynamics and heroin-related overdose, 1992-2008.

    Science.gov (United States)

    Unick, George; Rosenblum, Daniel; Mars, Sarah; Ciccarone, Daniel

    2014-11-01

    Heroin-related overdose is linked to polydrug use, changes in physiological tolerance and social factors. Individual risk can also be influenced by the structural risk environment including the illicit drug market. We hypothesized that components of the US illicit drug market, specifically heroin source/type, price and purity, will have independent effects on the number of heroin-related overdose hospital admissions. Yearly, from 1992 to 2008, Metropolitan Statistical Area (MSA) price and purity series were estimated from the US Drug Enforcement Administration data. Yearly heroin overdose hospitalizations were constructed from the Nationwide Inpatient Sample. Socio-demographic variables were constructed using several databases. Negative binomial models were used to estimate the effect of price, purity and source region of heroin on yearly hospital counts of heroin overdoses controlling for poverty, unemployment, crime, MSA socio-demographic characteristics and population size. Purity was not associated with heroin overdose, but each $100 decrease in the price per pure gram of heroin resulted in a 2.9% [95% confidence interval (CI) = 4.8%, 1.0%] increase in the number of heroin overdose hospitalizations (P = 0.003). Each 10% increase in the market share of Colombian-sourced heroin was associated with a 4.1% (95% CI = 1.7%, 6.6%) increase in number of overdoses reported in hospitals (P = 0.001) independent of heroin quality. Decreases in the price of pure heroin in the United States are associated with increased heroin-related overdose hospital admissions. Increases in market concentration of Colombian-source/type heroin is also associated with an increase in heroin-related overdose hospital admissions. Increases in US heroin-related overdose admissions appear to be related to structural changes in the US heroin market. © 2014 Society for the Study of Addiction.

  13. Drug involvement in fatal overdoses

    Directory of Open Access Journals (Sweden)

    Christopher J. Ruhm

    2017-12-01

    Full Text Available Death certificate data from the Multiple Cause of Death (MCOD files were analyzed to better understand the drug categories most responsible for the increase in fatal overdoses occurring between 1999 and 2014. Statistical adjustment methods were used to account for the understatement in reported drug involvement occurring because death certificates frequently do not specify which drugs were involved in the deaths. The frequency of combination drug use introduced additional uncertainty and so a distinction was made between any versus exclusive drug involvement. Many results were sensitive to the starting and ending years chosen for examination. Opioid analgesics played a major role in the increased drug deaths for analysis windows starting in 1999 but other drugs, particularly heroin, became more significant for recent time periods. Combination drug use was important for all time periods and needs to be accounted for when designing policies to slow or reverse the increase in overdose deaths.

  14. Sorption and desorption of carbamazepine from water by smectite clays.

    Science.gov (United States)

    Zhang, Weihao; Ding, Yunjie; Boyd, Stephen A; Teppen, Brian J; Li, Hui

    2010-11-01

    Carbamazepine is a prescription anticonvulsant and mood stabilizing pharmaceutical administered to humans. Carbamazepine is persistent in the environment and frequently detected in water systems. In this study, sorption and desorption of carbamazepine from water was measured for smectite clays with the surface negative charges compensated with K+, Ca2+, NH4+, tetramethylammonium (TMA), trimethylphenylammonium (TMPA) and hexadecyltrimethylammonium (HDTMA) cations. The magnitude of sorption followed the order: TMPA-smectite≥HDTMA-smectite>NH4-smectite>K-smectite>Ca-smectite⩾TMA-smectite. The greatest sorption of carbamazepine by TMPA-smectite is attributed to the interaction of conjugate aromatic moiety in carbamazepine with the phenyl ring in TMPA through π-π interaction. Partitioning process is the primary mechanism for carbamazepine uptake by HDTMA-smectite. For NH4-smectite the urea moiety in carbamazepine interacts with exchanged cation NH4+ by H-bonding hence demonstrating relatively higher adsorption. Sorption by K-, Ca- and TMA-smectites from water occurs on aluminosilicate mineral surfaces. These results implicate that carbamazepine sorption by soils occurs primarily in soil organic matter, and soil mineral fractions play a secondary role. Desorption of carbamazepine from the sorbents manifested an apparent hysteresis. Increasing irreversibility of desorption vs. sorption was observed for K-, Ca-, TMA-, TMPA- and HDTMA-clays as aqueous carbamazepine concentrations increased. Desorption hysteresis of carbamazepine from K-, Ca-, NH4-smectites was greater than that from TMPA- and HDTMA-clays, suggesting that the sequestrated carbamazepine molecules in smectite interlayers are more resistant to desorption compared to those sorbed by organic phases in smectite clays. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Preventing Prescription Drug Overdose PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the July 2014 CDC Vital Signs report. Every day, 46 people in the U.S. die from an overdose of prescription opioid painkillers. Learn what can be done to make painkiller prescribing safer and help prevent overdoses.

  16. Vital Signs-Preventing Prescription Drug Overdose

    Centers for Disease Control (CDC) Podcasts

    This podcast is based on the July 2014 CDC Vital Signs report. Every day, 46 people in the U.S. die from an overdose of prescription opioid painkillers. Learn what can be done to make painkiller prescribing safer and help prevent overdoses.

  17. Acute sirolimus overdose: a multicenter case series.

    Directory of Open Access Journals (Sweden)

    Alessandro Ceschi

    Full Text Available There are few data relating to sirolimus overdose in the medical literature. Our objectives were to describe all cases of overdose with sirolimus reported to Swiss, German and Austrian Poisons Centres between 2002-2013.An observational case-series analysis was performed to determine circumstances, magnitude, management and outcome of sirolimus overdose.Five cases of acute sirolimus overdose were reported--three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range.Acute sirolimus overdose occurred accidentally in the majority of cases. Even large overdoses appeared to be well-tolerated, however children might be at greater risk of developing complications. Further study of sirolimus overdose is needed.

  18. Tricyclic antidepressant overdose necessitating ICU admission ...

    African Journals Online (AJOL)

    Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1 000 ng/ml were associated ...

  19. Reducing the Risk of Methadone Overdose

    Centers for Disease Control (CDC) Podcasts

    2012-07-03

    This podcast is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

  20. Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

    2012-01-01

    It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. In a randomized double-blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8(th) and 12(th) weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity.

  1. Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup

    Science.gov (United States)

    Ghannoum, Marc; Yates, Christopher; Galvao, Tais F.; Sowinski, Kevin M.; Vo, Thi Hai Vân; Coogan, Andrew; Gosselin, Sophie; Lavergne, Valery; Nolin, Thomas D.; Hoffman, Robert S.

    2014-01-01

    Abstract Context. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Objectives. To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning. Methods. After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results. Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous

  2. Drug overdose surveillance using hospital discharge data.

    Science.gov (United States)

    Slavova, Svetla; Bunn, Terry L; Talbert, Jeffery

    2014-01-01

    We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000-2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison.

  3. Drug Overdose Surveillance Using Hospital Discharge Data

    Science.gov (United States)

    Bunn, Terry L.; Talbert, Jeffery

    2014-01-01

    Objectives We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. Methods We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000–2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Results Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. Conclusion The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison. PMID:25177055

  4. A comparison of carbamazepine Divitabs and a normal carbamazepine preparation in psychiatric and oligophrenic patients

    NARCIS (Netherlands)

    Nijdam, J.R.; Doorschot, C.H.; Van Bavel, L.P.; Loonen, A.J.M.

    1992-01-01

    Twenty patients who had become accustomed to a stable oral carbamazepine dose participated in an open, randomized, two-centre, cross-over study, in which ordinary tablets and Divitabs (a new sustained release preparation) were compared. Pharmacokinetic parameters, seizure control, effects on the

  5. A Massive Overdose of Dalfampridine

    Directory of Open Access Journals (Sweden)

    Laura J. Fil

    2015-12-01

    Full Text Available Multiple sclerosis (MS is an immune mediated inflammatory disease that attacks myelinated axons in the central nervous system. Dalfampridine (4-aminopyridine was approved by the Food and Drug Administration in January 2010 for treatment of MS. Our patient was a 34-year-old male with a history of MS, who was brought to the emergency department after being found unresponsive. His current medications were valacyclovir, temazepam, dalfampridine (4-AP and a tysabri intravenous (IV infusion. Fifteen minutes after arrival the patient seized. The seizures were refractory to benzodiazepines, barbiturates and phenytoin. The 4-AP level was 530ng/mL (25ng/mL and 49ng/ mL. The patient stopped seizing on hospital day 3 and was discharged 14 days later with normal mental status and neurologic exam. 4-AP is a potassium channel blocker that blocks the potassium ion current of repolarization following an action potential. The blockade of the potassium channel at the level of the membrane widens the action potential and enhances the release of acetylcholine, thus increasing post-synaptic action potentials. The treatment of patients with 4-AP overdose is supportive. Animal data suggest that patients with toxic levels of 4-AP may respond to phenytoin. Our case illustrates the highest recorded level of 4-AP in an overdose. Our patient appeared to be refractory to a combination of high doses of anticonvulsants and only improved with time.

  6. Hypothermic overdose, not all bad?

    Directory of Open Access Journals (Sweden)

    Timothy Petterson

    2013-01-01

    Full Text Available A 51-year-old woman was brought into the Emergency Department (ED following an intentional overdose of alcohol and her medication. Along with two bottles of wine it was estimated that she had taken 5800 mg of Quetiapine and 240 mg of Citalopram along with the wine. The ambient temperature in her flat was thought to be 10°C. On arrival to the ED her GCS was 8. She had agonal respirations with a pulse of 56/min, hypotensive 55/35 mmHg and a temperature 24°C. The patient was intubated and was given sodium bicarbonate, magnesium sulphate, calcium gluconate and an adrenaline infusion. She received active and passive rewarming measures. She had significant ECG findings related to her hypothermia and polypharmacy overdose which seemed to have been cumulative. The patient recovered and the only neurological deficit was numbness in her left leg which was thought to be related to prolonged immobility. Hypothermia may have contributed to her good outcome as hypothermia has been shown to improve both cardiac and neurological outcome.

  7. Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management.

    Science.gov (United States)

    Spiller, Henry A; Hays, Hannah L; Aleguas, Alfred

    2013-07-01

    The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The

  8. VSRR Provisional Drug Overdose Death Counts

    Data.gov (United States)

    U.S. Department of Health & Human Services — This data contains provisional counts for drug overdose deaths based on a current flow of mortality data in the National Vital Statistics System. National...

  9. Preventing Prescription Drug Overdose PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2014-07-01

    This 60 second public service announcement is based on the July 2014 CDC Vital Signs report. Every day, 46 people in the U.S. die from an overdose of prescription opioid painkillers. Learn what can be done to make painkiller prescribing safer and help prevent overdoses.  Created: 7/1/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 7/1/2014.

  10. Vital Signs-Preventing Prescription Drug Overdose

    Centers for Disease Control (CDC) Podcasts

    2014-07-01

    This podcast is based on the July 2014 CDC Vital Signs report. Every day, 46 people in the U.S. die from an overdose of prescription opioid painkillers. Learn what can be done to make painkiller prescribing safer and help prevent overdoses.  Created: 7/1/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 7/1/2014.

  11. Replacing carbamazepine slow-release tablets with carbamazepine suppositories: a pharmacokinetic and clinical study in children with epilepsy.

    Science.gov (United States)

    Arvidsson, J; Nilsson, H L; Sandstedt, P; Steinwall, G; Tonnby, B; Flesch, G

    1995-03-01

    A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration.

  12. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain. Sinan Mohammed Abdullah AL-Mahmood, Shahrin Tarmizi Bin Che Abdullah, Nik Nur Fatnoon Nik Ahmad, Abdul Hadi Bin Mohamed, Tariq Abdul Razak ...

  13. Carbamazepine induces mitotic arrest in mammalian Vero cells

    International Nuclear Information System (INIS)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V.; Hazen, M.J.

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells

  14. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Hazen, M.J. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)], E-mail: mariajose.hazen@uam.es

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells.

  15. The opioid overdose epidemic: opportunities for pharmacists

    Directory of Open Access Journals (Sweden)

    Wu LT

    2017-07-01

    Full Text Available Li-Tzy Wu,1–4 Udi E Ghitza,5 Anne L Burns,6 Paolo Mannelli,1 1Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University School of Medicine, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, 5Center for Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, 6American Pharmacists Association, Washington, DC, USA The USA is experiencing an opioid overdose epidemic. It has been driven largely by prescription opioids and intensified by a surge of illicit opioids (e.g., heroin and fentanyl.1,2 Drug-involved overdose, mainly opioids (e.g., prescription opioids and heroin, is a leading cause of accidental death in the USA. The opioid overdose epidemic has been escalating consistently for over a decade.2 Every day, an estimated 91 Americans die from opioid-related overdose.3 Opioid overdose appears to have disproportionally affected men, adults aged 25–64 years, and non-Hispanic whites.2

  16. Opioid Overdoses Treated in Emergency Departments PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the March 2018 CDC Vital Signs report. Opioid overdoses continue to increase in the United States. Learn what can be done to help prevent opioid overdose and death.

  17. Simultaneous Quantification of Three Polymorphic Forms of Carbamazepine in the Presence of Excipients Using Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Marco Farias

    2014-09-01

    Full Text Available The occurrence of polymorphic transitions is a serious problem for pharmaceutical companies, because it can affect the bioavailability of the final product. With several known polymorphic forms carbamazepine is one of the most problematic drugs in this respect. Raman spectroscopy is a vibrational technique that is becoming very important in the pharmaceutical field, mainly due to its highly specific molecular fingerprint capabilities and easy use as a process analytical tool. However, multivariate methods are necessary both for identification and quantification. In this work an analytical methodology using Raman spectroscopy and interval Partial Least Squares Regression (iPLS, was developed in order to quantify mixtures of carbamazepine polymorphs in the presence of the most common excipients. The three polymorphs CBZ I, CBZ III and CBZ DH (which is a dihydrate were synthesized and characterized by PXRD and DSC. Subsequently, tablets were manufactured using excipients and 15 different mixtures of carbamazepine polymorphs. The iPLS model presented average prediction validation errors of 1.58%, 1.04% and 0.22% wt/wt, for CBZ I, CBZ III and CBZ DH, respectively, considering the whole mass of the tablet. The model presents a good prediction capacity and the proposed methodology could be used to perform quality control in final products.

  18. The Prescription Opioid Pain Medication Overdose Epidemic

    Centers for Disease Control (CDC) Podcasts

    2016-04-19

    Overdose related to prescription opioids has become an epidemic. This podcast discusses the risks of this type of drug sometimes used to treat pain, and how to protect yourself. .  Created: 4/19/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/19/2016.

  19. 'Brugada ECG' elicited by imipramine overdose

    NARCIS (Netherlands)

    van den Berg, M. P.; Tulleken, J. E.; Wilde, A. A. M.

    2004-01-01

    The ECG hallmark of the Brugada syndrome is ST-segment elevation in the right precordial leads. However, a 'Brugada ECG' may also occasionally be caused by other conditions. We report a case of a Brugada ECG due to an overdose of imipramine, a tricyclic antidepressant. The patient, a 66-year-old

  20. Intravenous paracetamol overdose in a paediatric patient

    NARCIS (Netherlands)

    Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

    2013-01-01

    BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

  1. Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance.

    Science.gov (United States)

    Slavova, Svetla; Costich, Julia F; Bunn, Terry L; Luu, Huong; Singleton, Michael; Hargrove, Sarah L; Triplett, Jeremy S; Quesinberry, Dana; Ralston, William; Ingram, Van

    2017-08-01

    The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study

    DEFF Research Database (Denmark)

    Jentink, Janneke; Dolk, Helen; Loane, Maria A

    2010-01-01

    To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy.......To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy....

  3. Overdose experiences among injection drug users in Bangkok, Thailand

    Directory of Open Access Journals (Sweden)

    Wood Evan

    2010-05-01

    Full Text Available Abstract Background Although previous studies have identified high levels of drug-related harm in Thailand, little is known about illicit drug overdose experiences among Thai drug users. We sought to investigate non-fatal overdose experiences and responses to overdose among a community-recruited sample of injection drug users (IDU in Bangkok, Thailand. Methods Data for these analyses came from IDU participating in the Mit Sampan Community Research Project. The primary outcome of interest was a self-reported history of non-fatal overdose. We calculated the prevalence of past overdose and estimated its relationship with individual, drug-using, social, and structural factors using multivariate logistic regression. We also assessed the prevalence of ever witnessing an overdose and patterns of response to overdose. Results These analyses included 252 individuals; their median age was 36.5 years (IQR: 29.0 - 44.0 and 66 (26.2% were female. A history of non-fatal overdose was reported by 75 (29.8% participants. In a multivariate model, reporting a history of overdose was independently associated with a history of incarceration (Adjusted Odds Ratio [AOR] = 3.83, 95% Confidence Interval [CI]: 1.52 - 9.65, p = 0.004 and reporting use of drugs in combination (AOR = 2.48, 95% CI: 1.16 - 5.33, p = 0.019. A majority (67.9% reported a history of witnessing an overdose; most reported responding to the most recent overdose using first aid (79.5%. Conclusions Experiencing and witnessing an overdose were common in this sample of Thai IDU. These findings support the need for increased provision of evidence-based responses to overdose including peer-based overdose interventions.

  4. Impairment of the in vitro Release of Carbamazepine from Tablets

    Directory of Open Access Journals (Sweden)

    Alija Uzunović

    2010-08-01

    Full Text Available Carbamazepine belongs to the class II biopharmaceutical classification system (BCS which is characterized by a high per-oral dose, a low aqueous solubility and a high membrane permeability. The bioavailability of such a drug is limited by the dissolution rate. The present study deals with the formulations of immediate release tablets of poorly soluble carbamazepine. As model tablets for this investigation, two formulations (named “A” and “B” formulations of carbamazepine tablets labeled to contain 200 mg were evaluated. The aim of this study was to establish possible differences in dissolution profile of these two formulations purchased from the local market.The increased crystallinity together with enlarged particle size, enhanced aggregation and decreased wettability of the drug, resulted in insufficient dissolution rate for formulation “B’.’ From the dissolution point of view, this formulation was inferior to the formulation “A, due to the solubilization effect.

  5. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures.

    Science.gov (United States)

    Koch, Marcus W; Polman, Susanne Kl

    2009-10-07

    Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. To compare efficacy and tolerability of carbamazepine and oxcarbazepine monotherapy for partial onset seizures. We searched the Cochrane Epilepsy Group Specialised Register (4 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 3, 2009), MEDLINE (January 1966 to May 2008), reference lists of relevant articles and conference proceedings. We also contacted manufacturers and researchers in the field for published or unpublished data. Blinded and unblinded randomised controlled trials of carbamazepine versus oxcarbazepine monotherapy for partial onset seizures. Both authors independently assessed trial quality, according to the guidelines in the Cochrane Reviewer's Handbook, and extracted information about study population, type of intervention, outcome measures and study design. All analyses in this review are by intention-to-treat. We tested for statistical heterogeneity among the identified studies using the chi-squared test. Three trials (723 participants) were included. Only one trial used adequate outcome measures of efficacy; therefore, the results pertaining to efficacy are based on a single trial, whereas the results pertaining to adverse events are based on all three included trials. There was no overall difference in time to treatment withdrawal between the two drugs (hazard ratio (HR) of oxcarbazepine (OXC) versus carbamazepine (CBZ): 1.04, 95% confidence interval (CI) 0.78 to 1.39). Further analyses showed no significant difference in treatment withdrawal for unacceptable side effects (HR of OXC versus CBZ: 0.85, 95% CI 0.59 to 1.24) and in treatment withdrawal for inadequate seizure control (HR of OXC versus CBZ: 1.33, 95% CI 0.82 to 2.15). Oxcarbazepine and carbamazepine appeared to be similarly effective

  6. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy.

    Science.gov (United States)

    Berghuis, Bianca; van der Palen, Job; de Haan, Gerrit-Jan; Lindhout, Dick; Koeleman, Bobby P C; Sander, Josemir W

    2017-07-01

    To ascertain possible determinants of carbamazepine (CBZ)- and oxcarbazepine (OXC)-induced hyponatremia in a large cohort of people with epilepsy. We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L. We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  7. Why are some people who have received overdose education and naloxone reticent to call Emergency Medical Services in the event of overdose?

    Science.gov (United States)

    Koester, Stephen; Mueller, Shane R; Raville, Lisa; Langegger, Sig; Binswanger, Ingrid A

    2017-10-01

    Overdose Education and Naloxone Distribution (OEND) training for persons who inject drugs (PWID) underlines the importance of summoning emergency medical services (EMS). To encourage PWID to do so, Colorado enacted a Good Samaritan law providing limited immunity from prosecution for possession of a controlled substance and/or drug paraphernalia to the overdose victim and the witnesses who in good faith provide emergency assistance. This paper examines the law's influence by describing OEND trained PWIDs' experience reversing overdoses and their decision about calling for EMS support. Findings from two complementary studies, a qualitative study based on semi-structured interviews with OEND trained PWID who had reversed one or more overdoses, and an on-going fieldwork-based project examining PWIDs' self-identified health concerns were triangulated to describe and explain participants' decision to call for EMS. In most overdose reversals described, no EMS call was made. Participants reported several reasons for not doing so. Most frequent was the fear that despite the Good Samaritan law, a police response would result in arrest of the victim and/or witness for outstanding warrants, or sentence violations. Fears were based on individual and collective experience, and reinforced by the city of Denver's aggressive approach to managing homelessness through increased enforcement of misdemeanors and the imposition of more recent ordinances, including a camping ban, to control space. The city's homeless crisis was reflected as well in the concern expressed by housed PWID that an EMS intervention would jeopardize their public housing. Results suggest that the immunity provided by the Good Samaritan law does not address PWIDs' fear that their current legal status as well as the victim's will result in arrest and incarceration. As currently conceived, the Good Samaritan law does not provide immunity for PWIDs' already enmeshed in the criminal justice system, or PWID fearful of

  8. High prevalence of non-fatal overdose among people who inject drugs in Malaysia: Correlates of overdose and implications for overdose prevention from a cross-sectional study.

    Science.gov (United States)

    Bazazi, Alexander R; Zelenev, Alexei; Fu, Jeannia J; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L

    2015-07-01

    Overdose is the leading cause of death among opioid users, but no data are available on overdose among people who inject drugs in Malaysia. We present the first estimates of the prevalence and correlates of recent non-fatal overdose among people who inject drugs in Malaysia. In 2010, 460 people who inject drugs were recruited using respondent-driven sampling (RDS) in Klang Valley to assess health outcomes associated with injection drug use. Self-reported history of non-fatal overdose in the previous 6 months was the primary outcome. Sociodemographic, behavioral and structural correlates of non-fatal overdose were assessed using multivariable logistic regression. All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Most injected daily (91.3%) and were male (96.3%) and ethnically Malay (90.4%). Overall, 20% of participants had overdosed in the prior 6 months, and 43.3% had ever overdosed. The RDS-adjusted estimate of the 6-month period prevalence of overdose was 12.3% (95% confidence interval [CI] 7.9-16.6%). Having injected for more years was associated with lower odds of overdose (adjusted odds ratio [AOR] 0.6 per 5 years of injection, CI: 0.5-0.7). Rushing an injection from fear of the police nearly doubled the odds of overdose (AOR 1.9, CI: 1.9-3.6). Alcohol use was associated with recent non-fatal overdose (AOR 2.1, CI: 1.1-4.2), as was methamphetamine use (AOR 2.3, CI: 1.3-4.6). When adjusting for past-month drug use, intermittent but not daily methadone use was associated with overdose (AOR 2.8, CI: 1.5-5.9). This study reveals a large, previously undocumented burden of non-fatal overdose among people who inject drugs in Malaysia and highlights the need for interventions that might reduce the risk of overdose, such as continuous opioid substitution therapy, provision of naloxone to prevent fatal overdose, treatment of polysubstance use, and working with police to improve the risk environment. Copyright © 2014 Elsevier B

  9. Simple and accurate measurement of carbamazepine in surface water by use of porous membrane-protected micro-solid-phase extraction coupled with isotope dilution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Hui Ling [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); Wong, Lingkai [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Liu, Qinde, E-mail: liu_qinde@hsa.gov.sg [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Teo, Tang Lin; Lee, Tong Kooi [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Lee, Hian Kee, E-mail: chmleehk@nus.edu.sg [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore)

    2016-03-17

    To achieve fast and accurate analysis of carbamazepine in surface water, we developed a novel porous membrane-protected micro-solid-phase extraction (μ-SPE) method, followed by liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) analysis. The μ-SPE device (∼0.8 × 1 cm) was fabricated by heat-sealing edges of a polypropylene membrane sheet to devise a bag enclosing the sorbent. The analytes (both carbamazepine and isotope-labelled carbamazepine) were first extracted by μ-SPE device in the sample (10 mL) via agitation, then desorbed in an organic solvent (1 mL) via ultrasonication. Several parameters such as organic solvent for pre-conditioning of μ-SPE device, amount of sorbent, adsorption time, and desorption solvent and time were investigated to optimize the μ-SPE efficiency. The optimized method has limits of detection and quantitation estimated to be 0.5 ng L{sup −1} and 1.6 ng L{sup −1}, respectively. Surface water samples spiked with different amounts of carbamazepine (close to 20, 500, and 1600 ng L{sup −1}, respectively) were analysed for the validation of method precision and accuracy. Good precision was obtained as demonstrated by relative standard deviations of 0.7% for the samples with concentrations of 500 and 1600 ng kg{sup −1}, and 5.8% for the sample with concentration of 20 ng kg{sup −1}. Good accuracy was also demonstrated by the relative recoveries in the range of 96.7%–103.5% for all samples with uncertainties of 1.1%–5.4%. Owing to the same chemical properties of carbamazepine and isotope-labelled carbamazepine, the isotope ratio in the μ-SPE procedure was accurately controlled. The use of μ-SPE coupled with IDMS analysis significantly facilitated the fast and accurate measurement of carbamazepine in surface water. - Highlights: • μ-SPE coupled with IDMS for the measurement of carbamazepine. • The method is the first report of coupling μ-SPE with IDMS. • μ-SPE is fast, time

  10. Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

    Directory of Open Access Journals (Sweden)

    Jasmina Tonic – Ribarska

    2012-03-01

    Full Text Available Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

  11. Neuroleptic Malignant Syndrome Caused by a Combination of Carbamazepine and Amitriptyline

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2012-01-01

    Full Text Available A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.

  12. Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

    Science.gov (United States)

    Wilder, Christine M; Miller, Shannon C; Tiffany, Elizabeth; Winhusen, Theresa; Winstanley, Erin L; Stein, Michael D

    2016-01-01

    Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p opioid overdose risk factors (12.1 versus 13.5, p opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.

  13. A case of radiation overdose in radiotherapy

    International Nuclear Information System (INIS)

    Flatby, J.; Reitan, J.B.; Bjerke, H.; Olerud, H.

    1985-01-01

    The report describes a case of radiation overdose in the radiotherapeutic treatment of plantar warts. The treatment which caused necrosis and ostemyelitis in a big toe, implied a skin dose of 20 Gy to each of five partly overlapping treatment fields. A phantom test carried out by the National Institute of Radiation Hygiene, indicates doses to periosteum of appr. 70 Gy. It seems that the overdose mainly has been caused by high absorption in bone tissue and high photo emission from bone tissue. It is pointed out that most of the radiation treatment of benign diseases in Norway is carried out by roentgen diagnosticians. If the treatment of these diseases shall be maintained in the future, the educational consequenses should be thoroughly discussed

  14. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    GBP and CBZ, which may be applied in the treatment of pain in diabetic neuropathy. Keywords: Diabetic neuropathy, Carbamazepine, .... manifested at two levels: the peripheral and central levels. On the peripheral level, there is an ... It is an antiepileptic drug with a structure similar to GABA, which is a neurotransmitter that.

  15. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

    NARCIS (Netherlands)

    Berghuis, Bianca; van der Palen, Job; de Haan, Gerrit-Jan; Lindhout, Dick; Koeleman, Bobby P.C.; Sander, Josemir W.; Møller, Rikke S.; Nikanorova, Marina; Ingason, Andrés; Depondt, Chantal; Johnson, Michael R.; Langley, Sarah R; Klein, Karl Martin; McCormack, Mark; Delanty, Norman; Cavalleri, Gianpiero L.; van Zijl, Janic; Muhle, Hiltrud; Borghei, Mojgansadat; Donatello, Simona; Willis, Joseph; Leu, Costin; Heggeli, Kristin; Avbersek, Andreja; Sisodiya, Sanjay M.; Gamberdella, Antonio; Weckhuysen, Sarah; Kunz, Wolfram S.; Striano, Pasquale; Zara, Federico; Brodie, Martin J.; Stefánsson, Kári; Marson, Anthony G.; Jorgensen, Andrea; Auce, Pauls; Francis, Ben; Srivastava, Prashant; Sills, Graeme J.; Primec, Zvonka Rener; Krause, Roland; Wolking, Stefan; Weber, Yvonne G.; Rau, Sarah; Hengsbach, Christian; Lerche, Holger; Sonsma, Anja; Krenn, Martin; Zimprich, Fritz; Pataraia, Ekaterina

    2017-01-01

    Objective: To ascertain possible determinants of carbamazepine (CBZ)– and oxcarbazepine (OXC)–induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment

  16. Lichenoid reaction to carbamazepine in the oral mucosa: case report.

    Science.gov (United States)

    Artico, Gabriela; Bruno, Ingrid S; Seo, Juliana; Hirota, Silvio K; Acay, Renata; Migliari, Dante A

    2011-01-01

    Lichenoid drug reactions are more common in skin, but they may also occur in the oral mucosa. It is difficult to diagnose these lesions due to their clinical similarity to the idiopathic oral lichen planus lesions. The present article reports a case of lichenoid reaction in oral mucosa associated to the use of carbamazepine, emphasizing the diagnostic process.

  17. The effects of carbamazepine on thyroid functions in childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Mehmet İbrahim Turan

    2013-12-01

    Full Text Available Objective: To investigate the effects of carbamazepinetherapy on thyroid function tests in childrenMethods: The carbamazepine group consisted of 58 childrenunder observation for epilepsy, and the control groupof 54 healthy children. Age of onset, length of drug use,drug dosage and laboratory parameters including free triiodothyronine(FT3, free thyroxin (FT4 and thyrotropin(TSH were recorded. These data were then comparedagainst those from the control group.Results: In the carbamazepine group, FT3 was 3.86 ±0.43 pg/mL, FT4 was 1.15 ± 0.18 mg/dL and TSH: 2.58 ±1.33 ml U/L. In the control group, FT3 was 4.13 ± 0.59 pg/mL, FT4 1.34 ± 0.13 mg/dL and TSH was 2.06 ± 0.89 mlU/L. No statistically significant difference between rates ofsubclinical hypothyroidism was determined between thetwo groups (p=0.196.Conclusion: Although, carbamazepine reduces thyroidhormone concentrations, rarely causes hypothyroidism.Key words: Child, carbamazepine, thyroid function tests

  18. Pure red-cell aplasia associated with carbamazepine

    African Journals Online (AJOL)

    1990-08-18

    Aug 18, 1990 ... phenobarbitone and clonazepam without success. On 1. February 1988 medication was changed to carbamazepine (50 mg in the morning and 100 mg at night), which controlled the seizures satisfactorily. She received no other drugs. A full blood count done on 23 March 1988 was within normal limits.

  19. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

    DEFF Research Database (Denmark)

    Berghuis, Bianca; van der Palen, Job; de Haan, Gerrit-Jan

    2017-01-01

    OBJECTIVE: To ascertain possible determinants of carbamazepine (CBZ)- and oxcarbazepine (OXC)-induced hyponatremia in a large cohort of people with epilepsy. METHODS: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment...

  20. Exfoliative Dermatitis Due To Carbamazepine In An Epileptic Patient

    Directory of Open Access Journals (Sweden)

    Ghosh Sadhan Kr

    1995-01-01

    Full Text Available A young epileptic girl of 17 years who was being treated with carbamazepine suddenly developed exanthematous skin eruption all over the body resulting in exfoliative dermatitis within 2 days of onset. The drug was withdrawn and the patient responded well with symptomatic treatment.

  1. Comparative evaluation of carbamazepine release from single and ...

    African Journals Online (AJOL)

    In the present study the release rate and kinetics of carbamazepine as a model drug from various single and bi-polymeric matrices were studied. Matrices containing different percentages of hydroxylpropyl methylcellulose (HPMC), ethylcellulose (EC), Eudragit RS (EuRS) or various ratios of polymer blends based on HPMC ...

  2. Ecotoxicity of carbamazepine and its UV photolysis transformation products

    DEFF Research Database (Denmark)

    Donner, E.; Kosjek, T.; Qualmann, Signe

    2013-01-01

    the treatment period, together with concurrent increases in acridine and acridone concentrations. Ecotoxicity was shown to increase in parallel with carbamazepine degradation indicating that the mixture of degradation products formed was more toxic than the parent compound, and all three ecotoxicity endpoints...

  3. Vitamin B6 and homocysteine levels in carbamazepine treated ...

    African Journals Online (AJOL)

    Objectives: The study focused on the plasma levels of vitamin B6 and homocysteine in ... ed with carbamazepine were selected at out-patient De- .... Patients' demographic data and types of seizures are ex- .... morphisms that may alter the individual response to a .... genotype, homocysteine, and stroke risk: a meta-analy-.

  4. Carbamazepine in the treatment of Lyme disease-induced hyperacusis.

    Science.gov (United States)

    Nields, J A; Fallon, B A; Jastreboff, P J

    1999-01-01

    Lyme disease-induced hyperacusis can be an intensely disabling, chronic condition that is accompanied by posttraumatic stress disorder-like psychobehavioral sequelae. The authors describe effective treatment of 2 patients with carbamazepine. Speculations regarding a mode of action are offered.

  5. Sirenomelia after phenobarbital and carbamazepine therapy in pregnancy.

    Science.gov (United States)

    Tica, Oana Sorina; Tica, Andrei Adrian; Brailoiu, Cristina Gabriela; Cernea, Nicolae; Tica, Vlad Iustin

    2013-06-01

    Epilepsy still remains a serious challenge for any obstetrician due to the potential teratogenicity of all antiepileptics. However, without appropriate maternal therapy the seizures can reappear, with direct negative impact on fetus. Currently, sirenomelia is the most severe caudal pole dysgenesis, consequent to an abnormal vascular supply development in the fetal lower body. We report a stillborn, GA/LMP = 37 weeks, delivered by an epileptic woman, who received in the first four months of pregnancy phenobarbital (PH) 0.1 g/day and carbamazepine (CMZ) 0.4 g/day, followed only by PH 0.1 g/day, until delivery. The stillborn, weighing 2200 g, presented sirenomelia type II, with some of its "classic" features: oligohydramnios, absence of kidneys, bladder, rectum, uterus, and a single umbilical artery. Some other "particularities" included: no Potter's facies and no significant cardio-pulmonary abnormalities. Since PH and CMZ alone are responsible, commonly, for mild abnormalities, we hypothesized that combined therapy with PH and CMZ (both strong enzyme-inductors, especially PH) potentiated their teratogenicity, by producing supplementary quantities of epoxides and/or other oxides, which accumulated in the fetal tissues. Except for sirenomelia, all other mild abnormalities, theoretically associated with "fetal CMZ and/or PH syndrome," are rarely observed, fact which demonstrates the drug-drug interactions between the two antiepileptics. This report highlights the possibility that PH/CBZ therapy during fetal organogenesis can induce sirenomelia, by a synergistic teratogenic effect and support the recommendation to use only one drug in pregnant epileptic women. A careful ultrasound monitoring of these patients is mandatory due to the teratogenic risk of both seizures and therapy. Copyright © 2013 Wiley Periodicals, Inc.

  6. Association of elevated ambient temperature with death from cocaine overdose.

    Science.gov (United States)

    Auger, Nathalie; Bilodeau-Bertrand, Marianne; Labesse, Maud Emmanuelle; Kosatsky, Tom

    2017-09-01

    Ecologic data suggest that elevated outdoor temperature is correlated with mortality rates from cocaine overdose. Using non-aggregated death records, we studied the association of hot temperatures with risk of death from cocaine overdose. We carried out a case-crossover study of all deaths from cocaine or other drug overdose between the months of May and September, from 2000 through 2013 in Quebec, Canada. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between maximum outdoor temperature and death from cocaine or other drug overdose. The main outcome measure was death from cocaine overdose as a function of maximum temperature the day of death and the days immediately preceding death. There were 316 deaths from cocaine overdose and 446 from other drug overdoses during the study. Elevated temperature the preceding week was associated with the likelihood of death from cocaine but not other drug overdose. Compared with 20°C, a maximum weekly temperature of 30°C was associated with an OR of 2.07 for death from cocaine overdose (95% CI 1.15-3.73), but an OR of 1.03 for other drug overdoses (95% CI 0.60-1.75). Associations for cocaine overdose were present with maximum daily temperature the day of and each of the three days preceding death. Elevated ambient temperature is associated with the risk of death from cocaine overdose. Public health practitioners and drug users should be aware of the added risk of mortality when cocaine is used during hot days. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Is systematic training in opioid overdose prevention effective?

    Science.gov (United States)

    Bosque-Prous, Marina; Folch, Cinta; Sarasa-Renedo, Ana; Majó, Xavier; Casabona, Jordi; Brugal, M. Teresa

    2017-01-01

    The objectives were to analyze the knowledge about overdose prevention, the use of naloxone, and the number of fatal overdoses after the implementation of Systematic Training in Overdose Prevention (STOOP) program. We conducted a quasi-experimental study, and held face-to-face interviews before (n = 725) and after (n = 722) implementation of systematic training in two different samples of people who injected opioids attending harm reduction centers. We asked participants to list the main causes of overdose and the main actions that should be taken when witnessing an overdose. We created two dependent variables, the number of (a) correct and (b) incorrect answers. The main independent variable was Study Group: Intervention Group (IG), Comparison Group (CG), Pre-Intervention Group With Sporadic Training in Overdose Prevention (PREIGS), or Pre-Intervention Group Without Training in Overdose Prevention (PREIGW). The relationship between the dependent and independent variables was assessed using a multivariate Poisson regression analysis. Finally, we conducted an interrupted time series analysis of monthly fatal overdoses before and after the implementation of systematic program during the period 2006–2015. Knowledge of overdose prevention increased after implementing systematic training program. Compared to the PREIGW, the IG gave more correct answers (IRR = 1.40;95%CI:1.33–1.47), and fewer incorrect answers (IRR = 0.33;95%CI:0.25–0.44). Forty percent of people who injected opioids who received a naloxone kit had used the kit in response to an overdose they witnessed. These courses increase knowledge of overdose prevention in people who use opioids, give them the necessary skills to use naloxone, and slightly diminish the number of fatal opioid overdoses in the city of Barcelona. PMID:29088247

  8. Opiate addiction and overdose: experiences, attitudes, and appetite for community naloxone provision.

    LENUS (Irish Health Repository)

    Barry, Tomás

    2017-02-28

    More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare services. Naloxone is an effective overdose treatment and is now being considered for wider lay use.

  9. Adrenaline overdose in pediatric anaphylaxis: a case report.

    Science.gov (United States)

    Liew, Pui Yi Lily; Craven, John Andrew

    2017-05-08

    Adrenaline is the standard treatment for anaphylaxis but appropriate administration remains challenging, and iatrogenic overdose is easily overlooked. Despite the established importance of pediatric blood pressure measurement, its use remains inconsistent in clinical practice. We report a case of adrenaline overdose in a 9-year-old white boy with anaphylaxis, where signs of adrenaline overdose were indistinguishable from progressive shock until blood pressure measurement was taken. The consequences of under-dosing adrenaline in anaphylaxis are well-recognized, but the converse is less so. Blood pressure measurement should be a routine part of pediatric assessment as it is key to differentiating adrenaline overdose from anaphylactic shock.

  10. NAGD regimen for the coma of drug-related overdose.

    Science.gov (United States)

    Rappolt, R T; Gay, G R; Decker, W J; Inaba, D S

    1980-07-01

    A specific arousal therapy with NAGD (Naloxone, Activated Charcoal, Glucagon, Doxapram) is outlined for victims of drug overdose in comatose and semi-comatose states. Several direct benefits accrue if early awakening or lightening of such patients is safely accomplished. There are: 1) elimination of need for prolonged intubation or tracheostomy; 2) patient's ability to tell which drug(s) were taken; 3) excessively frantic and vigorous supportive treatment is obviated; and 4) the overall hospital stay is shortened. The NAGD regimen has been found to effectively, safely, and predictably reverse coma. Therapy consists of: naloxone 0.8 mg to 1.6 mg intravenously; large-bore orogastric tube instillation of 100 gm to 120 gm activated charcoal slurry; glucagon 1 mg to 2 mg intravenously; and, in selected cases, doxapram 1 mg/kg to 2 mg/kg intravenously.

  11. Vital Signs – Prescription Painkiller Overdoses

    Centers for Disease Control (CDC) Podcasts

    This podcast is based on the July 2013 CDC Vital Signs report. Prescription painkiller overdoses are an under-recognized and growing problem among women. This program includes things that women and health care providers can do to reduce the risk of overdose.

  12. Opioid Overdoses Treated in Emergency Departments PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2018-03-06

    This 60 second public service announcement is based on the March 2018 CDC Vital Signs report. Opioid overdoses continue to increase in the United States. Learn what can be done to help prevent opioid overdose and death.  Created: 3/6/2018 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/6/2018.

  13. Reducing the Risk of Methadone Overdose PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2012-07-03

    This 60 second PSA is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

  14. Zolpidem Overdose: A Medical and Ethical Dilemma.

    Science.gov (United States)

    Shuaib, Waqas; Beatrice, Cristina; Abazid, Ahmad G

    Acute altered mental status can be caused by a broad range of etiologies, including cerebrovascular, neurologic, traumatic, metabolic, infectious, psychiatric, medications, etc. We present a case of a 53-year-old healthcare professional with an acute altered mental status after a trip to Africa. The patient was extensively worked up for infectious, cardiovascular, and neurologic etiologies, and all results were within normal limits. Further history revealed an overdose of a self-medicated hypnotic (zolpidem) for insomnia. The patient was conservatively managed and discharged on trazadone for insomnia.

  15. Risk of overdose and death following codeine prescription among immigrants.

    Science.gov (United States)

    Ray, Joel G; Hollands, Simon; Gomes, Tara; Urquia, Marcelo L; Macdonald, Erin M; Li, Ping; Mamdani, Muhammad M; Juurlink, David N

    2014-11-01

    Immigrants may be at a higher risk of adverse drug reactions, in that poor language proficiency reduces individuals understanding of drug label instructions. Additionally, there are reports of severe or fatal toxicity due to CYP2D6 ultrarapid hepatic metabolism of codeine to morphine among some ethnic groups, especially those from Eastern Africa. Between 2002 and 2012 we conducted a population-based cohort study among residents of Ontario, Canada. We used administrative health databases that linked immigrants and Canadian-born individuals to both prescription medication use and emergency department visits and hospital admissions. The primary composite outcome was the risk of drug overdose or all-cause mortality within 30 days of codeine prescription, comparing patients from various world regions to Canadian-born individuals. A secondary analysis stratified by codeine dose and ability to speak English and/or French. There were 553 504 individuals exclusively prescribed codeine. Relative to an incidence rate of 57.1/100 000 person-days among Canadian-born codeine recipients, those who migrated from various world regions were at a lower risk of drug overdose or death. For example, Eastern Africans had an adjusted HR of 0.60 (95% CI 0.31 to 1.17) on controlling for potential confounders such as age, sex, income and physician visits. Patients unable to speak English or French who were prescribed codeine were at a lower risk of the composite outcome relative to those proficient in either language (adjusted HR 0.63, 95% CI 0.54 to 0.74). Overdose and death following the institution of codeine therapy are not more commonly observed among immigrants from world regions with a high prevalence of ultrarapid CYP2D6 status relative to those born in Canada. Lower proficiency in English or French also did not appear to heighten the risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Metabolite profiling of carbamazepine and ibuprofen in Solea senegalensis bile using high-resolution mass spectrometry.

    Science.gov (United States)

    Aceña, Jaume; Pérez, Sandra; Eichhorn, Peter; Solé, Montserrat; Barceló, Damià

    2017-09-01

    The widespread occurrence of pharmaceuticals in the aquatic environment has raised concerns about potential adverse effects on exposed wildlife. Very little is currently known on exposure levels and clearance mechanisms of drugs in marine fish. Within this context, our research was focused on the identification of main metabolic reactions, generated metabolites, and caused effects after exposure of fish to carbamazepine (CBZ) and ibuprofen (IBU). To this end, juveniles of Solea senegalensis acclimated to two temperature regimes of 15 and 20 °C for 60 days received a single intraperitoneal dose of these drugs. A control group was administered the vehicle (sunflower oil). Bile samples were analyzed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry on a Q Exactive (Orbitrap) system, allowing to propose plausible identities for 11 metabolites of CBZ and 13 metabolites of IBU in fish bile. In case of CBZ metabolites originated from aromatic and benzylic hydroxylation, epoxidation, and ensuing O-glucuronidation, O-methylation of a catechol-like metabolite was also postulated. Ibuprofen, in turn, formed multiple hydroxyl metabolites, O-glucuronides, and (hydroxyl)-acyl glucuronides, in addition to several taurine conjugates. Enzymatic responses after drug exposures revealed a water temperature-dependent induction of microsomal carboxylesterases. The metabolite profiling in fish bile provides an important tool for pharmaceutical exposure assessment. Graphical abstract Studies of metabolism of carbamazepine and ibuprofen in fish.

  17. Amelioration of erectile dysfunction following a switch from carbamazepine to oxcarbazepine: recent clinical experience.

    Science.gov (United States)

    Sachdeo, Rajesh; Sathyan, Revathi R

    2005-07-01

    Oxcarbazepine is an antiepileptic drug (AED) indicated for use as monotherapy and add-on therapy in adults and children 4 years of age and older. Despite being structurally related to carbamazepine, oxcarbazepine differs substantially in its pharmacokinetic and safety profile; oxcarbazepine has a much lower risk of pharmacokinetic drug-drug interactions than carbamazepine. Carbamazepine has also been shown to induce the hepatic synthesis of sex hormone-binding globulin, thus reducing free serum testosterone levels and possibly causing erectile dysfunction (ED) in some men; these effects have not been observed with oxcarbazepine. This paper provides a discussion of recent clinical experience with men who presented in private clinical practice with complaints of ED while being treated with carbamazepine for seizure disorders. The four illustrative case studies presented in this report suggest that switching AED treatment from carbamazepine to oxcarbazepine in men with epilepsy can reduce the ED side effects observed with carbamazepine.

  18. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    Science.gov (United States)

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  19. Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio).

    Science.gov (United States)

    Triebskorn, R; Casper, H; Scheil, V; Schwaiger, J

    2007-02-01

    In order to assess potential effects of human pharmaceuticals in aquatic wildlife, laboratory experiments were conducted with carbamazepine, clofibric acid, metoprolol, and diclofenac using fish as test organisms. For each substance, at least one environmentally relevant concentration was tested. In liver, kidney, and gills of trout and carp exposed to carbamazepine, clofibric acid, and metoprolol, ultrastructural effects were qualitatively described and semi-quantitatively assessed. The obtained assessment values were compared with previously published data for diclofenac-induced effects in rainbow trout tissues. Quantitative analyses of protein accumulated in kidneys of diclofenac-exposed trout corroborated previously published data which indicated that diclofenac induced a severe glomerulonephritis resulting in a hyaline droplet degeneration of proximal kidney tubules. The investigations provided information on the general health status of the pharmaceutical-exposed fish, and allowed a differential diagnosis of harmful effects caused by these human pharmaceuticals in non-target species. For the different cytological effects observed, lowest observed effect concentration (LOECs) for at least three of the test substances (diclofenac, carbamazepine, metoprolol) were in the range of environmentally relevant concentrations (1 microg/L).

  20. Reação cutânea grave induzida por carbamazepina no tratamento da neuralgia pós-herpética: relato de caso Reacción cutánea grave inducida por la carbamazepina en el tratamiento de la neuralgia postherpética: relato de caso Severe carbamazepine-induced cutaneous reaction in the treatment of post-herpetic neuralgia: case report

    Directory of Open Access Journals (Sweden)

    João Batista Santos Garcia

    2010-08-01

    . CONCLUSIONES: La SSJ/NET es una reacción cutánea grave con potencial para la morbilidade y mortalidad elevadas y que exige una intervención rápida y un manejo adecuado. También alertamos sobre el uso de la carbamazepina, que debe siempre ser inspeccionado, especialmente en los ancianos.BACKGROUND AND OBJECTIVES: Post-herpetic neuralgia (PHN is the main complication of herpes zoster. Carbamazepine (CBZ, a well-tolerated anticonvulsant, but frequently associated with severe cutaneous reactions, such as the Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN is used in the treatment of this complication. The objective of this article was to report a case of SJS/TEN secondary to CBZ in a patient with PHN. CASE REPORT: This is a female patient with continuous severe, burning, chock-like pain in the thoracic region and dorsum associated with reduced strength in the ipsilateral upper limb and diaphoresis. She had crusty and erythematous lesions in the dorsal region of the thorax with allodynia and dysesthesia in the affected dermatome. She was treated with CBZ 300 mg.day-1, amitriptyline (AMT 12.5 mg at bedtime, and infiltration with local anesthetic in the affected region. After 15 days, she developed malaise, fever, muscle pain, and arthralgia with a mild non-specific cutaneous rash. Carbamazepine was discontinued immediately. One week later, she was hospitalized with urticaria, generalized exanthema, erythematous cutaneous eruptions, bullae, and purpuric maculae all over her body. The impression was of carbamazepine-induced SJS/TEN. She evolved with progressive worsening of her symptoms, with increase in the number and size of cutaneous lesions, besides generalized erythematous macular rash, areas of necrosis, and erosions with symmetrical loosening of the epidermis in face, neck, thorax, dorsum, and limbs, affecting more that 50% of her body surface, besides involvement of buccal, conjunctival, and genital mucosa with vesicular erosions. She had progressive

  1. Zolpidem Overdose: A Dilemma in Mental Health.

    Science.gov (United States)

    Jung, Minsoo

    Sleeping pills are one of the most common drugs taken by adults when afflicted by insomnia. Adverse effects of pharmacotherapy, however, should not be overlooked, and monitoring is needed to check for an overdose of sleeping pills. We reviewed zolpidem overdose and patient suicide with benefits and disadvantages of pharmacotherapy. Cases of adverse effects concerning the central nervous system, including delirium and hallucination, as well as abnormal behavior during sleep, are commonly reported among patients who have taken zolpidem for more than 1 year. The serious problem of long-term prescription to medication can lead to a higher mortality rate of insomniac patients. An alternative to medication for treating insomnia is cognitive behavioral therapy, which can improve sleeping habits. Cognitive behavioral therapy induces patients to recognize and change the negative thoughts that affect their sleep. Medical providers should be aware of the adverse effects of sleep inducers and provide sufficient information to their patients about them. When establishing treatment plans, they should encourage patients to make the proper decisions and try to reduce the adverse effects of any medication as much as possible.

  2. Accidental hydroxychloroquine overdose resulting in neurotoxic vestibulopathy.

    Science.gov (United States)

    Chansky, Peter B; Werth, Victoria P

    2017-04-12

    Hydroxychloroquine is an oral antimalarial medication commonly used off-label for a variety of rheumatological conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and dermatomyositis. We present a case of a 64-year-old woman who presented with acute onset headache, bilateral tinnitus, and left-sided facial numbness and tingling in the setting of accidentally overdosing on hydroxychloroquine. By the next morning, the patient began to experience worsening in the tingling sensation and it eventually spread to her left arm, thigh and distal extremities. The patient also complained of new onset blurring of her peripheral vision and feeling 'off balance.' Despite a complete neurological and ophthalmological work-up with unremarkable imaging and blood work, the patient has had no improvement in her tinnitus, left-sided paresthesias, visual disturbance or ataxia. This is a unique case of hydroxychloroquine overdose resulting in permanent neurotoxic vestibulopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Most drug overdose deaths from nonprescription opioids

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2016-12-01

    Full Text Available No abstract available. Article truncated at 150 words. The Centers for Disease Control (CDC is reporting in Morbidity and Mortality Weekly that the number of people dying from an opioid overdose rose 15.5% from 2014 to 2015, but the increase had little to do with prescription painkillers such as oxycodone or hydrocodone (1. Roughly 52,000 people died from drug overdoses in 2015 and of those deaths 33,091 involved an opioid. The increases in “death rates were driven by synthetic opioids other than methadone (72.2%, most likely illicitly-manufactured fentanyl, and heroin (20.6%”. Deaths from methadone, which is usually prescribed by physicians, decreased 9.1%. The largest increase in deaths occurred in the South and Northeast with 3% and 24% increases in deaths from synthetic opioids from 2014 to 2015. In the Midwest and West, there were more modest 17% and 9% increases during the same period. States in the Southwest with “good” to “excellent” reporting included Colorado, Nevada, and New …

  4. Criminal justice continuum for opioid users at risk of overdose.

    Science.gov (United States)

    Brinkley-Rubinstein, Lauren; Zaller, Nickolas; Martino, Sarah; Cloud, David H; McCauley, Erin; Heise, Andrew; Seal, David

    2018-02-24

    The United States (US) is in the midst of an epidemic of opioid use; however, overdose mortality disproportionately affects certain subgroups. For example, more than half of state prisoners and approximately two-thirds of county jail detainees report issues with substance use. Overdose is one of the leading causes of mortality among individuals released from correctional settings. Even though the criminal justice (CJ) system interacts with a disproportionately high number of individuals at risk of opioid use and overdose, few CJ agencies screen for opioid use disorder (OUD). Even less provide access to medication assisted treatment (e.g. methadone, buprenorphine, and depot naltrexone), which is one of the most effective tools to combat addiction and lower overdose risk. However, there is an opportunity to implement programs across the CJ continuum in collaboration with law enforcement, courts, correctional facilities, community service providers, and probation and parole. In the current paper, we introduce the concept of a "CJ Continuum of Care for Opioid Users at Risk of Overdose", grounded by the Sequential Intercept Model. We present each step on the CJ Continuum and include a general overview and highlight opportunities for: 1) screening for OUD and overdose risk, 2) treatment and/or diversion, and 3) overdose prevention and naloxone provision. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Wendy Bayldon

    2016-04-01

    Full Text Available Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions.

  6. Prolonged QRS Widening After Aripiprazole Overdose.

    Science.gov (United States)

    Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

    2018-05-05

    Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

  7. Half pitch lower sound perception caused by carbamazepine.

    Science.gov (United States)

    Konno, Shyu; Yamazaki, Etsuko; Kudoh, Masako; Abe, Takashi; Tohgi, Hideo

    2003-09-01

    We report a 16-year-old woman with secondary generalization of partial seizure, who complained of an auditory disturbance after carbamazepine (CBZ) administration. She had been taking sodium valproate (VPA) from the age of 15. However, her seizures remained poorly controlled. We changed her antiepileptic drug from VPA to CBZ. At 1 week after CBZ administration, she noticed that electone musical performances were heard as a semitone lower. When oral administration of CBZ was stopped, her pitch perception returned to normal. If she had not been able to discern absolute pitch, she might have been unable to recognize her lowered pitch perception. Auditory disturbance caused by CBZ is reversible and very rare.

  8. Erythema multiforme as the result of taking carbamazepine

    Directory of Open Access Journals (Sweden)

    Maharani Laillyza Apriasari

    2010-06-01

    Full Text Available Background: Erythema multiforme is an acute mucocutaneus disease which is caused by the hypersensitivity reaction. It is characterized by target lesions on the skin or ulcerative oral lesion. Etiology of the disease is unknown, it is currently considered as immunologic disease. The triggering factors is the use of certain type of drugs like antibiotics, anticonvulsant, and NSAID. Most of the dentists do not know about it is mechanism, so a lot of people consider it as a malpractice. Purpose: This paper reported a case of a man, 46 years old which had ulcerative oral mucous, peeled and pain lips after taking carbamazepine drugs. Case: The clinical diagnosis of this case was erythema multiforme because of the hypersensitivity reaction as the result of taking carbamazepine. Case management: The final diagnosis based on anamnesis history of taking systemic drugs and clinical manifestation of erythema multiforme in the oral cavity. The drugs therapy that had been given were antihistamine, oral corticosteroid, gargle liquid contained of topical anesthetic, corticosteroid, and antibiotic. Conclusion: In this case, it can be concluded that erythema multiforme appeared was triggered by taking carbamazepine as the drug of choice for trigeminal neuralgia therapy. These drugs can cause type III hypersensitivity reaction. The final diagnosis based on anamnesis history of taking carbamazepine before lesions erupted and the characterized clinical manifestation.Latar belakang: Erythema multiforme adalah penyakit mukokutaneus akut yang menyerang kulit dan mukosa sebagai akibat dari reaksi hipersensitivitas. Secara karakteristik ditandai oleh lesi target pada kulit atau lesi ulserasi pada mukosa rongga mulut. Etiologi penyakit ini belum jelas, diduga karena adanya reaksi imunologi. Pencetusnya dikarenakan adanya pemakaian obat-obatan tertentu seperti antibiotik, antikonvulsan dan NSAID. Banyak dokter gigi kurang memahami mekanisme timbulnya penyakit ini, sehingga

  9. Secondary hypogammaglobilinemia after use of carbamazepine: case report and review

    Directory of Open Access Journals (Sweden)

    Castro Ana Paula B Moschione

    2001-01-01

    Full Text Available Immunologic disorders related to anticonvulsant therapy have been described in the last three decades, including cellular and humoral alterations that result in recurrent infections; however, the physiopathologic mechanisms are not completely understood. This report describes a patient with complex partial epilepsy and hypogammaglobulinemia while in treatment with carbamazepine, with significant improvement in clinical signs and laboratory tests after substitution to sodium valproate. The authors stress the importance of clinical and laboratory evaluation of patients in continuous anticonvulsant therapy, including immunoglobulins levels and peripheral blood evaluations.

  10. Alcohol Overdose: The Dangers of Drinking Too Much

    Science.gov (United States)

    ... The Dangers of Drinking Too Much Print version Alcohol Overdose: The Dangers of Drinking Too Much Celebrating ... excess. And the results can be deadly. Identifying Alcohol Poisoning Critical Signs and Symptoms of Alcohol Poisoning ...

  11. Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

    Science.gov (United States)

    Malhotra, S; Dixit, R K; Garg, S K

    2002-01-01

    The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

  12. Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac.

    Science.gov (United States)

    Ferrari, Benoît; Paxéus, Nicklas; Lo Giudice, Roberto; Pollio, Antonino; Garric, Jeanne

    2003-07-01

    In four countries (France, Greece, Italy, and Sweden) occurrence in sewage treatment plant (STP) effluents and ecotoxicity of the pharmaceuticals carbamazepine, clofibric acid, and diclofenac were investigated. Bioassays were performed on bacteria, algae, microcrustaceans, and fishes in order to calculate their predicted no-effect concentrations (PNEC) and to perform a first approach of risk characterization. For this aim, risk has been estimated by the predicted environmental concentration/PNEC ratio and the measured environmental concentration/PNEC ratio. First, regarding the PNEC, carbamazepine appears to be the more hazardous compound. Second, even though it is demonstrated that carbamazepine, clofibric acid, and diclofenac have been detected in effluents, only carbamazepine have been detected in all sewage treatment plants with the greatest concentrations. Third, risk quotients greater than unity were calculated only for carbamazepine, suggesting that risk for the water compartment is expected.

  13. Law enforcement attitudes toward overdose prevention and response

    Science.gov (United States)

    Green, Traci C.; Zaller, Nickolas; Palacios, Wilson R.; Bowman, Sarah E.; Ray, Madeline; Heimer, Robert; Case, Patricia

    2014-01-01

    Background Law enforcement is often the first to respond to medical emergencies in the community, including overdose. Due to the nature of their job, officers have also witnessed first-hand the changing demographic of drug users and devastating effects on their community associated with the epidemic of nonmedical prescription opioid use in the United States. Despite this seminal role, little data exist on law enforcement attitudes toward overdose prevention and response. Methods We conducted key informant interviews as part of a 12-week Rapid Assessment and Response (RAR) process that aimed to better understand and prevent nonmedical prescription opioid use and overdose deaths in locations in Connecticut and Rhode Island experiencing overdose “outbreaks.” Interviews with 13 law enforcement officials across three study sites were analyzed to uncover themes on overdose prevention and naloxone. Results Findings indicated support for law enforcement involvement in overdose prevention. Hesitancy around naloxone administration by laypersons was evident. Interview themes highlighted officers’ feelings of futility and frustration with their current overdose response options, the lack of accessible local drug treatment, the cycle of addiction, and the pervasiveness of easily accessible prescription opioid medications in their communities. Overdose prevention and response, which for some officers included law enforcement-administered naloxone, were viewed as components of community policing and good police-community relations. Conclusion Emerging trends, such as existing law enforcement medical interventions and Good Samaritan Laws, suggest the need for broader law enforcement engagement around this pressing public health crisis, even in suburban and small town locations, to promote public safety. PMID:24051061

  14. Vital Signs – Prescription Painkiller Overdoses

    Centers for Disease Control (CDC) Podcasts

    2013-07-02

    This podcast is based on the July 2013 CDC Vital Signs report. Prescription painkiller overdoses are an under-recognized and growing problem among women. This program includes things that women and health care providers can do to reduce the risk of overdose.  Created: 7/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/2/2013.

  15. Law enforcement attitudes toward overdose prevention and response.

    Science.gov (United States)

    Green, Traci C; Zaller, Nickolas; Palacios, Wilson R; Bowman, Sarah E; Ray, Madeline; Heimer, Robert; Case, Patricia

    2013-12-01

    Law enforcement is often the first to respond to medical emergencies in the community, including overdose. Due to the nature of their job, officers have also witnessed first-hand the changing demographic of drug users and devastating effects on their community associated with the epidemic of nonmedical prescription opioid use in the United States. Despite this seminal role, little data exist on law enforcement attitudes toward overdose prevention and response. We conducted key informant interviews as part of a 12-week Rapid Assessment and Response (RAR) process that aimed to better understand and prevent nonmedical prescription opioid use and overdose deaths in locations in Connecticut and Rhode Island experiencing overdose "outbreaks." Interviews with 13 law enforcement officials across three study sites were analyzed to uncover themes on overdose prevention and naloxone. Findings indicated support for law enforcement involvement in overdose prevention. Hesitancy around naloxone administration by laypersons was evident. Interview themes highlighted officers' feelings of futility and frustration with their current overdose response options, the lack of accessible local drug treatment, the cycle of addiction, and the pervasiveness of easily accessible prescription opioid medications in their communities. Overdose prevention and response, which for some officers included law enforcement-administered naloxone, were viewed as components of community policing and good police-community relations. Emerging trends, such as existing law enforcement medical interventions and Good Samaritan Laws, suggest the need for broader law enforcement engagement around this pressing public health crisis, even in suburban and small town locations, to promote public safety. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Ischemic colitis complicating imipramine overdose and alcohol ingestion. Case report

    DEFF Research Database (Denmark)

    Basse, Peter Neimann; Rørdam, P

    1992-01-01

    Patients on antidepressant medication are instructed to avoid alcohol because of possible additive effects on cognitive function. An unusual case of colonic gangrene following overdose of imipramine and alcohol is presented. The patient recovered.......Patients on antidepressant medication are instructed to avoid alcohol because of possible additive effects on cognitive function. An unusual case of colonic gangrene following overdose of imipramine and alcohol is presented. The patient recovered....

  17. Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2012-01-01

    Full Text Available Background/Aim. Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. Methods. Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatographyultraviolet (HPLC-UV method. Results. A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43 was similar to the mean ratio after its administration in therapeutic doses (0.39, but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. Conclusion. Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine.

  18. Epidemiology of tramadol overdose in Imam Khomeini hospital, Kermanshah, Iran (2008

    Directory of Open Access Journals (Sweden)

    Habib Ahmadi

    2011-03-01

    Full Text Available Background: Tramadol is an analgesic drug used for treatment of moderate to severe pain. According to side effects of Tramadol overdose, this study aimed to evaluate epidemiological characteristics of patients who admitted with Tramadol overdose in Imam Khomeini hospital - Kermanshah from March 2008 to March 2009.Methods: In this descriptive- analytical study, all profiles of poisoned subjects with Tramadol who have been referred to the hospital were reviewed. Considerable variables were extracted and data were analyzed using chi-square and Independent t test. Results: The result showed that majority of overdosed subjects was married (80.8% and aged 19 years old (11.2%. Suicide (98.7% was the most common cause of using Tramadol. 40% of cases showed a seizure symptom and seizure incidence in male subjects was higher than female (P<0.001. There was a significant correlation between Tramadol dosages and outbreak of a seizure symptoms. Conclusion: Abuse of Tramadol may leads to seizure and death, which threat young generation less than 30 years old committed to suicide. Increasing knowledge and restriction of Tramadol availability and distribution in community is necessary to prevent young generation from suicide commitment.

  19. Overdosed paracetamol (acetaminophen) prescriptions and subsequent pharmacist interventions in French hospitals.

    Science.gov (United States)

    Charpiat, B; Bedouch, P; Rose, F X; Juste, M; Roubille, R; Conort, O; Allenet, B

    2013-11-01

    Little is known about the manner in which hospital pharmacists intervene for overdosed paracetamol prescriptions. The aim of this retrospective study was to describe the number and nature of pharmacists' interventions (PIs) for overdosed paracetamol adult prescriptions in hospitals. We studied PIs that had been documented by pharmacists on the French Society of Clinical Pharmacy website tool between 2007 and 2010. We identified PIs that were related to paracetamol-containing prescriptions of one brand name only (type 1) particularly for patients with body weight ≤ 50 kg who were prescribed 4 g/day, and PIs that concerned the co-prescription of two paracetamol-containing products (type 2). Among 60 hospitals, seven did not report any paracetamol overdose-related PIs. Of the 53 hospitals that had at least one PI, 16 did not report any type 1 PIs. Bodyweight, liver disease, cirrhosis and chronic alcoholism were absent recorded criterion by most of the hospitals included in this study. Previously published studies have highlighted that the most frequent PIs are type 1, especially for patients whose body weight is ≤ 50 kg. We observed a broad variability in the number or type of PI that were related to overdosed paracetamol prescriptions compared with the total of all recorded types of PI. These data suggest that a significant number of hospital pharmacists are unaware of the risks that adult patients with low body weight are exposed to when receiving four grams paracetamol/day over several days. Pharmacist educational programs are needed. Copyright © 2013. Published by Elsevier Masson SAS.

  20. Physicochemical and mechanical properties of carbamazepine cocrystals with saccharin.

    Science.gov (United States)

    Rahman, Ziyaur; Samy, Raghu; Sayeed, Vilayat A; Khan, Mansoor A

    2012-01-01

    The aim of present research was to investigate the physicochemical, mechanical properties, and stability characteristics of cocrystal of carbamazepine (CBZ) using saccharin (SAC) as a coformer. The cocrystals were prepared by solubility method and characterized by pH-solubility profile, intrinsic dissolution by static disk method, and surface morphology by scanning electron microscopy (SEM), crystallinity by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), and mechanical properties by Heckel analysis. Stability of the cocrystals were assessed by storing them at 60 (°)C for two weeks, 25 (°)C/60%RH, 40 (°)C/75%RH and 40 (°)C/94%RH for one month and compared with the stability of CBZ. The solubility profile of cocrystal was similar to CBZ. The cocrystal and CBZ have shown the same stability profile at all the conditions of studies except at 40 (°)C/94%RH. Unlike the CBZ, cocrystal was stable against dihydrate transformation. The compacts of cocrystal have a greater tensile strength and more compressibility. The Heckel analysis suggested that plastic deformation started at low compression pressure in the cocrystal than CBZ. In summary, the cocrystal form of carbamazepine provides another avenue for product development which is more stable than the parent drug.

  1. Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

    Science.gov (United States)

    Powell, Graham; Holmes, Emily A F; Plumpton, Catrin O; Ring, Adele; Baker, Gus A; Jacoby, Ann; Pirmohamed, Munir; Marson, Anthony G; Hughes, Dyfrig A

    2015-11-01

    Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV. The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice. © 2015 The British Pharmacological Society.

  2. Outcomes from massive paracetamol overdose: a retrospective observational study.

    Science.gov (United States)

    Marks, Daniel J B; Dargan, Paul I; Archer, John R H; Davies, Charlotte L; Dines, Alison M; Wood, David M; Greene, Shaun L

    2017-06-01

    This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163-5. https://doi.org/10.1111/bcp.13279 AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAP pl ) and treatment nomogram thresholds at those time points (APAP t ) provides a useful assessment tool. This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l -1 , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAP pl :APAP t ratio (based on a treatment line through 100 mg l -1 at 4 h), and time to acetylcysteine. Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAP pl :APAP t  ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort. © 2016 The British Pharmacological Society.

  3. Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

    Directory of Open Access Journals (Sweden)

    Massimo Calderazzo

    2015-06-01

    Full Text Available We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6. The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml.

  4. Multiple Fentanyl Overdoses - New Haven, Connecticut, June 23, 2016.

    Science.gov (United States)

    Tomassoni, Anthony J; Hawk, Kathryn F; Jubanyik, Karen; Nogee, Daniel P; Durant, Thomas; Lynch, Kara L; Patel, Rushaben; Dinh, David; Ulrich, Andrew; D'Onofrio, Gail

    2017-02-03

    On the evening of June 23, 2016, a white powder advertised as cocaine was purchased off the streets from multiple sources and used by an unknown number of persons in New Haven, Connecticut. During a period of less than 8 hours, 12 patients were brought to the emergency department (ED) at Yale New Haven Hospital, experiencing signs and symptoms consistent with opioid overdose. The route of intoxication was not known, but presumed to be insufflation ("snorting") in most cases. Some patients required doses of the opioid antidote naloxone exceeding 4 mg (usual initial dose = 0.1-0.2 mg intravenously), and several patients who were alert after receiving naloxone subsequently developed respiratory failure. Nine patients were admitted to the hospital, including four to the intensive care unit (ICU); three required endotracheal intubation, and one required continuous naloxone infusion. Three patients died. The white powder was determined to be fentanyl, a drug 50 times more potent than heroin, and it included trace amounts of cocaine. The episode triggered rapid notification of public health and law enforcement agencies, interviews of patients and their family members to trace and limit further use or distribution of the fentanyl, immediate naloxone resupply and augmentation for emergency medical services (EMS) crews, public health alerts, and plans to accelerate naloxone distribution to opioid users and their friends and families. Effective communication and timely, coordinated, collaborative actions of community partners reduced the harm caused by this event and prevented potential subsequent episodes.

  5. Risk Factors for Opioid-Use Disorder and Overdose.

    Science.gov (United States)

    Webster, Lynn R

    2017-11-01

    Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.

  6. Anticholinergic syndrome following an unintentional overdose of scopolamine

    Directory of Open Access Journals (Sweden)

    Carmela E Corallo

    2009-09-01

    Full Text Available Carmela E Corallo1, Ann Whitfield2, Adeline Wu21Department of Pharmacy, The Alfred, Melbourne, Victoria, Australia; 2Intensive Care Unit, Box Hill Hospital, Melbourne, Victoria, AustraliaAbstract: Scopolamine hydrobromide (hyoscine is an antimuscarinic drug which is primarily used in the prophylaxis and treatment of motion sickness and as a premedication to dry bronchial and salivary secretions. In acute overdosage, the main clinical problem is central nervous system (CNS depression. In Australia, tablets containing scopolamine hydrobromide 0.3 mg are available over the counter in packs of ten. The recommended dose for adults is one to two tablets as a single dose, repeated four to six hours later, if required. The maximum dose stated on the pack is four tablets over a 24-hour period with a caution regarding drowsiness and blurred vision. We describe a patient who presented with symptoms of anticholinergic syndrome secondary to an unintentional overdose of scopolamine. Whilst at work, the patient noticed that he had forgotten his prescribed medication, domperidone, at home; a friend gave him some travel sickness medication which contained scopolamine for relief of nausea. On a previous occasion, he had experienced a similar, less severe reaction with another anticholinergic agent, loperamide. This report highlights the need to consider nonprescription products, ie, over the counter medications, herbal/nutritional supplements as causes of anticholinergic syndrome when a patient presents with symptoms suggestive of this diagnosis.Keywords: domperidone, scopolamine, nonprescription drugs, toxicity, anticholinergic syndrome

  7. Influence of kinnow juice on the bioavailability of carbamazepine in healthy male volunteers.

    Science.gov (United States)

    Garg, S K; Bhargava, V K; James, H; KuJan-Mar, N; Prabhakar, S; Naresh, Ku

    1998-01-01

    Kinnow juice produces a marked and variable increase in carbamazepine bioavailability. The pharmacokinetics of carbamazepine was studied after drug administration with 300 ml water or kinnow juice in a randomized cross over trial on nine healthy male volunteers. With kinnow juice peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) was significantly (P kinnow juice enhances carbamazepine bioavailability could be due to inhibition of cytochrome P-450 enzyme, since kinnow juice contains naringin which is considered to be inhibitor of liver microsomal dihydropyridine oxidation.

  8. Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data.

    Science.gov (United States)

    Akiskal, Hagop S; Fuller, Matthew A; Hirschfeld, Robert M A; Keck, Paul E; Ketter, Terence A; Weisler, Richard H

    2005-06-01

    This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on

  9. Palatal tremor after lithium and carbamazepine use: a case report

    Directory of Open Access Journals (Sweden)

    Kuruvilla Anju

    2010-06-01

    Full Text Available Abstract Introduction Palatal tremor, characterized by rhythmic contractions of the soft palate, can occur secondary to pathology in the dentato-rubro-olivary pathway, or in the absence of such structural lesions. Its pathogenesis is only partially understood. We describe a case of probable drug-induced palatal tremor. Case presentation A 27-year-old Indian man had taken carbamazepine and lithium for 7 years for the treatment of a manic episode. He presented with a one-year history of bilateral rhythmic oscillations of his soft palate and tremors of his tongue. There were no other abnormalities detected from his examination or after detailed investigation. Conclusion Palatal tremors may result from medication used in the treatment of psychiatric disorders.

  10. Law enforcement attitudes towards naloxone following opioid overdose training.

    Science.gov (United States)

    Purviance, Donna; Ray, Bradley; Tracy, Abigail; Southard, Erik

    2017-01-01

    Opioid intoxication and overdoses are life-threatening emergencies requiring rapid treatment. One response to this has been to train law enforcement to detect the signs of an opioid overdose and train them to administer naloxone to reverse the effects. Although not a new concept, few studies have attempted to examine this policy. At 4 different locations in Indiana, law enforcement personnel were trained to detect the signs of an opioid-related overdose and how to administer naloxone to reverse the effects of the overdose. Pre and post surveys were administered at each location (N = 97). To examine changes in attitudes following training, the authors included items from the Opioid Overdose Attitudes Scale (OOAS), which measures respondents' competency, concerns, and readiness to administer naloxone. Among the full sample, naloxone training resulted in significant increases in competency, concerns, and readiness. Examining changes in attitudes by each location revealed that the training had the greatest effect on competency to administer naloxone and in easing concerns that law enforcement personal might have in administering naloxone. This study adds to others in showing that law enforcement personnel are receptive to naloxone training and that the OOAS is able to capture these attitudes. This study advances this literature by examining pre-post changes across multiple locations. As the distribution of naloxone continues to proliferate, this study and the OOAS may be valuable towards the development of an evidence-based training model for law enforcement.

  11. Missed paracetamol (acetaminophen) overdose due to confusion regarding drug names.

    Science.gov (United States)

    Hewett, David G; Shields, Jennifer; Waring, W Stephen

    2013-07-01

    Immediate management of drug overdose relies upon the patient account of what was ingested and how much. Paracetamol (acetaminophen) is involved in around 40% of intentional overdose episodes, and remains the leading cause of acute liver failure in many countries including the United Kingdom. In recent years, consumers have had increasing access to medications supplied by international retailers via the internet, which may have different proprietary or generic names than in the country of purchase. We describe a patient that presented to hospital after intentional overdose involving 'acetaminophen' purchased via the internet. The patient had difficulty recalling the drug name, which was inadvertently attributed to 'Advil', a proprietary non-steroidal anti-inflammatory drug. The error was later recognised when the drug packaging became available, but the diagnosis of paracetamol overdose and initiation of acetylcysteine antidote were delayed. This case illustrates the benefit of routinely measuring paracetamol concentrations in all patients with suspected poisoning, although this is not universally accepted in practice. Moreover, it highlights the importance of the internet as a source of medications for intentional overdose, and emphasises the need for harmonisation of international drug names to improve patient safety.

  12. CDC Vital Signs: Prescription Painkiller Overdoses (Opioids): A Growing Epidemic, Especially Among Women

    Science.gov (United States)

    ... health care providers and the public about prescription drug misuse, abuse, suicide, and overdose, and the risks for women. Developing and evaluating programs and policies that prevent and treat prescription drug abuse and overdose, while making sure patients have access ...

  13. Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.

    Science.gov (United States)

    Wong, Anselm; Sivilotti, Marco L A; Gunja, Naren; McNulty, Richard; Graudins, Andis

    2018-03-01

    Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.

  14. Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

    Science.gov (United States)

    Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

    2007-04-01

    The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

  15. Relation between serum vitamin B12 level and duration of treatment with carbamazepine in epilepsy patients

    Directory of Open Access Journals (Sweden)

    Mohammad Tariqul Islam

    2016-12-01

    Full Text Available Vitamin B12 levels in the serum of 58 epileptic patients receiving only carbamazepine for at least 6 months were measured. Same number of epilepsy patients with no history of taking antiepileptic medicine were taken as control. The mean level of vitamin B12 in carbamazepine-treated epileptic patients was 265.5 pg/mL whereas it was 478.3 pg/mL in control. Increased duration of treatment of carbamazepine in epilepsy caused significantly decreased level of serum vitamin B12 (Pearson correlation coefficient, r = -0.9, p<0.0001. In conclusion, serum vitamin B12 level significantly decreased in relation to duration of carbamazepine treatment in epileptic patients.

  16. Parkinsonisme na toevoeging van fluoxetine aan behandeling met neuroleptica of carbamazepine

    NARCIS (Netherlands)

    Touw, D J; Gernaat, H B; van der Woude, J

    1992-01-01

    This article describes three patients who developed parkinsonism when fluoxetine was added to their existing medication (neuroleptics or carbamazepine). Based on published pharmacological and neuroanatomical research we postulate a serotonin-dopamine antagonism to be operative in the development of

  17. Adsorption of carbamazepine by carbon nanotubes: Effects of DOM introduction and competition with phenanthrene and bisphenol A

    International Nuclear Information System (INIS)

    Lerman, Ilya; Chen, Yona; Xing, Baoshan; Chefetz, Benny

    2013-01-01

    Carbon nanotubes, organic contaminants and dissolved organic matter (DOM) are co-introduced into the environment. Thus, the interactions between these components have to be evaluated to better understand their environmental behavior. In this study, single-walled carbon nanotubes (SWCNTs) were used as sorbent, carbamazepine was the primary adsorbate, and bisphenol A and phenanthrene were used as competitors. Strong competition with bisphenol A and no effect of phenanthrene on adsorption of carbamazepine was obtained. The hydrophobic neutral fraction of the DOM exhibited the strongest reductive effect on carbamazepine adsorption, most probably due to interactions in solution. In contrast, the hydrophobic acid fraction decreased carbamazepine adsorption mainly via direct competition. When DOM and bisphenol A were co-introduced, the adsorption of carbamazepine was significantly reduced. This study suggests that the chemical nature of DOM can significantly affect the sorptive behavior of polar organic pollutants with carbon nanotubes when all are introduced to the aquatic system. Highlights: •Bisphenol A is an efficient competitor for carbamazepine. •Phenanthrene does not compete with carbamazepine. •DOM exhibited strong reductive effect on carbamazepine adsorption by SWCNTs. •HoN fraction decreased carbamazepine adsorption due to interactions in solution. •HoA fraction decreased carbamazepine adsorption via direct competition. -- In multi-component system including the main adsorbate and competitor, DOM exhibited significant effect on adsorption of contaminants by carbon nanotubes

  18. Successful use of haemodialysis to treat phenobarbital overdose.

    Science.gov (United States)

    Hoyland, Kimberley; Hoy, Michael; Austin, Richard; Wildman, Martyn

    2013-11-21

    A 50-year-old woman presented with coma caused by a phenobarbital overdose, requiring intubation and admission to critical care. She was an international visitor and had been prescribed the drug for night-sedation. Phenobarbital is a long-acting barbiturate, which in an overdose can cause central nervous system depression, respiratory failure and haemodynamic instability; these patients can remain obtunded for many days. After initial supportive therapy, she was dialysed to help in the elimination of the drug. Haemodialysis resulted in a markedly reduced plasma level of phenobarbital, which decreased the length of intubation and stay in the critical care unit and aided full recovery.

  19. Study of efficacy of the combination of carbamazepine with nootropics on cognitive processes in epilepsy

    Directory of Open Access Journals (Sweden)

    Ivanov A.V.

    2013-03-01

    Full Text Available The authors studied the efficacy of combination of carbamazepine with nootropic drugs on cognitive processes in patients with epilepsy in experiment in order to reduce the side effects of anticonvulsant therapy. Analysis of anticonvulsant effect of the combination of drugs was carried out on 36 white nonlinear rats of both sexes weighing 160-180 g by the method of maximum electroshock, and the analysis of antiamnestic effect - using a model of retrograde amnesia on 80 white adult male rats weighing 160 - 200 g. For studying the mnemotropic activity of drug, the method of the conditioned reflex of active avoidance was used. The authors discovered that the isolated use of carbamazepine has the most negative influence on cognitive processes in animals, namely the formation of skill, memory engrams and consolidating memory trace as compared with the combined use of carbamazepine with neuroprotective drugs. It was found that the use of combinations of carbamazepine and nootropics in the experiment does not prevent the development of seizures completely, however, these combination can significantly reduce the duration of seizures (p <0.0001. Study of the effectiveness of the combined use of carbamazepine with nootropic drugs, revealed, that the tested drug combinations have a positive effect on cognitive processes and show neuroprotective effect on the brain structures of animals. The revealed effects of combined use of carbamazepine with nootropic drugs by the strength and intensity of the impact is much higher than isolated, while using carbamazepine. It was found, that the most effective combination is a combination of carbamazepine with Gliatilin.

  20. Solid-vapor interactions: Influence of environmental conditions on the dehydration of carbamazepine dihydrate

    OpenAIRE

    Surana, Rahul; Pyne, Abira; Suryanarayanan, Raj

    2003-01-01

    The goal of this research was a phenomenological study of the effect of environmental factors on the dehydration behavior of carbamazepine dihydrate. Dehydration experiments were performed in an automated vapor sorption apparatus under a variety of conditions, and weight loss was monitored as a function of time. In addition to lattice water, carbamazepine dihydrate contained a significant amount of physically bound water. Based on the kinetics of water loss, it was possible to differentiate b...

  1. The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures.

    Science.gov (United States)

    Donati, Filippo; Gobbi, Giuseppe; Campistol, Jaume; Rapatz, Guenter; Daehler, Maja; Sturm, Yvonne; Aldenkamp, Albert P

    2007-12-01

    To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

  2. Accidental Overdose Intoxication: A Hazard of Drug Smuggling

    Science.gov (United States)

    Arora, Sudhir; Tafreshi, Michael; Sobo, Steven; Krochmal, Paul; Alexander, Leslie L.

    1982-01-01

    Three patients involved in illicit drug smuggling via the swallowing of high dose, high purity drugs packed in multiple condoms are reported. Two of these patients experienced drug overdose symptoms due to leakage or rupture of the condoms in the GI tract. They were treated successfully. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:7120497

  3. Metabolic acidosis in a patient with metformin overdose

    African Journals Online (AJOL)

    gas findings taken at room temperature at this time are shown in Table 1. Calculation of the anion gap was not possible because ... Arterial blood gas findings on 30% oxygen at this time revealed a metabolic acidosis as shown in .... is ideal in acute overdose for effective removal of both metformin and circulating lactate.

  4. Young Adult's Immediate Reaction to a Personal Alcohol Overdose

    Science.gov (United States)

    Reis, Janet; Harned, Ilene; Riley, William

    2004-01-01

    Following an emergency medical transport for alcohol overdose, first-year college students were asked to complete a survey assessing their reactions to the transport experience, their assessment of why they required this emergency response, and plans for future personal alcohol consumption. Transported students who responded to a baseline survey…

  5. Plasmapheresis reverses all side-effects of a cisplatin overdose – a case report and treatment recommendation

    Directory of Open Access Journals (Sweden)

    Ploner Ferdinand

    2006-01-01

    Full Text Available Abstract Background Cisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death. Case presentation We report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m2 of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae. Conclusion To date, no general accepted guidelines for the treatment of cisplatin overdoses are available. Along with the experience from other published cases, our report shows that plasmapheresis is capable of lowering cisplatin plasma and serum levels efficiently. Therefore, plasma exchange performed as soon as possible can ameliorate all side effects of a cisplatin overdose and be a potential tool for clinicians for treatment. However, additional intensive supportive treatment-modalities are necessary to control all occurring side effects.

  6. Carbamazepine-Induced Acute Generalized Exanthematous Pustulosis: A Case Report

    Science.gov (United States)

    Skalli, Saadia; Barret, Pierre; Villier, Céline; Bussières, Jean-François

    2011-01-01

    A 15-year-old adolescent was admitted to the hospital for management of a generalized pruritic skin rash, which had appeared 10 days prior to admission. Carbamazepine (CBZ) and insulin were initiated 44 and 23 days prior to the onset of the skin rash (day 44), respectively. Clinical examination showed bluish lesions on the tongue and bilateral keratoconjunctivitis. His skin was very erythematous and pruritic without edema and covered with hundreds of nonfollicular pustules mainly on the trunk and skin folds. Laboratory assessment revealed leukocytosis, hypereosinophilia, and thrombocytopenia. A sample of superficial pus from a pustule on the trunk showed a significant number of leukocytes as well as a significant number of Staphylococcus aureus and Lancefield Group B β-hemolytic streptococci strains. An abdominal skin biopsy revealed acute to subacute folliculocentric spongiotic dermatitis with subcorneal pustules. All of these observations were consistent with a diagnosis of acute generalized exanthematous pustulosis (AGEP). Although we could not exclude with certainty the role of insulin initiated on day 21 and discontinued on day 55 with substitution to oral metformin and repaglinide, no cases of AGEP have ever been published with insulin, and skin lesions were not related to injection sites. This article describes a probable case of CBZ-induced acute generalized exanthematous pustulosis in a 15-year-old adolescent. PMID:22477826

  7. Pulsed corona discharge oxidation of aqueous carbamazepine micropollutant.

    Science.gov (United States)

    Ajo, Petri; Krzymyk, Ewelina; Preis, Sergei; Kornev, Iakov; Kronberg, Leif; Louhi-Kultanen, Marjatta

    2016-08-01

    The anti-epileptic drug carbamazepine (CBZ) receives growing attention due to slow biodegradation and inherent accumulation in the aquatic environment. The application of a gas-phase pulsed corona discharge (PCD) was investigated to remove CBZ from synthetic solutions and spiked wastewater effluent from a municipal wastewater treatment facility. The treated water was showered between high voltage (HV) wires and grounded plate electrodes, to which ultra-short HV pulses were applied. CBZ was readily oxidized and 1-(2-benzaldehyde)-4-hydroquinazoline-2-one (BQM) and 1-(2-benzaldehyde)-4-hydro-quinazoline-2,4-dione (BQD) were identified as the most abundant primary transformation products, which, contrary to CBZ ozonation data available in the literature, were further easily oxidized with PCD: BQM and BQD attributed to only a minor portion of the target compound oxidized. In concentrations commonly found in wastewater treatment plant effluents (around 5 µg L(-1)), up to 97% reduction in CBZ concentration was achieved at mere 0.3 kW h m(-3) energy consumption, and over 99.9% was removed at 1 kW h m(-3). The PCD application proved to be efficient in the removal of both the parent substance and its known transformation products, even with the competing reactions in the complex composition of wastewater.

  8. Uptake of Carbamazepine by rhizomes and endophytic bacteria of Phragmites australis

    Directory of Open Access Journals (Sweden)

    Andres eSauvetre

    2015-02-01

    Full Text Available Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely in Europe and North America. In the environment, it is found as a persistent and recalcitrant conta¬mi-nant, being one of the most prominent hazardous pharmaceuticals and personal care products (PPCPs in effluents of wastewater treatment plants (WWTPs. Phragmites australis is one of the species with both, the highest potential of detoxification and phytoremediation. It has been used successfully in the treatment of industrial and municipal wastewater. Recently, the identification of endophytic micro¬organisms from different plant species growing in contaminated sites has provided a list of candidates which could be used as bio-inoculants for bioremediation of difficult compounds. In this study, Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days the plants had removed 90% of the initial concentration. Endophytic bacteria were isolated from these plants and further characterized. Phylogenetic analysis based on 16S rDNA sequencing revealed that the majority of these isolates belong to three groups: Proteobacteria, Actinobacteria and Bacteroidetes. Carbamazepine uptake and plant growth promoting (PGP traits were analyzed among the isolates. Ninety percent of the isolates produce indole acetic acid (IAA and all of them possess at least one of the PGP traits tested. One isolate identified as Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP traits. Rhizobium daejeonense can remove carbamazepine and produces 23 µg/mL of IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show high siderophore production and phosphate solubilization. Alone or in combination, these isolates might be applied as inoculates in constructed wetlands in order to enhance the phyto-remediation of carbamazepine during wastewater

  9. Patients Who Attend the Emergency Department Following Medication Overdose: Self-Reported Mental Health History and Intended Outcomes of Overdose

    Science.gov (United States)

    Buykx, Penny; Ritter, Alison; Loxley, Wendy; Dietze, Paul

    2012-01-01

    Medication overdose is a common method of non-fatal self-harm. Previous studies have established which mental health disorders are commonly associated with the behaviour (affective, substance use, anxiety and personality disorders) and which medications are most frequently implicated (benzodiazepines, antidepressants, antipsychotics and non-opioid…

  10. A Case Report of Suicide with Chloroquine Overdose and Review of Literature

    Directory of Open Access Journals (Sweden)

    Maryam Hosseini

    2016-09-01

    Full Text Available Background & Objective: Suicide is considered as the tenth cause of death worldwide. There are several suicide reports consist in the use of certain unusual drugs, such as chloroquine. Case report: The cadaver of a 25-year-old single woman was found dead in her home and with suspect to using toxins or drugs was brought to Fars Province Forensic administration. She had history of psychiatric problems for which had referred to psychologist several times. Results: After the autopsy, there was no observation of pathologic lesions in her samples of liver, kidney, or heart. In bile samples, using Thin Layer Chromatography (TLC and High Performance Liquid Chromatography (HPLC methods, chloroquine was detected. In visceral and gut samples, chloroquine was found using TLC as +4 reactions and it was confirmed by HPLC and Gas Chromatography Mass Spectrometry (GC-MS. After examining all the aspects, eventually chloroquine overdose and its complications was determined as the cause of the death. Conclusion: Due to the high incidence of suicide in depressed patients and according to family and previous positive experience, preventive strategies based on the recognition and the treatment of depressed patients and also teaching the families to diagnose the illness in addition to the limitation of the free access to chloroquine and similar drugs is suggested to reduce overdose complications or suicide.

  11. Interaction of Carbamazepine with Herbs, Dietary Supplements, and Food: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Sophia Yui Kau Fong

    2013-01-01

    Full Text Available Background. Carbamazepine (CBZ is a first-line antiepileptic drug which may be prone to drug interactions. Systematic review of herb- and food-drug interactions on CBZ is warranted to provide guidance for medical professionals when prescribing CBZ. Method. A systematic review was conducted on six English databases and four Chinese databases. Results. 196 out of 3179 articles fulfilled inclusion criteria, of which 74 articles were reviewed and 33 herbal products/dietary supplement/food interacting with CBZ were identified. No fatal or severe interactions were documented. The majority of the interactions were pharmacokinetic-based (80%. Traditional Chinese medicine accounted for most of the interactions (n=17, followed by food (n=10, dietary supplements (n=3, and other herbs/botanicals (n=3. Coadministration of 11 and 12 of the studied herbal products/dietary supplement/food significantly decreased or increased the plasma concentrations of CBZ. Regarding pharmacodynamic interaction, Xiao-yao-san, melatonin, and alcohol increased the side effects of CBZ while caffeine lowered the antiepileptic efficacy of CBZ. Conclusion. This review provides a comprehensive summary of the documented interactions between CBZ and herbal products/food/dietary supplements which assists healthcare professionals to identify potential herb-drug and food-drug interactions, thereby preventing potential adverse events and improving patients’ therapeutic outcomes when prescribing CBZ.

  12. Phenytoin and carbamazepine in trigeminal neuralgia: marketing-based versus evidence-based treatment

    Directory of Open Access Journals (Sweden)

    Keppel Hesselink JM

    2017-07-01

    Full Text Available Jan M Keppel Hesselink,1 Michael E Schatman2,31Institute for Neuropathic Pain, Bosch en Duin, the Netherlands; 2Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 3Boston Pain Care, Waltham, MA, USAIntroductionMost review articles support carbamazepine as a first-line pharmacotherapy for idiopathic trigeminal neuralgia.1–3 However, the empirical support for this recommendation is somewhat suspect. Phenytoin, as the prototype for all anticonvulsants, was already positioned as an analgesic compound 70 years ago. Since these initial findings, the data that have been gathered have supported the use of anticonvulsants as painkillers – from phenytoin up to and including more recent anticonvulsants such as gabapentin and pregabalin. Since 1942, a number of papers supported phenytoin’s therapeutic effects in trigeminal neuralgia (Table 1. The introduction of carbamazepine in 1962 by Geigy shifted the interest of neurologists from phenytoin as a treatment for trigeminal neuralgia to carbamazepine, without sound scientific evidence. To date, no convincing randomized controlled trials (RCTs have been published supporting the role of carbamazepine in trigeminal neuralgia, and we could not identify a single study comparing the effects of phenytoin with those of carbamazepine. Accordingly, phenytoin should probably be considered more often as a viable therapy for (treatmentresistant trigeminal neuralgia.

  13. Attitudes and knowledge about naloxone and overdose prevention among detained drug users in Ningbo, China

    Directory of Open Access Journals (Sweden)

    Liu Yu

    2012-02-01

    Full Text Available Abstract Background To date there has been limited research on both the prevalence of overdose and drug user knowledge about overdose prevention and response methods in China. In addition, there has been no effort to integrate naloxone information and distribution into pre-release services for drug users detained in isolated compulsory detoxification facilities in China. Methods The authors conducted a survey of 279 heroin users in isolated compulsory detoxification centers in Ningbo, China in an attempt to evaluate the possibility of conducting prelease peer naloxone programs in Ningbo isolated compulsory detoxification centers. Respondents' demographic background, history of heroin overdoses, and attitudes/knowledge about overdose prevention and response were collected. Results While drug users in Ningbo's compulsory detoxification centers have limited understandings of how to effectively respond to overdoses, they expressed concern about the possibility of overdose, interest in participating in overdose prevention and response programs, and a willingness to help their peers. In general, there was no significant difference in history and attitudes/knowledge of overdose between male and female participants. Conclusion Based on the findings of this research, our survey provides preliminary evidence that detained drug users have considerable interest in overdose prevention and response information and willingness to help peers. However, drug users in Ningbo isolated compulsory detoxification centers currently have limited understandings of effective ways of helping to prevent overdose deaths.

  14. Anti-solvent co-crystallization of carbamazepine and saccharin.

    Science.gov (United States)

    Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

    2013-06-25

    The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Pharmacokinetics: time-dependent changes--autoinduction of carbamazepine epoxidation

    International Nuclear Information System (INIS)

    Bertilsson, L.; Tomson, T.; Tybring, G.

    1986-01-01

    Drugs labeled with stable isotopes have been useful to study time-dependent changes in kinetics. Early studies suggested that carbamazepine (CBZ) may induce its own metabolism, but this could not be proved until tetradeuterium-labeled CBZ (CBZ-D4) was synthesized and then given to patients. CBZ-D4 was administered to three children during long-term treatment of epilepsy with CBZ. After 17 to 32 days of treatment, the plasma clearance of CBZ-D4 was doubled, but during the next four months, there was no further increase, indicating that autoinduction was complete within one month. Two patients with chronic alcoholism were treated with CBZ for five days. Half of the first dose of 600 mg was comprised of CBZ-D4. The half-life of this CBZ-D4 dose in the two patients (20 and 26 hr, respectively) was similar to the post-steady-state half-life of CBZ (23 hr in both patients) measured later. A single dose of CBZ given one week after the last maintenance dose had a longer half-life (46 and 45 hr, respectively), which probably is close to the disposition of the drug before starting the treatment with CBZ. This shows that autoinduction of CBZ metabolism was completed during the very first doses of CBZ. Autoinduction also disappeared rapidly after stopping the treatment. We have shown that it is mainly the epoxide-diol pathway that is induced, both during autoinduction and after induction with other antiepileptic agents

  16. [Early macular edema after phacoemulsification and suspected overdose of cefuroxime: report of six cases].

    Science.gov (United States)

    Le Dû, B; Pierre-Kahn, V

    2014-03-01

    Antibiotic prophylaxis by intracameral cefuroxime injection, 1mg/0.1 mL after cataract surgery is increasing in popularity. Several cases of early postoperative macular edema have recently been reported after cefuroxime injection, most of them due to accidental cefuroxime overdose. We report six additional cases of macular involvement after cataract surgery, with intracameral cefuroxime injection imputed to cause retinal toxicity. Formal proof of cefuroxime overdose has never been possible, due to rapid wash-out in a few hours and the diagnosis of the macular edema the day after surgery or within a few days. Thus, this strong suspicion is based on clinical, pharmacokinetic, tomographic and retinographic criteria. In our series of six cases, the first four patients involved the same surgeon in the same hospital, and two of them on the same day. For the sixth case, the diagnosis was made retrospectively and based on history and medium-term tomographic characteristics. All the patients underwent optical coherence tomography (OCT) relatively early. As early as day one after surgery, there is macular edema predominantly in the outer retinal layers associated with serous retinal detachment, similar to the cases described in the literature. In the late stage, three patients had functional impairment related to photoreceptor damage on OCT. Three cases are described with additional retinal imaging (angiography, autofluorescence) to better characterize this macular toxicity associated with cefuroxime. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Serotonin Syndrome after Sertraline Overdose in a Child: A Case Report

    Directory of Open Access Journals (Sweden)

    Joana Grenha

    2013-01-01

    Full Text Available Serotonin syndrome is a potentially life-threatening drug effect. It may be misdiagnosed because it has mostly been reported in adults. Case Report. An 8-year-old girl with behavioral problems and medicated with risperidone and sertraline was admitted in the emergency department after she had taken voluntarily 1500 mg of sertraline (50 mg/kg. At admission, she had marked agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had fever and periods of hypertension. She also showed generalized rigidity and involuntary movements. She was treated with fluids and iv diazepam, midazolam, clemastine, and biperiden. As the patient presented a severe insomnia and a progressive rhabdomyolysis, she was transferred to pediatric intensive care unit (ICU, where she was under treatment with cyproheptadine, mechanical ventilation, and muscular paralysis for 11 days. She was discharged from hospital a few days later with no neurological sequelae. Conclusions. Serotonin syndrome is still not well recognized by physicians. In our patient, the diagnosis was made early due to the history of overdose with serotonin reuptake inhibitors and the triad of mental, neurological, and autonomic signs. Parents must be educated to prevent children from having free access to drugs, avoiding self-medication or overdose.

  18. Overdose prevention for injection drug users: lessons learned from naloxone training and distribution programs in New York City.

    Science.gov (United States)

    Piper, Tinka Markham; Rudenstine, Sasha; Stancliff, Sharon; Sherman, Susan; Nandi, Vijay; Clear, Allan; Galea, Sandro

    2007-01-25

    Fatal heroin overdose is a significant cause of mortality for injection drug users (IDUs). Many of these deaths are preventable because opiate overdoses can be quickly and safely reversed through the injection of Naloxone [brand name Narcan], a prescription drug used to revive persons who have overdosed on heroin or other opioids. Currently, in several cities in the United States, drug users are being trained in naloxone administration and given naloxone for immediate and successful reversals of opiate overdoses. There has been very little formal description of the challenges faced in the development and implementation of large-scale IDU naloxone administration training and distribution programs and the lessons learned during this process. During a one year period, over 1,000 participants were trained in SKOOP (Skills and Knowledge on Opiate Prevention) and received a prescription for naloxone by a medical doctor on site at a syringe exchange program (SEP) in New York City. Participants in SKOOP were over the age of 18, current participants of SEPs, and current or former drug users. We present details about program design and lessons learned during the development and implementation of SKOOP. Lessons learned described in the manuscript are collectively articulated by the evaluators and implementers of the project. There were six primary challenges and lessons learned in developing, implementing, and evaluating SKOOP. These include a) political climate surrounding naloxone distribution; b) extant prescription drug laws; c) initial low levels of recruitment into the program; d) development of participant appropriate training methodology; e) challenges in the design of a suitable formal evaluation; and f) evolution of program response to naloxone. Other naloxone distribution programs may anticipate similar challenges to SKOOP and we identify mechanisms to address them. Strategies include being flexible in program planning and implementation, developing evaluation

  19. Overdose prevention for injection drug users: Lessons learned from naloxone training and distribution programs in New York City

    Directory of Open Access Journals (Sweden)

    Nandi Vijay

    2007-01-01

    Full Text Available Abstract Background Fatal heroin overdose is a significant cause of mortality for injection drug users (IDUs. Many of these deaths are preventable because opiate overdoses can be quickly and safely reversed through the injection of Naloxone [brand name Narcan], a prescription drug used to revive persons who have overdosed on heroin or other opioids. Currently, in several cities in the United States, drug users are being trained in naloxone administration and given naloxone for immediate and successful reversals of opiate overdoses. There has been very little formal description of the challenges faced in the development and implementation of large-scale IDU naloxone administration training and distribution programs and the lessons learned during this process. Methods During a one year period, over 1,000 participants were trained in SKOOP (Skills and Knowledge on Opiate Prevention and received a prescription for naloxone by a medical doctor on site at a syringe exchange program (SEP in New York City. Participants in SKOOP were over the age of 18, current participants of SEPs, and current or former drug users. We present details about program design and lessons learned during the development and implementation of SKOOP. Lessons learned described in the manuscript are collectively articulated by the evaluators and implementers of the project. Results There were six primary challenges and lessons learned in developing, implementing, and evaluating SKOOP. These include a political climate surrounding naloxone distribution; b extant prescription drug laws; c initial low levels of recruitment into the program; d development of participant appropriate training methodology; e challenges in the design of a suitable formal evaluation; and f evolution of program response to naloxone. Conclusion Other naloxone distribution programs may anticipate similar challenges to SKOOP and we identify mechanisms to address them. Strategies include being flexible in

  20. Comparative efficacy of phenytoin, steroid and carbamazepine in herpes zoster and post herpetic neuralgia

    Directory of Open Access Journals (Sweden)

    Agarwal S

    1991-01-01

    Full Text Available Three hundred patients of different ages were sequentially assigned three therapy groups (100 in each group viz. phenytoin, steroid (prednisolone and carbamazepine. Effect of these drugs on herpes zoster neuralgia and in prevention of post herpetic neuralgia was studied. Phenytoin was found to be superior to both steroid and carbamazepine in relieving the pain of herpes zoster and in reducing the incidence of post herpetic neuralgia. Only 16.1% of the patients in phenytoin treated group developed post herpetic neuralgia lasting for 2-4 weeks while 22.7% and 29.6% of the steroid and carbamazepine treated patients respectively developed post herpetic neuralgia and that too lasting for longer duration. No patient under 40 years developed post herpetic neuralgia.

  1. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

    Directory of Open Access Journals (Sweden)

    Prasanna A. Datar

    2015-08-01

    Full Text Available Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application. Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quantitative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enumerates metabolites, and impurities reported so far. Keywords: Carbamazepine, HPLC, LC–MS/MS, HPTLC, RP-UFLC, Micellar electrokinetic chromatography

  2. Degradation of orange dyes and carbamazepine by soybean peroxidase immobilized on silica monoliths and titanium dioxide.

    Science.gov (United States)

    Calza, Paola; Zacchigna, Dario; Laurenti, Enzo

    2016-12-01

    In this paper, the removal of three common dyes (orange I, orange II, and methylorange) and of the anticonvulsant drug carbamazepine from aqueous solutions by means of enzymatic and photocatalytic treatment was studied. Soybean peroxidase (SBP) was used as biocatalyst, both free in solution and immobilized on silica monoliths, and titanium dioxide as photocatalyst. The combination of the two catalysts led to a faster (about two to four times) removal of all the orange dyes compared to the single systems. All the dyes were completely removed within 2 h, also in the presence of immobilized SBP. As for carbamazepine, photocatalytic treatment prevails on the enzymatic degradation, but the synergistic effect of two catalysts led to a more efficient degradation; carbamazepine's complete disappearance was achieved within 60 min with combined system, while up to 2 h is required with TiO 2 only.

  3. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  4. Atipamezole in the management of detomidine overdose in a pony.

    Science.gov (United States)

    Di Concetto, Stefano; Michael Archer, R; Sigurdsson, Sigurdur F; Clarke, Kw

    2007-01-01

    A pony undergoing elective castration accidentally received an overdose of IV detomidine (200 microg kg(-1)) before anaesthesia was induced with ketamine and midazolam. A further 100 microg kg(-1) IV dose of detomidine was administered during anaesthesia. The mistake was recognized only when the animal failed to recover from anaesthesia in the expected time. The overdose (300 microg kg(-1) in total) was treated successfully with atipamezole, initially given IV and subsequently IM and titrated to effect to a total dose of 1100 microg kg(-1). The pony regained the standing position. A further injection of atipamezole (76 microg kg(-1) IM) was given 5 hours later to counteract slight signs of re-sedation. Atipamezole proved an effective antagonist for detomidine in a pony at an initial dose 3.65 x and a final total dose 3.9 x greater than the alpha2 agonist.

  5. Rapid identification of drugs in the overdosed patient.

    Science.gov (United States)

    Hackett, L P; Dusci, L J

    1977-01-01

    A rapid analytical procedure is described for a variety of drugs that could be present in the overdosed patient. The technique used gives quantitative results for most of the drugs analyzed in serum using gas chromatography and incorporates thin-layer chromatography and spot tests for drug confirmation. The procedure is novel for it relies on the initial extraction of acidics, basics, and neutrals from serum acidified with hydroxhloric acid.

  6. Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose.

    Science.gov (United States)

    Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

    2018-01-01

    To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

  7. Escitalopram causes fewer seizures in human overdose than citalopram.

    Science.gov (United States)

    Yilmaz, Zeynep; Ceschi, Alessandro; Rauber-Lüthy, Christine; Sauer, Oliver; Stedtler, Uwe; Prasa, Dagmar; Seidel, Carola; Hackl, Elisabeth; Hoffmann-Walbeck, Petra; Gerber-Zupan, Gabriela; Bauer, Kathrin; Kupferschmidt, Hugo; Kullak-Ublick, Gerd-Achim; Wilks, Martin

    2010-03-01

    Seizures are a recognized complication of acute overdose with the racemic (1:1 ratio of R- and S-enantiomers) selective serotonin reuptake inhibitor antidepressant citalopram. We tested the hypothesis that escitalopram (the therapeutically active S-enantiomer of citalopram) causes fewer seizures in overdose than citalopram at comparable doses of the S-enantiomer. Multicenter retrospective review of cases with citalopram and escitalopram overdose reported to German, Austrian, and Swiss Poisons Centers between 1997 and 2006. 316 citalopram and 63 escitalopram cases were analyzed. Somnolence, nausea, vomiting, tachycardia, QT prolongation, and tremor occurred with similar frequency in both groups. There was a striking difference in the frequency of single and multiple seizures: 43 cases (13.5%) in the citalopram group and 1 case (1.6%) with a single seizure in the escitalopram group (p=0.0065). At comparable ingested doses of the S-enantiomer, the symptom profile for citalopram and escitalopram intoxications is similar except for seizures that occur more frequently in citalopram than in escitalopram poisoning.

  8. Sodium channel blockade with QRS widening after an escitalopram overdose.

    Science.gov (United States)

    Schreffler, Susan M; Marraffa, Jeanna M; Stork, Christine M; Mackey, Jennifer

    2013-09-01

    Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 μg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

  9. CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

    Directory of Open Access Journals (Sweden)

    Milovanovic Dragana Dragas

    2015-06-01

    Full Text Available Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08, indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26, higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47 and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79 of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

  10. Biomimetic oxidation of carbamazepine with hydrogen peroxide catalyzed by a manganese porphyrin

    Directory of Open Access Journals (Sweden)

    Cláudia M. B. Neves

    2012-01-01

    Full Text Available This laboratory project is planned for an undergraduate chemistry laboratory in which students prepare a manganese porphyrin able to mimic the oxidative metabolism of carbamazepine, one of the most frequently prescribed drugs in the treatment of epilepsy. The in vitro oxidation of carbamazepine results in the formation of the corresponding 10,11-epoxide, the main in vivo metabolite. The reaction is catalyzed by manganese porphyrin in the presence of H2O2, an environmentally-friendly oxidant. Through this project students will develop their skills in organic synthesis, coordination chemistry, chromatographic techniques such as TLC and HPLC, UV-visible spectrophotometry, and NMR spectroscopy.

  11. Biomimetic oxidation of carbamazepine with hydrogen peroxide catalyzed by a manganese porphyrin

    Energy Technology Data Exchange (ETDEWEB)

    Neves, Claudia M.B.; Simoes, Mario M.Q.; Domingues, Fernando M.J.; Neves, M. Graca P.M.S.; Cavaleiro, Jose A.S., E-mail: msimoes@ua.pt [Dept. de Quimica, QOPNA, Universidade de Aveiro (Portugal)

    2012-07-01

    This laboratory project is planned for an undergraduate chemistry laboratory in which students prepare a manganese porphyrin able to mimic the oxidative metabolism of carbamazepine, one of the most frequently prescribed drugs in the treatment of epilepsy. The in vitro oxidation of carbamazepine results in the formation of the corresponding 10,11-epoxide, the main in vivo metabolite. The reaction is catalyzed by manganese porphyrin in the presence of H{sub 2}O{sub 2}, an environmentally-friendly oxidant. Through this project students will develop their skills in organic synthesis, coordination chemistry, chromatographic techniques such as TLC and HPLC, UV-visible spectrophotometry, and NMR spectroscopy. (author)

  12. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    International Nuclear Information System (INIS)

    Lin, Ming-Chung; Chen, Chia-Ling; Yang, Tsan-Tzu; Choi, Pui-Ching; Hsing, Chung-Hsi; Lin, Chiou-Feng

    2012-01-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  13. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ming-Chung [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan (China); Chen, Chia-Ling [Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Yang, Tsan-Tzu; Choi, Pui-Ching [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan (China); Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin@mail.ncku.edu.tw [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China)

    2012-12-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  14. Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine.

    Science.gov (United States)

    Pirmohamed, M; Graham, A; Roberts, P; Smith, D; Chadwick, D; Breckenridge, A M; Park, B K

    1991-01-01

    1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1768568

  15. Prescription drug overdose: between patients and their doctors

    Directory of Open Access Journals (Sweden)

    Ling W

    2013-01-01

    Full Text Available Walter Ling,1 Li-Tzy Wu21Department of Psychiatry and Biobehavioral Science, Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA; 2Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USAPrescription drug overdoses, mainly involving prescription opioids, have reached epidemic proportions in the United States over the past 20 years.1,2 Since 2003, prescription opioids have been involved in more drug-related overdose deaths than heroin and cocaine combined. Among patients who were prescribed opioids, an estimated 20% were prescribed high doses of opioids by either single or multiple physicians, and these patients appeared to account for the majority of prescription opioid-related overdoses.1,3,4 The increase in prescription overdose deaths has coincided with a major increase in prescription opioid sales.2 The prescribing practices of some physicians are often believed to have contributed in part to the increase in these overdose deaths. In a recently published perspective, Anna Lembke speculated on why doctors prescribe opioids to known prescription opioid abusers.5 Her article raises a timely and troubling issue for all of us interested in this area of medicine. Lembke identifies the root of the problem to lie in the changing societal attitude towards pain and suffering, the ever-growing availability of opioid medications, the regulatory requirements promulgated, and the perceived shift in the role of the medical professional in this context. Central to her argument is that physicians must now practice according to a set of externally imposed expectations of patients, payers, and regulators, putting the prescriber in the position of being "damned if you do and damned if you don’t". If Lembke is right, the physician now prescribes not according to what he or she wants to do, but according to what he or she must do. The result, at one extreme, is the patient acting as their

  16. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Directory of Open Access Journals (Sweden)

    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  17. Fatal Metformin Overdose Presenting with Progressive Hyperglycemia

    Directory of Open Access Journals (Sweden)

    Suchard, Jeffrey R

    2008-08-01

    Full Text Available A 29-year-old man with no history of diabetes ingested over 60 grams of metformin in a suicide attempt. He presented to the emergency department with acute renal insufficiency, severe lactic acidosis, and rapidly-progressive hyperglycemia. The patient’s peak serum glucose level of 707 mg/dL is the highest yet reported in a case of metformin toxicity. Treatment included sodium bicarbonate infusion and hemodialysis, but the patient suffered several cardiac arrests with pulseless electrical activity and ultimately expired 25 hours after the ingestion.

  18. Focused use of drug screening in overdose patients increases impact on management.

    Science.gov (United States)

    Erdmann, Andreas; Werner, Dominique; Hugli, Olivier; Yersin, Bertrand

    2015-01-01

    Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first psychotic episode or cases demonstrating respiratory failure, coma, seizures, a sympathomimetic toxidrome, severe opiate overdose necessitating naloxone, hypotension, ventricular arrhythmia, acquired long QT or QRS >100 ms, and high-degree heart block. Retrospective analysis of Triage® TOX drug screen tests performed between September 2009 and November 2011, and between January 2013 and March 2014. A total of 262 patients were included, mean age 35 ± 14.6 (standard deviation) years, 63% men; 29% poisoning with alcohol, and 2.3% deaths. Indications for testing were as follows: 34% were first psychotic episodes; 20% had acute respiratory failure; 16% coma; 8% seizures; 8% sympathomimetic toxidromes; 7% severe opioid toxidromes; 4% hypotension; 3% ventricular arrhythmias or acquired long QT intervals on electrocardiogram. A total of 78% of the tests were positive (median two substances, maximum five). The test resulted in drug-specific therapy in 6.1%, drug specific diagnostic tests in 13.3 %, prolonged monitoring in 10.7% of methadone-positive tests, and psychiatric admission in 4.2%. Overall, 34.3% tests influenced patient management. In contrast to previous studies showing modest effects of toxicological testing, restricted use of rapid urinary drug testing increases the impact on management of suspected overdose patients in the ED.

  19. A retrospective study of carbamazepine therapy in the treatment of idiopathic generalised epilepsy

    LENUS (Irish Health Repository)

    O'Connor, G

    2011-05-01

    Objective: The exacerbation of idiopathic generalised epilepsy (IGE) by some anti-epileptic drugs (AEDs) such as carbamazepine (CBZ) has been well documented. However, it is unclear whether IGE is always worsened by the use of CBZ, or whether some patients with IGE benefit from its use. \\r\

  20. Relaxation and crystallization of amorphous carbamazepine studied by terahertz pulsed spectroscopy

    DEFF Research Database (Denmark)

    Zeitler, J Axel; Taday, Philip F; Pepper, Michael

    2007-01-01

    At the example of carbamazepine the crystallization of a small organic molecule from its amorphous phase was studied using in situ variable temperature terahertz pulsed spectroscopy (TPS). Even though terahertz spectra of disordered materials in the glassy state exhibit no distinct spectral featu...

  1. Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study

    Directory of Open Access Journals (Sweden)

    Thaiana Aragão Santana

    Full Text Available CONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV.DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life.RESULTS:None of the ten patients (0% presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life.CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population.

  2. Visualizing solvent mediated phase transformation behavior of carbamazepine polymorphs by principal component analysis

    DEFF Research Database (Denmark)

    Tian, Fang; Rades, Thomas; Sandler, Niklas

    2008-01-01

    The purpose of this research is to gain a greater insight into the hydrate formation processes of different carbamazepine (CBZ) anhydrate forms in aqueous suspension, where principal component analysis (PCA) was applied for data analysis. The capability of PCA to visualize and to reveal simplified...

  3. Intrauterine exposure to carbamazepine and specific congenital malformations : systematic review and case-control study

    NARCIS (Netherlands)

    Jentink, Janneke; Dolk, Helen; Loane, Maria A.; Morris, Joan K.; Wellesley, Diana; Garne, Ester; de Jong-van den Berg, Lolkje

    2010-01-01

    Objective To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. Design A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. Setting Review of

  4. Effect of pomegranate juice pre-treatment on the transport of carbamazepine across rat intestine

    Directory of Open Access Journals (Sweden)

    D Adukondalu

    2010-12-01

    Full Text Available "n  "nBackground and the purpose of the study: Many drug substances along with a variety of naturally occurring dietary or herbal components interact with the CYP enzyme system.The present study was aimed to investigate the effect of pomegranate juice pre-treatment on the transport of carbamazepine across the rat intestine "nMethods: The transport of carbamazepine across different parts of rat intestine was studied by everted and non-everted sac methods. The control and pomegranate juice (10 ml Kg-1 for 7 days pre-treated rats were sacrificed and isolated the intestine. The sacs of intestine were prepared, treated with carbamazepine solution and then placed in dulbeccos buffer. Samples were collected periodically and the drug content was estimated using HPLC. Results and conclusion: The results show that there was a significant (p<0.05 difference in the transport of carbamazepine from the intestinal sacs of pretreated with pomegranate juice and control. It seems that pomegranatejuice might have induced CYP3A4enzymes and hence drug is extensively metabolized.

  5. Transformation products and reaction pathways of carbamazepine during photocatalytic and sonophotocatalytic treatment

    International Nuclear Information System (INIS)

    Jelic, A.; Michael, I.; Achilleos, A.; Hapeshi, E.; Lambropoulou, D.; Perez, S.; Petrovic, M.; Fatta-Kassinos, D.; Barcelo, D.

    2013-01-01

    Highlights: • Degradation of CBZ during US, TiO 2 /UV and TiO 2 /UV/US processes has been evaluated. • The combined TiO 2 /UV/US oxidation resulted in significant enhancement of the CBZ degradation rate. • Transformation products were identified and the transformation pathways were proposed. • An acute toxicity test showed an increase in toxicity over the time-course of the studied processes. -- Abstract: This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO 2 -based heterogeneous photocatalysis under UV-A and simulated solar irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e. sonophotocatalysis) in demineralized water, ground water and effluent wastewater. The processes were compared with respect to substrate conversion rate and the extent of DOC reduction as a measure of mineralization. CBZ was degraded following a pseudo-first order kinetics. Sonophotocatalysis provided the highest rate of CBZ transformation over the time-course of the experiment while the degree of DOC removal in pure water was similar for all the studied treatments (around 40%), and always lower than CBZ conversion. This indicated that a considerable organic load remained in the treated solutions that could also be attributed to the presence of persistent oxidation products. UPLC–(+ESI)-QToF-MS was employed to determine major CBZ-related transformation products. Several recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A Daphnia magna bioassay was used to evaluate the potential toxicity of the samples collected at different time points showing that the mixtures were highly toxic to D. magna

  6. Transformation products and reaction pathways of carbamazepine during photocatalytic and sonophotocatalytic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jelic, A. [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Michael, I.; Achilleos, A.; Hapeshi, E. [Department of Civil and Environmental Engineering, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Nireas, International Water Research Centre, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Lambropoulou, D. [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Perez, S., E-mail: spsqam@idaea.csic.es [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Petrovic, M. [Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona (Spain); Fatta-Kassinos, D. [Department of Civil and Environmental Engineering, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Nireas, International Water Research Centre, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Barcelo, D. [Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona (Spain)

    2013-12-15

    Highlights: • Degradation of CBZ during US, TiO{sub 2}/UV and TiO{sub 2}/UV/US processes has been evaluated. • The combined TiO{sub 2}/UV/US oxidation resulted in significant enhancement of the CBZ degradation rate. • Transformation products were identified and the transformation pathways were proposed. • An acute toxicity test showed an increase in toxicity over the time-course of the studied processes. -- Abstract: This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO{sub 2}-based heterogeneous photocatalysis under UV-A and simulated solar irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e. sonophotocatalysis) in demineralized water, ground water and effluent wastewater. The processes were compared with respect to substrate conversion rate and the extent of DOC reduction as a measure of mineralization. CBZ was degraded following a pseudo-first order kinetics. Sonophotocatalysis provided the highest rate of CBZ transformation over the time-course of the experiment while the degree of DOC removal in pure water was similar for all the studied treatments (around 40%), and always lower than CBZ conversion. This indicated that a considerable organic load remained in the treated solutions that could also be attributed to the presence of persistent oxidation products. UPLC–(+ESI)-QToF-MS was employed to determine major CBZ-related transformation products. Several recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A Daphnia magna bioassay was used to evaluate the potential toxicity of the samples collected at different time points showing that the mixtures were highly toxic to D. magna.

  7. Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Hadjira Rabti

    2014-06-01

    Full Text Available Elementary osmotic pump (EOP is a unique extended release (ER drug delivery system based on the principle of osmosis. It has the ability to minimize the amount of the drug, accumulation and fluctuation in drug level during chronic uses. Carbamazepine (CBZ, a poorly water-soluble antiepileptic drug, has serious side effects on overdoses and chronic uses. The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance. Firstly, a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug. Then, designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance (ANOVA, respectively. The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone (PVP K30 and sodium lauryl sulfate (SLS. The plasticizer amount and molecular weight (MW together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane (SPM thickness inversely influence the release rate. In addition, the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core. Further, orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm. In this study we report the successful formulation of CBZ-EOP tablets, which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80% of CBZ at a rate of approximately zero order for up to 12 h.

  8. Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality

    Directory of Open Access Journals (Sweden)

    Maryam Akhgari

    2017-06-01

    Full Text Available Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

  9. Intoxication after Extreme Oral Overdose of Quetiapine to Attempt Suicide: Pharmacological Concerns of Side Effects

    Directory of Open Access Journals (Sweden)

    C. Müller

    2009-01-01

    Full Text Available Quetiapine is an atypical antipsychotic approved for the treatment of patients with psychotic disorders. Since approvement several case reports about intoxication with quetiapine were linked mainly with tachycardia, QTc-prolongation, somnolence, and hyperglycemia. Here, we present the first case report of an intoxication with an extreme overdose of quetiapine (36 g, ingested by a 32-year-old female (62 kg bodyweight to attempt suicide. Symptoms associated with intoxication were coma without arterial hypotension, persistent tachycardia, hyperglycemia, and transient hypothyreoidism. QTc-interval was moderately extended. Management consisted of intubation for airway protection, gastric lavage, the use of activated charcoal, i.v. saline, and observation for 17 hours on an intensive care unit. Despite the extremely high dose of quetiapine, the patient recovered completely without residual symptoms.

  10. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

    Energy Technology Data Exchange (ETDEWEB)

    Kaushik, Gaurav, E-mail: kausgaur@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Department of Medical Pathology and Laboratory Medicine, University of California at Davis, Davis, CA 95817 (United States); Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817 (United States); Huber, David P., E-mail: hubedavi@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Aho, Ken, E-mail: ahoken@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Finney, Bruce, E-mail: finney@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Bearden, Shawn, E-mail: bearshaw@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Zarbalis, Konstantinos S., E-mail: kzarbalis@ucdavis.edu [Department of Medical Pathology and Laboratory Medicine, University of California at Davis, Davis, CA 95817 (United States); Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817 (United States); Thomas, Michael A., E-mail: mthomas@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States)

    2016-05-27

    Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding {sup 2}H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post–conception days), and quantifying {sup 2}H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of {sup 2}H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at

  11. Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2009-01-01

    Full Text Available Background/Aim. Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Methods. Separation of the drug from matrix is achieved by reversedphase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1 at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10 using chlorophorm. Results. Calibration curves were in the range 0.1-5 μg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD of carbamazepine in serum and saliva were 0.166 and 0.178 μg/mL, respectively. Limits of quantification (LOQ in the serum and saliva were 0.237 and 0.226 μg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001. Conclusion. The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

  12. Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection.

    Science.gov (United States)

    Dordević, Snezana; Kilibarda, Vesna; Stojanović, Tomislav

    2009-05-01

    Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Separation of the drug from matrix is achieved by reversed-phase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1) at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10) using chlorophorm. Calibration curves were in the range 0.1-5 microg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD) of carbamazepine in serum and saliva were 0.166 and 0.178 microg/mL, respectively. Limits of quantification (LOQ) in the serum and saliva were 0.237 and 0.226 microg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001). The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

  13. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

    International Nuclear Information System (INIS)

    Kaushik, Gaurav; Huber, David P.; Aho, Ken; Finney, Bruce; Bearden, Shawn; Zarbalis, Konstantinos S.; Thomas, Michael A.

    2016-01-01

    Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding "2H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post–conception days), and quantifying "2H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of "2H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at typical

  14. Marked EEG worsening following Levetiracetam overdose: How a pharmacological issue can confound coma prognosis.

    Science.gov (United States)

    Bouchier, Baptiste; Demarquay, Geneviève; Guérin, Claude; André-Obadia, Nathalie; Gobert, Florent

    2017-01-01

    Levetiracetam is an anti-epileptic drug commonly used in intensive care when seizure is suspected as a possible cause of coma. We propose to question the cofounding effect of Levetiracetam during the prognostication process in a case of anoxic coma. We report the story of a young woman presenting a comatose state following a hypoxic cardiac arrest. After a first EEG presenting an intermediate EEG pattern, a seizure suspicion led to prescribe Levetiracetam. The EEG showed then the appearance of burst suppression, which was compatible with a very severe pattern of post-anoxic coma. This aggravation was in fact related to an overdose of Levetiracetam (the only medication introduced recently) and was reversible after Levetiracetam cessation. The increased plasmatic dosages of Levetiracetam confirming this overdose could have been favoured by a moderate reduction of renal clearance, previously underestimated because of a low body-weight. This EEG dynamic was unexpected under Levetiracetam and could sign a functional instability after anoxia. Burst suppression is classically observed with high doses of anaesthetics, but is not expected after a minor anti-epileptic drug. This report proposes that Levetiracetam tolerance might not be straightforward after brain lesions and engages us to avoid confounding factors during the awakening prognostication, which is mainly based on the severity of the EEG. Hence, prognosis should not be decided on an isolated parameter, especially if the dynamic is atypical after a new prescription, even for well-known drugs. For any suspicion, the drug's dosage and replacement should be managed before any premature care's withdrawal. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Overdosed prescription of paracetamol (acetaminophen) in a teaching hospital.

    Science.gov (United States)

    Charpiat, B; Henry, A; Leboucher, G; Tod, M; Allenet, B

    2012-07-01

    Paracetamol is the most commonly used analgesic and antipyretic. Reviews of hospital use of paracetamol are scarce. Little is known about the appropriateness of the dose of paracetamol prescribed for hospitalized adults. The aim of this study was to report on the nature and the frequency of the overdosed prescription of paracetamol observed in adult patients over a 4.5-year period in a teaching hospital. Prescription analysis by pharmacists was performed once a week in six medical and three surgical departments and daily in a post-emergency unit. In cases of prescription error, the pharmacist notified the physician through an electronic alert when a computerized prescription order entry system was available or otherwise by face-to-face discussion. For each drug-related problem detected, the pharmacists recorded relevant details in a database. From October 2006 to April 2011, 44,404 prescriptions were reviewed and 480 alerts related to the overdosed prescription of paracetamol were made (1% of analyzed prescriptions). The extent of errors of dosage was within the intervals [90-120 mg/kg/d] and greater than 120 mg/kg/d for 87 and 11 patients respectively, who were prescribed a single non-combination paracetamol containing product. Sixty alerts concerned co-prescription of at least two paracetamol containing products with similar frequency for computerized (1.4/1000) or handwritten (1.2/1000) prescriptions. Prescriptions of paracetamol for hospitalized adults frequently exceed the recommended dosage. These results highlight the need for increased awareness of unintentional paracetamol overdose and support the initiation of an educational program aimed at physicians and nurses. Copyright © 2012. Published by Elsevier Masson SAS.

  16. A Nomogram to predict parotid gland overdose in head and neck IMRT

    International Nuclear Information System (INIS)

    Castelli, J.; Simon, A.; Rigaud, B.; Lafond, C.; Chajon, E.; Ospina, J. D.; Haigron, P.; Laguerre, B.; Loubière, A. Ruffier; Benezery, K.; Crevoisier, R. de

    2016-01-01

    To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning

  17. Liver transplant associated with paracetamol overdose: Results from the seven-country SALT study

    NARCIS (Netherlands)

    S.E. Gulmez (Sinem Ezgi); D. Larrey (Dominique); G.P. Pageaux; J. Bernuau (Jacques); F. Bissoli (Franco); Y. Horsmans (Yves); D. Thorburn (Douglas); P.A. McCormick (P. Aiden); B.H.Ch. Stricker (Bruno); M. Toussi (Massoud); S. Lignot-Maleyran (Séverine); S. Micon (Sophie); F. Hamoud (Fatima); R. Lassalle (Régis); J. Jové (Jérémy); P. Blin (Patrick); N. Moore (Nicholas)

    2015-01-01

    textabstractAims Acute drug overdose, especially with paracetamol, may cause acute liver failure leading to registration for transplantation (ALFT). Population statistics and between-country differences for ALFT related to overdose have been poorly described. The aim of the present study was to

  18. CDC Vital Signs–Opioid Overdoses Treated in Emergency Departments

    Centers for Disease Control (CDC) Podcasts

    2018-03-06

    This podcast is based on the March 2018 CDC Vital Signs report. Opioid overdoses continue to increase in the United States. Learn what can be done to help prevent opioid overdose and death.  Created: 3/6/2018 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/6/2018.

  19. Tramadol Overdose Induced Transient Paresthesia and Decreased Muscle Strength: A Case Series

    Directory of Open Access Journals (Sweden)

    Khosrow Ghasempouri

    2014-06-01

    Conclusion: Transient paresthesia and transient symmetrical decline in muscle strength of upper and lower limbs are potential neurologic complications following tramadol abuse and overdose. Further studies are needed to fully clarify the pathogenesis and mechanism of these complications following tramadol overdose.

  20. Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme

    DEFF Research Database (Denmark)

    Tjagvad, C.; Skurtveit, Svetlana; Linnet, K.

    2016-01-01

    methadone-related overdose deaths in a liberal OMT programme. Methods: Drug-overdose deaths (n = 130) with detection of methadone in Copenhagen, Aarhus, and Odense Municipality, Denmark, during the period 2008-2011 were identified from a registry. Cases with and without prescribed methadone as OMT were...

  1. Lack of respiratory depression in paracetamol-codeine combination overdoses.

    Science.gov (United States)

    Heppell, Simon P E; Isbister, Geoffrey K

    2017-06-01

    Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone. We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression. From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR]: 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score depression, with only two given naloxone and none intubated for

  2. Overdose effect of aconite containing Ayurvedic Medicine ('Mahashankha Vati').

    Science.gov (United States)

    Panda, Ashok Kumar; Debnath, Saroj Kumar

    2010-07-01

    There are chances that the use of larger than recommended dose of Ayurvedic medicines containing aconite can produce drug reactions. Vatsanabha (Aconitum ferox Wall.) is a very well-known ingredient of Ayurvedic formulations and is prescribed as an antipyretic, analgesic, anti-rheumatic, appetizer and digestive. The recommended dose of purified Vatsanabha (A. ferox Wall.) root is 15 mg. We present a case of hypotension and bradycardia due to aconite poisoning caused by overdosing of an Ayurvedic medicine (Mahashankha Vati), which was primarily managed by Ayurvedic treatment.

  3. Prescription Painkiller Overdoses in the U.S. – What You Need to Know PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second PSA is based on the November, 2011 CDC Vital Signs report. Overdose deaths from prescription painkillers have skyrocketed in the past decade. Every year, nearly 15,000 people die from these overdoses—more than those who die from heroin and cocaine combined. Learn the steps you can take to prevent an overdose.

  4. Prescription Painkiller Overdoses in the U.S. – What You Need to Know

    Centers for Disease Control (CDC) Podcasts

    This podcast is based on the November, 2011 CDC Vital Signs report. Overdose deaths from prescription painkillers have skyrocketed in the past decade. Every year, nearly 15,000 people die from these overdoses—more than those who die from heroin and cocaine combined. Learn the steps you can take to prevent an overdose.

  5. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk

    DEFF Research Database (Denmark)

    Borg, Linda; Julkunen, Anna; Madsen, Kristian Rørbaek

    2016-01-01

    It is often advised that patients who have ingested an overdose of antidepressants (AD) or antipsychotics (AP) are monitored with continuous ECG for minimum of 12-24 hr. These patients are often observed in an ICU. Our aim was to identify the number of patients with AD and/or AP overdose without...... adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need...... intensive care treatment. This retrospective study was conducted in adult patients admitted to the ICU at Odense University Hospital after an overdose with AP and/or AD between 1 January 2009 and 1 September 2014. Patients with predefined adverse signs in the emergency department were excluded due...

  6. An Initial evaluation of law enforcement overdose training in Rhode Island.

    Science.gov (United States)

    Saucier, Cory D; Zaller, Nickolas; Macmadu, Alexandria; Green, Traci C

    2016-05-01

    To assess initial change in knowledge, self-efficacy, and anticipated behaviors among Rhode Island law enforcement officers on drug overdose response and prevention. Law enforcement officers (N=316) voluntarily completed a pre-post evaluation immediately before and after taking part in overdose prevention and response trainings. Assessment items included measures of knowledge (Brief Overdose Recognition and Response Assessment (BORRA)), self-efficacy, attitudes toward drugs and overdose prevention, awareness of the Good Samaritan Law, and open-ended items pertaining to overdose knowledge and response behaviors. Non-parametric tests measured within-group and between-group differences. Wilcoxon Signed Rank tests and Kruskal-Wallis tests evaluated changes in BORRA scores and self-efficacy items. McNemar's tests assessed changes regarding the Good Samaritan law and open-ended items. Wilcoxon Signed Rank tests measured post-training change in attitudes. Law enforcement officers demonstrated statistically significant improvements in self-efficacy (identifying signs of opioid overdose, naloxone indication, counseling witnesses in overdose prevention, and referring witnesses for more information), overdose identification knowledge (BORRA mean increased from 7.00 to 10.39), naloxone administration knowledge (BORRA mean increased from 10.15 to 12.59), Good Samaritan Law awareness (17.9% increase after training), and anticipated behaviors in response to future observed overdose (65.7% changed from passive to active response post training). Harm reduction programs can provide law enforcement officers with the knowledge and skills necessary to intervene and reduce overdose mortality. Given the statistically significant improvements in self-efficacy, attitudinal changes, and Good Samaritan law awareness, law enforcement officers are more prepared to actively interact with drug users during a drug-involved emergency. Copyright © 2016. Published by Elsevier Ireland Ltd.

  7. Neighborhood-Level and Spatial Characteristics Associated with Lay Naloxone Reversal Events and Opioid Overdose Deaths.

    Science.gov (United States)

    Rowe, Christopher; Santos, Glenn-Milo; Vittinghoff, Eric; Wheeler, Eliza; Davidson, Peter; Coffin, Philip O

    2016-02-01

    There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid-related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. We determined the locations of lay naloxone distribution sites and the number of unintentional opioid overdose deaths and reported reversal events in San Francisco census tracts (n = 195) from 2010 to 2012. We used Wilcoxon rank-sum tests to compare census tract characteristics across tracts adjacent and not adjacent to distribution sites and multivariable negative binomial regression models to assess the association between census tract characteristics, including distance to the nearest site, and counts of opioid overdose deaths and naloxone reversal events. Three hundred forty-two opioid overdose deaths and 316 overdose reversals with valid location data were included in our analysis. Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those immediate areas but suggests that alternative delivery methods may be necessary to reach individuals in other areas with less concentrated risk.

  8. Comparison of Effects and Side Effects of Two Naloxone-Based Regimens in Treatment of Methadone Overdose

    Directory of Open Access Journals (Sweden)

    Arash Yazdanbakhsh

    2015-11-01

    Full Text Available Background: Acute opioid overdose is a common cause of admission in emergency department. In spite of the fact that naloxone is the main therapy for decades, there are controversies about the proper way of its use. This study aimed to compare two most recommended administration modes for naloxone. Methods: In this single-blind clinical trial, 80 patients with methadone overdose syndrome were randomly divided into two equal groups. The patients in infusion group received a constant infusion of naloxone preparation; while in the patients in PRN group, naloxone was administered only if needed clinically. Severity of withdrawal syndrome was evaluated after 30 min, 3 h, and 12 h of the treatments in both groups. Results: Eighty patients completed the study (10 women and 70 men. Both groups were similar in terms of mean age, sex ratio, and the severity of intoxication. The severity of withdrawal symptom was significantly lower in the PRN group (P<0.001. Conclusion: Naloxone administration as PRN mode lowers the rate and severity of withdrawal syndrome. It is recommended as the preferred mode of naloxone administration.

  9. Acetaminophen overdose associated with double serum concentration peaks

    Directory of Open Access Journals (Sweden)

    Cristian Papazoglu

    2015-12-01

    Full Text Available Acetaminophen is the most commonly used analgesic–antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy.

  10. Bupropion Overdose Presenting as Status Epilepticus in an Infant.

    Science.gov (United States)

    Rivas-Coppola, Marianna S; Patterson, Amy L; Morgan, Robin; Wheless, James W

    2015-09-01

    Bupropion is a monocyclic antidepressant in the aminoketone class, structurally related to amphetamines. The Food and Drug Administration withdrew this product from the market in 1986 after seizures were reported in bulimic patients. It was later reintroduced in 1989 when the incidence of seizures was shown to be dose-related in the immediate release preparation. Massive bupropion ingestion has been associated with status epilepticus and cardiogenic shock in adults. Seizures have been reported in children, but not status epilepticus. This report highlights a patient who presented with status epilepticus and developed cardiopulmonary arrest after bupropion ingestion. False-positive amphetamine diagnosis from urine drug screen on presentation was reported. We review the presentation, clinical course, diagnostic studies, and outcome of this patient. We then review the literature regarding bupropion overdose in children. Symptoms of bupropion toxicity and risk for seizures are dose-dependent and fatalities have been reported. Our patient developed status epilepticus and cardiopulmonary arrest and then progressed to have a hypoxic ischemic encephalopathy and refractory symptomatic partial seizures. Our report highlights the need to keep this medication away from children in order to prevent accidental overdose. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Performance Measures of Diagnostic Codes for Detecting Opioid Overdose in the Emergency Department.

    Science.gov (United States)

    Rowe, Christopher; Vittinghoff, Eric; Santos, Glenn-Milo; Behar, Emily; Turner, Caitlin; Coffin, Phillip O

    2017-04-01

    Opioid overdose mortality has tripled in the United States since 2000 and opioids are responsible for more than half of all drug overdose deaths, which reached an all-time high in 2014. Opioid overdoses resulting in death, however, represent only a small fraction of all opioid overdose events and efforts to improve surveillance of this public health problem should include tracking nonfatal overdose events. International Classification of Disease (ICD) diagnosis codes, increasingly used for the surveillance of nonfatal drug overdose events, have not been rigorously assessed for validity in capturing overdose events. The present study aimed to validate the use of ICD, 9th revision, Clinical Modification (ICD-9-CM) codes in identifying opioid overdose events in the emergency department (ED) by examining multiple performance measures, including sensitivity and specificity. Data on ED visits from January 1, 2012, to December 31, 2014, including clinical determination of whether the visit constituted an opioid overdose event, were abstracted from electronic medical records for patients prescribed long-term opioids for pain from any of six safety net primary care clinics in San Francisco, California. Combinations of ICD-9-CM codes were validated in the detection of overdose events as determined by medical chart review. Both sensitivity and specificity of different combinations of ICD-9-CM codes were calculated. Unadjusted logistic regression models with robust standard errors and accounting for clustering by patient were used to explore whether overdose ED visits with certain characteristics were more or less likely to be assigned an opioid poisoning ICD-9-CM code by the documenting physician. Forty-four (1.4%) of 3,203 ED visits among 804 patients were determined to be opioid overdose events. Opioid-poisoning ICD-9-CM codes (E850.2-E850.2, 965.00-965.09) identified overdose ED visits with a sensitivity of 25.0% (95% confidence interval [CI] = 13.6% to 37.8%) and

  12. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine

    International Nuclear Information System (INIS)

    Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

    2011-01-01

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  13. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Werickson Fortunato de Carvalho [Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); National Institute of Metrology, Standardization and Industrial Quality, Inmetro, Dimci/Dquim - Directorate of Metrology, Science and Industry/Division of Chemical Metrology, Av. Nossa Senhora das Gracas 50, Building 6, 25250-020, Xerem, Duque de Caxias, RJ (Brazil); Poppi, Ronei Jesus, E-mail: ronei@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); National Institute of Science and Technology (INCT) for Bioanalytics, 13083-970 Campinas, SP (Brazil)

    2011-10-31

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  14. Effect of carbamazepine (Tegretol) on seizure and EEG patterns in monkeys with alumina-induced focal motor and hippocampal foci.

    Science.gov (United States)

    David, J; Grewal, R S

    1976-12-01

    Qualitative and quantitative aspects of chronic carbamazepine (Tegretol) medication on focal seizures and associated interictal EEG abnormalities in Rhesus monkeys with alumina-induced foci in either the sensorimotor cortex or the hipocampus was investigated. In both groups of animals, carbamazepine produced qualitative control of visible seizures and reduced intracortical spike propagation, but did not cause complete normalization of the background EEG; quantitative indices, such as spike density and amount of paroxysmal discharge representative of abnormal EEG activity, were significantly reduced with respect to predrug values during medication and after cessation as well. Threshold to pentylenetetrazol was elevated by carbamazepine in both groups of epileptic monkeys. Aggressivity and other clinical manifestations in monekys with hippocampal foci were markedly reduced by carbamazepine.

  15. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

    Science.gov (United States)

    Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2008-01-01

    The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

  16. Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

    Science.gov (United States)

    Dahlem, Chin Hwa Y; Horstman, Molly J; Williams, Brent C

    2016-01-01

    To describe the development, implementation, and preliminary evaluation of Opioid Overdose Response Protocol using intranasal (IN) naloxone in a homeless shelter. Opioid Overdose Response Protocol and training curriculum were developed using the Massachusetts Department of Public Health Opioid Overdose Education and Naloxone Distribution (OEND) flow chart, the American Heart Association (AHA) simplified adult basic life support algorithm, and resources through Harms Reduction Coalition. Intranasal naloxone offers a safe and effective method for opioid reversal. To combat the rising incidence of opioid overdose, IN naloxone should be made available at homeless shelters and other facilities with high frequency of opioid overdose, including the training of appropriate staff. This project has demonstrated the effective training and implementation of an Opioid Overdose Response Protocol, based on feedback received from cardiopulmonary resuscitation (CPR) trained nonhealthcare staff. Nurse practitioners (NPs), with our focus on patient care, prevention, and education, are well suited to the deployment of this life-saving protocol. NPs are in critical positions to integrate opioid overdose prevention education and provide naloxone rescue kits in clinical practices. ©2015 American Association of Nurse Practitioners.

  17. A PLS-based extractive spectrophotometric method for simultaneous determination of carbamazepine and carbamazepine-10,11-epoxide in plasma and comparison with HPLC

    Science.gov (United States)

    Hemmateenejad, Bahram; Rezaei, Zahra; Khabnadideh, Soghra; Saffari, Maryam

    2007-11-01

    Carbamazepine (CBZ) undergoes enzyme biotransformation through epoxidation with the formation of its metabolite, carbamazepine-10,11-epoxide (CBZE). A simple chemometrics-assisted spectrophotometric method has been proposed for simultaneous determination of CBZ and CBZE in plasma. A liquid extraction procedure was operated to separate the analytes from plasma, and the UV absorbance spectra of the resultant solutions were subjected to partial least squares (PLS) regression. The optimum number of PLS latent variables was selected according to the PRESS values of leave-one-out cross-validation. A HPLC method was also employed for comparison. The respective mean recoveries for analysis of CBZ and CBZE in synthetic mixtures were 102.57 (±0.25)% and 103.00 (±0.09)% for PLS and 99.40 (±0.15)% and 102.20 (±0.02)%. The concentrations of CBZ and CBZE were also determined in five patients using the PLS and HPLC methods. The results showed that the data obtained by PLS were comparable with those obtained by HPLC method.

  18. Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine epoxide in human plasma by high-performance liquid chromatography with ultraviolet detection.

    Science.gov (United States)

    Bhatti, M M; Hanson, G D; Schultz, L

    1998-03-01

    The Bioanalytical Chemistry Department at the Madison facility of Covance Laboratories, has developed and validated a simple and sensitive method for the simultaneous determination of phenytoin (PHT), carbamazepine (CBZ) and 10,11-carbamazepine epoxide (CBZ-E) in human plasma by high-performance liquid chromatography with 10,11 dihydrocarbamazepine as the internal standard. Acetonitrile was added to plasma samples containing PHT, CBZ and CBZ-E to precipitate the plasma proteins. After centrifugation, the acetonitrile supernatant was transferred to a clean tube and evaporated under N2. The dried sample extract was reconstituted in 0.4 ml of mobile phase and injected for analysis by high-performance liquid chromatography. Separation was achieved on a Spherisorb ODS2 analytical column with a mobile phase of 18:18:70 acetonitrile:methanol:potassium phosphate buffer. Detection was at 210 nm using an ultraviolet detector. The mean retention times of CBZ-E, PHT and CBZ were 5.8, 9.9 and 11.8 min, respectively. Peak height ratios were fit to a least squares linear regression algorithm with a 1/(concentration)2 weighting. The method produces acceptable linearity, precision and accuracy to a minimum concentration of 0.050 micrograms ml-1 in human plasma. It is also simple and convenient, with no observable matrix interferences.

  19. Fatal Toxic Epidermal Necrolysis Induced by Carbamazepine Treatment in a Patient Who Previously had Carbamazepine-induced Stevens-Johnson Syndrome

    Directory of Open Access Journals (Sweden)

    Li-Yen Huang

    2007-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a rare but life-threatening skin disease that is most commonly drug-induced. It has recently been suggested that Stevens-Johnson syndrome (SJS belongs to the same group of skin disorders, although it has a lower mortality rate than TEN. We report the case of a 26-year-old male schizophrenic patient with a history of carbamazepine-induced SJS 5 years earlier. At the time of his current admission, he was admitted to our psychiatry department with acute agitation due to schizophrenia. However, the patient and his family denied history of drug allergy. After 3 days of carbamazepine treatment, the patient developed TEN (body surface area > 90%. He was transferred to the burn center, but despite appropriate treatment, including intravenous hydrocortisone 200 mg q6h and being covered with sterile biological material, he died. It is important to note that re-administration of a drug that previously caused SJS may lead to TEN, which has a very high mortality rate.

  20. Monitoring of carbamazepine concentrations in wastewater and groundwater to quantify sewer leakage.

    Science.gov (United States)

    Fenz, R; Blaschke, A P; Clara, M; Kroiss, H; Mascher, D; Zessner, M

    2005-01-01

    Monitoring of carbamazepine concentrations in wastewater and groundwater enables us to identify and quantify sewer exfiltration. The antiepileptic drug carbamazepine is hardly removed in wastewater treatment plants and not or just slightly attenuated during bank infiltration and subsoil flow. Concentrations in wastewater are generally 1000 times higher than the limit of quantification. In contrast to . many other wastewater tracers carbamazepine is discharged to the environment only via domestic wastewater. The results from this study carried out in Linz, Austria indicate an average exfiltration rate of 1%, expressed as percentage of the dry weather flow that is lost to the groundwater on the city-wide scale. This rate is lower than sewage losses reported in most other studies which attempted to quantify exfiltration on the basis of groundwater pollution. However, it was also possible to identify one area with significantly higher sewage losses. This method seems to be very suitable for the verification of leakage models used to assess sewer exfiltration on a regional scale.

  1. Amorphous is not always better—A dissolution study on solid state forms of carbamazepine

    DEFF Research Database (Denmark)

    Jensen, Linda G.; Skautrup, Frederik B.; Müllertz, Anette

    2017-01-01

    state forms of carbamazepine, crystalline or amorphous drug, with or without either polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) and glass solutions of the drug with both polymers (2:1, 4:1 and 10:1 (w/w) drug-to-polymer ratio) were tested with respect to their dissolution behaviour...... in a biorelevant gastric medium (for 30 min) and subsequently in intestinal conditions (for 2 h). Carbamazepine form III in the absence of polymer dissolved to a drug concentration of 540 μg/ml, but the concentration decreased after around 70 min due to precipitation of the dihydrate form, and reached 436 μg....../ml after 2.5 h dissolution testing. The presence of PVP led to a similar dissolution profile with a slightly earlier onset of decrease in drug concentration, while in the presence of HPMC no decline in dissolved drug concentration was observed. Surprisingly, amorphous carbamazepine did not result in any...

  2. Mass balance analysis of triclosan, diethyltoluamide, crotamiton and carbamazepine in sewage treatment plants.

    Science.gov (United States)

    Nakada, N; Yasojima, M; Okayasu, Y; Komori, K; Suzuki, Y

    2010-01-01

    The behavior of antibacterial triclosan, insect-repellent diethyltoluamide (DEET), anticonvulsant carbamazepine, and antipruritic crotamiton was investigated at two sewage treatment plants (STPs) to clarify their complete mass balance. Twenty-four-hour flow-proportional composite samples were collected from the influent and effluent of primary and final sedimentation tanks, a biofiltration tank and disinfection tanks. Sludge samples (i.e., activated and excess sludge) and samples of the return flow from the sludge treatment process were collected in the same manner. The analytes in both the dissolved and particulate phases were individually determined by a gas chromatograph equipped with mass spectrometer. Triclosan was dominantly detected in the particulate phase especially in the early stage of treatment (up to 83%) and was efficiently removed (over 90%) in STPs, mainly by sorption to sewage sludge. Limited removal was observed for DEET (55+/-24%), while no significant removal was demonstrated for crotamiton or carbamazepine. The solid-water distribution coefficients (K(d), n=4) for triclosan (log K(d): 3.7-5.1), DEET (1.3-1.9) and crotamiton (1.1-1.6) in the sludge samples are also determined in this study. These findings indicate the limitations of current sewage treatment techniques for the removal of these water-soluble drugs (i.e. DEET, carbamazepine, and crotamiton).

  3. Hospitalizations for Suicide-Related Drug Poisonings and Co-Occurring Alcohol Overdoses in Adolescents (Ages 12-17) and Young Adults (Ages 18-24) in the United States, 1999-2008: Results from the Nationwide Inpatient Sample

    Science.gov (United States)

    White, Aaron M.; MacInnes, Erin; Hingson, Ralph W.; Pan, I-Jen

    2013-01-01

    Drug poisoning is the leading method of suicide-related deaths among females and third among males in the United States. Alcohol can increase the severity of drug poisonings, yet the prevalence of alcohol overdoses in suicide-related drug poisonings (SRDP) remains unclear. Data from the Nationwide Inpatient Sample was examined to determine rates…

  4. Occurrence and fate of the angiotensin II receptor antagonist transformation product valsartan acid in the water cycle--a comparative study with selected β-blockers and the persistent anthropogenic wastewater indicators carbamazepine and acesulfame.

    Science.gov (United States)

    Nödler, Karsten; Hillebrand, Olav; Idzik, Krzysztof; Strathmann, Martin; Schiperski, Ferry; Zirlewagen, Johannes; Licha, Tobias

    2013-11-01

    The substantial transformation of the angiotensin II receptor antagonist valsartan to the transformation product 2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-carboxylic acid (referred to as valsartan acid) during the activated sludge process was demonstrated in the literature and confirmed in the here presented study. However, there was a severe lack of knowledge regarding the occurrence and fate of this compound in surface water and its behavior during drinking water treatment. In this work a comparative study on the occurrence and persistency of valsartan acid, three frequently used β-blockers (metoprolol, atenolol, and sotalol), atenolol acid (one significant transformation product of atenolol and metoprolol), and the two widely distributed persistent anthropogenic wastewater indicators carbamazepine and acesulfame in raw sewage, treated wastewater, surface water, groundwater, and tap water is presented. Median concentrations of valsartan acid in the analyzed matrices were 101, 1,310, 69, waters valsartan acid was found just as relevant as the analyzed β-blockers and the anticonvulsant carbamazepine. Regarding its persistency in surface waters it was comparable to carbamazepine and acesulfame. Furthermore, removal of valsartan acid during bank filtration was poor, which demonstrated the relevance of this compound for drinking water suppliers. Regarding drinking water treatment (Muelheim Process) the compound was resistant to ozonation but effectively eliminated (≥90%) by subsequent activated carbon filtration. However, without applying activated carbon filtration the compound may enter the drinking water distribution system as it was demonstrated for Berlin tap water. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Michael R Due

    Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

  6. An evaluation of a heroin overdose prevention and education campaign.

    Science.gov (United States)

    Horyniak, Danielle; Higgs, Peter; Lewis, Jennifer; Winter, Rebecca; Dietze, Paul; Aitken, Campbell

    2010-01-01

    Following detection of an upward trend in the frequency of fatal heroin overdoses in Victoria between 2001 and 2003, Victoria's Department of Human Services planned a campaign aimed at increasing injecting drug users' (IDU) awareness of overdose risks and prevention strategies. Stickers, wallet cards and posters featuring five key messages were distributed via needle and syringe programs (NSP) and other drug and alcohol services between November 2005 and April 2006. An evaluation of the campaign was commissioned to be conducted in late 2006. The evaluation consisted of analysis of three independent data sets--quantitative data collected from IDU during the campaign period (n = 855 at baseline; and a range of 146-656 at follow up); qualitative interviews with IDU who were NSP clients during the campaign period (n = 16) and qualitative interviews with NSP staff and other key stakeholders (n = 9). While key experts felt that the campaign messages had engendered lasting impact for at least some IDU, these positive impressions were not borne out by the NSP client data, with less than one quarter of all campaign messages being mentioned by a significantly higher proportion of clients during the post-campaign period compared with baseline. Key experts perceived the greatest weakness of the campaign to be the delay between issue identification and the introduction of campaign materials. While IDU are generally responsive to health promotion campaigns, future initiatives in this domain should be designed and implemented rapidly and in ways that are sufficiently flexible to cope with shifts in drug markets which could influence the reception of key messages.

  7. Making sense of differing overdose mortality: contributions to improved understanding of European patterns.

    Science.gov (United States)

    Waal, Helge; Gossop, Michael

    2014-01-01

    The European Monitoring Centre for Drugs and Drug Addiction, EMCDDA, publishes statistics for overdose deaths giving a European mean number, and ranking nations in a national 'league table' for overdose deaths. The interpretation of differing national levels of mortality is more problematic and more complex than is usually recognised. Different systems are used to compile mortality data and this causes problems for cross-national comparisons. Addiction behaviour can only be properly understood within its specific social and environmental ecology. Risk factors for overdose, such as the type of drug consumed, and the route of administration, are known to differ across countries. This paper describes problems associated with ranking and suggests how mortality data might be used in high-level countries aiming at reduction in the number of overdose deaths. Copyright © 2013 S. Karger AG, Basel.

  8. Brain Histamine -Methyltransferase as a Possible Target of Treatment for Methamphetamine Overdose

    Directory of Open Access Journals (Sweden)

    Junichi Kitanaka

    2016-01-01

    Full Text Available Stereotypical behaviors induced by methamphetamine (METH overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N -methyltransferase (HMT is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood-brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.

  9. Beware the yellow slimming pill: fatal 2,4-dinitrophenol overdose.

    Science.gov (United States)

    Holborow, Alexander; Purnell, Richard M; Wong, Jenny Frederina

    2016-04-04

    An industrial chemical, 2,4-dinitrophenol (DNP), has found use as a weight loss drug. It is extremely toxic in overdose and has a narrow therapeutic window with significant interindividual variability in metabolism. The rise in internet-based sales and distribution of this drug has seen an increased incidence of both accidental and intentional overdose presenting to emergency departments across the UK. No antidote currently exists and overdose is often fatal despite management based on current recommendations. We report a case of intentional overdose of DNP in a young man and discuss the current treatment guidelines. The case highlights the need for an increased awareness among frontline medical staff of the effects of DNP poisoning and questions the need for a more aggressive approach in the management of acute toxicity. 2016 BMJ Publishing Group Ltd.

  10. Targeted metabolomic profiling indicates structure-based perturbations in serum phospholipids in children with acetaminophen overdose

    Directory of Open Access Journals (Sweden)

    Sudeepa Bhattacharyya

    Full Text Available Phospholipids are an important class of lipids that act as building blocks of biological cell membranes and participate in a variety of vital cellular functions including cell signaling. Previous studies have reported alterations in phosphatidylcholine (PC and lysophosphatidylcholine (lysoPC metabolism in acetaminophen (APAP-treated animals or cell cultures. However, little is known about phospholipid perturbations in humans with APAP toxicity. In the current study, targeted metabolomic analysis of 180 different metabolites including 14 lysoPCs and 73 PCs was performed in serum samples from children and adolescents hospitalized for APAP overdose. Metabolite profiles in the overdose group were compared to those of healthy controls and hospitalized children receiving low dose APAP for treatment of pain or fever (therapeutic group. PCs and lysoPCs with very long chain fatty acids (VLCFAs were significantly decreased in the overdose group, while those with comparatively shorter chain lengths were increased in the overdose group compared to the therapeutic and control groups. All ether linked PCs were decreased in the overdose group compared to the controls. LysoPC-C26:1 was highly reduced in the overdose group and could discriminate between the overdose and control groups with 100% sensitivity and specificity. The PCs and lysoPCs with VLCFAs showed significant associations with changes in clinical indicators of drug metabolism (APAP protein adducts and liver injury (alanine aminotransferase, or ALT. Thus, a structure-dependent reduction in PCs and lysoPCs was observed in the APAP-overdose group, which may suggest a structure-activity relationship in inhibition of enzymes involved in phospholipid metabolism in APAP toxicity. Keywords: Metabolomics, Phospholipids, Acetaminophen, Hepatotoxicity, Drug

  11. Overdose prevention training with naloxone distribution in a prison in Oslo, Norway: a preliminary study.

    Science.gov (United States)

    Petterson, Aase Grønlien; Madah-Amiri, Desiree

    2017-11-21

    Prison inmates face a ten times increased risk of experiencing a fatal drug overdose during their first 2 weeks upon release than their non-incarcerated counterparts. Naloxone, the antidote to an opioid overdose, has been shown to be feasible and effective when administered by bystanders. Given the particular risk that newly released inmates face, it is vital to assess their knowledge about opioid overdoses, as well as the impact of brief overdose prevention training conducted inside prisons. Prison inmates nearing release (within 6 months) in Oslo, Norway, voluntarily underwent a brief naloxone training. Using a questionnaire, inmates were assessed immediately prior to and following a naloxone training. Descriptive statistics were performed for main outcome variables, and the Wilcoxon signed-rank test was used to compare the participants' two questionnaire scores from pre-and post-training. Participating inmates (n = 31) were found to have a high baseline knowledge of risk factors, symptoms, and care regarding opioid overdoses. Nonetheless, a brief naloxone training session prior to release significantly improved knowledge scores in all areas assessed (p < 0.001). The training appears to be most beneficial in improving knowledge regarding the naloxone, including its use, effect, administration, and aftercare procedures. Given the high risk of overdosing that prison inmates face upon release, the need for prevention programs is critical. Naloxone training in the prison setting may be an effective means of improving opioid overdose response knowledge for this particularly vulnerable group. Naloxone training provided in the prison setting may improve the ability of inmates to recognize and manage opioid overdoses after their release; however, further studies on a larger scale are needed.

  12. In-line monitoring of cocrystallization process and quantification of carbamazepine-nicotinamide cocrystal using Raman spectroscopy and chemometric tools

    Science.gov (United States)

    Soares, Frederico L. F.; Carneiro, Renato L.

    2017-06-01

    A cocrystallization process may involve several molecular species, which are generally solid under ambient conditions. Thus, accurate monitoring of different components that might appear during the reaction is necessary, as well as quantification of the final product. This work reports for the first time the synthesis of carbamazepine-nicotinamide cocrystal in aqueous media with a full conversion. The reactions were monitored by Raman spectroscopy coupled with Multivariate Curve Resolution - Alternating Least Squares, and the quantification of the final product among its coformers was performed using Raman spectroscopy and Partial Least Squares regression. The slurry reaction was made in four different conditions: room temperature, 40 °C, 60 °C and 80 °C. The slurry reaction at 80 °C enabled a full conversion of initial substrates into the cocrystal form, using water as solvent for a greener method. The employment of MCR-ALS coupled with Raman spectroscopy enabled to observe the main steps of the reactions, such as drug dissolution, nucleation and crystallization of the cocrystal. The PLS models gave mean errors of cross validation around 2.0 (% wt/wt), and errors of validation between 2.5 and 8.2 (% wt/wt) for all components. These were good results since the spectra of cocrystals and the physical mixture of the coformers present some similar peaks.

  13. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

    Directory of Open Access Journals (Sweden)

    Claudia Gregoriano

    Full Text Available Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5. Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8 times the usual dose in adults. Twelve cases (30% had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.

  14. Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

    Science.gov (United States)

    Rando, Jessica; Broering, Derek; Olson, James E; Marco, Catherine; Evans, Stephen B

    2015-09-01

    This study sought to answer the question, "Can police officers administer intranasal naloxone to drug overdose victims to decrease the opioid overdose death rate?" This prospective interventional study was conducted in Lorain County, OH, from January 2011 to October 2014. Starting October 2013, trained police officers administered naloxone to suspected opioid overdose victims through a police officer naloxone prescription program (NPP). Those found by the county coroner to be positive for opioids at the time of death and those who received naloxone from police officers were included in this study. The rate of change in the total number of opioid-related deaths in Lorain County per quarter year, before and after initiation of the NPP, and the trend in the survival rate of overdose victims who were given naloxone were analyzed by linear regression. Significance was established a priori at P police officer NPP with average deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the first 9 months of 2013. After initiation of the police officer NPP, the number of opioid overdose deaths decreased each quarter with an overall average of 13.4. Of the 67 participants who received naloxone by police officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up. Intranasal naloxone administration by police first responders is associated with decreased deaths in opioid overdose victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Prescription Painkiller Overdoses in the U.S. – What You Need to Know

    Centers for Disease Control (CDC) Podcasts

    2011-11-01

    This podcast is based on the November, 2011 CDC Vital Signs report. Overdose deaths from prescription painkillers have skyrocketed in the past decade. Every year, nearly 15,000 people die from these overdoses—more than those who die from heroin and cocaine combined. Learn the steps you can take to prevent an overdose.  Created: 11/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 11/1/2011.

  16. The relationship between drug use settings, roles in the drug economy, and witnessing a drug overdose in Baltimore, Maryland.

    Science.gov (United States)

    Latkin, Carl A; Edwards, Catie; Davey-Rothwell, Melissa A; Yang, Cui; Tobin, Karin E

    2018-02-12

    There has been a dramatic increase in drug overdose deaths in the United States. In the current study, the authors examined factors associated with witnessing a drug overdose. A sample of 450 substance users in Baltimore, Maryland, were recruited for a behavioral intervention and were administered a survey. Multinomial logistic regression models were used to compare participants who never witnessed a drug overdose with those who witnessed one in the prior 6 months and those who witnessed an overdose over 6 months ago. Most (58%) participants were male, 40% experienced homelessness in the prior 6 months, 63% reported a history of heroin injecting, 84% had snorted heroin, 75% reported witnessing a drug overdose, and 38% experienced an overdose. In multinomial logistic regression models, witnessing an overdose in the past 6 months was associated with number of different types of places where drugs were used (adjusted odds ratio [aOR] = 1.34), history of experiencing an overdose (aOR = 1.80), injecting heroin and/or speedball (aOR = 1.78), and snorting heroin (aOR = 1.54). Witnessing an overdose more than 6 months ago was associated with number of different places where drugs were used (aOR = 1.25), history of experiencing an overdose (aOR = 1.61), snorting heroin (aOR = 1.42), and injecting heroin or speedball (aOR = 1.47). These data suggest that people who engage in more public and frequent drug use, and hence are more likely to witness an overdose, should be targeted for interventions to prevent and treat drug overdose.

  17. Propafenone Overdose-induced Arrhythmia and Subsequent Correction After Administration of Sodium Bicarbonate

    Directory of Open Access Journals (Sweden)

    Patrick Bruss, MD

    2018-04-01

    Full Text Available History of present illness: 71-year old woman presented to the emergency department with near-syncope, chest pain, and shortness of breath. She has a history of hypertension, congestive heart failure and an “irregular heartbeat.” She cannot remember what medications she takes. She recently saw her cardiologist and had some of her medications adjusted, but she can’t remember what specific changes were made. An electrocardiogram was performed, one ampule of sodium bicarbonate was administered and a repeat ECG obtained; patient felt improvement of her symptoms after administration of sodium bicarbonate. Significant findings: The first ECG in this case showed sinus tachycardia with a widened QRS (black arrow, a rightward axis, prolonged corrected QT interval (QTc, and terminal R wave in AVR (white arrow. There are several potential causes for these ECG findings, but put together with the patient’s history, we were suspicious of sodium channel blockers being the most likely cause. The second ECG, after sodium bicarbonate was administered, demonstrated a normal QRS (black arrow and no rightward axis deviation, reduction of the QTC and resolution of the terminal R wave (white arrow. We later learned that the patient’s cardiologist recently increased her propafenone dose. Discussion: Propafenone is a class 1C anti-arrhythmic that slows influx of sodium ions into the cells. It slows the rate of increase of the action potential thereby prolonging conduction and refractoriness in all areas of the myocardium.1 The mortality from acute Class 1C toxicity has been reported as high as 22.5%.1 The degree of propafenone toxicity is directly correlated to the QRS interval,1 so monitoring said interval is very helpful in determining resolution of the drug’s cardiotoxic effects. The electrocardiac effect of tricyclic antidepressants (TCAs is a well-known and often tested finding. These effects include prolongation of the QRS and QTc, right axis deviation

  18. Hippocampal agenesis in an individual who engaged in violent criminal behaviors after discontinuing carbamazepine and paroxetine treatment.

    Science.gov (United States)

    Hanada, Hiroaki; Akiyoshi, Jotaro; Kanehisa, Masayuki; Ishitobi, Yoshinobu; Tsuru, Jusen; Tanaka, Yoshihiro; Shimomura, Tsuyoshi; Kawano, Yoshihisa

    2013-01-01

    Antidepressant discontinuation syndrome (ADS) occurs after abrupt discontinuation of an antidepressant medication. A 23-year-old man with right hippocampal agenesis demonstrated sexual crime (hypersexuality) since the age of eight and had been successfully treated with carbamazepine since the age of 13. He had required increased doses of paroxetine and carbamazepine owing to the development of an unstable affect after quitting his job. He abruptly stopped taking his medication for 3 days and his criminal behaviors re-emerged. We examined changes in brain structure and activity before and after medication cessation, using MRI and functional MRI (fMRI). The image of a girl in a swimsuit increased activity in the thalamus only after medication discontinuation. The alteration in thalamic activity might induce hypersexuality. We conclude that a primary hypersexuality had been suppressed with carbamazepine and paroxetine treatment, and the discontinuation of the medication caused the hypersexuality. © 2012 American Academy of Forensic Sciences.

  19. Prolonged Toxic Encephalopathy following Accidental 4-Aminopyridine Overdose

    Directory of Open Access Journals (Sweden)

    Maria Ballesta Méndez

    2014-01-01

    Full Text Available Background. 4-Aminopyridine (4-AP is a drug that is used to improve motor fatigue in patients suffering from multiple sclerosis (MS. Medication error can occur, as commercial preparation may not be available in some countries. Case Presentation. A 58-year-old woman with progressive MS presented with status epilepticus. She was receiving 4-AP for more than 3 years. The symptoms started soon after the ingestion of a single pill that was supposed to contain 10 mg 4-AP, but further investigations revealed that each pill had been inadvertently prepared with an 100 mg 4-AP concentration. The patient was admitted to the intensive care unit (ICU for appropriate management (orotracheal intubation, sedation, and antiepileptic drugs. The first electroencephalogram (EEG showed abundant irregular spike-waves on the left central regions. Neurological condition gradually improved from day 7, while the EEG did not reveal any more electrical seizures but was still consistent with toxic encephalopathy. The patient stayed in the ICU until day 13. At discharge from the rehabilitation ward (2.5 months later, the patient had not yet recovered her previous cognitive and functional condition. Conclusion. A single 100 mg 4-AP accidental overdose may cause serious immediate complications, with a slow and incomplete neurological recovery.

  20. Social learning and peer education in responding to opiate overdose among injection drug users in Ukraine

    Directory of Open Access Journals (Sweden)

    Anna Tokar

    2014-06-01

    Full Text Available BACKGROUND: Opiate overdoses (OD constitute one of the leading causes of avoidable deaths among people aged 20-40 years old. As peer-administered help in cases of overdose was found to be effective, we aimed to explore how much the subjects of the intervention are able to learn from one another and from their own experience. METHODS: Secondary data analysis was performed with the 2008 dataset of peer-driven intervention among IDUs who were not involved in harm reduction programs earlier; recruiting was performed with respondent driven sampling methodology combined with peer education covering overdose response. Subsample of 6667 opiate users was considered. Data on overdose response strategies experienced by respondents were considered predictors and data on intended response strategies as outcomes. To reveal relationships between the experienced and intended responses, binary logistic regression analysis was performed. RESULTS: With recommended strategies including calling ambulance, putting a person in recovery position, fixing the tongue, applying mouth-to-mouth resuscitation and cardiac massage, percentages of those planning to apply them was considerably higher (on average, 2.3 times higher than the percentage of those having experienced them. With other strategies including applying cold, pain, ammonia, percentages of those who experienced the strategy and those who planned to practice it were rather close and on average differed just by 1.1. With all the strategies, the intention to apply a particular response in future was strongly associated with personal experience of having had this applied when having an overdose episode. Peer-education to larger extent determines the intentions of those who have not experienced particular overdose responses themselves. On the other hand, social learning contributes to persisting of those experienced strategies which cannot be recommended. CONCLUSIONS: Social learning can impact intended overdose

  1. Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial

    OpenAIRE

    Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

    2012-01-01

    Background: It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus.Methods: In a randomized double–blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tin...

  2. Molecular structure and spectroscopic characterization of Carbamazepine with experimental techniques and DFT quantum chemical calculations

    Science.gov (United States)

    Suhasini, M.; Sailatha, E.; Gunasekaran, S.; Ramkumaar, G. R.

    2015-04-01

    A systematic vibrational spectroscopic assignment and analysis of Carbamazepine has been carried out by using FT-IR, FT-Raman and UV spectral data. The vibrational analysis were aided by electronic structure calculations - ab initio (RHF) and hybrid density functional methods (B3LYP) performed with standard basis set 6-31G(d,p). Molecular equilibrium geometries, electronic energies, natural bond order analysis, harmonic vibrational frequencies and IR intensities have been computed. A detailed interpretation of the vibrational spectra of the molecule has been made on the basis of the calculated Potential Energy Distribution (PED) by VEDA program. UV-visible spectrum of the compound was also recorded and the electronic properties, such as HOMO and LUMO energies and λmax were determined by HF/6-311++G(d,p) Time-Dependent method. The thermodynamic functions of the title molecule were also performed using the RHF and DFT methods. The restricted Hartree-Fock and density functional theory-based nuclear magnetic resonance (NMR) calculation procedure was also performed, and it was used for assigning the 13C and 1H NMR chemical shifts of Carbamazepine.

  3. Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions

    Directory of Open Access Journals (Sweden)

    Mônia Aparecida Lemos Pinto

    2014-12-01

    Full Text Available Carbamazepine (CBZ, a widely used anticonvulsant drug, can crystallize and exhibits four polymorphic forms and one dihydrate. Anhydrous CBZ can spontaneously absorb water and convert to the hydrate form whose different crystallinity leads to lower biological activity. The present study was concerned to the possibility of recovering the hydrated form by heating. The thermal behavior of spontaneously hydrated carbamazepine was investigated by TG/DTG-DTA and DSC in dynamic atmospheres of air and nitrogen, which revealed that the spontaneous hydration of this pharmaceutical resulted in a Form III hydrate with 1.5 water molecules. After dehydration, this anhydrous Form III converted to Form I, which melted and decomposed in a single event, releasing isocyanic acid, as shown by evolved gas analysis using TG-FTIR. Differential scanning calorimetry analyses revealed that Form III melted and crystallized as Form I, and that subsequent cooling cycles only generated Form I by crystallization. Solid state decomposition kinetic studies showed that there was no change in the substance after the elimination of water by heating to 120 °C. Activation energies of 98 ± 2 and 93 ± 2 kJ mol-1 were found for the hydrated and dried samples, respectively, and similar profiles of activation energy as a function of conversion factor were observed for these samples.

  4. [Utilization of carbamazepine and oxcarbazepine in pediatric patients with partial epilepsy in Spain. An observational study].

    Science.gov (United States)

    Rufo Campos, M; Carreño, M

    2009-01-01

    It is important to conduct studies on the utilization of new antiepileptic drugs in order to improve their use. Our objective is to describe the use patterns of carbamazepine and oxcarbazepine. Observational, cross-sectional, national study with 58 investigators that included 185 pediatric patients with partial epilepsy. We recorded prescription patterns, quality of life (QoL) using the QoL scale in childhood epilepsy (CAVE) and use of resources. 134 patients were under treatment with oxcarbazepine (72.4 %), with a mean dose of 22.3 mg/kg/day; standard deviation (SD): 8.04; 95 % confidence interval (CI): 20.9 to 23.7, and 51 (27.6%) with carbamazepine, mean dose of 14 mg/kg/day; SD: 6.2; 95 % CI: 12.3 to 15.8. A total of 19.4% and 21.6 %, respectively, followed multiple drug treatment. The mean scores on functional dimensions of CAVE were (out of 5): school attendance: 4.5; SD: 0.7; social relationships: 4.1; SD: 0.9, and autonomy: 3.9; SD: 1.9. Patients receiving multiple drug therapy had worse results in quality of life (p used in lower doses than recommended and the dosing is not adjusted for weight. Underdosing may lead to regimes of multiple drug therapy that should be reviewed individually.

  5. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    Directory of Open Access Journals (Sweden)

    Okujava Michael

    2001-11-01

    Full Text Available Abstract Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry influences the blood oxygenation level dependent (BOLD contrast changes induced by neuronal activation and measured by functional MRI (fMRI. We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE. Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

  6. Generation of 1:1 Carbamazepine:Nicotinamide cocrystals by spray drying.

    Science.gov (United States)

    Patil, Shashank P; Modi, Sameer R; Bansal, Arvind K

    2014-10-01

    The present study investigates the potential of spray drying as a technique for generation of pharmaceutical cocrystals. Carbamazepine-Nicotinamide cocrystal (CNC) was chosen as model cocrystal system for this study. Firstly, CNC was generated using liquid assisted grinding and used for generation of phase solubility diagram (PSD) and ternary phase diagram (TPD). Both PSD and TPD were carefully evaluated for phase behavior of CNC when equilibrated with solvent. The undersaturated region with respect to CNC, as depicted by TPD, was selected as target region to initiate cocrystallization experiments. Various points in this region, representative of different compositions of Carbamazepine, Nicotinamide and CNC, were selected and spray drying was carried out. The spray dried product was characterized for solid state properties and was compared with CNC generated by liquid assisted grinding. Spray drying successfully generated CNC of similar quality as those generated by liquid assisted grinding. Moreover, there was no significant impact of process variables on formation of CNC. Spray drying, owing to its simplicity and industrial scalability, can be a promising method for large scale cocrystal generation. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Analytical method by high resolution liquid chromatography for the determination of carbamazepine in human plasma

    International Nuclear Information System (INIS)

    Jimenez Aleman, Narda M; Calero Carbonell, Jorge E; Padron Yaquis, Alejandro S; Izquierdo Lozano, Julio C

    2007-01-01

    One of the requirements to develop the studies of bioavailability and bioequivalence is to have analytic methodologies validated for the work with samples in biological fluids. A method was developed by high resolution liquid chromatography for the determination of carbamazepine in human plasma. A mixture of hydrogen phosphate of sodium: acetonitrile (65:35) adjusted to pH= 3.3 with phosphoric acid, flow of 1.2 mL/min and ultraviolet detection at 210 nm, was used as mobile phase. Propylparabene was used as an internal standard. According to the established regulations for the validation of the methods in biological fluids, the following parameters were studied: stability of the samples, lineality, specificity, precision, accuracy and limit of detection and quantification. The method proved to be specific and sensitive with a detection and quantification limit of 0.9 and 1.0 ng, respectively. The method was lineal, precise and exact in the range of concentrations of 1. 07 at 12.67 μg/mL. The mean recovery was not statistically different from 100.0 %. The analito in the proposed biological matrix remained in the studied period. The methodology described in this work is applied in our case to the study that evaluates the bioavailability and bioequivalence of a Cuban formulation of carbamazepine in healthy volunteers. (Author)

  8. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010

    Science.gov (United States)

    Bachhuber, Marcus A.; Saloner, Brendan; Cunningham, Chinazo O.; Barry, Colleen L.

    2015-01-01

    IMPORTANCE Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them. OBJECTIVE To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality. DESIGN, SETTING, AND PARTICIPANTS A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included. EXPOSURES Presence of a law establishing a medical cannabis program in the state. MAIN OUTCOMES AND MEASURES Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate. RESULTS Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4

  9. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.

    Science.gov (United States)

    Bachhuber, Marcus A; Saloner, Brendan; Cunningham, Chinazo O; Barry, Colleen L

    2014-10-01

    Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them. To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality. A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included. Presence of a law establishing a medical cannabis program in the state. Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate. Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, -37.5% to -9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (-19.9%; 95% CI, -30.6% to -7.7%; P = .002), year 2 (-25.2%; 95% CI, -40.6% to -5.9%; P = .01), year 3 (-23.6%; 95% CI, -41.1% to -1.0%; P = .04), year 4 (-20.2%; 95% CI, -33.6% to -4.0%; P = .02), year 5 (-33.7%; 95% CI, -50.9% to -10.4%; P = .008), and year 6 (-33.3%; 95% CI, -44.7% to

  10. Bleeding and asymptomatic overdose in patients under Vitamin K antagonist therapy: Frequency and risk factors

    Directory of Open Access Journals (Sweden)

    F. Ben Mbarka

    2018-03-01

    Full Text Available Background: Vitamin K antagonists are widely used in the treatment and prevention of thromboembolic disease. However, these drugs can cause serious side effects, especially bleeding. This study aims to evaluate frequency and risk factors of both bleeding and asymptomatic overdose in North African patients undergoing Vitamin K antagonist therapy. Methods: We performed a cross-sectional study in patients undergoing Vitamin K antagonist therapy. A statistical analysis has been conducted to identify overdose and bleeding risk factors by using chi-square test (p < .05. Results: One hundred and eleven patients were included. We recorded 14 cases of bleeding and 26 cases of asymptomatic overdose. Advanced age, poor adherence, concomitant use of paracetamol and history of previous bleeding are significant risk factors of over-anticoagulation. An INR value over 6 at admission, a high therapeutic target range for INR, concomitant use of acetylsalicylic acid, lack of information on overdose signs and measures to be taken in case of bleeding were identified as risk factors for bleeding. Conclusion: Most of the risk factors identified in our study seem to be related to patients lack of information and education. These results highlight the importance of creating a therapeutic patient education program. Keywords: Vitamin K antagonist, Bleeding, Risk factor, Overdose

  11. Serotonin syndrome following overdose of a non-prescription slimming product containing sibutramine: a case report.

    Science.gov (United States)

    Lam, Pui Kin; Leung, K S; Wong, T W; Lee, H H C; Tang, M H Y; Mak, T W L

    2012-04-01

    Non-prescription slimming products are popular and can be easily purchased from the Internet. However, adulteration of these products with undeclared substances including prescription drugs is not uncommon. We report a case of serotonin syndrome after an overdose of a non-prescription product containing sibutramine. A 21-year-old woman presented with somnolence, sinus tachycardia, generalised increase in tone, hyper-reflexia and clonus more prominent in the lower limbs after an intentional overdose of a non-prescription slimming product obtained from the Internet. The product was later found to contain sibutramine and other substances such as animal thyroid tissues, caffeine and phenolphthalein. Quantitative analysis of patient's serum on presentation revealed a sibutramine concentration of 112 ng/mL, which far exceeded the reported peak serum concentration after a single oral dose of 15 mg (the maximum daily recommended dose). No other culpable agent was identified. The overall clinical presentation was compatible with serotonin syndrome associated with sibutramine overdose. The patient made a full recovery after supportive management. This case highlighted the health threat posed by non-prescription slimming products sold over the Internet. Sibutramine overdose can result in serotonin syndrome, as in overdose of other serotonergic agents. Early recognition and timely supportive treatment are essential to ensure a good clinical outcome.

  12. Dissipation of triclosan, triclocarban, carbamazepine and naproxen in agricultural soil following surface or sub-surface application of dewatered municipal biosolids

    International Nuclear Information System (INIS)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Lapen, David R.; Topp, Edward

    2015-01-01

    In many jurisdictions land application of municipal biosolids is a valued source of nutrients for crop production. The practice must be managed to ensure that crops and adjacent water are not subject to contamination by pharmaceuticals or other organic contaminants. The broad spectrum antimicrobial agents triclosan (TCS) and triclocarban (TCC), the anti-epileptic drug carbamazepine (CBZ), and the nonsteroidal anti-inflammatory drug naproxen (NAP) are widely used and are carried in biosolids. In the present study, the effect of biosolids and depth of placement in the soil profile on the rates of TCS, TCC, CBZ, and NAP dissipation were evaluated under semi-field conditions. Aggregates of dewatered municipal biosolids (DMBs) supplemented with 14 C-labeled residues were applied either on the soil surface or in the subsurface of the soil profile, and incubated over several months under ambient outdoor conditions. The dissipation of TCS, TCC and NAP was significantly faster in sub-surface than surface applied biosolid aggregates. In contrast the dissipation rate for CBZ was the same in surface applied and incorporated aggregates. Overall, the present study has determined a significant effect of depth of placement on the dissipation rate of biodegradable molecules. - Highlights: • We characterized the soil fate of four organic contaminants carried in biosolids. • Biosolids were placed on the soil surface or incorporated within the soil profile. • Naproxen, triclosan and triclocarban were dissipated more rapidly when incorporated. • Depth of placement did not influence the rate of carbamazepine dissipation. • Soil incorporation of biosolids will result in more rapid dissipation of contaminants

  13. Dissipation of triclosan, triclocarban, carbamazepine and naproxen in agricultural soil following surface or sub-surface application of dewatered municipal biosolids

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne [Agriculture and Agri-Food Canada, London, ON N5V 4T3 (Canada); Lapen, David R. [Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6 (Canada); Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON N5V 4T3 (Canada); Department of Biology, Western University, London, ON N6A 5B7 (Canada)

    2015-04-15

    In many jurisdictions land application of municipal biosolids is a valued source of nutrients for crop production. The practice must be managed to ensure that crops and adjacent water are not subject to contamination by pharmaceuticals or other organic contaminants. The broad spectrum antimicrobial agents triclosan (TCS) and triclocarban (TCC), the anti-epileptic drug carbamazepine (CBZ), and the nonsteroidal anti-inflammatory drug naproxen (NAP) are widely used and are carried in biosolids. In the present study, the effect of biosolids and depth of placement in the soil profile on the rates of TCS, TCC, CBZ, and NAP dissipation were evaluated under semi-field conditions. Aggregates of dewatered municipal biosolids (DMBs) supplemented with {sup 14}C-labeled residues were applied either on the soil surface or in the subsurface of the soil profile, and incubated over several months under ambient outdoor conditions. The dissipation of TCS, TCC and NAP was significantly faster in sub-surface than surface applied biosolid aggregates. In contrast the dissipation rate for CBZ was the same in surface applied and incorporated aggregates. Overall, the present study has determined a significant effect of depth of placement on the dissipation rate of biodegradable molecules. - Highlights: • We characterized the soil fate of four organic contaminants carried in biosolids. • Biosolids were placed on the soil surface or incorporated within the soil profile. • Naproxen, triclosan and triclocarban were dissipated more rapidly when incorporated. • Depth of placement did not influence the rate of carbamazepine dissipation. • Soil incorporation of biosolids will result in more rapid dissipation of contaminants.

  14. Bad Luck or Bad Decisions: College Students' Perceptions of the Reasons for and Consequences of Their Alcohol Overdose

    Science.gov (United States)

    Reis, Janet

    2007-01-01

    Reasons for and immediate consequences of an alcohol overdose were explored for 217 undergraduate students requiring a medical emergency transport because of excessive alcohol consumption. The sample was categorized into 26 students attributing their overdose solely to bad luck and 191 students citing bad decision making as an explanation. A…

  15. The use of quantum chemistry in pharmaceutical research as illustrated by case studies of indometacin and carbamazepine

    DEFF Research Database (Denmark)

    Gordon, Keith C; McGoverin, Cushla M; Strachan, Clare J

    2007-01-01

    A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed...

  16. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4

    DEFF Research Database (Denmark)

    Andreasen, Astrid-Helene; Brøsen, Kim; Damkier, Per

    2007-01-01

    PURPOSE: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. We...

  17. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    Science.gov (United States)

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

  18. Do carbamazepine, gabapentin, or other anticonvulsants exert sufficient radioprotective effects to alter responses from trigeminal neuralgia radiosurgery?

    Science.gov (United States)

    Flickinger, John C; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S; Arai, Yoshio; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas; Flickinger, John C

    2012-07-15

    Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age ≤70 years, and Type 1 typical

  19. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  20. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    International Nuclear Information System (INIS)

    Flickinger, John C.; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S.; Arai, Yoshio; Niranjan, Ajay; Lunsford, L. Dade; Kondziolka, Douglas; Flickinger, John C.

    2012-01-01

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6–153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with

  1. Implementing an overdose education and naloxone distribution program in a health system.

    Science.gov (United States)

    Devries, Jennifer; Rafie, Sally; Polston, Gregory

    To design and implement a health system-wide program increasing provision of take-home naloxone in patients at risk for opioid overdose, with the downstream aim of reducing fatalities. The program includes health care professional education and guidelines, development, and dissemination of patient education materials, electronic health record changes to promote naloxone prescriptions, and availability of naloxone in pharmacies. Academic health system, San Diego, California. University of California, San Diego Health (UCSDH), offers both inpatient and outpatient primary care and specialty services with 563 beds spanning 2 hospitals and 6 pharmacies. UCSDH is part of the University of California health system, and it serves as the county's safety net hospital. In January 2016, a multisite academic health system initiated a system-wide overdose education and naloxone distribution program to prevent opioid overdose and opioid overdose-related deaths. An interdisciplinary, interdepartmental team came together to develop and implement the program. To strengthen institutional support, naloxone prescribing guidelines were developed and approved for the health system. Education on naloxone for physicians, pharmacists, and nurses was provided through departmental trainings, bulletins, and e-mail notifications. Alerts in the electronic health record and preset naloxone orders facilitated co-prescribing of naloxone with opioid prescriptions. Electronic health record reports captured naloxone prescriptions ordered. Summary reports on the electronic health record measured naloxone reminder alerts and response rates. Since the start of the program, the health system has trained 252 physicians, pharmacists, and nurses in overdose education and take-home naloxone. There has been an increase in the number of prescriptions for naloxone from a baseline of 4.5 per month to an average of 46 per month during the 3 months following full implementation of the program including

  2. Overdose beliefs and management practices among ethnic Vietnamese heroin users in Sydney, Australia

    Directory of Open Access Journals (Sweden)

    Maher Lisa

    2009-04-01

    Full Text Available Abstract Background Ethnic Vietnamese injecting drug users (IDUs in Australia draw on a range of beliefs and etiologic models, sometimes simultaneously, in order to make sense of health and illness. These include understandings of illness as the result of internal imbalances and Western concepts of disease causation including germ/pollution theory. Methods Observational fieldwork and in-depth interviews were conducted between 2001 and 2006 in neighbourhoods characterised by high proportions of Asian background IDUs and street-based drug markets. Eligibility criteria for the study were: 1 ethnic Vietnamese cultural background; 2 aged 16 years and over and; 3 injected drugs in the last 6 months. Results Participants commonly attempted to treat heroin overdose by withdrawing blood (rút máu from the body. Central to this practice are cultural beliefs about the role and function of blood in the body and its relationship to illness and health. Participants' beliefs in blood were strongly influenced by understandings of blood expressed in traditional Chinese and Vietnamese medicine. Many participants perceived Western drugs, particularly heroin, as "hot" and "strong". In overdose situations, it was commonly believed that an excessive amount of drugs (particularly heroin entered the bloodstream and traveled to the heart, making the heart work too hard. Withdrawing blood was understood to reduce the amount of drugs in the body which in turn reduced the effects of drugs on the blood and the heart. Conclusion The explanatory model of overdose employed by ethnic Vietnamese IDUs privileges traditional beliefs about the circulatory, rather than the respiratory, system. This paper explores participants' beliefs about blood, the effects of drugs on blood and the causes of heroin overdose in order to document the explanatory model of overdose used by ethnic Vietnamese IDUs. Implications for overdose prevention, treatment and management are identified and

  3. Application of experimental design in examination of the dissolution rate of carbamazepine from formulations: Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

    Directory of Open Access Journals (Sweden)

    Krstić Marko

    2015-01-01

    Full Text Available Poor solubility is one of the key reasons for the poor bioavailability of these drugs. This paper displays a formulation of a solid surfactant system with carbamazepine, in order to increase its dissolution rate. Solid state surfactant systems are formed by application of fractal experimental design. Poloxamer 237 and Poloxamer 338 were used as surfactants and Brij® 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite and a synthetic adsorbent carrier (Neusiline UFL2 on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influence of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR, PXRD. It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions. [Projekat Ministarstva nauke Republike Srbije, br. TR34007

  4. Characteristics of Suicides Caused by Drug Overdose in the State of Maryland

    Directory of Open Access Journals (Sweden)

    Ling Li

    2015-01-01

    Full Text Available Suicidal drug overdose is a major public health issue. In the United States, every year more than 33,000 people commit suicides. Our study focused on the characteristics of suicide victims in the state of Maryland. Material and methods: This study was a retrospective review of autopsy cases of all suicide deaths caused by drug (s or drug (s with alcohol intoxication investigated by the OCME in Maryland over a 7-year period from January 2004 to December 2011. All deaths investigated by the OCME that require autopsy examination are subject to comprehensive toxicology testing for drugs and alcohol. The screen tests were performed using gas chromatography (GC and radioimmunoassay techniques. All detected drugs and/or metabolites were confirmed using GC-mass spectrometry (GC-MS. Results: From 2004 to 2011, 434 deaths were certified as suicide. Of the 434 suicidal overdose deaths, 84% were white, 11% were African-American, and about 5% were either Hispanic or Asian. The male and female ratio was almost equal. Their ages ranged 15-82 years. Of the 434 suicidal drug overdose deaths, 277 victims (63.8% consumed a single drug type and 157 (36.2% consumed more than one type of drug. Of the 277 single-drug overdose cases, 71.1% suicides were due to prescription drugs, 23.5% due to over-the-counter drugs, and 5.4% due to street/recreational drugs. Among single-type prescription drugs, analgesic (N = 76, antidepressant (N = 45, and neuroleptic (N = 35 classes were the three leading type of drugs used in suicidal deaths. Oxycodone, morphine, quetiapine, and amitriptyline were the most common prescription drugs in suicidal overdose. Diphenhydramine was the leading over-the-counter drug. Of the 157 victims who consumed more than one drug, combined prescription drugs were present in 54.1%, mixed prescription and over-the-counter drugs in 29.3%, and prescription drugs/over-the-counter drugs and street drugs in 16.6% of cases. Of the multiple-drug overdose suicides

  5. Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths in British Columbia, Canada: An observational analysis.

    Science.gov (United States)

    Baldwin, Nicholas; Gray, Roger; Goel, Anirudh; Wood, Evan; Buxton, Jane A; Rieb, Launette Marie

    2018-04-01

    Due to the alarming rise in opioid-related overdose deaths, a public health emergency was declared in British Columbia (BC). In this study, we examined the relationship between illicit fentanyl and heroin found in seized drugs and illicit overdose deaths in BC. An observational cross-sectional survey was conducted using BC data from Health Canada's Drug Analysis Service, which analyzes drug samples seized by law enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate regression analysis were performed to describe the potential relationship between seized illicit fentanyl samples and overdose deaths and to determine if this differed from seized heroin and overdose deaths. Fentanyl samples were analyzed for other drug content. Fentanyl is increasingly being found combined with other opioid and non-opioid illicit drugs. Strong positive relationships were found between the number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A positive association was found between the number of seized heroin samples and total overdose deaths (R2 = 0.78). This research contributes to the expanding body of evidence implicating illicit fentanyl use (often combined with heroin or other substances) in overdose deaths in BC. Policy makers and healthcare providers are urged to implement drug treatment and harm reduction strategies for people at risk of overdose associated with current trends in illicit opioid use. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Epidemiology, pathophysiology and putative genetic basis of carbamazepine- and oxcarbazepine-induced hyponatremia.

    Science.gov (United States)

    Berghuis, B; de Haan, G-J; van den Broek, M P H; Sander, J W; Lindhout, D; Koeleman, B P C

    2016-09-01

    The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ- and OXC-induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway. © 2016 EAN.

  7. Removal of carbamazepine and clofibric acid from water using double templates-molecularly imprinted polymers.

    Science.gov (United States)

    Dai, Chao-meng; Zhang, Juan; Zhang, Ya-lei; Zhou, Xue-fei; Duan, Yan-ping; Liu, Shu-guang

    2013-08-01

    A novel double templates-molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using carbamazepine (CBZ) and clofibric acid (CA) as the double templates molecular and 2-vinylpyridine as functional monomer. The equilibrium data of MIP was well described by the Freundlich isotherm model. Two kinetic models were adopted to describe the experimental data, and the pseudo second-order model well-described adsorption of CBZ and CA on the MIP. Adsorption experimental results showed that the MIP had good selectivity and adsorption capacity for CBZ and CA in the presence of competitive compounds compared with non-imprinted polymer, commercial powdered activated carbon, and C18 adsorbents. The feasibility of removing CBZ and CA from water by the MIP was demonstrated using tap water, lake water, and river water.

  8. Spray Drying as a Reliable Route to Produce Metastable Carbamazepine Form IV.

    Science.gov (United States)

    Halliwell, Rebecca A; Bhardwaj, Rajni M; Brown, Cameron J; Briggs, Naomi E B; Dunn, Jaclyn; Robertson, John; Nordon, Alison; Florence, Alastair J

    2017-07-01

    Carbamazepine (CBZ) is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least 5 polymorphic forms. Metastable form IV was originally discovered from crystallization with polymer additives; however, it has not been observed from subsequent solvent-only crystallization efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic CBZ solution. Characterization of the material was carried out using diffraction, scanning electron microscopy, and differential scanning calorimetry. In situ Raman spectroscopy was used to monitor the spray-dried product during the spray drying process. This work demonstrates that spray drying provides a robust method for the production of form IV CBZ, and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallization approaches to produce metastable crystalline forms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Treatment strategies for early presenting acetaminophen overdose: a survey of medical directors of poison centers in North America and Europe.

    Science.gov (United States)

    Kozer, E; McGuigan, M

    2002-03-01

    Acetaminophen is frequently used in self-poisoning in Western countries. Although treatment with N-acetylcysteine (NAC) reduces liver injury, no consensus exists on the preferred management of acetaminophen toxicity. To describe the approach taken by toxicologists in North America and Europe toward the management of acetaminophen toxicity. Medical directors of poison centers in the US, Canada, and Europe were surveyed by means of a questionnaire presenting two clinical scenarios of acetaminophen overdose: a healthy adolescent with no risk factors who had an acute ingestion of acetaminophen, and an adult with both acute ingestion and possible risk factors. For each case, several questions about the management of these patients were asked. Questionnaires were sent to medical directors of 76 poison centers in North America and 48 in Europe, with response rates of 62% and 44%, respectively. Forty percent of responders suggested using charcoal 4 hours after ingestion of a potential toxic dose of acetaminophen, and 90% recommended treatment with NAC when levels were above 150 microg/mL but below 200 microg/mL 4 hours after ingestion. Duration of treatment with oral NAC ranged from 24 to 96 hours; 38 responders suggested a duration of 72 hours. Of 49 centers recommending oral NAC, 18 (36.7%) said they might consider treatment for less than 72 hours. Eleven of 29 (37.9%) responders suggested treatment with intravenous NAC for more than 20 hours as their usual protocol or a protocol for specific circumstances. Our study showed large variability in the management of acetaminophen overdose. Variations in treatment protocols should be addressed in clinical trials to optimize the treatment for this common problem.

  10. Photochemical degradation of atenolol, carbamazepine, meprobamate, phenytoin and primidone in wastewater effluents

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Mei Mei [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States); Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Trenholm, Rebecca [Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Rosario-Ortiz, Fernando L., E-mail: Fernando.rosario@colorado.edu [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States)

    2015-01-23

    Highlights: • The photochemical degradation of 5 compounds was evaluated in wastewater effluents. • Attenuation by sensitized photolysis was the most important degradation pathway. • Hydroxyl radical accounted for most of the degradation for aliphatic compounds. • Other transient oxidants could also significantly impact the degradation of the compounds. - Abstract: The photochemical degradation of five pharmaceuticals was examined in two secondary wastewater effluents. The compounds, which included atenolol, carbamazepine, meprobamate, phenytoin and primidone, were evaluated for both direct and sensitized photolysis. In the two wastewaters, direct photolysis did not lead to significant compound degradation; however, sensitized photolysis was an important removal pathway for the five pharmaceuticals. Upon solar irradiation, hydroxyl radical (HO·) was quantified using the hydroxylation of benzene and singlet oxygen ({sup 1}O{sub 2}) formation was monitored following the degradation of furfuryl alcohol. Degradation via sensitized photolysis was observed following five-day exposures for atenolol (69–91%), carbamazepine (67–98%), meprobamate (16–52%), phenytoin (44–85%), and primidone (34–88%). Varying removal is likely a result of the differences in reactivity with transient oxidants. Averaged steady state HO· concentrations ranged from 1.2 to 4.0 × 10{sup −16} M, whereas the concentrations of {sup 1}O{sub 2} were 6.0–7.6 × 10{sup −14} M. Partial removal due to presence of HO· indicates it was not the major sink for most compounds examined. Other transient oxidants, such as {sup 1}O{sub 2} and triplet state effluent organic matter, are likely to play important roles in fates of these compounds.

  11. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  12. Behavioral intervention to reduce opioid overdose among high-risk persons with opioid use disorder: A pilot randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Phillip Oliver Coffin

    Full Text Available The United States is amidst an opioid epidemic, including synthetic opioids that may result in rapid death, leaving minimal opportunity for bystander rescue. We pilot tested a behavioral intervention to reduce the occurrence of opioid overdose among opioid dependent persons at high-risk for subsequent overdose.We conducted a single-blinded randomized-controlled trial of a repeated dose motivational interviewing intervention (REBOOT to reduce overdose versus treatment as usual, defined as information and referrals, over 16 months at the San Francisco Department of Public Health from 2014-2016. Participants were 18-65 years of age, had opioid use disorder by Structured Clinical Interview, active opioid use, opioid overdose within 5 years, and prior receipt of naloxone kits. The intervention was administered at months 0, 4, 8, and 12, preceded by the assessment which was also administered at month 16. Dual primary outcomes were any overdose event and number of events, collected by computer-assisted personal interview, as well as any fatal overdose events per vital records.A total of 78 persons were screened and 63 enrolled. Mean age was 43 years, 67% were born male, 65% White, 17% African-American, and 14% Latino. Ninety-two percent of visits and 93% of counseling sessions were completed. At baseline, 33.3% of participants had experienced an overdose in the past four months, with a similar mean number of overdoses in both arms (p = 0.95; 29% overdosed during follow-up. By intention-to-treat, participants assigned to REBOOT were less likely to experience any overdose (incidence rate ratio [IRR] 0.62 [95%CI 0.41-0.92, p = 0.019 and experienced fewer overdose events (IRR 0.46, 95%CI 0.24-0.90, p = 0.023, findings that were robust to sensitivity analyses. There were no differences between arms in days of opioid use, substance use treatment, or naloxone carriage.REBOOT reduced the occurrence of any opioid overdose and the number of overdoses

  13. Cause and motivation in cases of non-fatal drug overdoses in opiate addicts.

    Science.gov (United States)

    Pfab, R; Eyer, F; Jetzinger, E; Zilker, Thomas

    2006-01-01

    Drug overdose (OD) is a frequent incident among opiate addicts. Survivors of ODs are at risk for additional and eventually fatal ODs. ODs may be classified as accidental (aOD) or deliberate (dOD). Investigations into the connection between OD and suicide attempts have led to insconsistent results. (1) to determine how many non-fatal ODs were dODs and how many were aODs; (2) to determine how many cases of dODs were motivated by explicit or by ambivalent suicidal intentions; (3) to determine how many cases of aODs had causes that might respond to preventative measures; (4) to compare the addiction histories of dODs and aODs; (5) to compare the drugs causing the ODs; and (6) to compare the severity of the ODs in both groups. Prospective study utilizing a standardized questionnaire to evaluate opiate-addicted patients admitted to our treatment unit for OD. All cases underwent standardized drug testing to identify drug use patterns. Seventy-four cases of OD underwent standardized interviews after awakening. Forty-three percent of the cases were dOD. Cases of dOD had significantly more OA in substitution programs, more previous ODs, and more often consumed methadone and cocaine. Among dODs, 22.5% had suicidal intention and 9.6% were ambivalent about committing suicide; background motivations were most often conflicts with spouses. Fifty-seven percent of the cases were aOD. Cases of aODs had significantly more potential lethal intoxications and had heroin detected more frequently. aODs happened with unexpected pure heroin (46%), in combination with alcohol (36%), as relapse after abstinence (40%) or after institutionalized treatment (19%). This group should be accessible for targeted education.

  14. Dental pain as a risk factor for accidental acetaminophen overdose: a case-control study.

    Science.gov (United States)

    Vogel, Jody; Heard, Kennon J; Carlson, Catherine; Lange, Chad; Mitchell, Garrett

    2011-11-01

    Patients frequent take acetaminophen to treat dental pain. One previous study found a high rate of overuse of nonprescription analgesics in an emergency dental clinic. The purpose of this study is to determine if patients with dental pain are more likely to be treated for accidental acetaminophen poisoning than patients with other types of pain. We conducted a case-control study at 2 urban hospitals. Cases were identified by chart review of patients who required treatment for accidental acetaminophen poisoning. Controls were self-reported acetaminophen users taking therapeutic doses identified during a survey of emergency department patients. For our primary analysis, the reason for taking acetaminophen was categorized as dental pain or not dental pain. Our primary outcome was the odds ratio of accidental overdose to therapeutic users after adjustment for age, sex, alcoholism, and use of combination products using logistic regression. We identified 73 cases of accidental acetaminophen poisoning and 201 therapeutic users. Fourteen accidental overdose patients and 4 therapeutic users reported using acetaminophen for dental pain. The adjusted odds ratio for accidental overdose due to dental pain compared with other reasons for use was 12.8 (95% confidence interval, 4.2-47.6). We found that patients with dental pain are at increased risk to accidentally overdose on acetaminophen compared with patients taking acetaminophen for other reasons. Emergency physicians should carefully question patients with dental pain about overuse of analgesics. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. 76 FR 71348 - Role of Naloxone in Opioid Overdose Fatality Prevention; Public Workshop; Request for Comments

    Science.gov (United States)

    2011-11-17

    ... discussion about the potential value of making naloxone more widely available outside of conventional medical... registration on the day of the public workshop will be based on space availability. If registration reaches..., is an injectable medicine that can rapidly reverse the overdose of either prescription (e.g., Oxy...

  16. Altered intensity coding in the salicylate-overdose animal model of tinnitus

    Czech Academy of Sciences Publication Activity Database

    Wan, I.; Pokora, O.; Chiu, T.; Lánský, Petr; Poon, P. W.

    2015-01-01

    Roč. 136, Oct 2015 (2015), s. 113-119 ISSN 0303-2647 R&D Projects: GA ČR(CZ) GA15-08066S Institutional support: RVO:67985823 Keywords : auditory evoked potential * electrocorticogram * Fisher information * salicylate-overdose * tinnitus * rat Subject RIV: BD - Theory of Information Impact factor: 1.495, year: 2015

  17. Anhydrate to hydrate solid-state transformations of carbamazepine and nitrofurantoin in biorelevant media studied in situ using time-resolved synchrotron X-ray diffraction

    DEFF Research Database (Denmark)

    Bøtker, Johan Peter; Rantanen, Jukka; Arnfast, Lærke

    2016-01-01

    with different biorelevant media, simulated fasted and fed state intestinal fluids containing bile salt and dioleoylphosphatidylcholine (DOPC) micelles, DOPC/sodium dodecyl sulfate (SDS) mixture, bile salt solution and water. Two anhydrate compounds (carbamazepine, CBZ and nitrofurantoin, NF) with different...

  18. Latent classes of polydrug and polyroute use and associations with human immunodeficiency virus risk behaviours and overdose among people who inject drugs in Tijuana, Baja California, Mexico.

    Science.gov (United States)

    Meacham, Meredith C; Roesch, Scott C; Strathdee, Steffanie A; Lindsay, Suzanne; Gonzalez-Zuniga, Patricia; Gaines, Tommi L

    2018-01-01

    Patterns of polydrug use among people who inject drugs (PWID) may be differentially associated with overdose and unique human immunodeficiency virus (HIV) risk factors. Subgroups of PWID in Tijuana, Mexico, were identified based on substances used, route of administration, frequency of use and co-injection indicators. Participants were PWID residing in Tijuana age ≥18 years sampled from 2011 to 2012 who reported injecting an illicit substance in the past month (n = 735). Latent class analysis identified discrete classes of polydrug use characterised by 11 indicators of past 6 months substance use. Multinomial logistic regression examined class membership association with HIV risk behaviours, overdose and other covariates using an automated three-step procedure in mplus to account for classification error. Participants were classified into five subgroups. Two polydrug and polyroute classes were defined by use of multiple substances through several routes of administration and were primarily distinguished from each other by cocaine use (class 1: 5%) or no cocaine use (class 2: 29%). The other classes consisted primarily of injectors: cocaine, methamphetamine and heroin injection (class 3: 4%); methamphetamine and heroin injection (class 4: 10%); and heroin injection (class 5: 52%). Compared with the heroin-only injection class, memberships in the two polydrug and polyroute use classes were independently associated with both HIV injection and sexual risk behaviours. Substance use patterns among PWID in Tijuana are highly heterogeneous, and polydrug and polyroute users are a high-risk subgroup who may require more tailored prevention and treatment interventions. [Meacham MC, Roesch SC, Strathdee SA, Lindsay S, Gonzalez-Zuniga P, Gaines TL. Latent classes of polydrug and polyroute use and associations with human immunodeficiency virus risk behaviours and overdose among people who inject drugs in Tijuana, Baja California, Mexico. Drug Alcohol Rev 2018;37:128-136].

  19. Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose.

    Science.gov (United States)

    Scheuermeyer, Frank X; DeWitt, Christopher; Christenson, Jim; Grunau, Brian; Kestler, Andrew; Grafstein, Eric; Buxton, Jane; Barbic, David; Milanovic, Stefan; Torkjari, Reza; Sahota, Indy; Innes, Grant

    2018-03-09

    Fentanyl overdoses are increasing and few data guide emergency department (ED) management. We evaluate the safety of an ED protocol for patients with presumed fentanyl overdose. At an urban ED, we used administrative data and explicit chart review to identify and describe consecutive patients with uncomplicated presumed fentanyl overdose (no concurrent acute medical issues) from September to December 2016. We linked regional ED and provincial vital statistics databases to ascertain admissions, revisits, and mortality. Primary outcome was a composite of admission and death within 24 hours. Other outcomes included treatment with additional ED naloxone, development of a new medical issue while in the ED, and length of stay. A prespecified subgroup analysis assessed low-risk patients with normal triage vital signs. There were 1,009 uncomplicated presumed fentanyl overdose, mainly by injection. Median age was 34 years, 85% were men, and 82% received out-of-hospital naloxone. One patient was hospitalized and one discharged patient died within 24 hours (combined outcome 0.2%; 95% confidence interval [CI] 0.04% to 0.8%). Sixteen patients received additional ED naloxone (1.6%; 95% CI 1.0% to 2.6%), none developed a new medical issue (0%; 95% CI 0% to 0.5%), and median length of stay was 173 minutes (interquartile range 101 to 267). For 752 low-risk patients, no patients were admitted or developed a new issue, and one died postdischarge; 3 (0.4%; 95% CI 0.01% to 1.3%) received ED naloxone. In our cohort of ED patients with uncomplicated presumed fentanyl overdose-typically after injection-deterioration, admission, mortality, and postdischarge complications appear low; the majority can be discharged after brief observation. Patients with normal triage vital signs are unlikely to require ED naloxone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  20. Cognitive impairment in patients clinically recovered from central nervous system depressant drug overdose.

    Science.gov (United States)

    Dassanayake, Tharaka L; Michie, Patricia T; Jones, Alison; Carter, Gregory; Mallard, Trevor; Whyte, Ian

    2012-08-01

    Central nervous system depressant drugs (CNS-Ds) are known to impair cognitive functions. Overdose of these drugs is common, and most of the hospital-treated patients are discharged within 24 to 48 hours. No previous studies have examined whether they have residual impairment at the time of discharge. Our aim was to evaluate whether patients with CNS-D overdose are impaired in cognitive domains important in daily activities at that time. We compared visuomotor skills (Trail-Making Test A and Choice Reaction Time), executive functions (viz attentional set-shifting: Trail-Making Test B; and planning: Stockings of Cambridge Task from the Cambridge Neuropsychological Test Automated Battery), working memory (Letter-Number Sequencing), and impulsivity and decision making (Cambridge Neuropsychological Test Automated Battery Information Sampling) in 107 patients with CNS-D overdose (benzodiazepines, opioids, or antipsychotics) with a control group of 68 with non-CNS-D overdose (acetaminophen, selective serotonin reuptake inhibitors, and serotonin noradrenaline reuptake inhibitors) on discharge from hospital. Outcome measures were adjusted for demographic and clinical covariates in multivariate regression models. Compared with the controls, patients in the CNS-D group were significantly impaired in all domains: they had prolonged Trail-Making completion times and reaction times, poorer working memory and planning and were more impulsive in decision making. Their Stockings of Cambridge Task performance was comparable to that of the control group for simple problems but worsened with increasing task complexity. The results show that patients with CNS-D overdose could be impaired in multiple cognitive domains underlying everyday functioning even at the time they are deemed medically fit to be discharged. Such impairments could adversely affect social and professional lives of this relatively young population during the immediate postdischarge period.

  1. Can naloxone prescription and overdose training for opioid users work in family practice?

    Science.gov (United States)

    Leece, Pamela; Orkin, Aaron; Shahin, Rita; Steele, Leah S.

    2015-01-01

    Abstract Objective To explore family physicians’ attitudes toward prescribing naloxone to at-risk opioid users, as well as to determine the opportunities and challenges for expanding naloxone access to patients in family practice settings. Design One-hour focus group session and SWOT (strengths, weaknesses, opportunities, and threats) analysis. Setting Workshop held at the 2012 Family Medicine Forum in Toronto, Ont. Participants Seventeen conference attendees from 3 Canadian cities who practised in various family practice settings and who agreed to participate in the workshop. Methods The workshop included an overview of information about naloxone distribution and overdose education programs, followed by group discussion in smaller focus groups. Participants were instructed to focus their discussion on the question, “Could this [overdose education and naloxone prescription] work in your practice?” and to record notes using a standardized discussion guide based on a SWOT analysis. Two investigators reviewed the forms, extracting themes using an open coding process. Main findings Some participants believed that naloxone could be used safely among family practice patients, that the intervention fit well with their clinical practice settings, and that its use in family practice could enhance engagement with at-risk individuals and create an opportunity to educate patients, providers, and the public about overdose. Participants also indicated that the current guidelines and support systems for prescribing or administering naloxone were inadequate, that medicolegal uncertainties existed for those who prescribed or administered naloxone, and that high-quality evidence about the intervention’s effectiveness in family practice was lacking. Conclusion Family physicians believe that overdose education and naloxone prescription might provide patients at risk of opioid overdose in their practices with broad access to a potentially lifesaving intervention. However, they

  2. Application of experimental design in examination of the dissolution rate of carbamazepine from formulations: Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

    OpenAIRE

    Krstić Marko; Ražić Slavica; Vasiljević Dragana; Spasojević Đurđija; Ibrić Svetlana

    2015-01-01

    Poor solubility is one of the key reasons for the poor bioavailability of these drugs. This paper displays a formulation of a solid surfactant system with carbamazepine, in order to increase its dissolution rate. Solid state surfactant systems are formed by application of fractal experimental design. Poloxamer 237 and Poloxamer 338 were used as surfactants and Brij® 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied...

  3. Prescription Painkiller Overdoses in the U.S. – What You Need to Know PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2011-11-01

    This 60 second PSA is based on the November, 2011 CDC Vital Signs report. Overdose deaths from prescription painkillers have skyrocketed in the past decade. Every year, nearly 15,000 people die from these overdoses—more than those who die from heroin and cocaine combined. Learn the steps you can take to prevent an overdose.  Created: 11/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 11/1/2011.

  4. The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

    2006-11-01

    In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

  5. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine

    OpenAIRE

    Krstić Marko Z.; Ibrić Svetlana R.

    2016-01-01

    One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol® (1:...

  6. Chemometrics enhanced HPLC-DAD performance for rapid quantification of carbamazepine and phenobarbital in human serum samples.

    Science.gov (United States)

    Vosough, Maryam; Ghafghazi, Shiva; Sabetkasaei, Masoumeh

    2014-02-01

    This paper describes development and validation of a simple and efficient bioanalytical procedure for simultaneous determination of phenobarbital and carbamazepine in human serum samples using high performance liquid chromatography with photodiode-array detection (HPLC-DAD) regarding a fast elution methodology in less than 5 min. Briefly, this method consisted of a simple deproteinization step of serum samples followed by HPLC analysis on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH=7.5) buffer solution (45:55). Due to the presence of serum endogenous components as non-calibrated components in the sample, second-order calibration based on multivariate curve resolution-alternating least squares (MCR-ALS), has been applied on a set of absorbance matrices collected as a function of retention time and wavelengths. Acceptable resolution and quantification results were achieved in the presence of matrix interferences and the second-order advantage was fully exploited. The average recoveries for carbamazepine and phenobarbital were 89.7% and 86.1% and relative standard deviation values were lower than 9%. Additionally, computed elliptical joint confidence region (EJCR) confirmed the accuracy of the proposed method and indicated the absence of both constant and proportional errors in the predicted concentrations. The developed method enabled the determination of the analytes in different serum samples in the presence of overlapped profiles, while keeping experimental time and extraction steps at minimum. Finally, the serum concentration levels of carbamazepine in three time intervals were reported for morphine-dependents who had received carbamazepine for treating their neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

  7. Effects of pharmaceutical micropollutants on the membrane fouling of a submerged MBR treating municipal wastewater: case of continuous pollution by carbamazepine.

    Science.gov (United States)

    Li, Chengcheng; Cabassud, Corinne; Reboul, Bernard; Guigui, Christelle

    2015-02-01

    Membrane bioreactor (MBR) is increasingly used for municipal wastewater treatment and reuse and great concerns have been raised to some emerging trace pollutants found in aquatic environment in the last decade, notably the pharmaceuticals. As a consequence the removal of pharmaceutical micropollutants by MBRs has been extensively investigated. But there is still a lack of knowledge on the effects of the current presence of pharmaceutical micropollutants in domestic wastewaters on MBR fouling. Among the different pharmaceuticals, it was decided to focus on carbamazepine (CBZ), an anti-epileptic drug, because of its occurrence in domestic wastewaters and persistency in biological processes including MBRs. This paper focuses on the effects of continuous carbamazepine pollution on MBR fouling. A continuous introduction of CBZ into the MBR via the feed (about 90 μg L(-1) CBZ in the feed) provoked a TMP jump. It occurred just 1 day after the addition of CBZ in MBR and a significantly higher increase rate of TMP was also observed after 1 day after addition of CBZ in MBR, as compared to that before addition of CBZ. This indicates that the pharmaceutical stress induced by CBZ causes more severe membrane fouling. Addition of CBZ was shown to induce a significant increase of the concentration of proteins in the supernatant at the beginning several days then stabilized to original level whereas no significant change was found for polysaccharides. HPLC-SEC analysis showed that addition of CBZ induced a decrease of 100-1000 kDa protein-like SMPs and a more significant increase of 10-100 kDa protein-like SMPs in the supernatant. Moreover it was found that addition of CBZ in the MBR affected the sludge microbial activities, as a slight inhibition (about 20%) of the exogenous respiration rate was observed. The increased membrane fouling could be related to the change in biomass characteristics and supernatant quality after addition of CBZ in MBR. This study allows also

  8. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    International Nuclear Information System (INIS)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N.

    1999-01-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au)

  9. Sensory abnormalities and masticatory function after microvascular decompression or balloon compression for trigeminal neuralgia compared with carbamazepine and healthy controls.

    Science.gov (United States)

    Ichida, Michelle Cristina; de Almeida, Antonio Nogueira; da Nobrega, Jose Claudio Marinho; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu Tesseroli; de Siqueira, Silvia R D T

    2015-06-01

    Idiopathic trigeminal neuralgia (iTN) is a neurological condition treated with pharmacotherapy or neurosurgery. There is a lack of comparative papers regarding the outcomes of neurosurgery in patients with iTN. The objective of this study was to investigate sensory thresholds and masticatory function in 78 patients with iTN who underwent microvascular decompression (MVD) or balloon compression (BC), and compare these treatments with carbamazepine and 30 untreated healthy controls. The authors conducted a case-controlled longitudinal study. Patients were referred to 1 of 3 groups: MVD, BC, or carbamazepine. All patients were evaluated before and after treatment with a systematic protocol composed of a clinical orofacial questionnaire, Research Diagnostic Criteria for temporomandibular disorders, Helkimo indices, and a quantitative sensory-testing protocol (gustative, olfactory, cold, warm, touch, vibration, superficial, and deep pain thresholds). Both MVD and BC were effective at reducing pain intensity (p = 0.012) and carbamazepine doses (p sweet (p = 0.014) and salty (p = 0.003) thresholds. The sour threshold decreased (p = 0.003) and cold and warm thresholds increased (p sensorial and motor deficits after BC need to be included as targets directly associated with the success of the surgery and need to be assessed and relieved as goals in the treatment of iTN.

  10. A new herb–drug interaction of Polygonum cuspidatum, a resveratrol‐rich nutraceutical, with carbamazepine in rats

    International Nuclear Information System (INIS)

    Chi, Ying-Chang; Lin, Shiuan-Pey; Hou, Yu-Chi

    2012-01-01

    Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE), an active metabolite. This study investigated the acute and chronic effects of Polygonum cuspidatum (PC), a resveratrol‐rich nutraceutical, on the pharmacokinetics of CBZ in rats and the underlying mechanisms. Rats were orally administered CBZ (200 mg/kg) alone and coadministered with a single dose and the 7th dose of PC (2 g/kg) in a crossover design. The concentrations of CBZ and CBZE in serum and various tissues were determined by HPLC method. The results showed that PC significantly increased the AUC 0-t of CBZ and CBZE, whereas the formation rate of CBZE was decreased. Tissue analysis showed that the concentrations of CBZ and CBZE in brain, liver and kidney were significantly increased by PC. Cell studies indicated that the efflux function of MRP 2 was inhibited by the serum metabolites of PC. In conclusion, PC markedly increased the systemic exposure and brain concentration of CBZ and CBZE through inhibiting the activities of CYP 3A and MRP 2. Highlights: ► Polygonum cuspidatum elevated brain carbamazepine (CBZ) levels. ► Polygonum cuspidatum inhibited the activities of CYP 3A and MRP 2. ► Coadministration of PC with CBZ may enhance efficacy or toxicity.

  11. A new herb–drug interaction of Polygonum cuspidatum, a resveratrol‐rich nutraceutical, with carbamazepine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Ying-Chang [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, 40402, Taiwan (China); Lin, Shiuan-Pey [School of Pharmacy, China Medical University, Taichung, 40402, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, 40402, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan (China)

    2012-09-15

    Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE), an active metabolite. This study investigated the acute and chronic effects of Polygonum cuspidatum (PC), a resveratrol‐rich nutraceutical, on the pharmacokinetics of CBZ in rats and the underlying mechanisms. Rats were orally administered CBZ (200 mg/kg) alone and coadministered with a single dose and the 7th dose of PC (2 g/kg) in a crossover design. The concentrations of CBZ and CBZE in serum and various tissues were determined by HPLC method. The results showed that PC significantly increased the AUC{sub 0-t} of CBZ and CBZE, whereas the formation rate of CBZE was decreased. Tissue analysis showed that the concentrations of CBZ and CBZE in brain, liver and kidney were significantly increased by PC. Cell studies indicated that the efflux function of MRP 2 was inhibited by the serum metabolites of PC. In conclusion, PC markedly increased the systemic exposure and brain concentration of CBZ and CBZE through inhibiting the activities of CYP 3A and MRP 2. Highlights: ► Polygonum cuspidatum elevated brain carbamazepine (CBZ) levels. ► Polygonum cuspidatum inhibited the activities of CYP 3A and MRP 2. ► Coadministration of PC with CBZ may enhance efficacy or toxicity.

  12. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N. [Psychiatric Hospital, Dept. of Biological Psychiatry, Risskov (Denmark)

    1999-02-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au) 46 refs.

  13. Sorption of carbamazepine by commercial graphene oxides: a comparative study with granular activated carbon and multiwalled carbon nanotubes.

    Science.gov (United States)

    Cai, Nan; Larese-Casanova, Philip

    2014-07-15

    Graphene nanosheet materials represent a potentially new high surface area sorbent for the treatment of endocrine disrupting compounds (EDCs) in water. However, sorption behavior has been reported only for laboratory graphene prepared by a laborious and hazardous graphite exfoliation process. A careful examination of commercially available, clean, high-volume produced graphene materials should reveal whether they are appropriate for sorbent technologies and which physicochemical properties most influence sorption performance. In this study, three commercially available graphene oxide powders of various particle sizes, specific surface areas, and surface chemistries were evaluated for their sorption performance using carbamazepine and nine other EDCs and were compared to that of conventional granular activated carbon (GAC) and multi-walled carbon nanotubes (MWCNTs). Sorption kinetics of carbamazepine on graphene oxide powders was rapid and reversible with alcohol washing, consistent with π-π interactions. The various sorption extents as described by Freundlich isotherms were best explained by available surface area, and only the highest surface area graphene oxide (771 m(2)/g) out-performed GAC and MWCNTs. Increasing pH caused more negative surface charge, a twofold decrease in sorption of anionic ibuprofen, a onefold increase in sorption of cationic atenolol, and no change for neutral carbamazepine, highlighting the role of electrostatic interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia

    Directory of Open Access Journals (Sweden)

    Xue H

    2018-04-01

    Full Text Available Hui Xue,1,2 Wenping Xiang,2 Yichuan Yu,3 Guorong Liu,2 Yi Chong,2 Jiying Zhou1 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Neurology, Baotou Central Hospital, Inner Mongolia, Baotou, China; 3Department of Emergency, Yongchuan Hospital of Chongqing Medical University, Chongqing, China Background: Vestibular paroxysmia (VP is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ plus betahistine mesilate tablets (BMT (CBZ+BMT and oxcarbazepine (OXC plus BMT (OXC+BMT in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT.Methods: VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed.Results: In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group (p=0.04. Subgroup analysis found that patients receiving BMT (18 mg had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg.Conclusion: These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ

  15. Engagement in the Overdose RIsk InfOrmatioN (ORION) e-Health Tool for Opioid Overdose Prevention and Self-Efficacy: A Preliminary Study.

    Science.gov (United States)

    Carrà, Giuseppe; Crocamo, Cristina; Humphris, Gerald; Tabacchi, Tommaso; Bartoli, Francesco; Neufeind, Julia; Scherbaum, Norbert; Baldacchino, Alexander

    2017-12-01

    Increasing awareness of, and information about, overdose risk is an appropriate approach in risk reduction. e-Health technology in substance use disorders is an opportunity to support behavioral changes related to public health concerns. The present study aimed to evaluate the short-term impact of an innovative e-health psychoeducational software, the Overdose RIsk InfOrmatioN (ORION) tool. The ORION programme provided relevant information to opioid-dependent individuals about the risk of suffering a drug overdose as a result of high risky and dysfunctional behaviors. Seven aggregate risk factors were identified through a systematic review and their outputs included in a risk estimation model. We recruited 194 opioid-dependent treatment-seeking individuals from the United Kingdom, Germany, Italy, and Denmark. All participants were given at study entry, and after their use of the software, the General Self-Efficacy (GSE) Scale. We found comparable pre- and post-ORION administration mean GSE scores (SD), 28.49 (5.50) and 28.32 (5.90), respectively (p = 0.297). However, there was an inverse correlation between the number of risk factors and reported levels of self-efficacy (p ORION was able to identify individuals who are most in need of reducing their modifiable risk factors with appropriate interventions. However, a one-shot e-health tool cannot influence complex domains such as self-efficacy unless this is used with other effective interventions. Nonetheless, the ORION tool is unique in its style and content of delivery, that is translating risks combination into a clear estimation, and will need further development such as (a) integration in smartphone-based e-health apps and (b) testing in other high-risk populations.

  16. Hediste diversicolor as bioindicator of pharmaceutical pollution: Results from single and combined exposure to carbamazepine and caffeine.

    Science.gov (United States)

    Pires, Adília; Almeida, Ângela; Calisto, Vânia; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

    2016-10-01

    Several environmental stressors have been identified as key and/or emerging drivers of habitat change that could significantly influence marine near-shore ecosystems. These include increasing discharges of pharmaceutical contaminants into the aquatic coastal systems. Pharmaceutical drugs are often detected in aquatic environments but still information on their toxicity impacts on inhabiting species is scarce, especially when acting in combination. Furthermore, almost no information is available on the impacts of pharmaceuticals in polychaetes, often the most abundant taxon in benthic communities and commonly used as indicator species of environmental conditions. Therefore, the present study aimed to evaluate the biochemical alterations induced in the polychaete Hediste diversicolor, from a low contaminated area at the Ria de Aveiro lagoon (Portugal), by the antiepileptic drug carbamazepine (0.0 - control, 0.3, 3.0, 6.0 and 9.0μg/L) and the stimulant caffeine (0.0 - control, 0.5, 3.0, and 18.0μg/L), acting alone and in combination (0.3 CBZ+0.5 CAF and 6.0 CBZ+3.0 CAF). Glutathione S-transferases (GSTs), superoxide dismutase (SOD) and catalase (CAT) activities was determined in Hediste diversicolor from each condition. Lipid peroxidation (LPO), glutathione reduced and oxidized (GSH and GSSG), glycogen and electron transport system (ETS) were also measured. The results obtained clearly revealed that both drugs induced oxidative stress in H. diversicolor, shown by the increase on LPO levels and decrease on total glutathione and GSH/GSSG ratio with the increase of exposure concentrations. Furthermore, the present findings demonstrated that polychaetes biotransformation capacity as well as antioxidant defense mechanisms were not sufficiently efficient to fight against the excess of reactive oxygen species (ROS) leading to LPO when organisms were exposed to both drugs. Our results also demonstrated that polychaetes tended to decrease the activity of ETS when exposed to

  17. Do co-intoxicants increase adverse event rates in the first 24 hours in patients resuscitated from acute opioid overdose?

    Science.gov (United States)

    Mirakbari, Seyed Mostafa; Innes, Grant D; Christenson, Jim; Tilley, Jessica; Wong, Hubert

    2003-01-01

    Patients frequently arrive in emergency departments (EDs) after being resuscitated from opioid overdose. Autopsy studies suggest that multidrug intoxication is a major risk factor for adverse outcomes after acute heroin overdose in patients. If this is true, there may be high-risk drug combinations that identify patients who require more intensive monitoring and prolonged observation. Our objective was to determine the impact of co-intoxication with alcohol, cocaine, or CNS depressant drugs on short-term adverse event rates in patients resuscitated from acute opioid overdose. Data were extracted from the database of a prospective opioid overdose cohort study conducted between May 1997 and 1999. Patients were prospectively enrolled if they received naloxone for presumed opioid overdose. Investigators gathered clinical, demographic, and other predictor variables, including co-intoxicants used. Patients were followed to identify prespecified adverse outcome events occurring within 24 h, and multiple logistic regression was used to determine the association of concomitant drug use on short-term adverse event rates. Of 1155 patients studied, 58 (5%) had pure opioid overdose and 922 (80%) reported co-intoxicants, including alcohol, cocaine, and CNS depressants. Overall, out of 1056 patients with known outcome status there were 123 major adverse events (11.6%) and 194 minor adverse events (18.4%). After adjustment for age, gender, HIV status, cardiovascular disease, pulmonary disease and diabetes, we found that coadministration of alcohol, cocaine, or CNS depressants, alone or in combination, was not associated with increased risk of death or adverse events during the 24 h follow-up period. In patients resuscitated from acute opioid overdose, short-term outcomes are similar for patients with pure opioid overdose and multidrug intoxications. A history of cointoxication cannot be used to identify high-risk patients who require more intensive ED monitoring or prolonged

  18. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine

    Directory of Open Access Journals (Sweden)

    Krstić Marko Z.

    2016-01-01

    Full Text Available One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS. Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS consisting of oil phase (caprilic-capric triglycerides, a surfactant (Polisorbat 80 and Labrasol® (1:1 and cosurfactant (Transcutol® HP are formed by applying mixture design. 16 formulations were formulated, where proportion of lipids, surfactant and cosurfactant were varied (input parameters in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water, the droplet size and polydispersity index (PdI of the obtained emulsions (output parameters were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin® UFl2, Neusilin® FL2, Sylysia® 320, diatomite were used as the carriers. The ratio of SNEDDS:carrier varied (1:1, 2:1. Dissolution testing was carried out in the rotation paddles apparatus. Caracterization of solid SNEDDS was performed using the hot stage microscopy (HSM, thermogravimetric analysis (TGA, differential scanning calorimetry (DSC, infrared spectrophotometry with Fourier transformation (FT-IR, scanning electron microscopy (SEM and X-ray diffraction (PXRD. Selected SNEDDS consisting of lipids (21.12%, surfactant (42.24% and cosurfactant (36.64% had a droplet size 157.02±34.09 nm and PDI 0.184±0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia® 320. It can be concluded that in all

  19. Reducing risk of overdose with midazolam injection in adults: an evaluation of change in clinical practice to improve patient safety in England.

    Science.gov (United States)

    Flood, Chris; Matthew, Linda; Marsh, Rachel; Patel, Bhavesh; Mansaray, Mariama; Lamont, Tara

    2015-02-01

    This study sought to evaluate potential reductions in risk associated with midazolam injection, a sedating medication, following a UK National Patient Safety Alert. This alert, 'Reducing risk of overdose with midazolam injection in adults', was sent to all National Health Service organizations as a Rapid Response Report detailing actions services should take to minimize risks. To evaluate any potential changes arising from this alert, a number of data sources were explored including reported incidents to a national reporting system for health care error, clinician survey and audit data, pharmaceutical purchasing patterns and feedback from National Health Service managers. Prior to the Rapid Response Report, 498 incidents were received by the National Patient Safety Agency including three deaths. Post-implementation of the Rapid Response Report (June 2009), no incidents resulting in death or severe harm had been received. All organizations reported having completed the Rapid Response Report actions. Purchase and use of risk-prone, high-strength sedating midazolam by health care organizations decreased significantly as did the increased use of safer, lower strength doses (as recommended in the Rapid Response Report). Organizations can achieve safer medication practices, better knowledge, awareness and implementation of national safer practice recommendations. Risks from inadvertent overdose of midazolam injection were reduced post-implementation of national recommendations. Ongoing monitoring of this particular adverse event will be required with a sustained patient safety message to health services to maintain awareness of the issue and reduction in the number of midazolam-related errors. © 2014 John Wiley & Sons, Ltd.

  20. Assessment of the effects of the carbamazepine on the endogenous endocrine system of Daphnia magna.

    Science.gov (United States)

    Oropesa, A L; Floro, A M; Palma, P

    2016-09-01

    In the present study, the endocrine activity of the antiepileptic pharmaceutical carbamazepine (CBZ) in the crustacean Daphnia magna was assessed. To assess the hormonal activity of the drug, we exposed maternal daphnids and embryos to environmental relevant concentrations of CBZ (ranging from 10 to 200 μg/L) and to mixtures of CBZ with fenoxycarb (FEN; 1 μg/L). Chronic exposure to CBZ significantly decreased the reproductive output and the number of molts of D. magna at 200 μg/L. This compound induced the production of male offspring (12 ± 1.7 %), in a non-concentration-dependent manner, acting as a weak juvenile hormone analog. Results showed that this substance, at tested concentrations, did not antagonize the juvenoid action of FEN. Further, CBZ has shown to be toxic to daphnid embryos through maternal exposure interfering with their normal gastrulation and organogenesis stages but not producing direct embryo toxicity. These findings suggest that CBZ could act as an endocrine disruptor in D. magna as it decreases the reproductive output, interferes with sex determination, and causes development abnormality in offspring. Therefore, CBZ could directly affect the population sustainability.

  1. Thermodynamic Solubility Profile of Carbamazepine-Cinnamic Acid Cocrystal at Different pH.

    Science.gov (United States)

    Keramatnia, Fatemeh; Shayanfar, Ali; Jouyban, Abolghasem

    2015-08-01

    Pharmaceutical cocrystal formation is a direct way to dramatically influence physicochemical properties of drug substances, especially their solubility and dissolution rate. Because of their instability in the solution, thermodynamic solubility of cocrystals could not be determined in the common way like other compounds; therefore, the thermodynamic solubility is calculated through concentration of their components in the eutectic point. The objective of this study is to investigate the effect of an ionizable coformer in cocrystal with a nonionizable drug at different pH. Carbamazepine (CBZ), a nonionizable drug with cinnamic acid (CIN), which is an acidic coformer, was selected to prepare CBZ-CIN cocrystal and its thermodynamic solubility was studied in pH range 2-7. Instead of HPLC that is a costly and time-consuming method, a chemometric-based approach, net analyte signal standard addition method, was selected for simultaneous determination of CBZ and CIN in solution. The result showed that, as pH increases, CIN ionization leads to change in CBZ-CIN cocrystal solubility and stability in solution. In addition, the results of this study indicated that there is no significant difference between intrinsic solubility of CBZ and cocrystal despite the higher ideal solubility of cocrystal. This verifies that ideal solubility is not good parameter to predict cocrystal solubility. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Metabolism of carbamazepine in plant roots and endophytic rhizobacteria isolated from Phragmites australis.

    Science.gov (United States)

    Sauvêtre, Andrés; May, Robert; Harpaintner, Rudolf; Poschenrieder, Charlotte; Schröder, Peter

    2018-01-15

    Carbamazepine (CBZ) is a pharmaceutical frequently categorized as a recalcitrant pollutant in the aquatic environment. Endophytic bacteria previously isolated from reed plants have shown the ability to promote growth of their host and to contribute to CBZ metabolism. In this work, a horseradish (Armoracia rusticana) hairy root (HR) culture has been used as a plant model to study the interactions between roots and endophytic bacteria in response to CBZ exposure. HRs could remove up to 5% of the initial CBZ concentration when they were grown in spiked Murashige and Skoog (MS) medium. Higher removal rates were observed when HRs were inoculated with the endophytic bacteria Rhizobium radiobacter (21%) and Diaphorobacter nitroreducens (10%). Transformation products resulting from CBZ degradation were identified using liquid chromatography-ultra high-resolution quadrupole time of flight mass spectrometry (LC-UHR-QTOF-MS). CBZ metabolism could be divided in four pathways. Metabolites involving GSH conjugation and 2,3-dihydroxylation, as well as acridine related compounds are described in plants for the first time. This study presents strong evidence that xenobiotic metabolism and degradation pathways in plants can be modulated by the interaction with their endophytic community. Hence it points to plausible applications for the elimination of recalcitrant compounds such as CBZ from wastewater in CWs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Carbamazepine and oxcarbazepine in adult patients with Dravet syndrome: Friend or foe?

    Science.gov (United States)

    Snoeijen-Schouwenaars, F M; Veendrick, M J B M; van Mierlo, P; van Erp, G; de Louw, A J A; Kleine, B U; Schelhaas, H J; Tan, I Y

    2015-07-01

    In newly diagnosed patients with Dravet syndrome sodium channel blockers are usually avoided. However, in many adult patients the diagnosis was made long after the initiation of therapy. The purpose of our study was to acquire information concerning the potential risks and benefits of (ox)carba(ma)zepine withdrawal in adult patients with genetically confirmed Dravet syndrome. We identified 16 adults with Dravet syndrome, living in a tertiary care facility for people with epilepsy and an intellectual disability. We reviewed clinical history, genetic findings, the type and duration of sodium channels blockers that were used, seizure types and frequency, and the effect of a change in these medications. The study population consisted of 9 men and 7 women. Median age was 35 years (range 20-61 years). An attempt to withdraw carbamazepine (CBZ) was made in 9 patients. In 3 of these patients an increase in tonic-clonic seizures was observed. An attempt to withdraw oxcarbazepine (OXC) was made in 3 patients, leading to a complete stop in 2 patients. 3 of the 4 deaths in the withdrawal-group were related to epilepsy. In adult patients with Dravet syndrome withdrawal of CBZ or OXC is not without risks. We suggest that (ox)carba(ma)zepine withdrawal should be considered in these patients but only if there is a good reason to do so and only if they are closely monitored. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. N-Doped TiO₂-Coated Ceramic Membrane for Carbamazepine Degradation in Different Water Qualities.

    Science.gov (United States)

    Luster, Enbal; Avisar, Dror; Horovitz, Inna; Lozzi, Luca; Baker, Mark A; Grilli, Rossana; Mamane, Hadas

    2017-07-31

    The photocatalytic degradation of the model pollutant carbamazepine (CBZ) was investigated under simulated solar irradiation with an N-doped TiO₂-coated Al₂O₃ photocatalytic membrane, using different water types. The photocatalytic membrane combines photocatalysis and membrane filtration in a single step. The impact of each individual constituent such as acidity, alkalinity, dissolved organic matter (DOM), divalent cations (Mg 2+ and Ca 2+ ), and Cl - on the degradation of CBZ was examined. CBZ in water was efficiently degraded by an N-doped TiO₂-coated Al₂O₃ membrane. However, elements added to the water, which simulate the constituents of natural water, had an impact on the CBZ degradation. Water alkalinity inhibited CBZ degradation mostly due to increase in pH while radical scavenging by carbonate was more dominant at higher values (>200 mg/L as CaCO₃). A negative effect of Ca 2+ addition on photocatalytic degradation was found only in combination with phosphate buffer, probably caused by deposition of CaHPO₄ or CaHPO₄·2H₂O on the catalyst surface. The presence of Cl - and Mg 2+ ions had no effect on CBZ degradation. DOM significantly inhibited CBZ degradation for all tested background organic compounds. The photocatalytic activity of N-doped TiO₂-coated Al₂O₃ membranes gradually decreased after continuous use; however, it was successfully regenerated by 0.1% HCl chemical cleaning. Nevertheless, dissolution of metals like Al and Ti should be monitored following acid cleaning.

  5. Inhibition of the solid state transformation of carbamazepine in aqueous solution: impact of polymeric properties.

    Science.gov (United States)

    Gift, Alan D; Hettenbaugh, Jacob A; Quandahl, Rachel A; Mapes, Madison

    2017-11-06

    The effects of polymers on the anhydrate-to-hydrate transformation of carbamazepine (CBZ) was investigated. The three types of polymers studied were polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and substituted celluloses which included hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC). Anhydrous CBZ was added to dilute aqueous polymer solutions and Raman spectroscopy measurements were collected to monitor the kinetics of the solution-mediated transformation to CBZ dihydrate. Polymers exhibiting the greatest inhibition were able to reduce the growth phase of the solution-mediated transformation and change the habit of the hydrate crystal indicating polymer adsorption to the hydrate crystal surface as the mechanism of inhibition. The results of the various polymers showed that short chain substituted celluloses (HPMC and MC) inhibited the CBZ transformation to a much greater extent than longer chains. The same trend was observed for PVP and PVA, but to a lesser extent. These chain length effects were attributed to changes in polymer confirmation when adsorbed on the crystal surface. Additionally, decreasing the percentage of hydroxyl groups on the PVA polymer backbone reduced the ability of the polymer to inhibit the transformation and changing the degree of substitutions of methyl and hydroxypropyl groups on the cellulosic polymer backbone had no effect on the transformation.

  6. Effects of carbamazepine on dexamethasone suppression and sleep electroencephalography in borderline personality disorder.

    Science.gov (United States)

    De la Fuente, José M; Bobes, Julio; Vizuete, Coro; Mendlewicz, Julien

    2002-01-01

    The pathophysiology of borderline personality disorder (BPD) remains obscure, but there is mounting evidence of brain dysfunction without focal abnormality. The dexamethasone suppression test (DST) and sleep electroencephalography (sleep EEG) have been studied in BPD, but the findings seem to be related to a concomitant axis I diagnosis of major depression (MD) rather than to BPD itself. There is no effective treatment for BPD. Carbamazepine (CBZ) has shown contradictory results and in a previous study, our results were negative. In this study, we investigated the effects of CBZ versus placebo on the DST and sleep EEG in a sample of 20 BPD patients without concomitant MD. CBZ given at doses that are therapeutic for epilepsy and affective disorders may have an effect on the DST and sleep EEG in BPD. CBZ significantly increased the postdexamethasone plasma cortisol values. This did not parallel MD or an increase in the Hamilton depression rating scores. CBZ also increased slow wave sleep (SWS). The mechanisms by which CBZ increased postdexamethasone plasma cortisol levels and SWS in BPD are discussed. Copyright 2002 S. Karger AG, Basel

  7. Biosorption of clofibric acid and carbamazepine in aqueous solution by agricultural waste rice straw.

    Science.gov (United States)

    Liu, Zhanguang; Zhou, Xuefei; Chen, Xiaohua; Dai, Chaomeng; Zhang, Juan; Zhang, Yalei

    2013-12-01

    Due to their widespread use, clofibric acid (CA) and carbamazepine (CBZ) have been frequently detected simultaneously at relatively high concentrations in aquatic environments. In this study, agricultural waste rice straw was employed as a potentially low-cost, effective and easy-to-operate biosorbent (RSB) to remove CA and CBZ. The adsorption of both pharmaceuticals followed pseudo second-order kinetics, and intraparticle diffusion was an important rate-limiting step. The adsorption isotherms of both drugs were fit well with Freundlich model. The adsorption of CA onto RSB was exothermic and was more likely to be dominated by physical processes, while the adsorption of CBZ was endothermic. Solution pH was determined to be the most important factor for CA adsorption, such that the adsorption capacity of CA onto RSB increased with the decline of solution pH. In the lower range of solution pH below 3.1, the CA removal efficiency was enhanced with the increase of biosorbent dosage. The CBZ removal efficiency was enhanced with the increase of RSB dosage without pH control. The maximum adsorption capacities were 126.3 mg/g for CA and 40.0 mg/g for CBZ.

  8. Carbamazepine and diclofenac: removal in wastewater treatment plants and occurrence in water bodies.

    Science.gov (United States)

    Zhang, Yongjun; Geissen, Sven-Uwe; Gal, Carmen

    2008-11-01

    In the aquatic environment, pharmaceuticals have been widely found. Among them, carbamazepine and diclofenac were detected at the highest frequency. To evaluate the worldwide environmental impacts of both drugs, their global consumption volumes are estimated, based on the dose per capita. The metabolites of these pharmaceuticals are also of environmental concerns, especially trans-10,11-dihydro-10,11- dihydroxycarbamazepine (CBZ-diol) which probably has a similar concentration in water bodies to that of its parent drug. The removal efficiencies and mechanisms of both drugs in the wastewater treatment plants (WWTPs) are discussed with the actual state of knowledge. The occurrences of both drugs are examined in various water bodies including WWTP effluents, surface waters, groundwater and drinking water. Their chemical, physical and pharmacological properties are also addressed in context, which can largely influence their environmental behaviors. The ecotoxicological studies of both drugs imply that they do not easily cause acute toxic effects at their environmental concentrations. However their chronic effects need cautious attention.

  9. Carbamazepine-Fumaric Acid Co-Crystal Screening Using Solution Based Method

    Directory of Open Access Journals (Sweden)

    Abd Rahim Syarifah

    2016-01-01

    Full Text Available Co-crystals is a multi-component system which connected by non-covalent interactions, present physically as a solid form under ambient conditions. Nowadays, co-crystal has becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ and fumaric acid (FUM co-crystal former (CCF using non-stoichiometric method (addition of CBZ to CCF saturated solution and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD, Differential Scanning Calorimetry (DSC and Fourier Transform Infrared (FT-IR. The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method where no crystal was found precipitate. The findings from this study revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvent systems.

  10. Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain

    Directory of Open Access Journals (Sweden)

    Shanshan Liu

    2018-01-01

    Full Text Available Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs. The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm with high drug loading (around 35% and high entrapment efficiency (around 80%. The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.

  11. Application of nanofiltration for the removal of carbamazepine, diclofenac and ibuprofen from drinking water sources.

    Science.gov (United States)

    Vergili, I

    2013-09-30

    Pharmaceutical active compounds (PhACs) are persistent during the process used to treat drinking water and, because drinking water treatment plants are not specifically designed to remove PhACs, these compounds are found in drinking water. Although there are currently no regulations or drinking water directives for PhACs, precautionary principles suggest ensuring maximal removal of PhACs through improved or existing treatment techniques. This study was designed to investigate the performance of a nanofiltration membrane in cross-flow filtration equipment for the removal of three PhACs [carbamazepine (CBZ), diclofenac (DIC) and ibuprofen (IBU)] that were spiked in water taken from a drinking water treatment plant using surface water. Because of their low solubilities, high log Kow values, low dipole moments and negative charges, higher rejection values were obtained for DIC and IBU. Low to moderate rejection values were most likely due to the small molecular sizes of the PhACs (i.e., MW water. Flux declines obtained from DIC studies was attributed to the adsorption of DIC ions inside the membrane pores, which decreases the flux. The most evident change in the FT-IR spectrum after nanofiltration was the appearance of new intense bands at 1072 cm(-1) and 1011 cm(-1), indicating the deposition of calcium salts on the membrane surface. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. A microbial electro-fenton cell for removing carbamazepine in wastewater with electricity output.

    Science.gov (United States)

    Wang, Wei; Lu, Yaobin; Luo, Haiping; Liu, Guangli; Zhang, Renduo; Jin, Song

    2018-03-27

    High electrical energy is required for the electro-Fenton process to remove pharmaceuticals and personal care products (PPCPs) in wastewater. The aim of this study was to develop a novel and more cost-effective process, specifically a microbial electro-Fenton cell (MeFC), for treating PPCPs in wastewater. Acetylene black was selected as the catalyst for H 2 O 2 electrogeneration and Fe-Mn binary oxide for hydroxyl radical production. In addition to lowering energy needs, the MeFC produced a maximum power density of 112 ± 11 mW/m 2 with 1 g/L acetate as a representative substrate and 10 mg/L carbamazepine (CBZ) as a typical PPCP. Comparing with electro-Fenton process, the CBZ removal in the MeFC was 38% higher within 24 h operation (90% vs. 62%). Furthermore, the CBZ removal rate in the MeFC was 10-100 times faster than that in other biological treatment processes. Such enhanced degradation of CBZ in the MeFC was attributed to the synergistic reactions between radical oxidation of CBZ and biodegradation of degradative intermediates. The MeFC provides a promising method to remove PPCPs from wastewater coupling with efficient removal of other biodegradable organics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. [Drug rash with eosinophilia and systemic symptoms syndrome induced by carbamazepine: Case report].

    Science.gov (United States)

    Marín, Jorge Alonso; Ortega, Mayra Alexandra; Sánchez, Isaura Pilar; Pacheco, José Armando

    2017-06-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases.We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient's condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.

  14. COMMUNICATING RISK IN THE CONTEXT OF METHADONE FORMULATION CHANGES: A QUALITATIVE STUDY OF OVERDOSE WARNING POSTERS IN VANCOUVER, CANADA

    Science.gov (United States)

    Markwick, Nicole; McNeil, Ryan; Anderson, Solanna; Small, Will; Kerr, Thomas

    2015-01-01

    BACKGROUND British Columbia, Canada’s provincial methadone program recently replaced their existing methadone formulation with a formulation ten times more concentrated. The transition raised concerns about heightened risk of accidental overdose, leading two organizations to disseminate methadone overdose warning posters during the transitional period. This study explores people who use drugs’ (PWUD) perceptions of these warning posters. METHODS Qualitative interviews were conducted with thirty-four PWUD enrolled in methadone maintenance treatment in Vancouver. Participants were recruited from ongoing cohort studies of drug-using individuals. Interview transcripts were analyzed thematically, focusing on participants’ perceptions of the warning posters and potential impacts on drug-related risks. RESULTS Overdose warning posters constituted a key source of information about the methadone formulation change, but did not provide adequate information for all participants. Participants articulated a preference for descriptive language, focusing on changes in concentration rather than “strength”, and universal hazard symbols to effectively communicate overdose risks. CONCLUSION Participants indicated that warnings employing descriptive language more effectively communicated risk of methadone overdose. Future overdose warnings for drug-using populations must provide adequate information for the intended audience, and be communicated to PWUD through multiple channels. PMID:26644025

  15. Opioid overdose prevention training with naloxone, an adjunct to basic life support training for first-year medical students.

    Science.gov (United States)

    Berland, Noah; Fox, Aaron; Tofighi, Babak; Hanley, Kathleen

    2017-01-01

    Opioid overdose deaths have reached epidemic proportions in the United States. This problem stems from both licit and illicit opioid use. Prescribing opioids, recognizing risky use, and initiating prevention, including opioid overdose prevention training (OOPT), are key roles physicians play. The American Heart Association (AHA) modified their basic life support (BLS) algorithms to consider naloxone in high-risk populations and when a pulse is appreciated; however, the AHA did not provide OOPT. The authors' intervention filled this training deficiency by teaching medical students opioid overdose resuscitation with a Train-the-Trainer model as part of mandatory BLS training. The authors introduced OOPT, following a Train-the-Trainer model, into the required basic life support (BLS) training for first-year medical students at a single medical school in a large urban area. The authors administered pre- and post-evaluations to assess the effects of the training on opioid overdose knowledge, self-reported preparedness to respond to opioid overdoses, and attitudes towards patients with substance use disorders (SUDs). In the fall 2014, 120 first-year medical students received OOPT. Seventy-three students completed both pre- and posttraining evaluations. Improvements in knowledge about and preparedness to respond to opioid overdoses were statistically significant (P support dissemination of OOPT as a part of BLS training for all medical students, and potentially all BLS providers.

  16. The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose.

    Science.gov (United States)

    Craig, D G; Zafar, S; Reid, T W D J; Martin, K G; Davidson, J S; Hayes, P C; Simpson, K J

    2012-06-01

    The sequential organ failure assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose, but has not been evaluated following staggered (multiple supratherapeutic doses over >8 h, resulting in cumulative dose of >4 g/day) overdoses. To evaluate the prognostic accuracy of the SOFA score following staggered paracetamol overdose. Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual timed laboratory samples were correlated with corresponding clinical parameters and the daily SOFA scores were calculated. A total of 39/50 (78%) patients developed hepatic encephalopathy. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2-95.7), 94.3 (95% CI 82.5-99.1), and 98.4 (95% CI 84.3-100.0) at 0, 24 and 48 h, respectively, postadmission. A SOFA score of paracetamol overdose, is associated with a good prognosis. Both the SOFA and APACHE II scores could improve triage of high-risk staggered paracetamol overdose patients. © 2012 Blackwell Publishing Ltd.

  17. Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

    Science.gov (United States)

    Phillpotts, Simon; Tash, Elliot; Sen, Sambit

    2014-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Escalation with Overdose Control Using Ordinal Toxicity Grades for Cancer Phase I Clinical Trials

    Directory of Open Access Journals (Sweden)

    Mourad Tighiouart

    2012-01-01

    Full Text Available We extend a Bayesian adaptive phase I clinical trial design known as escalation with overdose control (EWOC by introducing an intermediate grade 2 toxicity when assessing dose-limiting toxicity (DLT. Under the proportional odds model assumption of dose-toxicity relationship, we prove that in the absence of DLT, the dose allocated to the next patient given that the previously treated patient had a maximum of grade 2 toxicity is lower than the dose given to the next patient had the previously treated patient exhibited a grade 0 or 1 toxicity at the most. Further, we prove that the coherence properties of EWOC are preserved. Simulation results show that the safety of the trial is not compromised and the efficiency of the estimate of the maximum tolerated dose (MTD is maintained relative to EWOC treating DLT as a binary outcome and that fewer patients are overdosed using this design when the true MTD is close to the minimum dose.

  19. Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course.

    Science.gov (United States)

    Foulke, G E; Albertson, T E; Walby, W F

    1986-11-01

    There is controversy regarding the appropriate utilization of health care resources in the management of tricyclic antidepressant overdosage. Antidepressant overdose patients presenting to the emergency department (ED) are routinely admitted to intensive care units, but only a small proportion develop cardiac arrhythmias or other complications requiring such an environment. The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose. They found that major manifestations of toxicity on ED evaluation (altered mental status, seizures, arrhythmias, and conduction defects) were commonly associated with a complicated hospital course. Patients with the isolated findings of sinus tachycardia or QTc prolongation had no complications. No patient experienced a serious toxic event without major evidence of toxicity on ED evaluation and continued evidence of toxicity during the hospital course. These data support the concept that proper ED evaluation can identify a large body of patients with trivial ingestions who may not require hospital observation.

  20. A behavioral typology of opioid overdose risk behaviors among recent veterans in New York City.

    Directory of Open Access Journals (Sweden)

    Alex S Bennett

    Full Text Available To identify meaningful classes of opioid-using military veterans in terms of self-reported opioid overdose risk behaviors.The study recruited a sample of 218 military veterans in the NYC area who were discharged from active duty service after September 11, 2001 and reported past-month opioid use. Survey data including measures of mental health, social stressors, substance use, and opioid-related overdose risk behaviors were analyzed using Latent Class Analysis (LCA.A five group solution had excellent fit scores and interpretability. Factor analysis confirmed the existence of two major dimensions of variation: non-adherence and heroin use. The five groups included lower-risk prescription opioid users, non-adherent prescription opioid users and heroin users. The non-adherent prescription opioid users and heroin user classes were both further subdivided into "occasional" and "regular" use categories. In addition to endorsing a greater number of overdose risk behaviors, users in the regular use classes were more likely to screen positive for alcohol and substance use disorders, reported greater self-medicating opioid use to relieve anxiety, reported greater problems with physical pain, were more likely to have had mental health, alcohol and drug treatment, and were less likely to be employed or in school. Heroin users also were less likely to report stable housing.Findings indicate that opioid overdose risk classes are grounded in contextual factors related to experiences of psychological, physiological, and social adjustment pain and distress which should be addressed in tailored interventions targeting opioid users' unique constellations of risk behaviors and comorbid conditions.

  1. Noncardiogenic Pulmonary Edema after Amlodipine Overdose without Refractory Hypotension and Bradycardia

    Directory of Open Access Journals (Sweden)

    M. Hedaiaty

    2015-01-01

    Full Text Available Amlodipine overdose can be life-threatening when manifesting as noncardiogenic pulmonary edema. Treatment remains challenging. We describe a case of noncardiogenic pulmonary edema without refractory hypotension and bradycardia after ingestion of 500 milligram amlodipine with suicidal intent. Mechanical ventilation, dexamethasone, atrovent HFA (ipratropium, pulmicort inhalation, and antibiotic therapy were used for the management. Length of hospital stay was 11 days. The patient was discharged with full recovery.

  2. Performance of a multi-disciplinary emergency department observation protocol for acetaminophen overdose.

    Science.gov (United States)

    Beauchamp, Gillian A; Hart, Kimberly W; Lindsell, Christopher J; Lyons, Michael S; Otten, Edward J; Smith, Carol L; Ward, Michael J; Wright, Stewart W

    2013-09-01

    The availability of 20-h N-acetylcysteine (NAC) infusion for low-risk acetaminophen (APAP) overdose enabled our center to implement an Emergency Department observation unit (OU) protocol as an alternative to hospitalization. Our objective was to evaluate our early experience with this protocol. This retrospective cohort study included all patients treated for low-risk APAP overdose in our academic hospital between 2006 and 2011. Cases were identified using OU and pharmacy records. Successful OU discharge was defined as disposition with no inpatient admission. Differences in medians with 95 % confidence intervals were used for comparisons. One hundred ninety-six patients received NAC for APAP overdose with a mean age of 35 years (SD 14); 73 % were white, and 43 % were male. Twenty (10 %) received care in the OU; 3/20(15 %) met criteria for inclusion in the OU protocol and 13/20(65 %) were discharged successfully. Out of the 196 patients, 10 met criteria for inclusion in the OU protocol but instead received care in the inpatient setting. The median total length of stay from presentation to ED discharge was 41 h for all patients treated in the OU, compared to 68 h for ten patients who met criteria for inclusion in the OU protocol but who were admitted (difference 27 h, 95 % CI 18-72 h). ED observation for APAP overdose can be a viable alternative to inpatient admission. Most patients were successfully discharged from the OU. This evaluation identified both over- and under-utilization of the OU. OU treatment resulted in shorter median length of stay than inpatient admission.

  3. The Syndemic of Opioid Misuse, Overdose, HCV, and HIV: Structural-Level Causes and Interventions.

    Science.gov (United States)

    Perlman, David C; Jordan, Ashly E

    2018-04-01

    This article reviews the case for recognizing (1) the epidemics of opioid misuse, overdose, hepatitis C virus, and HIV as a syndemic and (2) the importance of examining and addressing structural factors in responses to this syndemic. We focus on the current syndemic in the US, but also consider data from other locations to highlight the issues existing and arising in various contexts. Advances in multi-level theory and statistical methods allow sound ecologic and multi-level analyses of the impact of structural factors on the syndemic. Studies of opioid misuse, overdoses, hepatitis C virus, and HIV demonstrate that area-level access to healthcare, medication-assisted treatment of opioid use disorders, sterile injection equipment, and overdose prevention with naloxone, as well as factors such as opioid marketing, income inequality, intensity of policing activities, and health care policies, are related to the prevalence of substance misuse, overdoses, infection risk, and morbidity. Structural variables can predict area-level vulnerability to the syndemic. The implementation of combined prevention and treatment interventions can control and reverse components of the syndemic. Recognizing and monitoring potent structural factors can facilitate the identification of areas at risk of vulnerability to the syndemic. Further, many structural factors are modifiable through intervention and policy to reduce structural vulnerability and create health-enabling environments. Evidence supports the immediate implementation of broader HCV and HIV testing and substance use screening, medication-assisted treatment, needle/syringe exchange programs, naloxone programs, increased population-level implementation of HCV treatment, and further attention to structural-level factors predicting, and contributing to, area-level vulnerability, such as degrees of opioid marketing, distribution, and prescribing.

  4. Pharmacists' role in opioid overdose: Kentucky pharmacists' willingness to participate in naloxone dispensing.

    Science.gov (United States)

    Freeman, Patricia R; Goodin, Amie; Troske, SuZanne; Strahl, Audra; Fallin, Amanda; Green, Traci C

    To assess pharmacists' willingness to initiate the dispensing of naloxone. As of 2015, Kentucky law permits certified pharmacists to dispense naloxone under a physician-approved protocol. Electronic survey (e-mail) gauging perception of pharmacists' role in opioid overdose and attitudes toward, and barriers to, naloxone dispensing. All Kentucky pharmacists with active licenses in 2015. Ordinal logistic regression was used to estimate the impact of pharmacist characteristics and attitudes on willingness to initiate naloxone dispensing, where the dependent variable was operationalized as a Likert-type question on a scale of 1 (not at all willing) to 6 (very willing). Of 4699 practicing Kentucky pharmacists, 1282 responded, of which 834 were community practitioners (response rate 27.3%). Pharmacists reported varying willingness to initiate naloxone dispensing, with 37.3% very willing (score 5 or 6) and 27.9% not willing (score 1 or 2). However, a majority of pharmacists reported willingness to dispense naloxone with a valid prescription (54.0%, score 5 or 6). Women pharmacists were 1.3 times more likely than men to be willing to initiate naloxone dispensing (95% confidence interval [CI] 1.0-1.6). Those who reported confidence in identifying individuals at risk for overdose were 1.2 times more likely to initiate dispensing, and those who reported confidence in ability to educate patients about overdose were 1.6 times more likely to express willingness to initiate naloxone dispensing (95% CIs, respectively, 1.0-1.3 and 1.4-1.8). Community pharmacists reported barriers to naloxone access at higher rates than pharmacists from other practice settings. Kentucky pharmacists are divided in their willingness to initiate naloxone dispensing; however, those who are confident in their ability to identify overdose risks are more willing. Increasing pharmacist confidence through appropriately designed education programs could facilitate pharmacist participation in naloxone

  5. Supply-side response to declining heroin purity: fentanyl overdose episode in New Jersey.

    Science.gov (United States)

    Hempstead, Katherine; Yildirim, Emel O

    2014-06-01

    The inelastic price demand observations characteristic of illegal drug markets have led to the conclusion that the burden of a negative supply shock would be completely reflected to consumers. This paper argues that the increasing availability of prescription opioids may threaten heroin sellers' profit margin and force them to find alternative methods to compensate buyers in the event of a supply shock. We investigate the 2006 fentanyl overdose episode in New Jersey and argue that the introduction of non-pharmaceutical fentanyl, its spatial distribution, and the timing of overdose deaths may have been related to trends in heroin purity. Using medical examiner data, as well as data from the Drug Enforcement Administration, Office of Diversion Control on retail sales of prescription opioids in a negative binomial specification, we show that month-to-month fluctuations in heroin purity have a significant effect on fentanyl-related overdoses, particularly in those areas where prescription opioids are highly available. Copyright © 2013 John Wiley & Sons, Ltd.

  6. Protection afforded by pre- or post-treatment with 4-phenylbutyrate against liver injury induced by acetaminophen overdose in mice.

    Science.gov (United States)

    Shimizu, Daisuke; Ishitsuka, Yoichi; Miyata, Keishi; Tomishima, Yoshiro; Kondo, Yuki; Irikura, Mitsuru; Iwawaki, Takao; Oike, Yuichi; Irie, Tetsumi

    2014-09-01

    Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is a widely used analgesic/antipyretic drug with few adverse effects at therapeutic doses; suicidal or unintentional overdose of APAP frequently induces severe hepatotoxicity. To explore a new and effective antidote for APAP hepatotoxicity, this study examined the effects of sodium 4-phenylbutyrate (4-PBA) on liver injury induced by APAP overdose in mice. Liver injury was induced in C57BL/6 male mice by intraperitoneal injection of APAP (400mg/kg). The effects of 4-PBA (100-200mg/kg) treatment at 1h before the APAP injection were evaluated with serum alanine aminotransferase (ALT) and blood ammonia levels, hepatic pathological changes, including histopathology, DNA damage, nitrotyrosine formation, and mRNA or protein expression involved in the development of hepatotoxicity, such as X-box binding protein-1 (XBP1), c-Jun N-terminal kinase (JNK), C/EBP homologous protein (CHOP) and B-cell lymphoma 2 interacting mediator of cell death (Bim). In addition, glutathione depletion and CYP2E1 protein expression, which are measures of the metabolic conversion of APAP to a toxic metabolite, were examined. Furthermore, we examined the effects of post-treatment with 4-PBA against APAP-induced hepatotoxicity in mice. When administered at 1h before APAP injection, 4-PBA significantly prevented the increase in serum ALT and blood ammonia levels, centrilobular necrosis of hepatocytes, DNA fragmentation, and nitrotyrosine formation induced by APAP in mice. 4-PBA also inhibited hepatic Xbp1 mRNA splicing and JNK phosphorylation induced by APAP, but did not suppress CHOP and Bim mRNA and protein expression. In addition, 4-PBA had little effect on hepatic glutathione depletion and CYP2E1 expression, parameters of toxic APAP metabolite production. Post-treatment with 4-PBA administration at 1 or 2h after APAP injection also attenuated the increase in serum ALT and blood ammonia levels and hepatic pathological changes in APAP

  7. Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor, alleviates liver injury induced by acetaminophen overdose in mice

    Directory of Open Access Journals (Sweden)

    Tomishima Yoshiro

    2013-01-01

    Full Text Available Abstract Background Overdosed acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP causes severe liver injury. We examined the effects of ozagrel, a selective thromboxane A2 (TXA2 synthase inhibitor, on liver injury induced by APAP overdose in mice. Methods Hepatotoxicity was induced to ICR male mice by an intraperitoneal injection with APAP (330 mg/kg. The effects of ozagrel (200 mg/kg treatment 30 min after the APAP injection were evaluated with mortality, serum alanine aminotransferase (ALT levels and hepatic changes, including histopathology, DNA fragmentation, mRNA expression and total glutathione contents. The impact of ozagrel (0.001-1 mg/mL on cytochrome P450 2E1 (CYP2E1 activity in mouse hepatic microsome was examined. RLC-16 cells, a rat hepatocytes cell line, were exposed to 0.25 mM N-acetyl-p-benzoquinone imine (NAPQI, a hepatotoxic metabolite of APAP. In this model, the cytoprotective effects of ozagrel (1–100 muM were evaluated by the WST-1 cell viability assay. Results Ozagel treatment significantly attenuated higher mortality, elevated serum alanine aminotransferase levels, excessive hepatic centrilobular necrosis, hemorrhaging and DNA fragmentation, as well as increase in plasma 2,3-dinor thromboxane B2 levels induced by APAP injection. Ozagrel also inhibited the hepatic expression of cell death-related mRNAs induced by APAP, such as jun oncogene, FBJ osteosarcoma oncogene (fos and C/EBP homologous protein (chop, but did not suppress B-cell lymphoma 2-like protein11 (bim expression and hepatic total glutathione depletion. These results show ozagrel can inhibit not all hepatic changes but can reduce the hepatic necrosis. Ozagrel had little impact on CYP2E1 activity involving the NAPQI production. In addition, ozagrel significantly attenuated cell injury induced by NAPQI in RLC-16. Conclusions We demonstrate that the TXA2 synthase inhibitor, ozagrel, dramatically alleviates liver injury induced by APAP in mice, and suggest

  8. Co-administration of fresh grape fruit juice (GFJ and bergamottin prevented paracetamol induced hepatotoxicity after paracetamol overdose in rats

    Directory of Open Access Journals (Sweden)

    Refuoe Baleni

    2015-01-01

    Full Text Available The aim of this study was to evaluate small doses of known cytochrome P450 enzyme inhibitors, grapefruit juice (GFJ and one of its components, bergamottin (BGT, for the prevention of paracetamol (PAR-induced hepatotoxicity after overdose in rats. Six groups of 15 Sprague Dawley (SD rats each were treated with single oral doses of either saline, PAR only 1725 mg/kg, PAR + GFJ low dose (2 ml and PAR + GFJ high dose (3 ml, PAR + BGT 0.05 mg/kg (BGT-low and PAR + BGT 0.22 mg/kg (BGT-high. Thereafter, 5 rats from each group were sacrificed after 24, 48 and 72 h and, on each occasion, blood samples were collected for determination of liver and renal function, full blood count (FBC and PAR concentration. A piece of liver was sent for histopathology. By 48 h the liver enzymes in the PAR-only group were significantly (P < 0.05 higher than in the PAR + GFJ and PAR + BGT groups, i.e., alanine transaminase (ALT 837 ± 268 u/L and aspertate transaminase (AST 1359 ± 405 for PAR only; versus ALT 34 ± 48.8 u/L and AST 238 ± 221 for PAR + GFJ-high; ALT 22 ± 13.9 and AST168 ± 49.6 for PAR + BGT-high; and ALT 52 ± 7.2 u/L and AST 147 ± 153 for the control group. The results correlated with the histopathology findings where livers of the PAR-only group exhibited severe centrilobular and hepatocyte necrosis. In conclusion, GFJ and BGT prevented PAR-induced hepatotoxicity after PAR overdose in rats, and this calls for appropriate observation studies in humans.

  9. Molecular toxicity of triclosan and carbamazepine to green algae Chlorococcum sp.: A single cell view using synchrotron-based Fourier transform infrared spectromicroscopy.

    Science.gov (United States)

    Xin, Xiaying; Huang, Guohe; Liu, Xia; An, Chunjiang; Yao, Yao; Weger, Harold; Zhang, Peng; Chen, Xiujuan

    2017-07-01

    Although pharmaceuticals and personal care products have been used and introduced into the environment in large quantities, little information on potential ecological risks is currently available considering their effects on living organisms. We verified the feasibility of using synchrotron-based Fourier Transform Infrared (SR-FTIR) spectromicroscopy to explore in vivo toxic effects on single living Chlorococcum sp. cells. The study provided important information to achieve a better understanding of the toxic mechanism of triclosan and carbamazepine on living algae Chlorococcum sp.. Triclosan and carbamazepine had distinctive toxic effects on unicellular living algae. Most strikingly, triclosan had more dramatic toxic effects on biochemical components than carbamazepine. Triclosan can affect algae primarily by inhibiting fatty acid synthesis and causing protein aggregation. The toxicity response was irreversible at higher concentration (100.000 μM), but attenuated at lower concentration (0.391 μM) as time extended. Carbamazepine can produce hydrophobic interactions to affect the phospholipid bilayer and work on specific proteins to disfunction the cell membrane. Carbamazepine-exposed cells developed a resistance while extending exposure time. This is the first demonstration from an ecological standpoint that SR-FTIR can provide an innovative approach to reveal the toxicity of emerging pollutants in aquatic environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Overdose Deaths Related to Fentanyl and Its Analogs - Ohio, January-February 2017.

    Science.gov (United States)

    Daniulaityte, Raminta; Juhascik, Matthew P; Strayer, Kraig E; Sizemore, Ioana E; Harshbarger, Kent E; Antonides, Heather M; Carlson, Robert R

    2017-09-01

    Ohio is experiencing unprecedented loss of life caused by unintentional drug overdoses (1), with illicitly manufactured fentanyl (IMF) emerging as a significant threat to public health (2,3). IMF is structurally similar to pharmaceutical fentanyl, but is produced in clandestine laboratories and includes fentanyl analogs that display wide variability in potency (2); variations in chemical composition of these drugs make detection more difficult. During 2010-2015, unintentional drug overdose deaths in Ohio increased 98%, from 1,544 to 3,050.* In Montgomery County (county seat: Dayton), one of the epicenters of the opioid epidemic in the state, unintentional drug overdose deaths increased 40% in 1 year, from 249 in 2015 to 349 in 2016 (estimated unadjusted mortality rate = 57.7 per 100,000) (4). IMFs have not been part of routine toxicology testing at the coroner's offices and other types of medical and criminal justice settings across the country (2,3). Thus, data on IMF test results in the current outbreak have been limited. The Wright State University and the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory (MCCO/MVRCL) collaborated on a National Institutes of Health study of fentanyl analogs and metabolites and other drugs identified in 281 unintentional overdose fatalities in 24 Ohio counties during January-February 2017. Approximately 90% of all decedents tested positive for fentanyl, 48% for acryl fentanyl, 31% for furanyl fentanyl, and 8% for carfentanil. Pharmaceutical opioids were identified in 23% of cases, and heroin in 6%, with higher proportions of heroin-related deaths in Appalachian counties. The majority of decedents tested positive for more than one type of fentanyl. Evidence suggests the growing role of IMFs, and the declining presence of heroin and pharmaceutical opioids in unintentional overdose fatalities, compared with 2014-2016 data from Ohio and other states (3-5). There is a need to include testing for IMFs as part

  11. Degradation of carbamazepine using hydrodynamic cavitation combined with advanced oxidation processes.

    Science.gov (United States)

    Thanekar, Pooja; Panda, Mihir; Gogate, Parag R

    2018-01-01

    Degradation of carbamazepine (CBZ), a widely detected recalcitrant pharmaceutical in sewage treatment plant (STP) effluent, has been studied in the present work using combination of hydrodynamic cavitation (HC) and advanced oxidation processes (AOPs). Due to its recalcitrant nature, it cannot be removed effectively by the conventional wastewater treatment plants (WWTPs) which make CBZ a pharmaceutical of very high environmental relevance and impact as well as stressing the need for developing new treatment schemes. In the present study, the effect of inlet pressure (3-5bar) and operating pH (3-11) on the extent of degradation have been initially studied with an objective of maximizing the degradation using HC alone. The established optimum conditions as pressure of 4bar and pH of 4 resulted in maximum degradation of CBZ as 38.7%. The combined approaches of HC with ultraviolet irradiation (HC+UV), hydrogen peroxide (HC+H 2 O 2 ), ozone (HC+O 3 ) as well as combination of HC, H 2 O 2 and O 3 (HC+H 2 O 2 +O 3 ) have been investigated under optimized pressure and operating pH. It was observed that a significant increase in the extent of degradation is obtained for the combined operations of HC+H 2 O 2 +O 3 , HC+O 3 , HC+H 2 O 2 , and HC+UV with the actual extent of degradation being 100%, 91.4%, 58.3% and 52.9% respectively. Kinetic analysis revealed that degradation of CBZ fitted into first order kinetics model for all the approaches. The processes were also compared on the basis of cavitational yield and also in terms of total treatment cost. Overall, it has been demonstrated that combined process of HC, H 2 O 2 and O 3 can be effectively used for treatment of wastewater containing CBZ. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Preventive Effect of Vitamin B6 on Developmental Toxicity of Carbamazepine in Mice

    Directory of Open Access Journals (Sweden)

    Mohammad Afshar

    2011-03-01

    Full Text Available Objective(sCarbamazepine (CBZ is an antiepileptic drug that is used widely for the treatment of epileptic seizures. Neural tube defects (NTDs, growth retardation, and nail hypoplasia are the most common features of teratogenic effects of this drug. The purpose of this study was to examine the effect of vitamin B6 on the developmental toxicity of CBZ on mice.Materials and MethodsSixty BALB/c pregnant mice were divided into four experimental and two control groups. Two experimental groups received daily intraperitoneal injection (IP of 30 mg/kg (I or 60 mg/kg (II of CBZ on gestational days (GD 6 to 15. Two other experimental groups received daily IP injection of 30 mg/kg (III or 60 mg/kg (IV of CBZ with 10 mg/kg/day vitamin B6 by gavage 10 days prior to gestation and on GD 6 to 15. Two control groups received normal saline or Tween 20. Dams underwent Cesarean section on GD 18 and embryos were harvested. External/macroscopic observation of fetuses was done by stereomicroscope and external examination for malformations was recorded. Data analyzed by ANOVA and X2 test using SPSS software.ResultsThe mean weight and crown-rump of the fetuses in both CBZ-treated experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, eye malformations, NTDs, vertebral deformity, brachydactyly and growth retardation. Vitamin B6 treatment significantly reduced various CBZ-induced malformations.ConclusionThis study showed that vitamin B6 has a preventive effect on the developmental toxicity of CBZ in mice that can be pursued further for clinical research.

  13. Carbamazepine but not valproate induces CYP2A6 activity in smokers with mental illness

    Science.gov (United States)

    Williams, Jill M; Gandhi, Kunal K; Benowitz, Neal L

    2010-01-01

    BACKGROUND Anti-epileptic drugs (AED) are increasingly used in the management of serious mental illness yet their effects on nicotine metabolism have not been studied. METHODS This study investigated the effects of 3 AED (carbamazepine, CBZ; oxcarbazepine, OCB or valproic acid, VPA) on nicotine and nicotine metabolite levels in 149 smokers with schizophrenia and bipolar disorder who participated in an afternoon blood draw for nicotine, cotinine, and 3’-hydroxycotinine (3HC). The ratio of 3HC to cotinine was calculated as a marker of CYP2A6 metabolic activity. Eight smokers were taking CBZ, six were taking OCB and 40 were taking VPA. RESULTS The 3HC/cotinine ratio was significantly higher in individuals taking CBZ or OCB (combined, n=14) vs. those not taking it (mean 0.993 vs. 0.503; p< 0.001). The cotinine/cigarette per day ratio was significantly lower in individuals taking CBZ or OCB. The 3HC/cotinine ratios were also significantly higher in the subgroup of individuals taking CBZ (n=8) vs. those not taking it. There were no significant differences in nicotine or cotinine levels or 3HC/cotinine ratios in individuals taking VPA vs. those not taking it. We conducted backward stepwise linear regression models to identify predictors of the log transformed 3HC/cotinine ratios. Taking CBZ and number of cigarettes smoked per day were significant determinants of log 3HC/Cotinine. CONCLUSIONS CBZ likely induces hepatic metabolism via CYP2A6 and is associated with increased 3HC/Cotinine ratios. IMPACT Increased nicotine metabolism in individuals using AED has implications for increased smoking behavior and exposure to more tobacco toxins that warrants further study. PMID:20719908

  14. Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia.

    Science.gov (United States)

    Xue, Hui; Xiang, Wenping; Yu, Yichuan; Liu, Guorong; Chong, Yi; Zhou, Jiying

    2018-01-01

    Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ) plus betahistine mesilate tablets (BMT) (CBZ+BMT) and oxcarbazepine (OXC) plus BMT (OXC+BMT) in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT. VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed. In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group ( p =0.04). Subgroup analysis found that patients receiving BMT (18 mg) had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg). These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ hypersensitivity, and the synergistic effect could be increased along with the increased dose of BMT.

  15. Fate and transport of carbamazepine in soil aquifer treatment (SAT) infiltration basin soils.

    Science.gov (United States)

    Arye, Gilboa; Dror, Ishai; Berkowitz, Brian

    2011-01-01

    The transport and fate of the pharmaceutical carbamazepine (CBZ) were investigated in the Dan Region Reclamation Project (SHAFDAN), Tel-Aviv, Israel. Soil samples were taken from seven subsections of soil profiles (150 cm) in infiltration basins of a soil aquifer treatment (SAT) system. The transport characteristics were studied from the release dynamics of soil-resident CBZ and, subsequently, from applying a pulse input of wastewater containing CBZ. In addition, a monitoring study was performed to evaluate the fate of CBZ after the SAT. Results of this study indicate adsorption, and consequently retardation, in CBZ transport through the top soil layer (0-5 cm) and to a lesser extent in the second layer (5-25 cm), but not in deeper soil layers (25-150 cm). The soluble and adsorbed fractions of CBZ obtained from the two upper soil layers comprised 45% of the total CBZ content in the entire soil profile. This behavior correlated to the higher organic matter content observed in the upper soil layers (0-25 cm). It is therefore deduced that when accounting for the full flow path of CBZ through the vadose zone to the groundwater region, the overall transport of CBZ in the SAT system is essentially conservative. The monitoring study revealed that the average concentration of CBZ decreased from 1094 ± 166 ng L⁻¹ in the recharged wastewater to 560 ± 175 ng L⁻¹ after the SAT. This reduction is explained by dilution of the recharged wastewater with resident groundwater, which may occur as it flows to active reclamation wells. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. UV/chlorine treatment of carbamazepine: Transformation products and their formation kinetics.

    Science.gov (United States)

    Pan, Yanheng; Cheng, ShuangShuang; Yang, Xin; Ren, Jingyue; Fang, Jingyun; Shang, Chii; Song, Weihua; Lian, Lushi; Zhang, Xinran

    2017-06-01

    Carbamazepine (CBZ) is one of the pharmaceuticals most frequently detected in the aqueous environment. This study investigated the transformation products when CBZ is degraded by chlorine under ultraviolet (UV) irradiation (the UV/chlorine process). Detailed pathways for the degradation of CBZ were elucidated using ultra-high performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry (QTOF-MS). CBZ is readily degraded by hydroxyl radicals (HO) and chlorine radicals (Cl) in the UV/chlorine process, and 24 transformation products were identified. The products indicate that the 10,11-double bond and aromatic ring in CBZ are the sites most susceptible to attack by HO and Cl. Subsequent reaction produces hydroxylated and chlorinated aromatic ring products. Four specific products were quantified and their evolution was related with the chlorine dose, pH, and natural organic matter concentration. Their yields showed an increase followed by a decreasing trend with prolonged reaction time. CBZ-10,11-epoxide (I), the main quantified transformation product from HO oxidation, was observed with a peak transformation yield of 3-32% depending on the conditions. The more toxic acridine (IV) was formed involving both HO and Cl with peak transformation yields of 0.4-1%. All four quantified products together amounted to a peak transformation yield of 34.5%. The potential toxicity of the transformation products was assayed by evaluating their inhibition of the bioluminescence of the bacterium Vibrio Fischeri. The inhibition increased at first and the decreased at longer reaction times, which was in parallel with the evolution of transformation products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Carbamazepine (Tegretol) inhibits in vivo iodide uptake and hormone synthesis in rat thyroid glands

    International Nuclear Information System (INIS)

    Villa, S.M.; Alexander, N.M.

    1987-01-01

    Decreased serum concentrations of T3 and T4 occur in patients treated with the anticonvulsant drug carbamazepine (CBZ), but with rare exception, these patients remain euthyroid. The mechanism that accounts for diminished hormone levels is unknown, and our objective was to study the direct effect of CBZ on iodide uptake and hormone synthesis in thyroid glands of CBZ-treated and pair-fed control rats. Chronic ingestion (per os) of CBZ in male rats reduced the four hour thyroid 131I-iodide uptake by approximately 60%. This inhibition occurred after the animals had received sufficient CBZ to attain plasma CBZ concentrations of 0.8 microgram/ml. Continued treatment with CBZ ranging from 560 to 800 mg/kg/day for 14 days did not result in further inhibition of iodide uptake even though the plasma CBZ concentrations had increased 6-20 fold. No inhibition of iodide uptake was apparent when the animals initially received CBZ ranging from 40 to 152 mg/kg body weight for 22 days when there were no detectable levels of plasma CBZ. Overall growth rates of CBZ-treated rats were slightly (6-10%) less than the pair-fed control animals. Plasma T4 concentrations were reduced by 18% (p less than 0.05) in the CBZ-fed animals, while T3 concentrations were diminished by 53% (p less than 0.01). CBZ appeared to alter thyroidal iodide transport because the thyroid:plasma iodide ratios were decreased by 26% in the drug-treated rats. The distribution of radioiodine in thyroidal iodoamino acids was essentially the same in both groups of rats but the absolute quantities of radioiodine were more than 2.5 times greater in the control rats. CBZ failed to inhibit peroxidase-catalyzed iodide and guaiacol oxidation in vitro

  18. Metabolic syndrome and anticonvulsants: A comparative study of valproic acid and carbamazepine.

    Science.gov (United States)

    Rakitin, Aleksei; Kõks, Sulev; Haldre, Sulev

    2016-05-01

    The aim of this study was to compare the risk of metabolic syndrome (MS) and evaluate related factors for MS among people with epilepsy treated with valproate (VPA) or carbamazepine (CBZ). A total of 213 adult patients with epilepsy treated with VPA (n=118) or CBZ (n=95) monotherapy were included in the study. Participants were evaluated for the presence of MS, diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. In the multiple logistic regression analysis, the risk of MS in CBZ- and VPA-treated patients was similar (odds ratio [OR]=0.99; 95% confidence interval [CI], 0.43-2.26; P=0.979). A lower proportion of CBZ-treated patients had abnormally low levels of high-density lipoprotein cholesterol (OR=0.10; 95% CI, 0.02-0.42; P=0.002), whereas a lower proportion of VPA-treated patients had abnormally high concentrations of fasting blood glucose (OR=0.30; 95% CI, 0.13-0.69; P=0.004). Females treated with VPA tended to have a higher risk of MS (OR=1.48; 95% CI, 0.50-4.41; P=0.485) compared to males (OR=0.74; 95% CI, 0.28-1.96; P=0.551), although this difference was not statistically significant. Although the overall risk of MS was similar in patients with epilepsy who were treated with VPA or CBZ, the distribution of MS components differed between treatment groups. Patients treated with CBZ or VPA less frequently had decreased high-density lipoprotein cholesterol levels or increased blood glucose concentrations, respectively. Females on VPA treatment could be at higher risk of MS than males. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  19. Enantioselective assay for therapeutic drug monitoring of eslicarbazepine acetate: no interference with carbamazepine and its metabolites.

    Science.gov (United States)

    Alves, Gilberto; Fortuna, Ana; Sousa, Joana; Direito, Rosa; Almeida, Anabela; Rocha, Marília; Falcão, Amílcar; Soares-da-Silva, Patrício

    2010-08-01

    As add-on therapy, phase III clinical trials of eslicarbazepine acetate (ESL) conducted in patients with refractory partial-onset seizures have shown good efficacy, safety, and tolerability, even in patients taking carbamazepine (CBZ) at baseline (approximately 60% of the enrolled patients). Thus, considering the pharmacological disadvantages of CBZ and the similar efficacy spectrum of CBZ and ESL, switching to ESL may be successful in many patients. As ESL is a prodrug almost instantaneously converted to S-licarbazepine (S-Lic; approximately 95%), an interest in therapeutic drug monitoring (TDM) of S-Lic is likely to develop in the future. This study investigated the plasma concentrations of S-Lic and R-licarbazepine (R-Lic) enantiomers in patients under CBZ long-term treatment to assess the potential interference of CBZ or its metabolites in the enantioselective TDM of ESL (using S-Lic concentrations). A chiral high-performance liquid chromatography assay with ultraviolet detection (HPLC-UV) previously developed and validated by our research group was used. Twenty-four patients admitted to the Coimbra University Hospital and supposedly receiving CBZ long-term treatment were identified. Blood samples were collected from patients and serum CBZ concentrations were measured by the usual TDM protocol. Aliquots of plasma from such patients were also submitted to a chiral HPLC-UV analysis. The bioanalytical data indicated that S-Lic and R-Lic were not present at detectable concentrations in plasma samples of the CBZ-treated patients. The chromatograms generated by the analysis of patient plasma samples, when compared with those obtained from blank plasma samples spiked with S-Lic and R-Lic, clearly showed the absence of interferences at the retention times of both Lic enantiomers. These data support the usefulness of the chiral HPLC-UV method used for the enantioselective TDM of ESL (using S-Lic) for programs in which switching from CBZ to ESL is implemented.

  20. Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes (Danio rerio).

    Science.gov (United States)

    Fraz, Shamaila; Lee, Abigail H; Wilson, Joanna Y

    2018-05-01

    Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17.5 ± 1.78 and 11.2 ± 1.08 μg/L respectively. A 67 day exposure led to reduced reproductive output and lowered whole body, plasma, and testicular 11-ketotestosterone (11-KT). Testicular production of 11-KT was examined post exposure (42 days) using ex vivo cultures to determine basal and stimulated steroid production. The goal was to ascertain the step impaired in the steroidogenic pathway by each compound. Ex vivo 11-KT production in testes from males chronically exposed to GEM and CBZ was lower than that from unexposed males. Although hCG, 25-OH cholesterol, and pregnenolone stimulation increased 11-KT production in all treatment groups over basal levels, hCG stimulated 11-KT production remained significantly less in testes from exposed males compared to controls. 25-OH cholesterol and pregnenolone stimulated 11-KT production was similar between GEM and control groups but the CBZ group had lower 11-KT production than controls with both stimulants. We therefore propose that chronic GEM and CBZ exposure can reduce production of 11-KT in testes through direct effects independent of mediation through HPG axis. The biochemical processes for steroid production appear un-impacted by GEM exposure; while CBZ exposure may influence steroidogenic enzyme expression or function. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Trends in drug overdose deaths in England and Wales 1993-98: methadone does not kill more people than heroin.

    Science.gov (United States)

    Hickman, Matthew; Madden, Peter; Henry, John; Baker, Allan; Wallace, Chris; Wakefield, Jon; Stimson, Gerry; Elliott, Paul

    2003-04-01

    To test the hypothesis that methadone is responsible for a greater increase in overdose deaths than heroin, and causes proportionally more overdose deaths than heroin at weekends. Multivariate analysis of 3961 death certificates mentioning heroin, morphine and/or methadone held on the Office for National Statistics drug-related poisoning mortality database from 1993 to 1998 in England and Wales. Percentage increase in deaths by year by drug, odds ratio (OR) of dying at the weekend from methadone-related overdose compared to dying from heroin/morphine overdose. From 1993 to 1998, annual opiate overdose deaths increased from 378 to 909. There was a 24.7% (95% confidence interval (CI) 22-28%) yearly increase in heroin deaths compared to 9.4% (95% CI 6-13%) for methadone only. This difference was significant (P < 0.001 by test of interaction) after adjustment for sex, age group, polydrug use, area of residence and underlying cause of death. The largest number of deaths occurred on Saturday (673). The OR of death from methadone overdose on Saturday and Sunday was 1.48 (95% CI 1.29-1.71) for methadone-only deaths compared to dying from heroin/morphine at the weekend after adjustment for other covariates, but the OR was not significant (1.09, 95% CI 0.95-1.25) if the weekend was defined as Friday and Saturday. There was no evidence that the threefold increase in deaths over time was due to methadone. There was equivocal support only for the hypothesis that there was an excess of deaths from methadone at weekends. Increased interventions to prevent overdose among injectors in England and Wales are long overdue.

  2. Impact of different pack sizes of paracetamol in the United Kingdom and Ireland on intentional overdoses: a comparative study

    LENUS (Irish Health Repository)

    Hawton, Keith

    2011-06-10

    Abstract Background In order to reduce fatal self-poisoning legislation was introduced in the UK in 1998 to restrict pack sizes of paracetamol sold in pharmacies (maximum 32 tablets) and non-pharmacy outlets (maximum 16 tablets), and in Ireland in 2001, but with smaller maximum pack sizes (24 and 12 tablets). Our aim was to determine whether this resulted in smaller overdoses of paracetamol in Ireland compared with the UK. Methods We used data on general hospital presentations for non-fatal self-harm for 2002 - 2007 from the Multicentre Study of Self-harm in England (six hospitals), and from the National Registry of Deliberate Self-harm in Ireland. We compared sizes of overdoses of paracetamol in the two settings. Results There were clear peaks in numbers of non-fatal overdoses, associated with maximum pack sizes of paracetamol in pharmacy and non-pharmacy outlets in both England and Ireland. Significantly more pack equivalents (based on maximum non-pharmacy pack sizes) were used in overdoses in Ireland (mean 2.63, 95% CI 2.57-2.69) compared with England (2.07, 95% CI 2.03-2.10). The overall size of overdoses did not differ significantly between England (median 22, interquartile range (IQR) 15-32) and Ireland (median 24, IQR 12-36). Conclusions The difference in paracetamol pack size legislation between England and Ireland does not appear to have resulted in a major difference in sizes of overdoses. This is because more pack equivalents are taken in overdoses in Ireland, possibly reflecting differing enforcement of sales advice. Differences in access to clinical services may also be relevant.

  3. Temporal differences in gamma-hydroxybutyrate overdoses involving injecting drug users versus recreational drug users in Helsinki: a retrospective study

    Directory of Open Access Journals (Sweden)

    Boyd James J

    2012-02-01

    Full Text Available Abstract Background Gamma-hydroxybutyrate (GHB and gamma-butyrolactone (GBL have been profiled as 'party drugs' used mainly at dance parties and in nightclubs on weekend nights. The purpose of this study was to examine the frequency of injecting drug use among GHB/GBL overdose patients and whether there are temporal differences in the occurrence of GHB/GBL overdoses of injecting drug and recreational drug users. Methods In this retrospective study, the ambulance and hospital records of suspected GHB- and GBL overdose patients treated by the Helsinki Emergency Medical Service from January 1st 2006 to December 31st 2007 were reviewed. According to the temporal occurrence of the overdose, patients were divided in two groups. In group A, the overdose occurred on a Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. Group B consisted of overdoses occurring on outside this time frame. Results Group A consisted of 39 patient contacts and the remaining 61 patient contacts were in group B. There were statistically significant differences between the two groups in (group A vs. B, respectively: history of injecting drug abuse (33% vs. 59%, p = 0.012, reported polydrug and ethanol use (80% vs. 62%, p = 0.028, the location where the patients were encountered (private or public indoors or outdoors, 10%, 41%, 41% vs. 25%, 18%, 53%, p = 0.019 and how the knowledge of GHB/GBL use was obtained (reported by patient/bystanders or clinical suspicion, 72%, 28% vs. 85%, 10%, p = 0.023. Practically all (99% patients were transported to emergency department after prehospital care. Conclusion There appears to be at least two distinct groups of GHB/GBL users. Injecting drug users represent the majority of GHB/GBL overdose patients outside weekend nights.

  4. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

    Science.gov (United States)

    Wang, Xu; Wu, Qinghua; Liu, Aimei; Anadón, Arturo; Rodríguez, José-Luis; Martínez-Larrañaga, María-Rosa; Yuan, Zonghui; Martínez, María-Aránzazu

    2017-11-01

    Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

  5. An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine.

    Science.gov (United States)

    Plósz, Benedek Gy; Langford, Katherine H; Thomas, Kevin V

    2012-11-01

    Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM-X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full-scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re-transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between

  6. Reproductive performance and embriotoxicity of rats exposed to carbamazepine Performance reprodutiva e embriotoxicidade de ratos expostos à carbamazepina

    Directory of Open Access Journals (Sweden)

    Marli Gerenutti

    2008-09-01

    Full Text Available To study the possible effects of carbamazepine in rats during pregnancy and fetuses' physical development, carbamazepine solubilized in propilenglycol was orally administered (20 and 40 mg/kg to the female rats from the 2nd to the 19th days of pregnancy. Propilenglycol was administered to the control group. The animals were sacrificed on the 20th day, when 50% of the offspring were fixed in Bouin's solution and the remaining 50% were submitted to diaphanization. The carbamazepine administration caused reduction on weight gain of pregnant rats and did not damage the females' reproductive performance. In the fetuses' physical development, it was observed a flattening on the skull soft tissues and bones; delay in the skull bone development; cartilage calcification increase between hip and femur and reduction in the number of the sternum ossifications. Although carbamazepine has not caused general changes over female rats' reproductive performance, it produced significant alterations in the development of the fetuses' skeletal parameters.Este trabalho teve como objetivo estudar os possíveis efeitos da administração da carbamazepina na gestação de ratas. A solução glicólica de carbamazepina foi administrada por via oral (20 mg/kg e 40 mg/kg, às ratas do 2º ao 19º dia de gestação. O grupo controle recebeu solução de propilenoglicol. Após a realização da cesária, no 20º dia, 50% dos filhotes foram fixados em Bouin e os outros 50% passaram por processo de diafanização. Estes estudos mostraram que embora a administração de carbamazepina tenha promovido redução do ganho de peso de ratas prenhes, não prejudicou a performance reprodutiva de fêmeas. Nos fetos, observou-se achatamento de tecidos moles e ossos do crânio, retardo no desenvolvimento ósseo do crânio, aumento da calcificação da cartilagem entre o quadril e o fêmur e redução no número de ossificações do esterno. Estes dados, tomados em conjunto, indicam que a

  7. Removal of ibuprofen, naproxen and carbamazepine in aqueous solution onto natural clay: equilibrium, kinetics, and thermodynamic study

    Science.gov (United States)

    Khazri, Hassen; Ghorbel-Abid, Ibtissem; Kalfat, Rafik; Trabelsi-Ayadi, Malika

    2017-10-01

    This study aimed to describe the adsorption of three pharmaceuticals compounds (ibuprofen, naproxen and carbamazepine) onto natural clay on the basis of equilibrium parameters such as a function of time, effect of pH, varying of the concentration and the temperature. Adsorption kinetic data were modeled using the Lagergren's first-order and the pseudo-second-order kinetic equations. The kinetic results of adsorption are described better using the pseudo-second order model. The isotherm results were tested in the Langmuir, Freundlich and Dubinin-Radushkevich models. The thermodynamic parameters obtained indicate that the adsorption of pharmaceuticals on the clay is a spontaneous and endothermic process.

  8. A case report of cardiotoxicity due to homeopathic drug overdose

    Directory of Open Access Journals (Sweden)

    MilindChandurkar,Girish Patrike, NitinChauhan, SanketMulay, Manoj Vethekar, JaweedAkhtar, Mallikarjun Reddy

    2014-11-01

    Full Text Available Aconite is one of the most toxic plants. Aconitine and related alkaloids found in the Aconitum species are highly toxic cardiotoxins and neurotoxins. Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots. The toxic components of Aconitum as aconitine and related alkaloids cause cardiotoxicity, neurotoxicity and gastrointestinal toxicity through their actions on sodium channels. Cardiac manifestations include hypotension and ventricular tachyarrhythmias. Ventricular tachyarrhythmias and refractory cardiovascular collapse, such as in the case of this patient account for life-threatening toxicities in severe aconite poisoning. In general, vagal slowing is seen in 10 to 20% of fatal intoxications. If higher concentrations are present, supraventricular tachycardia, ventricular tachycardia, torsades de pointes, and other conduction disturbances may be seen. Ventricular fibrillation may be seen, and is often the cause of death. Available clinical evidence suggests that drugs like amiodarone and flecainide are reasonable first-line treatment.

  9. Use of lipid emulsion therapy in local anesthetic overdose

    Directory of Open Access Journals (Sweden)

    Ozgur Karcioglu

    2017-10-01

    Full Text Available The use of intravenous lipid emulsion (ILE therapy as antidote in systemic toxicity of certain agents has gained widespread support. There are increasing data suggesting use of ILE in reversing from local anesthetic-induced systemic toxicity severe, life-threatening cardiotoxicity, although findings are contradictory. Efficiency of ILE was demonstrated in animal studies in the treatment of severe impairment of cardiac functions, via a mechanism for trapping lipophilic drugs in an expanded plasma lipid compartment (“lipid sink”. In patients with hemodynamic compromise and/or cardiovascular collapse due to lipid-soluble agents, ILE may be considered for resuscitation in the acute setting by emergency physicians. The most common adverse effects from standard ILE include hypertriglyceridemia, fat embolism, infection, vein irritation, pancreatitis, electrolyte disturbances and allergic reactions. The advantages of ILE include an apparent wide margin of safety, relatively low cost, long shelf-life, and ease of administration.

  10. Composted biosolids and treated wastewater as sources of pharmaceuticals and personal care products for plant uptake: A case study with carbamazepine

    International Nuclear Information System (INIS)

    Ben Mordechay, Evyatar; Tarchitzky, Jorge; Chen, Yona; Shenker, Moshe; Chefetz, Benny

    2018-01-01

    Irrigation with treated wastewater (TWW) and application of biosolids to arable land expose the agro-environment to pharmaceuticals and personal care products (PPCPs) which can be taken up by crops. In this project, we studied the effect of a carrier medium (e.g., biosolids and TWW) on plant (tomato, wheat and lettuce) uptake, translocation and metabolism of carbamazepine as a model for non-ionic PPCPs. Plant uptake and bioconcentration factors were significantly lower in soils amended with biosolids compared to soils irrigated with TWW. In soils amended with biosolids and irrigated with TWW, the bioavailability of carbamazepine for plant uptake was moderately decreased as compared to plants grown in soils irrigated with TWW alone. While TWW acts as a continuous source of PPCPs, biosolids act both as a source and a sink for these compounds. Moreover, it appears that decomposition of the biosolids in the soil after amendment enhances their adsorptive properties, which in turn reduces the bioavailability of PPCPs in the soil environment. In-plant metabolism of carbamazepine was found to be independent of environmental factors, such as soil type, carrier medium, and absolute amount implemented to the soil, but was controlled by the total amount taken up by the plant. - Highlights: • Bioaccumulation of carbamazepine is higher in plants irrigated with TWW than in plants grown in soils applied with biosolids. • Application of composted biosolids reduces the bioavailability of carbamazepine originated from TWW irrigation. • Plant metabolism of carbamazepine is affected by the total amount taken-up by the plant. - Bioavailability of PPCPs originated from biosolids amendment is lower than the bioavailability of those introduced by irrigation with treated wastewater.

  11. [Acetaminophen: Knowledge, use and overdose risk in urban patients consulting their general practitioner. A prospective, descriptive and transversal study].

    Science.gov (United States)

    Cipolat, Lauriane; Loeb, Ouriel; Latarche, Clotilde; Pape, Elise; Gillet, Pierre; Petitpain, Nadine

    2017-09-01

    Acetaminophen is the most involved active substance in both unintentional and intentional drug poisoning. However, its availability outside community pharmacies is being debated in France. We made, via a self-administered questionnaire, a prospective assessment of knowledge, use and acetaminophen overdose risk in patients consulting their general practitioner, in the Metz Métropole urban area, between May 2015 and February 2016. We estimated the prevalence of potential unintentional overdosage by capture-recapture method. Among 819 responding patients, only 17.9 % had a sufficient knowledge and 20.3 % were at risk for potential unintentional overdose. The risk was higher for patients aged over 55 years or belonging to socioprofessional categories of laborers and inactive. A good knowledge score was a protective factor for overdose risk (P<0.0001). The liver toxicity of acetaminophen was particularly unknown. The prevalence of potential unintentional acetaminophen overdose was estimated at 1 to2 % of the population. Proposing acetaminophen outside of pharmacies cannot be recommended in France in such conditions. Information campaigns are needed to limit the risk of unintentional overdose and its consequences on liver toxicity. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  12. Influence of carbamazepin and diclofenac on the radio-T3/T4-distribution and the maximal binding capacity of thyroid hormone binding proteins

    International Nuclear Information System (INIS)

    Sternad, H.; Albrecher, B.; Langsteger, W.; Eber, O.

    1993-01-01

    Marked changes in plasma thyroid function parameters due to medication have been described in literature. We, therefore, studied the influence of routine administration of carbamazepine and diclofenac upon the radio T3/T4 distribution to specific thyroid transport proteins as well as their maximal binding capacity (MBC) for T4. Both drugs have been found to lead to changes in T3 and T4 distribution but not to any influence upon MBC. The parameters of thyroid function mostly revealed reduced FT3 and FT4 values while bTSH was affected only by carbamazepine administration. (authors)

  13. Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes

    Directory of Open Access Journals (Sweden)

    Chen Chia-Hui

    2012-05-01

    Full Text Available Abstract Background Carbamazepine (CBZ has been used in the treatment of bipolar disorder, both in acute mania and maintenance therapy, since the early 1970s. Here, we report a follow-up study of CBZ-treated bipolar patients in the Taipei City Psychiatric Centre. Methods Bipolar patients diagnosed according to the DSM-IV system and treated with CBZ at the Taipei City Psychiatric Centre had their charts reviewed to evaluate the efficacy and side effects of this medication during an average follow-up period of 10 years. Results A total of 129 bipolar patients (45 males, mean age: 45.7 ± 10.9 year were included in the analysis of CBZ efficacy used alone (n = 63 or as an add-on after lithium (n = 50 or valproic acid (n = 11, or the both of them (n = 5. The mean age of disease onset was 24.6 ± 9.5 years. The mean duration of CBZ use was 10.4 ± 5.2 year. The mean dose used was 571.3 ± 212.6 mg/day with a mean plasma level of 7.8 ± 5.9 μg/mL. Mean body weight increased from 62.0 ± 13.4 kg to 66.7 ± 13.1 kg during treatment. The frequencies of admission per year before and after CBZ treatment were 0.33 ± 0.46 and 0.14 ± 0.30, respectively. The most common side effects targeted the central nervous system (24%, including dizziness, ataxia and cognitive impairment. Other common side effects were gastrointestinal disturbances (3.6%, tremor (3.6%, skin rash (2.9%, and blurred vision (2.9%. Eighty-eight patients (68.2% were taking antipsychotics concomitantly. Ninety-six patients (74.4% needed to use benzodiazepines concomitantly. Sixty-three (48.8% patients had zero episodes in a 10-year follow-up period, compared to all patients having episodes prior to treatment. Using variable analysis, we found better response to CBZ in males than in females. Conclusions CBZ is efficacious in the maintenance treatment of bipolar disorder in naturalistic clinical practice, either as monotherapy

  14. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

    Directory of Open Access Journals (Sweden)

    Ghaydaa A Shehata

    2009-10-01

    Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

  15. Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal

    Science.gov (United States)

    van Gorp, Freek; Duffull, Stephen; Hackett, L Peter; Isbister, Geoffrey K

    2012-01-01

    AIMS To describe the pharmacokinetics and pharmacodynamics (PKPD) of escitalopram in overdose and its effect on QT prolongation, including the effectiveness of single dose activated charcoal (SDAC). METHODS The data set included 78 escitalopram overdose events (median dose, 140 mg [10–560 mg]). SDAC was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK) analysis followed by a PKPD analysis. The developed PKPD model was used to predict the probability of having an abnormal QT as a surrogate for torsade de pointes. RESULTS A one compartment model with first order input and first-order elimination described the PK data, including uncertainty in dose and a baseline concentration for patients taking escitalopram therapeutically. SDAC reduced the fraction absorbed by 31% and reduced the individual predicted area under the curve adjusted for dose (AUCi/dose). The absolute QT interval was related to the observed heart rate with an estimated individual heart rate correction factor (α = 0.35). The heart rate corrected QT interval (QTc) was linearly dependent on predicted escitalopram concentration [slope = 87 ms/(mg l–1)], using a hypothetical effect-compartment (half-life of effect-delay, 1.0h). Administration of SDAC significantly reduced QT prolongation and was shown to reduce the risk of having an abnormal QT by approximately 35% for escitalopram doses above 200 mg. CONCLUSIONS There was a dose-related lengthening of the QT interval that lagged the increase in drug concentration. SDAC resulted in a moderate reduction in fraction of escitalopram absorbed and reduced the risk of the QT interval being abnormal. PMID:21883384

  16. A novel approach for estimating ingested dose associated with paracetamol overdose.

    Science.gov (United States)

    Zurlinden, Todd J; Heard, Kennon; Reisfeld, Brad

    2016-04-01

    In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. © 2015 The British Pharmacological Society.

  17. Production method of carbamazepine/saccharin cocrystal particles by using two solution mixing based on the ternary phase diagram

    Science.gov (United States)

    Kudo, Shoji; Takiyama, Hiroshi

    2014-04-01

    In the pharmaceutical field, improvement of drug solubility is required, and an interest in cocrystals is growing. Crystallization methods for industrial production of cocrystals have not been developed enough whereas many cocrystals have been prepared in order to find a new crystal form by screening in the laboratory. The objective of this study was the development of the crystallization method which is useful for the industrial production of cocrystal particles based on the phase diagram. A cocrystal of carbamazepine and saccharin was selected as a model substance. The ternary phase diagram of carbamazepine and saccharin in methanol at 303 K was measured. A cocrystallization method of mixing two kinds of different eutectic solutions was designed based on the ternary phase diagram. In order to adjust the cocrystallization conditions, the determination method of the driving force for cocrystal deposition such as supersaturation based on mass balance was proposed. The cocrystal particles were obtained under all the conditions of the five mixing ratios. From these experimental results, the relationship between the supersaturation and the induction time for nucleation was confirmed as well as conventional crystallization. In conclusion, the crystallization method for industrial production of cocrystal particles including the determination of the supersaturation was suggested.

  18. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Majeed Ullah

    2015-01-01

    Full Text Available The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25 in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS. At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

  19. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Science.gov (United States)

    Ullah, Majeed; Ullah, Hanif; Mahmood, Qaisar; Hussain, Izhar

    2015-01-01

    The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted. PMID:26380301

  20. Photocatalytic degradation of clofibric acid, carbamazepine and iomeprol using conglomerated TiO2 and activated carbon in aqueous suspension.

    Science.gov (United States)

    Ziegmann, Markus; Frimmel, Fritz H

    2010-01-01

    The combination of powdered activated carbon (PAC) and TiO(2) has been tested for synergistic/antagonistic effects in the photocatalytic degradation of carbamazepine, clofibric acid and iomeprol. Synergistic effects are thought to be caused by rapid adsorption on the PAC surface followed by diffusion to the TiO(2) surface and photocatalytic degradation. The Freundlich constant K(F) was used for comparing the sorption properties of the three substances and it was found that K(F) for clofibric acid was 3 times lower than for carbamazepine and iomeprol, regardless of the kind of PAC used. A PAC with a distinct tendency to form conglomerates was selected so that a high percentage of the PAC surface was in direct proximity to the TiO(2) surface. The photocatalytic degradation of the pharmaceutically active compounds studied followed pseudo-first order kinetics. Synergistic effects only occurred for clofibric acid (factor 1.5) and an inverse relationship between adsorption affinity and synergistic effects was found. High affinity of the target substances to the PAC surface seemed to be counterproductive for the photocatalytic degradation.

  1. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

    Science.gov (United States)

    Beig, Avital; Lindley, David; Miller, Jonathan M.; Agbaria, Riad; Dahan, Arik

    2016-01-01

    Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure. PMID:27826241

  2. Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

    Directory of Open Access Journals (Sweden)

    Avital Beig

    2016-10-01

    Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

  3. Dose-dependent adsorptive capacity of activated charcoal for gastrointestinal decontamination of a simulated paracetamol overdose in human volunteers

    DEFF Research Database (Denmark)

    Gude, Anne-Bolette Jill; Hoegberg, Lotte Christine Groth; Riis Angelo, Helle

    2010-01-01

    The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal-drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated...... whether this reserve capacity exists in vivo. This is clinically relevant in cases of large overdoses or if the full standard dose of 50 g activated charcoal cannot be administered. We performed a randomized, cross-over study (n = 16). One hour after a standard breakfast, 50 mg/kg paracetamol...... was administered, followed 1 hr later by an activated charcoal-Water slurry containing 50 (control), 25 or 5 g activated charcoal. The areas under the serum concentration-time curve (AUC) for paracetamol were used to estimate the efficacy of each activated charcoal dose. The AUC of the 25-g dose was found...

  4. Successful reversal of life threatening cardiac effect following dosulepin overdose using intravenous lipid emulsion

    DEFF Research Database (Denmark)

    Boegevig, Soeren; Rothe, Anders; Tfelt-Hansen, Jacob

    2011-01-01

    CONTEXT. We report a successful acute reversal of potential life threatening QRS complex widening and prolonged QT interval following dosulepin overdose using intravenous lipid emulsion 20% in an unstable patient. CASE DETAILS. A 36-year-old female following the ingestion of 5.25 g of dosulepin...... became shorter. DISCUSSION. Cyclic antidepressants affect the cardiac conduction system and the myocardium. The exact mechanism of action from intravenous lipid emulsions may not be determined from the data presented, and the obtained effect does not rule out the supposed effects of alkalinisation...

  5. Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

    Science.gov (United States)

    Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

    2018-04-15

    Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

  6. Overdose effect of aconite containing Ayurvedic Medicine (‘Mahashankha Vati’)

    Science.gov (United States)

    Panda, Ashok Kumar; Debnath, Saroj Kumar

    2010-01-01

    There are chances that the use of larger than recommended dose of Ayurvedic medicines containing aconite can produce drug reactions. Vatsanabha (Aconitum ferox Wall.) is a very well-known ingredient of Ayurvedic formulations and is prescribed as an antipyretic, analgesic, anti-rheumatic, appetizer and digestive. The recommended dose of purified Vatsanabha (A. ferox Wall.) root is 15 mg. We present a case of hypotension and bradycardia due to aconite poisoning caused by overdosing of an Ayurvedic medicine (Mahashankha Vati), which was primarily managed by Ayurvedic treatment. PMID:21170213

  7. Transient thyrotoxicosis from thyroiditis induced by sibutramine overdose: a case report.

    Science.gov (United States)

    Kim, S K; Lee, S M; Yoo, S S; Hahm, J R; Jung, J H; Kim, H S; Kim, S; Chung, S I; Jung, T S

    2013-08-01

    Sibutramine is an antiobesity drug that inhibits the reuptake of serotonin and noradrenalin in the hypothalamus. A 37-year-old Korean man presented to the emergency room for the oral intake of 280 mg of sibutramine. The patient was in thyrotoxic state. The (99m)Technetium-pertechnetate thyroid scan showed irregular uptake of radioisotope and thyroid-stimulating hormone receptor antibody and thyroperoxidase antibody were negative. Thyroid function normalized after that. The patient had transient thyrotoxicosis with thyroiditis. We report a case of thyrotoxicosis accompanied by thyroiditis resulting from the intentional overdose of sibutramine.

  8. Social and economic inequalities in fatal opioid and cocaine related overdoses in Luxembourg: a case-control study.

    Science.gov (United States)

    Origer, Alain; Le Bihan, Etienne; Baumann, Michèle

    2014-09-01

    To investigate social and economic inequalities in fatal overdose cases related to opioid and cocaine use, recorded in Luxembourg between 1994 and 2011. Cross-examination of national data from law enforcement and drug use surveillance sources and of forensic evidence in a nested case-control study design. Overdose cases were individually matched with four controls, when available, according to sex, year of birth, drug administration route and duration of drug use. 272 cases vs 1056 controls were analysed. Conditional logistic regression analysis was performed to assess the respective impact of a series of socioeconomic variables. Being professionally active [OR=0.66 (95% CI 0.45-0.99)], reporting salary as main legal income source [OR=0.42 (95% CI 0.26-0.67)] and education attainment higher than primary school [OR=0.50 (95% CI 0.34-0.73)] revealed to be protective factors, whereas the professional status of the father or legal guardian of victims was not significantly associated to fatal overdoses. Socioeconomic inequalities in drug users impact on the occurrence of fatal overdoses. Compared to their peers, users of illicit drugs with lower socioeconomic profiles show increased odds of dying from overdose. However, actual and self-referred socioeconomic characteristics of drug users, such as educational attainment and employment, may have a greater predictive value of overdose mortality than the parental socioeconomic status. Education, vocational training and socio-professional reintegration should be part of drug-related mortality prevention policies. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

    Science.gov (United States)

    Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

    2015-06-01

    In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100

  10. Measuring a Crisis: Questioning the Use of Naloxone Administrations as a Marker for Opioid Overdoses in a Large U.S. EMS System.

    Science.gov (United States)

    Grover, Joseph M; Alabdrabalnabi, Taibah; Patel, Mehul D; Bachman, Michael W; Platts-Mills, Timothy F; Cabanas, Jose G; Williams, Jefferson G

    2018-01-01

    The United States is currently experiencing a public health crisis of opioid overdoses. To determine where resources may be most needed, many public health officials utilize naloxone administration by EMS as an easily-measured surrogate marker for opioid overdoses in a community. Our objective was to evaluate whether naloxone administration by EMS accurately represents EMS calls for opioid overdose. We hypothesize that naloxone administration underestimates opioid overdose. We conducted a chart review of suspected overdose patients and any patients administered naloxone in Wake County, North Carolina, from January 2013 to December 2015. Patient care report narratives and other relevant data were extracted from electronic patient care records and the resultant database was analyzed by two EMS physicians. Cases were divided into categories including "known opioid use," "presumed opioid use," "no known opioid," "altered mental status," "cardiac arrest with known opioid use," "cardiac arrest with no known opioid use," or "suspected alcohol intoxication," and then further separated based on whether naloxone was administered. Patient categories were compared by patient demographics and incident year. Using the chart review classification as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of naloxone administration for opioid overdose. A total of 4,758 overdose cases from years 2013-15 were identified. During the same period, 1,351 patients were administered naloxone. Of the 1,431 patients with known or presumed opioid use, 57% (810 patients) received naloxone and 43% (621 patients) did not. The sensitivity of naloxone administration for the identification of patients with known or presumed opioid use was 57% (95% CI: 54%-59%) and the PPV was 60% (95% CI: 57%-63%). Among patients receiving care in this large urban EMS system in the United States, the overall sensitivity and positive predictive value for naloxone administration for

  11. Acute renal failure associated with an accidental overdose of colchicine.

    Science.gov (United States)

    Borrás-Blasco, J; Enriquez, R; Sirvent, A E; Amoros, F; Navarro-Ruiz, A; Reyes, A

    2005-10-01

    A 47-year-old man with a history of polyarticular gout was admitted to the nephrology service because of severe renal insufficiency (creatinine 6.25 mg/dl). Three days before admission he had a pain crisis in his knees and ankles and self-administered 20 x 1 mg granules of colchicine p.o. over a period of 4 - 5 hours together with six suppositories each containing 100 mg of indomethacin. The patient began vomiting within 24 hours, experienced diarrhea which persisted for three days and then came to the hospital. The patient reported oliguria during the preceding 24 hours. In hospital, attempts to correct water and electrolyte balance were initiated. The patient became stabilized hemo-dynamically, the diarrhea disappeared within 24 hours, diuresis resumed and the renal function progressively improved. Leukopenia and thrombopenia were diagnosed, the transaminases increased: AST = 79 U/l, ALT = 132 U/l on the eighth day after taking the colchicine. The serology for hepatitis A, B, C and HIV viruses was negative; the serology for CMV and VEB revealed a previous infection. After being discharged from hospital 11 days after admission, the patient presented with the following parameters: hematocrit 39%, leukocytes 5,920/microl (3 470 neutrophils), prothrombin time 13 seconds, urea 44 mg/dl, creatinine 1.29 mg/dl, AST 16 U/l and ALT 35 U/l. The patient mistakenly ingested 20 mg ofcolchicine p.o. (0.22 mg/kg). The intoxication was associated with gastroenterocolitis, dehydration and renal failure during the first three days after ingestion. The patient also developed leukopenia, thrombopenia and mild hepatocellular injury. Renal failure due to colchicine intoxication is due to various factors such as depletion of volume/hypotension, rhabdomyolysis and multiorgan failure. In this case, the hypovolemia was probably the fundamental cause of the acute renal insufficiency as demonstrated by the quick recovery after administering fluids. It is possible that indomethacin may have

  12. How life history influences the responses of the clam Scrobicularia plana to the combined impacts of carbamazepine and pH decrease

    International Nuclear Information System (INIS)

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J.; Esteves, Valdemar I.; Wrona, Frederick J.; Soares, Amadeu M.V. M.; Figueira, Etelvina

    2015-01-01

    In the present study, the bivalve Scrobicularia plana, collected from two contrasting areas (pristine location and mercury contaminated area), was selected to assess the biochemical alterations imposed by pH decrease, carbamazepine (an antiepileptic) and the combined effect of both stressors. The effects on oxidative stress related biomarkers after 96 h exposure revealed that pH decrease and carbamazepine induced alterations on clams, with greater impacts on individuals from the contaminated area which presented higher mortality, higher lipid peroxidation and higher glutathione S-transferase activity. These results emphasize the risk of extrapolating results from one area to another, since the same species inhabiting different areas may be affected differently when exposed to the same stressors. Furthermore, the results obtained showed that, when combined, the impact of pH decrease and carbamazepine was lower than each stressor acting alone, which could be related to the defence mechanism of valves closure when bivalves are under higher stressful conditions. - Highlights: • Environmentally relevant concentrations of CBZ and pH 7.1 impacted the performance of Scrobicularia plana. • The combination of CBZ and pH 7.1 did not induce higher impacts compared with stressors acting alone. • Clams from a polluted area showed greater alterations than clams collected from an unpolluted area. - pH decrease and carbamazepine induced biochemical alterations on clams (Scrobicularia plana), with greater impacts on individuals from the contaminated area

  13. Chloroquine is grossly overdosed and overused but well tolerated in Guinea-Bissau

    DEFF Research Database (Denmark)

    Ursing, Johan; Kofoed, Poul-Erik; Rodrigues, Amabelia

    2009-01-01

    High chloroquine doses are commonly prescribed in Guinea-Bissau. Double dose chloroquine has been shown to be more efficacious (92% efficacy) than the standard dose (80% efficacy). However, chloroquine is toxic when overdosed and it is not known if the high doses prescribed in Guinea-Bissau are t...... prescribed to children without parasitaemia. Use of high dose CQ is concurrent with an exceptionally low prevalence of chloroquine resistant P. falciparum.......High chloroquine doses are commonly prescribed in Guinea-Bissau. Double dose chloroquine has been shown to be more efficacious (92% efficacy) than the standard dose (80% efficacy). However, chloroquine is toxic when overdosed and it is not known if the high doses prescribed in Guinea......-Bissau are taken or whether they cause adverse effects. We aimed to determine the dosage of chloroquine commonly prescribed, the doses commonly taken and if there were concentration dependent adverse events in routine practice. Chloroquine prescriptions by 8 physicians and chloroquine intake by 102 children were...

  14. Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na(+) and Ca(2+) Channels Permeability.

    Science.gov (United States)

    Sitges, María; Chiu, Luz María; Reed, Ronald C

    2016-04-01

    Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na(+) and Ca(2+) channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro-convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca(2+) induced by high K(+), or on the selective increase in Na(+) induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca(2+) induced by 4-AP, which was dependent on the out-in Na(+) gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca(2+) induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na(+) or Ca(2+) channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na(+) or Ca(2+) channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na(+) and/or Ca(2+) channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated.

  15. Investigation and risk evaluation of the occurrence of carbamazepine, oxcarbazepine, their human metabolites and transformation products in the urban water cycle.

    Science.gov (United States)

    Brezina, Elena; Prasse, Carsten; Meyer, Johannes; Mückter, Harald; Ternes, Thomas A

    2017-06-01

    Trace organic contaminants such as pharmaceuticals, personal care products and industrial chemicals are frequently detected in the urban water cycle, including wastewater, surface water and groundwater, as well as drinking water. These also include human metabolites (HMs), which are formed in the human body and then excreted via urine or feces, as well as transformation products (TPs) formed in engineered treatment systems and the aquatic environment. In the current study, the occurrence of HMs as well as their TPs of the anticonvulsants carbamazepine (CBZ) and oxcarbazepine (OXC) were investigated using LC tandem MS in effluents of wastewater treatment plants (WWTPs), surface water and groundwater. Highest concentrations were observed in raw wastewater for 10,11-dihydro-10,11-dihydroxycarbamazepine (DiOHCBZ), 10,11-dihydro-10-hydroxy-cabamazepine (10OHCBZ) and CBZ with concentrations ranging up to 2.7 ± 0.4, 1.7 ± 0.2 and 1.07 ± 0.06 μg L -1 , respectively. Predictions of different toxicity endpoints using a Distributed Structure-Searchable Toxicity (DSSTox) expert system query indicated that several HMs and TPs, in particular 9-carboxy-acridine (9-CA-ADIN) and acridone (ADON), may exhibit an increased genotoxicity compared to the parent compound CBZ. As 9-CA-ADIN was also detected in groundwater, a detailed investigation of the genotoxicity of 9-CA-ADIN is warranted. Investigations of an advanced wastewater treatment plant further revealed that the discharge of the investigated compounds into the aquatic environment could be substantially reduced by ozonation followed by granular activated carbon (GAC) filtration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Risk stratification after paracetamol overdose using mechanistic biomarkers: results from two prospective cohort studies.

    Science.gov (United States)

    Dear, James W; Clarke, Joanna I; Francis, Ben; Allen, Lowri; Wraight, Jonathan; Shen, Jasmine; Dargan, Paul I; Wood, David; Cooper, Jamie; Thomas, Simon H L; Jorgensen, Andrea L; Pirmohamed, Munir; Park, B Kevin; Antoine, Daniel J

    2018-02-01

    Paracetamol overdose is common but patient stratification is suboptimal. We investigated the usefulness of new biomarkers that have either enhanced liver specificity (microRNA-122 [miR-122]) or provide mechanistic insights (keratin-18 [K18], high mobility group box-1 [HMGB1], and glutamate dehydrogenase [GLDH]). The use of these biomarkers could help stratify patients for their risk of liver injury at hospital presentation. Using data from two prospective cohort studies, we assessed the potential for biomarkers to stratify patients who overdose with paracetamol. We completed two independent prospective studies: a derivation study (MAPP) in eight UK hospitals and a validation study (BIOPAR) in ten UK hospitals. Patients in both cohorts were adults (≥18 years in England, ≥16 years in Scotland), were diagnosed with paracetamol overdose, and gave written informed consent. Patients who needed intravenous acetylcysteine treatment for paracetamol overdose had circulating biomarkers measured at hospital presentation. The primary endpoint was acute liver injury indicating need for continued acetylcysteine treatment beyond the standard course (alanine aminotransferase [ALT] activity >100 U/L). Receiver operating characteristic (ROC) curves, category-free net reclassification index (cfNRI), and integrated discrimination index (IDI) were applied to assess endpoint prediction. Between June 2, 2010, and May 29, 2014, 1187 patients who required acetylcysteine treatment for paracetamol overdose were recruited (985 in the MAPP cohort; 202 in the BIOPAR cohort). In the derivation and validation cohorts, acute liver injury was predicted at hospital presentation by miR-122 (derivation cohort ROC-area under the curve [AUC] 0·97 [95% CI 0·95-0·98]), HMGB1 (0·95 [0·93-0·98]), and full-length K18 (0·95 [0·92-0·97]). Results were similar in the validation cohort (miR-122 AUC 0·97 [95% CI 0·95-0·99], HMGB1 0·98 [0·96-0·99], and full-length K18 0·93 [0·86-0·99]). A

  17. Development, validation and clinical application of an online-SPE-LC-HRMS/MS for simultaneous quantification of phenobarbital, phenytoin, carbamazepine, and its active metabolite carbamazepine 10,11-epoxide.

    Science.gov (United States)

    Qu, Lihua; Fan, Yuanjie; Wang, Wenjun; Ma, Kai; Yin, Zheng

    2016-09-01

    A simple and efficient bioanalytical method for simultaneous determination of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and its active metabolite carbamazepine 10,11-epoxide (CBZE) in human plasma using online solid phase extraction (SPE)-liquid chromatography (LC) coupled with high resolution mass spectrum (HRMS) under targeted MS/MS (t-MS(2)) analysis mode has been developed. The procedure integrated an automated sample clean-up of human plasma by Oasis®HLB SPE cartridge, a separation by ZORBAX SB-C18 analysis column, and a quantification by Q-Exactive Hybrid Quadrupole-Orbitrap. The total running time was 13min. The lower limit of quantification (LLOQ) of PB, PHT, CBZ, and CBZE were 0.008, 0.008, 0.0016 and 0.0016μgmL(-1) respectively and the linearities were in the range of 0.008-2.500, 0.008-2.500, 0.0016-0.500 and 0.0016-0.500μgmL(-1) respectively. The mean recovery was between 91.82% and 108.27% and the matrix effect was between 93.29% and 102.09%. The relative standard deviations of interday and intraday were less than 6.41%. The method has been successfully applied in therapeutic drug monitoring (TDM) of four Chinese epilepsy patients. This fully automated, simple, sensitive and reliable online-SPE-LC-HRMS/MS method serves well for TDM of PB, PHT, CBZ and CBZE at clinics for either single or combination treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Massive venlafaxine overdose resulted in a false positive Abbott AxSYM (R) urine immunoassay for phencyclidine

    NARCIS (Netherlands)

    Bond, GR; Steele, PE; Uges, DRA

    2003-01-01

    Case report: A 13-yr-old girl overdosed on 48 x 150 mg venlafaxine (Effexor XR(R)). She was taking venlafaxine regularly for depression. Her only other medications included topical Benzamycin and pyridoxine 50 mg daily for acne. The Abbott AxSYM(R) assay was positive only for phencyclidine, but

  19. Treatment of opioid overdose in a physician-based prehospital EMS: frequency and long-term prognosis

    DEFF Research Database (Denmark)

    Nielsen, Karina Skafte; Nielsen, Søren Louman; Siersma, Volkert Dirk

    2011-01-01

    Prehospital treatment of opioid overdose accounts for a significant proportion of the workload of the emergency system in most major cities. Treatment consists of basic life support and administering naloxone. In our physician-manned mobile emergency care unit (MECU), most patients are released...

  20. Influence of sodium lauryl sulfate and tween 80 on carbamazepine-nicotinamide cocrystal solubility and dissolution behaviour.

    Science.gov (United States)

    Li, Mingzhong; Qiao, Ning; Wang, Ke

    2013-10-11

    The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine-nicotinamide (CBZ-NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ-NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ-NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ-NIC cocrystal but they had totally opposite effects on the IDR of the CBZ-NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ-NIC cocrystal while Tween 80 decreased its IDR.

  1. Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring.

    Science.gov (United States)

    Andretta, Rhayza Roberta; Okada, Fatima Kazue; Paccola, Camila Cicconi; Stumpp, Taiza; de Oliva, Samara Urban; Miraglia, Sandra M

    2014-04-01

    Carbamazepine (CBZ) is an anti-epileptic drug that acts on Leydig cells, affecting steroidogenesis and causes fetal malformation. The aim of this study was to investigate the effects of CBZ on male sexual maturation and other male parameters. Rat dams were treated with CBZ during pregnancy and breastfeeding. The anogenital distance (AGD) and the anogenital index (AGI) were obtained. Testicular descent and preputial separation were also evaluated. The offspring was euthanized at PND 41 and 63. The accessory glands were weighed and the testes were collected for histopathological, morphometric and sterological analyses. The numerical density of Leydig cells and hormone dosage were obtained. CBZ caused an increase of AGI and a delay of testicular descent and of preputial separation. CBZ also caused a decrease of testosterone level and of sperm count and an increase of abnormal sperm. These results indicate that CBZ delays puberty onset and affects steroidogenesis and sperm quality. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. An elevated neutrophil-lymphocyte ratio is associated with adverse outcomes following single time-point paracetamol (acetaminophen) overdose: a time-course analysis.

    Science.gov (United States)

    Craig, Darren G; Kitto, Laura; Zafar, Sara; Reid, Thomas W D J; Martin, Kirsty G; Davidson, Janice S; Hayes, Peter C; Simpson, Kenneth J

    2014-09-01

    The innate immune system is profoundly dysregulated in paracetamol (acetaminophen)-induced liver injury. The neutrophil-lymphocyte ratio (NLR) is a simple bedside index with prognostic value in a number of inflammatory conditions. To evaluate the prognostic accuracy of the NLR in patients with significant liver injury following single time-point and staggered paracetamol overdoses. Time-course analysis of 100 single time-point and 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Timed laboratory samples were correlated with time elapsed after overdose or admission, respectively, and the NLR was calculated. A total of 49/100 single time-point patients developed hepatic encephalopathy (HE). Median NLRs were higher at both 72 (P=0.0047) and 96 h after overdose (P=0.0041) in single time-point patients who died or were transplanted. Maximum NLR values by 96 h were associated with increasing HE grade (P=0.0005). An NLR of more than 16.7 during the first 96 h following overdose was independently associated with the development of HE [odds ratio 5.65 (95% confidence interval 1.67-19.13), P=0.005]. Maximum NLR values by 96 h were strongly associated with the requirement for intracranial pressure monitoring (Pparacetamol overdoses. Future studies should assess the value of incorporating the NLR into existing prognostic and triage indices of single time-point paracetamol overdose.

  3. Heroin overdose

    Science.gov (United States)

    ... is the gateway to heroin use for many people. This is because the street price of heroin is often the cheaper than ... There is no legal medical use for heroin. Street names for heroin include "junk", "smack", dope, brown sugar, white horse, China white, and "skag".

  4. Estrogen overdose

    Science.gov (United States)

    ... treated. Treatment may include: Activated charcoal (in extreme cases) Blood and urine ... Rosen's Emergency Medicine: Concepts and Clinical Practice . 9th ed. Philadelphia, PA: Elsevier; 2018:chap ...

  5. Bacitracin overdose

    Science.gov (United States)

    ... amount of the product. This can be by accident or on purpose. This article is for information ... water for at least 15 minutes. If the chemical was swallowed, give the person water or milk right ... A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  6. Pentazocine overdose

    Science.gov (United States)

    ... have signs of opioid intoxication. Opioids are powerful painkillers. Symptoms may include: Bluish skin color (cyanosis) Breathing ... naloxone (Narcan), an antidote to help reverse the effect of the poison, multiple doses may be needed. ...

  7. Prochlorperazine overdose

    Science.gov (United States)

    ... AND THROAT Blurred vision Drooling Dry mouth Nasal congestion Small pupils Yellow eyes STOMACH AND INTESTINES Constipation ... symptoms Activated charcoal Laxative Breathing support, including a tube through the mouth into the lungs and connected ...

  8. Thioridazine overdose

    Science.gov (United States)

    ... AND THROAT Blurred vision Drooling Dry mouth Nasal congestion Swallowing difficulties Ulcers in the mouth, on the ... urine tests Breathing support, including oxygen and a tube through the mouth into the lungs CT scan ( ...

  9. Acetaminophen overdose

    Science.gov (United States)

    ... of Drugs . 16th ed. Waltham, MA: Elsevier; 2016:474-493. Hendrickson RG, McKeown, MJ. Acetaminophen. In: Marx ... RSS Follow us Disclaimers Copyright Privacy Accessibility Quality Guidelines Viewers & Players MedlinePlus Connect for EHRs For Developers ...

  10. Morphine overdose

    Science.gov (United States)

    ... tests Chest x-ray EKG (electrocardiogram, or heart tracing) Fluids through a vein (IV) Laxative Naloxone, a ... Toxicology Data Network. Morphine. Toxnet.nlm.nih.gov Web site. toxnet.nlm.nih.gov/cgi-bin/sis/ ...

  11. Iron overdose

    Science.gov (United States)

    ... tracing) X-ray to detect and track iron tablets through the stomach and intestines Treatment may include: ... BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016: ...

  12. Mouthwash overdose

    Science.gov (United States)

    ... are: Chlorhexidine gluconate Ethanol (ethyl alcohol) Hydrogen peroxide Methyl salicylate ... amounts of alcohol (drunkenness). Swallowing large amounts of methyl salicylate and hydrogen peroxide may also cause serious stomach ...

  13. Phenindamine overdose

    Science.gov (United States)

    ... Goldfrank's Toxicologic Emergencies . 10th ed. New York, NY: McGraw Hill-Medical; 2015:chap 49. Monte AA, Hoppe ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  14. Pheniramine overdose

    Science.gov (United States)

    ... Goldfrank's Toxicologic Emergencies . 10th ed. New York, NY: McGraw Hill-Medical; 2015:chap 49. Monte AA, Hoppe ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  15. Doxepin overdose

    Science.gov (United States)

    ... Goldfrank's Toxicologic Emergencies . 10th ed. New York, NY: McGraw Hill-Medical; 2015:chap 71. Review Date 7/ ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  16. Opioid Overdose

    Science.gov (United States)

    ... Updated: 03/10/2016 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

  17. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    International Nuclear Information System (INIS)

    Lozano, Valeria A.; Escandar, Graciela M.

    2013-01-01

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  18. Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO_2 mediated heterogeneous activation of peroxymonosulfate

    International Nuclear Information System (INIS)

    Ding, Yaobin; Tang, Hebin; Zhang, Shenghua; Wang, Songbo; Tang, Heqing

    2016-01-01

    Highlights: • CuFeO_2 microparticles were prepared by a microwave-assisted hydrothermal method. • CuFeO_2 microparticles efficiently catalyzed the activation of peroxymonosulfate. • Quenching experiments confirmed sulfate radicals as the major reactive radicals. • Carbamazepine was rapidly degraded by micro-CuFeO_2/peroxymonosulfate. • Feasibility of CuFeO_2/peroxymonosulfate was tested for treatment of actual water. - Abstract: Microscaled CuFeO_2 particles (micro-CuFeO_2) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO_2 was of pure phase and a rhombohedral structure with size in the range of 2.8 ± 0.6 μm. The micro-CuFeO_2 efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO_4·−), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO_2 was observed to be 6.9 and 25.3 times that of micro-Cu_2O and micro-Fe_2O_3, respectively. The enhanced activity of micro-CuFeO_2 for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO_2 can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu_2O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO_2 was effective in the studied actual aqueous environmental systems.

  19. Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO{sub 2} mediated heterogeneous activation of peroxymonosulfate

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yaobin, E-mail: yaobinding@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Tang, Hebin [College of Pharmacy, South-Central University for Nationalities, Wuhan 430074 (China); Zhang, Shenghua; Wang, Songbo [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Tang, Heqing, E-mail: tangheqing@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China)

    2016-11-05

    Highlights: • CuFeO{sub 2} microparticles were prepared by a microwave-assisted hydrothermal method. • CuFeO{sub 2} microparticles efficiently catalyzed the activation of peroxymonosulfate. • Quenching experiments confirmed sulfate radicals as the major reactive radicals. • Carbamazepine was rapidly degraded by micro-CuFeO{sub 2}/peroxymonosulfate. • Feasibility of CuFeO{sub 2}/peroxymonosulfate was tested for treatment of actual water. - Abstract: Microscaled CuFeO{sub 2} particles (micro-CuFeO{sub 2}) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO{sub 2} was of pure phase and a rhombohedral structure with size in the range of 2.8 ± 0.6 μm. The micro-CuFeO{sub 2} efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO{sub 4}·−), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO{sub 2} was observed to be 6.9 and 25.3 times that of micro-Cu{sub 2}O and micro-Fe{sub 2}O{sub 3}, respectively. The enhanced activity of micro-CuFeO{sub 2} for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO{sub 2} can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu{sub 2}O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO{sub 2} was effective in the studied actual aqueous environmental systems.

  20. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Valeria A.; Escandar, Graciela M., E-mail: escandar@iquir-conicet.gov.ar

    2013-06-11

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  1. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-11-15

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD{sub 7} m{sup -3}d{sup -1}. Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k{sub biol}) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g{sub SS}{sup −1} d{sup −1}. Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k{sub biol} constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge.

  2. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    International Nuclear Information System (INIS)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-01-01

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD 7 m -3 d -1 . Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k biol ) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g SS −1 d −1 . Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k biol constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge

  3. Intranasal naloxone and related strategies for opioid overdose intervention by nonmedical personnel: a review

    Directory of Open Access Journals (Sweden)

    Lewis CR

    2017-10-01

    Full Text Available Christa R Lewis,1,2 Hoa T Vo,1 Marc Fishman1,3 1Maryland Treatment Centers, Baltimore, MD, USA; 2Department of Psychology, Towson University, Towson, MD, USA; 3Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Deaths due to prescription and illicit opioid overdose have been rising at an alarming rate, particularly in the USA. Although naloxone injection is a safe and effective treatment for opioid overdose, it is frequently unavailable in a timely manner due to legal and practical restrictions on its use by laypeople. As a result, an effort spanning decades has resulted in the development of strategies to make naloxone available for layperson or “take-home” use. This has included the development of naloxone formulations that are easier to administer for nonmedical users, such as intranasal and autoinjector intramuscular delivery systems, efforts to distribute naloxone to potentially high-impact categories of nonmedical users, as well as efforts to reduce regulatory barriers to more widespread distribution and use. Here we review the historical and current literature on the efficacy and safety of naloxone for use by nonmedical persons, provide an evidence-based discussion of the controversies regarding the safety and efficacy of different formulations of take-home naloxone, and assess the status of current efforts to increase its public distribution. Take-home naloxone is safe and effective for the treatment of opioid overdose when administered by laypeople in a community setting, shortening the time to reversal of opioid toxicity and reducing opioid-related deaths. Complementary strategies have together shown promise for increased dissemination of take-home naloxone, including 1 provision of education and training; 2 distribution to critical populations such as persons with opioid addiction, family members, and first responders; 3 reduction of prescribing barriers to access; and 4 reduction of legal

  4. Illicit use of opioid substitution drugs: prevalence, user characteristics, and the association with non-fatal overdoses.

    Science.gov (United States)

    Bretteville-Jensen, Anne Line; Lillehagen, Mats; Gjersing, Linn; Andreas, Jasmina Burdzovic

    2015-02-01

    Diversion of opioid substitution drugs (OSD) is of public concern. This study examined the prevalence, frequency, and predictors of illicit OSD use in a group of injecting drug users (IDUs) and assessed if such use was associated with non-fatal overdoses. Semi-annual cross-sectional interviews conducted in Oslo, Norway (2006-2013), from 1355 street-recruited IDUs. Hurdle, logistic, and multinomial regression models were employed. Overall, 27% reported illicit OSD use in the past four weeks; 16.8% methadone, 12.5% buprenorphine, and 2.9% both drugs. Almost 1/10 reported at least one non-fatal overdose in the past four weeks, and roughly 1/3 reported such experience in the past year. Use of additional drugs tended to be equally, or more prevalent among illicit OSD users than other IDUs. In terms of illicit OSD use being a risk factor for non-lethal overdoses, our results showed significant associations only for infrequent buprenorphine use (using once or less than once per week). Other factors associated with non-fatal overdoses included age, education, homelessness, as well as the benzodiazepines, stimulants, and heroin use. Users of diverted OSD may represent a high-risk population, as they used more additional drugs and used them more frequently than other IDUs. However, illicit OSD use may be less harmful than previously assumed. After accounting for an extensive set of covariates, only infrequent illicit buprenorphine use, but not methadone use, was associated with non-fatal overdoses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Technical Note: A novel leaf sequencing optimization algorithm which considers previous underdose and overdose events for MLC tracking radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wisotzky, Eric, E-mail: eric.wisotzky@charite.de, E-mail: eric.wisotzky@ipk.fraunhofer.de; O’Brien, Ricky; Keall, Paul J., E-mail: paul.keall@sydney.edu.au [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006 (Australia)

    2016-01-15

    Purpose: Multileaf collimator (MLC) tracking radiotherapy is complex as the beam pattern needs to be modified due to the planned intensity modulation as well as the real-time target motion. The target motion cannot be planned; therefore, the modified beam pattern differs from the original plan and the MLC sequence needs to be recomputed online. Current MLC tracking algorithms use a greedy heuristic in that they optimize for a given time, but ignore past errors. To overcome this problem, the authors have developed and improved an algorithm that minimizes large underdose and overdose regions. Additionally, previous underdose and overdose events are taken into account to avoid regions with high quantity of dose events. Methods: The authors improved the existing MLC motion control algorithm by introducing a cumulative underdose/overdose map. This map represents the actual projection of the planned tumor shape and logs occurring dose events at each specific regions. These events have an impact on the dose cost calculation and reduce recurrence of dose events at each region. The authors studied the improvement of the new temporal optimization algorithm in terms of the L1-norm minimization of the sum of overdose and underdose compared to not accounting for previous dose events. For evaluation, the authors simulated the delivery of 5 conformal and 14 intensity-modulated radiotherapy (IMRT)-plans with 7 3D patient measured tumor motion traces. Results: Simulations with conformal shapes showed an improvement of L1-norm up to 8.5% after 100 MLC modification steps. Experiments showed comparable improvements with the same type of treatment plans. Conclusions: A novel leaf sequencing optimization algorithm which considers previous dose events for MLC tracking radiotherapy has been developed and investigated. Reductions in underdose/overdose are observed for conformal and IMRT delivery.

  6. Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

    Science.gov (United States)

    Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

    2017-06-01

    The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

  7. Massive Accidental Overdose of Hydroxyurea in a Young Child with Sickle Cell Anemia

    Science.gov (United States)

    Miller, Scott T.; Rey, Kathy; He, Jin; Flanagan, Jonathan; Fish, Billie J.; Rogers, Zora R.; Wang, Winfred C.; Ware, Russell E.

    2011-01-01

    The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) confirmed safety and efficacy of hydroxyurea therapy for infants with sickle cell anemia. Treatment was associated with reduction in rates of pain, acute chest syndrome, hospitalizations and blood transfusions; improved hematologic values; and, perhaps, preservation of organ function. During the study, a two year-old ingested at one time an entire 35-day supply of hydroxyurea (612 mg/kg body-weight). Despite a serum level of 7,756 μM four hours post-ingestion, the only toxicity was transient mild myelosuppression. With wider usage of hydroxyurea anticipated, conservative management of future overdoses seems reasonable. (ClinicalTrials.gov NCT00006400) PMID:21744485

  8. The Case for Improved Interprofessional Care: Fatal Analgesic Overdose Secondary to Acute Dental Pain during Pregnancy

    Directory of Open Access Journals (Sweden)

    Sarah K. Y. Lee

    2016-01-01

    Full Text Available Prenatal oral health extends beyond the oral cavity, impacting the general well-being of the pregnant patient and her fetus. This case report follows a 19-year-old pregnant female presenting with acute liver failure secondary to acetaminophen overdose for management of dental pain following extensive dental procedures. Through the course of her illness, the patient suffered adverse outcomes including fetal demise, acute kidney injury, spontaneous bacterial peritonitis, and septic shock before eventual death from multiple organ failure. In managing the pregnant patient, healthcare providers, including physicians and dentists, must recognize and optimize the interconnected relationships shared by the health disciplines. An interdisciplinary approach of collaborative and coordinated care, the timing, sequence, and treatment for the pregnant patient can be improved and thereby maximize overall quality of health. Continued efforts toward integrating oral health into general healthcare education through interprofessional education and practice are necessary to enhance the quality of care that will benefit all patients.

  9. A case of near-fatal flecainide overdose in a neonate successfully treated with sodium bicarbonate.

    Science.gov (United States)

    Jang, David H; Hoffman, Robert S; Nelson, Lewis S

    2013-04-01

    Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate. An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220-240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child's cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 μg/L (therapeutic, 200-1000 μg/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses. Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Increase in Drug Overdose Deaths Involving Fentanyl-Rhode Island, January 2012-March 2014.

    Science.gov (United States)

    Mercado, Melissa C; Sumner, Steven A; Spelke, M Bridget; Bohm, Michele K; Sugerman, David E; Stanley, Christina

    2018-03-01

    This study identified sociodemographic, substance use, and multiple opioid prescriber and dispenser risk factors among drug overdose decedents in Rhode Island, in response to an increase in overdose deaths (ODs) involving fentanyl. This cross-sectional investigation comprised all ODs reviewed by Rhode Island's Office of the State Medical Examiners (OSME) during January 2012 to March 2014. Data for 536 decedents were abstracted from OSME's charts, death certificates, toxicology reports, and Prescription Monitoring Program (PMP) databases. Decedents whose cause of death involved illicit fentanyl (N = 69) were compared with decedents whose causes of death did not involve fentanyl (other drug decedents; N = 467). Illicit-fentanyl decedents were younger than other drug decedents (P = 0.005). While more other-drug decedents than illicit fentanyl decedents had postmortem toxicological evidence of consuming heroin (31.9% vs 19.8%, P < 0.001) and various pharmaceutical substances (P = 0.002-0.027), third party reports indicated more recent heroin use among illicit fentanyl decedents (62.3% vs 45.6%, P = 0.002). Approximately 35% of decedents filled an opioid prescription within 90 days of death; of these, one-third had a mean daily dosage greater than 100 morphine milligram equivalents (MME/day). Most decedents' opioid prescriptions were filled at one to two dispensers (83.9%) and written by one to two prescribers (75.8%). Notably, 29.2% of illicit fentanyl and 10.5% of other drug decedents filled prescriptions for buprenorphine, which is used to treat opioid use disorders. Illicit-fentanyl deaths frequently involved other illicit drugs (e.g., cocaine, heroin). The proportion of all decedents acquiring greater than 100 MME/day prescription dosages written and/or filled by few prescribers and dispensers is concerning. To protect patients, prescribers and dispensers should review PMP records and substance abuse history prior to providing opioids.

  11. Kinetic study of photocatalytic degradation of carbamazepine, clofibric acid, iomeprol and iopromide assisted by different TiO2 materials--determination of intermediates and reaction pathways.

    Science.gov (United States)

    Doll, Tusnelda E; Frimmel, Fritz H

    2004-02-01

    The light-induced degradation of clofibric acid, carbamazepine, iomeprol and iopromide under simulated solar irradiation has been investigated in aqueous solutions suspended with different TiO2 materials (P25 and Hombikat UV100). Kinetic studies showed that P25 had a better photocatalytic activity for clofibric acid and carbamazepine than Hombikat UV100. For photocatalytic degradation of iomeprol Hombikat UV100 was more suitable than P25. The results can be explained by the higher adsorption capacity of Hombikat UV100 for iomeprol. The study also focuses on the identification and quantification of possible degradation products. The degradation process was monitored by determination of sum parameters and inorganic ions. In case of clofibric acid various aromatic and aliphatic degradation products have been identified and quantified. A possible multi-step degradation scheme for clofibric acid is proposed. This study proves the high potential of the photocatalytic oxidation process to transform and mineralize environmentally relevant pharmaceuticals and contrast media in water.

  12. Knowledge of Opioid Overdose and Attitudes to Supply of Take-Home Naloxone Among People with Chronic Noncancer Pain Prescribed Opioids.

    Science.gov (United States)

    Nielsen, Suzanne; Peacock, Amy; Lintzeris, Nicholas; Bruno, Raimondo; Larance, Briony; Degenhardt, Louisa

    2018-03-01

    Take-home naloxone (THN) is recommended in response to pharmaceutical opioid-related mortality. Some health professionals are reluctant to discuss THN for fear of causing offense. The aims of this study were to assess knowledge of opioid overdose and attitudes toward THN for opioid overdose reversal in people with chronic noncancer pain (CNCP). Prospective cohort study. Australia, September to October 2015. A subset of participants (N = 208) from a cohort of people prescribed restricted opioids for CNCP. Questions added in the two-year telephone interviews examined knowledge of overdose symptoms and attitudes toward community supply of naloxone. Associations with overdose risk factors and naloxone supply eligibility criteria with attitudes toward naloxone were explored. Fourteen percent reported ever experiencing opioid overdose symptoms. Participants correctly identified fewer than half of the overdose signs and symptoms. After receiving information on naloxone, most participants (60%), thought it was a "good" or "very good" idea. Few participants reported that they would be "a little" (N = 21, 10%) or "very" offended (N = 7, 3%) if their opioid prescriber offered them naloxone. Positive attitudes toward THN were associated with male gender (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.09-3.50), past year cannabis use (OR = 2.52, 95% CI = 1.03-6.16), and past year nicotine use (OR = 2.11, 95% CI = 1.14-3.91). Most participants had positive attitudes toward THN but low knowledge about opioid overdose symptoms. Strategies for educating patients and their caregivers on opioid toxicity are needed. THN may be best targeted toward those with risk factors in terms of overdose prevention and acceptability.

  13. A novel disposable electrochemical sensor for determination of carbamazepine based on Fe doped SnO{sub 2} nanoparticles modified screen-printed carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Lavanya, N. [Department of Biosensors and Bioelectronics, Alagappa University, Karaikudi 630003, TN (India); Department of Electronic Engineering, Chemistry and Materials Engineering, University of Messina, Messina 98166 (Italy); Sekar, C., E-mail: Sekar2025@gmail.com [Department of Biosensors and Bioelectronics, Alagappa University, Karaikudi 630003, TN (India); Ficarra, S.; Tellone, E. [Department of Chemical Sciences, University of Messina, Messina 98166 (Italy); Bonavita, A.; Leonardi, S.G.; Neri, G. [Department of Electronic Engineering, Chemistry and Materials Engineering, University of Messina, Messina 98166 (Italy)

    2016-05-01

    An effective strategy to fabricate a novel disposable screen printing carbon electrode modified by iron doped tin dioxide nanoparticles for carbamazepine (CBZ) detection has been developed. Fe–SnO{sub 2} (Fe = 0 to 5 wt.%) NPs were synthesized by a simple microwave irradiation method and assessed for their structural and morphological changes due to Fe doping into SnO{sub 2} matrix by X-ray diffraction and scanning and transmission electron microscopy. The electrochemical behaviour of carbamazepine at the Fe–SnO{sub 2} modified screen printed carbon electrode (SPCE) was investigated by cyclic voltammetry and square wave voltammetry. Electron transfer coefficient α (0.63) and electron transfer rate constant k{sub s} (0.69 s{sup −1}) values of the 5 wt.% Fe–SnO{sub 2} modified SPCE indicate that the diffusion controlled process takes place on the electrode surface. The fabricated sensor displayed a good electrooxidation response towards the detection of CBZ at a lower oxidation potential of 0.8 V in phosphate buffer solution at pH 7.0. Under the optimal conditions, the sensor showed fast and sensitive current response to CBZ over a wide linear range of 0.5–100 μM with a low detection limit of 92 nM. Furthermore, the practical application of the modified electrode has been investigated by the determination of CBZ in pharmaceutical products using standard addition method. - Highlights: • A novel mediator-free disposable screen printed carbon electrode has been fabricated based on Fe- SnO{sub 2} nanoparticles for determination of carbamazepine • The Fe-SnO{sub 2}/SPCE showed wide linear range (0.5–100 μM), low detection limit (92 nM), high sensitivity, good stability and reproducibility. • The carbamazepine sensor was successfully applied to the analysis of pharmaceutical products with satisfactory recoveries.

  14. Composted biosolids and treated wastewater as sources of pharmaceuticals and personal care products for plant uptake: A case study with carbamazepine.

    Science.gov (United States)

    Ben Mordechay, Evyatar; Tarchitzky, Jorge; Chen, Yona; Shenker, Moshe; Chefetz, Benny

    2018-01-01

    Irrigation with treated wastewater (TWW) and application of biosolids to arable land expose the agro-environment to pharmaceuticals and personal care products (PPCPs) which can be taken up by crops. In this project, we studied the effect of a carrier medium (e.g., biosolids and TWW) on plant (tomato, wheat and lettuce) uptake, translocation and metabolism of carbamazepine as a model for non-ionic PPCPs. Plant uptake and bioconcentration factors were significantly lower in soils amended with biosolids compared to soils irrigated with TWW. In soils amended with biosolids and irrigated with TWW, the bioavailability of carbamazepine for plant uptake was moderately decreased as compared to plants grown in soils irrigated with TWW alone. While TWW acts as a continuous source of PPCPs, biosolids act both as a source and a sink for these compounds. Moreover, it appears that decomposition of the biosolids in the soil after amendment enhances their adsorptive properties, which in turn reduces the bioavailability of PPCPs in the soil environment. In-plant metabolism of carbamazepine was found to be independent of environmental factors, such as soil type, carrier medium, and absolute amount implemented to the soil, but was controlled by the total amount taken up by the plant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Carbamazepine degradation using a N-doped TiO_2 coated photocatalytic membrane reactor: Influence of physical parameters

    International Nuclear Information System (INIS)

    Horovitz, Inna; Avisar, Dror; Baker, Mark A.; Grilli, Rossana; Lozzi, Luca; Di Camillo, Daniela; Mamane, Hadas

    2016-01-01

    Highlights: • UV–vis N-doped TiO_2 was deposited by sol-gel onto Al_2O_3 microfiltration membranes. • Coating decreased permeability by 50 and 12% for 200- and 800-nm Al_2O_3 membranes. • Flow through membrane results in higher reaction rates compared to flow on top. • Higher vis photocatalytic activity for N-doped TiO_2 vs. non-doped TiO_2 membranes. • Mass transfer is a critical parameter for the design of immobilized PMR. - Abstract: Commercial α-Al_2O_3 photocatalytic membranes with a pore size of 200 and 800-nm were coated with N-doped TiO_2 photocatalytic film using a sol-gel technique for concurrent bottom-up filtration and photocatalytic oxidation. X-ray diffraction confirmed that the deposited N-doped TiO_2 films are in the form of anatase with 78–84% coverage of the membrane surface. The concentration of N found by X-ray photoelectron spectroscopy was in the range of 0.3–0.9 atomic percentage. Membrane permeability after coating decreased by 50% and 12% for the 200- and 800-nm membrane substrates, respectively. The impact of operational parameters on the photocatalytic activity (PCA) of the N-doped TiO_2-coated membranes was examined in a laboratory flow cell based on degradation of the model micropollutant carbamazepine, using a solar simulator as the light source. The significant gap in degradation rate between flow through the membrane and flow on the surface of the membrane was attributed both to the hydraulic effect and in-pore PCA. N-doped TiO_2-coated membranes showed enhanced activity for UV wavelengths, in addition to activity under visible light. Experiments of PCA under varying flow rates concluded that the process is in the mass-transfer control regime. Carbamazepine removal rate increased with temperature, despite the decrease in dissolved oxygen concentration.

  16. Carbamazepine degradation using a N-doped TiO{sub 2} coated photocatalytic membrane reactor: Influence of physical parameters

    Energy Technology Data Exchange (ETDEWEB)

    Horovitz, Inna [School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); The Hydro-Chemistry Laboratory, Faculty of Geography and the Environment, Tel Aviv University, Tel Aviv 69978 (Israel); Avisar, Dror [The Hydro-Chemistry Laboratory, Faculty of Geography and the Environment, Tel Aviv University, Tel Aviv 69978 (Israel); Baker, Mark A.; Grilli, Rossana [The Surface Analysis Laboratory, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom); Lozzi, Luca; Di Camillo, Daniela [Department of Physical and Chemical Sciences, University of L' Aquila, Via Vetoio, I-67100 L' Aquila (Italy); Mamane, Hadas, E-mail: hadasmg@post.tau.ac.il [School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel)

    2016-06-05

    Highlights: • UV–vis N-doped TiO{sub 2} was deposited by sol-gel onto Al{sub 2}O{sub 3} microfiltration membranes. • Coating decreased permeability by 50 and 12% for 200- and 800-nm Al{sub 2}O{sub 3} membranes. • Flow through membrane results in higher reaction rates compared to flow on top. • Higher vis photocatalytic activity for N-doped TiO{sub 2} vs. non-doped TiO{sub 2} membranes. • Mass transfer is a critical parameter for the design of immobilized PMR. - Abstract: Commercial α-Al{sub 2}O{sub 3} photocatalytic membranes with a pore size of 200 and 800-nm were coated with N-doped TiO{sub 2} photocatalytic film using a sol-gel technique for concurrent bottom-up filtration and photocatalytic oxidation. X-ray diffraction confirmed that the deposited N-doped TiO{sub 2} films are in the form of anatase with 78–84% coverage of the membrane surface. The concentration of N found by X-ray photoelectron spectroscopy was in the range of 0.3–0.9 atomic percentage. Membrane permeability after coating decreased by 50% and 12% for the 200- and 800-nm membrane substrates, respectively. The impact of operational parameters on the photocatalytic activity (PCA) of the N-doped TiO{sub 2}-coated membranes was examined in a laboratory flow cell based on degradation of the model micropollutant carbamazepine, using a solar simulator as the light source. The significant gap in degradation rate between flow through the membrane and flow on the surface of the membrane was attributed both to the hydraulic effect and in-pore PCA. N-doped TiO{sub 2}-coated membranes showed enhanced activity for UV wavelengths, in addition to activity under visible light. Experiments of PCA under varying flow rates concluded that the process is in the mass-transfer control regime. Carbamazepine removal rate increased with temperature, despite the decrease in dissolved oxygen concentration.

  17. Assessment of the safety and ease of use of the naloxone auto-injector for the reversal of opioid overdose

    Directory of Open Access Journals (Sweden)

    Merlin MA

    2015-06-01

    Full Text Available Mark A Merlin,1,2 Navin Ariyaprakai,1 Faizan H Arshad1,2 1Newark Beth Israel Medical Center, Newark, NJ, USA; 2Monmouth Ocean Hospital Service Corporation (MONOC, Wall Township, NJ, USA Abstract: Over the last decade, opioid-related deaths in the United States have increased at an alarming rate. The use of naloxone by laypersons is a newer concept and its utilization can benefit patients by rapid administration due to it being readily available immediately after an opioid overdose. The US Food and Drug Administration approved a naloxone auto-injector on April 3, 2014 for adults and pediatrics, designed for use by anyone including patients, family members, bystanders, and medical professionals. This device (EZVIO™ is the first device of its kind available on the market. The auto-injector is a battery-operated disposable 0.4 mg/0.4 mL prefilled device for use in the lateral thigh by patients, bystanders, or health care professionals. It utilizes auditory and visual commands for ease of administration and instructs patients to seek further medical care after injection. EVZIO costs about $600 for two auto-injectors and a trainer. Additionally, in August 2013, the Substance Abuse and Mental Health Services Administration introduced the Opioid Overdose Toolkit, a federal resource promoting safety and prevention information. This extensive document provides information for medical professionals, first responders, patients, caregivers, and overdose survivors. It outlines many strategies for dealing with this health care crisis. Most importantly, it highlights the importance of rapid recognition and treatment of opioid overdoses as well as routine conversations with patients assessing the need for naloxone prescriptions. The auto-injector is a safe, portable device with limited instruction needed and should routinely be made available to anyone who has contact with an opioid user. Keywords: narcotics, abuse, heroin, EZVIO

  18. Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose.

    Science.gov (United States)

    Zaurova, Milana; Hoffman, Robert S; Vlahov, David; Manini, Alex F

    2016-12-01

    Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

  19. Nonprescription naloxone and syringe sales in the midst of opioid overdose and hepatitis C virus epidemics: Massachusetts, 2015.

    Science.gov (United States)

    Stopka, Thomas J; Donahue, Ashley; Hutcheson, Marguerite; Green, Traci C

    To determine the prevalence of nonprescription naloxone and sterile syringe sales, factors associated with nonprescription sales, geospatial access to nonprescription naloxone and syringe-selling pharmacies, and targets for potential interventions. Cross-sectional study. Massachusetts has experienced steep increases in reported opioid overdoses and hepatitis C virus cases in the past decade. Pharmacists have the potential to play a substantial role in increasing access to nonprescription naloxone and sterile syringes, which can reverse opioid overdoses and decrease hepatitis C virus transmission, respectively. We completed brief telephone surveys with 809 of 1042 retail pharmacies across Massachusetts (response rate = 77.6%) during 2015 to assess experience with nonprescription sales of naloxone and sterile syringes. Our primary outcomes were the stocking and selling of naloxone in the pharmacy (yes or no) for nonprescription sales and nonprescription syringe sales (yes or no). We conducted multivariable regression analyses and created maps using a geographic information system to identify factors associated with nonprescription sales of naloxone and sterile syringes, and to improve our understanding of geospatial access to pharmacy-based naloxone and syringe sales. More than 97% of pharmacies reported selling sterile syringes without requiring a prescription, and 45% of pharmacies reported stocking and selling naloxone. Factors associated with nonprescription sales included hours of operation, experience with and interest in harm reduction activities, and presence in an opioid overdose hotspot. Geographic access to nonprescription sale of sterile syringes is widespread, whereas geospatial access to naloxone is limited. Training to understand the benefits, applications, and distribution needs of naloxone is of interest to surveyed pharmacists. Access to sterile syringes through nonprescription sales is strong across Massachusetts, and although more than 350

  20. Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose

    OpenAIRE

    Đorđević Snežana; Jović-Stošić Jasmina; Kilibarda Vesna; Šegrt Zoran; Perković-Vukčević Nataša

    2016-01-01

    Backgound/Aim. Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylli...

  1. Basic and Advanced EMS Providers Are Equally Effective in Naloxone Administration for Opioid Overdose in Northern New England.

    Science.gov (United States)

    Gulec, Nazey; Lahey, Joseph; Suozzi, James C; Sholl, Matthew; MacLean, Charles D; Wolfson, Daniel L

    2018-01-01

    Overdose mortality from illicit and prescription opioids has reached epidemic proportions in the United States, especially in rural areas. Naloxone is a safe and effective agent that has been shown to successfully reverse the effects of opioid overdose in the prehospital setting. The National EMS Scope of Practice Model currently only recommends advanced life support (ALS) providers to administer naloxone; however, some individual states have expanded this scope of practice to include intranasal (IN) administration of naloxone by basic life support (BLS) providers, including the Northern New England states. This study compares the effectiveness and appropriateness of naloxone administration between BLS and ALS providers. All Vermont, New Hampshire, and Maine EMS patient encounters between April 1, 2014 and December 31, 2016 where naloxone was administered were examined and 3,219 patients were identified. The proportion of successful reversals of opioid overdose, based on improvement in the Glasgow Coma Scale (GCS), respiratory rate (RR), and provider global assessment (GA) of response to medication was compared between BLS and ALS providers using a Chi-Squared statistic, Fisher's exact or Wilcoxon rank-sum test. There was no significant difference in the percent improvement in GCS between BLS and ALS (64% and 64% P = 0.94). There was no significant difference in the percentage of improvement in RR between BLS and ALS (45% and 48% P = 0.43). There was a significant difference in the percentage of improvement of GA between BLS and ALS (80% and 67% P < 0.001). There was no significant difference in determining appropriate cases to administer naloxone where RR < 12 and GCS < 15 between BLS and ALS (42% and 43% P = 0.94). BLS providers were as effective as ALS providers in improving patient outcome measures after naloxone administration and in identifying patients for whom administration of naloxone is appropriate. These findings support expanding the National EMS Scope

  2. Opioid prescriptions for pain and epidemic of overdose death: can the dramatic reduction in anesthesia mortality serve as an example?

    Directory of Open Access Journals (Sweden)

    Kissin I

    2016-06-01

    Full Text Available Igor Kissin Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: The annual number of US deaths from prescription-opioid overdose quadrupled between 1999 and 2010 and in 2010 alone reached 16,651. Deaths from opioid overdose have now surpassed the historic death toll from another drug-related epidemic – anesthesia mortality. In 1954, Beecher and Todd published reliable data on anesthesia-related mortality in the US, estimating the annual number of deaths to be nearly 5,000. Presently anesthesia/anesthetics are reported as the underlying cause in approximately 34 deaths in the US annually. This spectacular decline in anesthesia-related mortality could serve as an example for attempts to curb the epidemic of opioid overdose death. The main reason that led to the dramatic decline in anesthesia-related mortality is the context in which anesthetics are used. It includes training of the anesthesia providers, the introduction of specific standards of patient safety, and anesthesia monitoring. I suggest that the introduction of a similar multifactorial proper context for the use of opioids in the treatment of chronic nonmalignant pain might be the same “game changer” it was for safety in anesthesia. Keywords: chronic pain, addiction, opioid-use disorder, treatment compliance, apprenticeship, metrics of opioid effectiveness, aberrant opioid-related behavior

  3. Sono-photo-degradation of carbamazepine in a thin falling film reactor: Operation costs in pilot plant.

    Science.gov (United States)

    Expósito, A J; Patterson, D A; Monteagudo, J M; Durán, A

    2017-01-01

    The photo-Fenton degradation of carbamazepine (CBZ) assisted with ultrasound radiation (US/UV/H 2 O 2 /Fe) was tested in a lab thin film reactor allowing high TOC removals (89% in 35min). The synergism between the UV process and the sonolytic one was quantified as 55.2%. To test the applicability of this reactor for industrial purposes, the sono-photo-degradation of CBZ was also tested in a thin film pilot plant reactor and compared with a 28L UV-C conventional pilot plant and with a solar Collector Parabolic Compound (CPC). At a pilot plant scale, a US/UV/H 2 O 2 /Fe process reaching 60% of mineralization would cost 2.1 and 3.8€/m 3 for the conventional and thin film plant respectively. The use of ultrasound (US) produces an extra generation of hydroxyl radicals, thus increasing the mineralization rate. In the solar process, electric consumption accounts for a maximum of 33% of total costs. Thus, for a TOC removal of 80%, the cost of this treatment is about 1.36€/m 3 . However, the efficiency of the solar installation decreases in cloudy days and cannot be used during night, so that a limited flow rate can be treated. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Study of the intensification of solar photo-Fenton degradation of carbamazepine with ferrioxalate complexes and ultrasound.

    Science.gov (United States)

    Expósito, A J; Monteagudo, J M; Durán, A; San Martín, I; González, L

    2018-01-15

    The intensification of the solar photo-Fenton system with ferrioxalate photoactive complexes and ultrasound applied to the mineralization of 15mg/L carbamazepine aqueous solution (CBZ) was evaluated. The experiments were carried out in a solar compound parabolic collector (CPC) pilot plant reactor coupled to an ultrasonic processor. The dynamic behavior of hydroxyl radicals generated under the different studied reaction systems was discussed. The initial concentrations of hydrogen peroxide and ferrous/oxalic acid and pH were found to be the most significant variables (32.79%, 25.98% and 26.04%, respectively). Under the selected optimal conditions ([H 2 O 2 ] 0 =150mg/L; [Fe 2+ ] 0 =2.5mg/L/[(COOH) 2 ] 0 =12.1mg/L; pH=5) CBZ was fully degraded after 5min and 80% of TOC was removed using a solar photo-Fenton system intensified with ferrioxalate (SPFF). However, no improvement in the mineralization using SPFF process combined with ultrasound was observed. More mild pH conditions could be used in the SPFF system if compared to the traditional photo-Fenton (pH 3) acidic systems. Finally, a possible reaction pathway for the mineralization of CBZ by the SPFF system was proposed and therein discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Carbamazepine as a Possible Anthropogenic Marker in Water: Occurrences, Toxicological Effects, Regulations and Removal by Wastewater Treatment Technologies

    Directory of Open Access Journals (Sweden)

    Faisal I. Hai

    2018-01-01

    Full Text Available Carbamazepine (CBZ, a pharmaceutical compound, has been proposed as an anthropogenic marker to assess water quality due to its persistence in conventional treatment plants and widespread presence in water bodies. This paper presents a comprehensive literature review on sources and occurrences of CBZ in water bodies, as well as toxicological effects and regulations of the drug. Given the documented side effects of CBZ on the human body when taken medicinally, its careful monitoring in water is recommended. CBZ residues in drinking water may provide a pathway to embryos and infants via intrauterine exposure or breast-feeding, which may cause congenital malformations and/or neurodevelopmental problems over long term exposure. An in-depth technical assessment of the conventional and advanced treatment technologies revealed the inadequacy of the standalone technologies. Compared to conventional activated sludge and membrane bioreactor processes, effective removal of CBZ can be achieved by nanofiltration and reverse osmosis membranes. However, recent studies have revealed that harsh chemical cleaning, as required to mitigate membrane fouling, can often reduce the long-term removal efficiency. Furthermore, despite the efficient performance of activated carbon adsorption and advanced oxidation processes, a few challenges such as cost of chemicals and regeneration of activated carbon need to be carefully considered. The limitations of the individual technologies point to the advantages of combined and hybrid systems, namely, membrane bioreactor coupled with nanofiltration, adsorption or advanced oxidation process.

  6. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

    Science.gov (United States)

    McKee, P J; Blacklaw, J; Forrest, G; Gillham, R A; Walker, S M; Connelly, D; Brodie, M J

    1994-01-01

    1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction. PMID:8148215

  7. Efficacy and acceptability of oxcarbazepine vs. carbamazepine with betahistine mesilate tablets in treating vestibular paroxysmia: a retrospective review.

    Science.gov (United States)

    Yi, Chong; Wenping, Xiang; Hui, Xue; Xin, He; Xiue, Li; Jun, Zhang; Shangyong, Geng

    2016-06-01

    Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder that can cause acute short attacks of vertigo. This study aimed to compare the efficacy and acceptability of carbamazepine (CBZ), CBZ plus betahistine mesilate tablets (BMT) and oxcarbazepine (OXC) plus BMT in treating VP within 12 weeks. A retrospective analysis of data from 196 VP patients treated in our hospital was conducted. There were 73 patients receiving CBZ, 65 patients receiving CBZ+BMT and 58 patients receiving OXC+BMT. The frequency of vertigo, vertigo duration, vertigo score, response rate (RR) and side effects were compared between groups to assess efficacy and acceptability at the end of 12(th) week. After 12 weeks' treatment, the CBZ+BMT group had a greater reduction in the frequency of vertigo, vertigo duration and vertigo score than the other two groups. The RR was highest in the CBZ+BMT group, second in the OXC+BMT group and lowest in the CBZ group. The incidence of side-effects was highest in the CBZ group, second in the CBZ+BMT group and lowest in the OXC+BMT group. Two patients in the CBZ group were withdrawn. These results indicated that using BMT as an augmentation for CBZ or OXC might be a good choice in treating VP.

  8. pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin cocrystals in aqueous media.

    Science.gov (United States)

    Alhalaweh, Amjad; Roy, Lilly; Rodríguez-Hornedo, Naír; Velaga, Sitaram P

    2012-09-04

    Cocrystals constitute an important class of pharmaceutical solids for their remarkable ability to modulate solubility and pH dependence of water insoluble drugs. Here we show how cocrystals of indomethacin-saccharin (IND-SAC) and carbamazepine-saccharin (CBZ-SAC) enhance solubility and impart a pH-sensitivity different from that of the drugs. IND-SAC exhibited solubilities 13 to 65 times higher than IND at pH values of 1 to 3, whereas CBZ-SAC exhibited a 2 to 10 times higher solubility than CBZ dihydrate. Cocrystal solubility dependence on pH predicted from mathematical models using cocrystal K(sp), and cocrystal component K(a) values, was in excellent agreement with experimental measurements. The cocrystal solubility increase relative to drug was predicted to reach a limiting value for a cocrystal with two acidic components. This limiting value is determined by the ionization constants of cocrystal components. Eutectic constants are shown to be meaningful indicators of cocrystal solubility and its pH dependence. The two contributions to solubility, cocrystal lattice and solvation, were evaluated by thermal and solubility determinations. The results show that solvation is the main barrier for the aqueous solubility of these drugs and their cocrystals, which are orders of magnitude higher than their lattice barriers. Cocrystal increase in solubility is thus a result of decreasing the solvation barrier compared to that of the drug. This work demonstrates the favorable properties of cocrystals and strategies that facilitate their meaningful characterization.

  9. Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs.

    Science.gov (United States)

    O'Brien, Laura E; Timmins, Peter; Williams, Adrian C; York, Peter

    2004-10-29

    The solid-state transformation of carbamazepine from form III to form I was examined by Fourier Transform Raman spectroscopy. Using a novel environmental chamber, the isothermal conversion was monitored in situ at 130 degrees C, 138 degrees C, 140 degrees C and 150 degrees C. The rate of transformation was monitored by taking the relative intensities of peaks arising from two CH bending modes; this approach minimised errors due to thermal artefacts and variations in power intensities or scattering efficiencies from the samples in which crystal habit changed from a characteristic prism morphology (form III) to whiskers (form I). The solid-state transformation at the different temperatures was fitted to various solid-state kinetic models of which four gave good fits, thus indicating the complexity of the process which is known to occur via a solid-gas-solid mechanism. Arrhenius plots from the kinetic models yielded activation energies from 344 kJ mol(-1) to 368 kJ mol(-1) for the transformation. The study demonstrates the value of a rapid in situ analysis of drug polymorphic type which can be of value for at-line in-process control.

  10. Figures of merit for the determination of the polymorphic purity of carbamazepine by infrared spectroscopy and multivariate calibration.

    Science.gov (United States)

    Braga, Jez Willian B; Poppi, Ronei Jesus

    2004-08-01

    Polymorphism is an important property in the quality control of pharmaceutical products. In this regard, partial least squares regression and the net analytical signal were used to build and validate a multivariate calibration model using diffuse reflectance infrared spectroscopy in the region of 900-1100 cm(-1) for the determination of the polymorphic purity of carbamazepine. Physical mixtures of the polymorphs were made by weight, from 80 to 100% (w/w) form III mixed with form I. Figures of merit, such as sensitivity, analytical sensitivity, selectivity, confidence limits, precision (mean, repeatability, intermediate), accuracy, and signal-to-noise ratio were calculated. Feasible results were obtained with maximum absolute error of 2% and an average error of 0.53%, indicating that the proposed methodology can be used by the pharmaceutical industry as an alternative to the X-ray diffraction (United States Pharmacopoeiamethod). Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2124-2134, 2004

  11. Biodegradation of carbamazepine using freshwater microalgae Chlamydomonas mexicana and Scenedesmus obliquus and the determination of its metabolic fate.

    Science.gov (United States)

    Xiong, Jiu-Qiang; Kurade, Mayur B; Abou-Shanab, Reda A I; Ji, Min-Kyu; Choi, Jaeyoung; Kim, Jong Oh; Jeon, Byong-Hun

    2016-04-01

    This study evaluated the toxicity and cellular stresses of carbamazepine (CBZ) on Chlamydomonas mexicana and Scenedesmus obliquus, and its biodegradation by both microalgal species. The growth of both microalgal species decreased with increase of CBZ concentration. The growth of S. obliquus was significantly inhibited (97%) at 200 mg CBZ L(-1), as compared to the control after 10days; whereas, C. mexicana showed 30% inhibition at the same experimental conditions. Biochemical characteristics including total chlorophyll, carotenoid contents and enzyme activities (SOD and CAT) for both species were affected by CBZ at relatively high concentration. C. mexicana and S. obliquus could achieve a maximum of 35% and 28% biodegradation of CBZ, respectively. Two metabolites (10,11-dihydro-10,11-expoxycarbamazepine and n-hydroxy-CBZ) were identified by UPLC-MS, as a result of CBZ biodegradation by C. mexicana. This study demonstrated that C. mexicana was more tolerant to CBZ and could be used for treatment of CBZ contaminated wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.

    Science.gov (United States)

    Djuris, Jelena; Ioannis, Nikolakakis; Ibric, Svetlana; Djuric, Zorica; Kachrimanis, Kyriakos

    2014-02-01

    This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate. Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate. © 2013 Royal Pharmaceutical Society.

  13. Heroin-related overdose: The unexplored influences of markets, marketing and source-types in the United States.

    Science.gov (United States)

    Mars, Sarah G; Fessel, Jason N; Bourgois, Philippe; Montero, Fernando; Karandinos, George; Ciccarone, Daniel

    2015-09-01

    Heroin overdose, more accurately termed 'heroin-related overdose' due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black 'tar' heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007-12) and of users in San Francisco (1994-2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out the

  14. A case report: Pavlovian conditioning as a risk factor of heroin 'overdose' death

    Directory of Open Access Journals (Sweden)

    Bácskai Erika

    2005-07-01

    Full Text Available Abstract Background The authors present a case illustrating a mechanism leading directly to death which is not rare but has received little attention. Case presentation The case was evaluated by autopsy, investigation of morphine concentration in the blood, and clinical data. The heroin dose causing the 'overdose' death of a young man who had previously been treated a number of times for heroin addiction did not differ from his dose of the previous day taken in the accustomed circumstances. The accustomed dose taken in a strange environment caused fatal complications because the conditioned tolerance failed to operate. The concentration of morphine in the blood did not exceed the level measured during earlier treatment. Conclusion These results are in line with the data in the literature indicating that morphine concentrations measured in cases of drug-related death do not differ substantially from those measured in cases where the outcome is not fatal. A knowledge of the conditioning mechanism can contribute to prevention of fatal cases of a similar type. The harm reduction approach places great stress on preventive intervention based on data related to drug-related death.

  15. "Nifedipine in the treatment of liver toxicity induced by Acetaminophen overdose in mice "

    Directory of Open Access Journals (Sweden)

    Kalantari H

    2000-11-01

    Full Text Available Acetaminophen is an analgesic and antipyretic drug, which is widely used by public and poisoning with this drug, is common. One of the most important adverse effects of acetaminophen poisoning is centrilobullar necrosis in hepatic cells, which depends on activity of microsomal cytochrome P-450 (CYP enzymes. The aim of this investigation was to find out the protective effect of nifedipine against liver toxicity caused by acetaminophen overdose (700 mg/kg as calcium channel blocker. In this study doses of 5, 50, 100, 250, 500 mg/kg of nifedipine were administered to mice orally one hour before acetaminophen administration. The negative control group receive normal saline. The positive control group was administered with acetaminophen at a dose of 700 mg/kg one hour after nifedipine administration. After 24 hours, enzyme activity (ALT, AST, histopathological examination and liver weight were compared with the control groups. The results revealed that nifedipine at dose of 500 mg/kg was the most effective and protected damage from acetaminophen toxicity.

  16. Implications of prescription drug monitoring and medical cannabis legislation on opioid overdose mortality.

    Science.gov (United States)

    Phillips, Elyse; Gazmararian, Julie

    To determine whether specific state legislation has an effect on opioid overdose mortality rates compared to states without those types of legislation. Ecological study estimating opioid-related mortality in states with and without a prescription drug monitoring program (PDMP) and/or medical cannabis legislation. Opioid-related mortality rates for 50 states and Washington DC from 2011 to 2014 were obtained from CDC WONDER. PDMP data were obtained from the National Alliance for Model State Drug Laws, and data on medical cannabis legislation from the National Organization for the Reform of Marijuana Laws. The relationship between PDMPs with mandatory access provisions, medical cannabis legislation, and opioid-related mortality rates. Multivariate repeated measures analysis performed with software and services. Medical cannabis laws were associated with an increase of 21.7 percent in mean age-adjusted opioid-related mortality (p cannabis (p = 0.049) and 5.8 percent for states with a PDMP (p = 0.005). Interaction between both types of legislation produced a borderline significant decrease of 10.1 percent (p = 0.055). For every year states had both types of legislation, interaction resulted in a 0.6 percent decrease in rate (p = 0.013). When combined with the availability of medical cannabis as an alternative analgesic therapy, PDMPs may be more effective at decreasing opioid-related mortality.

  17. Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

    Science.gov (United States)

    Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

    2008-05-01

    Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

  18. Presentations and Preceding factors of Drug Overdose amongst adolescents admitted to a Large Regional Hospital.

    LENUS (Irish Health Repository)

    Maduemem, KE

    2018-04-01

    Suicide is the third most common cause of death among adolescents globally, and poisoning is the leading method of attempted suicide. Survival after self-poisoning or drug overdose (OD) is common, providing an opportunity for secondary prevention. The aim of this study was to highlight pattern of presentations and preceding factors of OD in an adolescent population. We retrospectively evaluated the data of 85 adolescents presenting to a large regional hospital with OD over a 3-year period. The female-to-male ratio was 4.3:1. The median age of adolescents was 15.83 (range: 11.32 – 16.98) years. History of deliberate self-harm (DSH) was documented in 44.7%. Twenty-eight (33%) patients had been under the care of the CAMHS prior to index admission. Acetaminophen was the commonest drug used. Depression was the most common cause of mental illness in the study group. Substance abuse and conduct disorder were significantly commoner in males (p<0.05). Self-poisoning including OD in adolescence is a strong predictor of suicide; understanding the probable triggers can be significant in establishing appropriate prevention strategies.

  19. Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in Metropolitan and Nonmetropolitan Areas - United States.

    Science.gov (United States)

    Mack, Karin A; Jones, Christopher M; Ballesteros, Michael F

    2017-10-20

    Drug overdoses are a leading cause of injury death in the United States, resulting in approximately 52,000 deaths in 2015. Understanding differences in illicit drug use, illicit drug use disorders, and overall drug overdose deaths in metropolitan and nonmetropolitan areas is important for informing public health programs, interventions, and policies. Illicit drug use and drug use disorders during 2003-2014, and drug overdose deaths during 1999-2015. The National Survey of Drug Use and Health (NSDUH) collects information through face-to-face household interviews about the use of illicit drugs, alcohol, and tobacco among the U.S. noninstitutionalized civilian population aged ≥12 years. Respondents include residents of households and noninstitutional group quarters (e.g., shelters, rooming houses, dormitories, migratory workers' camps, and halfway houses) and civilians living on military bases. NSDUH variables include sex, age, race/ethnicity, residence (metropolitan/nonmetropolitan), annual household income, self-reported drug use, and drug use disorders. National Vital Statistics System Mortality (NVSS-M) data for U.S. residents include information from death certificates filed in the 50 states and the District of Columbia. Cases were selected with an underlying cause of death based on the ICD-10 codes for drug overdoses (X40-X44, X60-X64, X85, and Y10-Y14). NVSS-M variables include decedent characteristics (sex, age, and race/ethnicity) and information on intent (unintentional, suicide, homicide, or undetermined), location of death (medical facility, in a home, or other [including nursing homes, hospices, unknown, and other locations]) and county of residence (metropolitan/nonmetropolitan). Metropolitan/nonmetropolitan status is assigned independently in each data system. NSDUH uses a three-category system: Core Based Statistical Area (CBSA) of ≥1 million persons; CBSA of illicit drugs, the prevalence was highest for the large metropolitan areas compared with

  20. Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

    Science.gov (United States)

    Okumura, Yasuyuki; Sakata, Nobuo; Takahashi, Kunihiko; Nishi, Daisuke; Tachimori, Hisateru

    2017-08-01

    Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  1. In vivo and in vitro evaluation of the mutagenic potential of carbamazepine: does melatonin have anti-mutagenic activity?

    Science.gov (United States)

    Awara, W M; El-Gohary, M; El-Nabi, S H; Fadel, W A

    1998-01-16

    The mutagenic potential of carbamazepine (CBZ) therapy has been evaluated both in vivo and in vitro. Analysis of chromosome aberrations (CA), sister chromatid exchanges (SCEs), mitotic and proliferation indices (PRI) were performed. The in vivo study was carried out on 30 patients with idiopathic epilepsy end undergoing treatment with CBZ for different periods starting from 6 months up to 15 years. Plasma CBZ levels were also determined for each patient. The results showed that the total CA and SCEs were significantly increased in CBZ-treated patients. There was no significant correlation between CA and either duration of treatment or the plasma CBZ levels for each patient. The mitotic and proliferation indices were found to be slightly but non-significantly decreased compared to control values. On the other hand, in vitro analysis showed a significant dose-dependent increase in CA and SCEs in human lymphocyte cultures treated with CBZ (4-12 microg/ml). The mitotic and proliferation indices were also found to be decreased but only significantly in case of high doses of CBZ (12 microg/ml). Pretreatment of human lymphocytes with melatonin (0.5 mM) exhibited a significant decrease in the frequencies of CBZ-induced CA and SCEs as compared with non-treated cultures. The depressed mitotic and proliferation indices were also found to be improved in cultures pretreated with melatonin. In conclusion, these observations suggest that CBZ monotherapy may lead to chromosome damaging effects (genotoxic) and the use of melatonin as anti-mutagenic agent for human protection against CBZ-induced chromosome damage should be considered.

  2. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide.

    Science.gov (United States)

    Hebeisen, Simon; Pires, Nuno; Loureiro, Ana I; Bonifácio, Maria João; Palma, Nuno; Whyment, Andrew; Spanswick, David; Soares-da-Silva, Patrício

    2015-02-01

    This study aimed at evaluating the effects of eslicarbazepine, carbamazepine (CBZ), oxcarbazepine (OXC) and lacosamide (LCM) on the fast and slow inactivated states of voltage-gated sodium channels (VGSC). The anti-epileptiform activity was evaluated in mouse isolated hippocampal slices. The anticonvulsant effects were evaluated in MES and the 6-Hz psychomotor tests. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, CBZ, OXC and LCM on sodium channels endogenously expressed in N1E-115 mouse neuroblastoma cells. CBZ and eslicarbazepine exhibit similar concentration dependent suppression of epileptiform activity in hippocampal slices. In N1E-115 mouse neuroblastoma cells, at a concentration of 250 μM, the voltage dependence of the fast inactivation was not influenced by eslicarbazepine, whereas LCM, CBZ and OXC shifted the V0.5 value (mV) by -4.8, -12.0 and -16.6, respectively. Eslicarbazepine- and LCM-treated fast-inactivated channels recovered similarly to control conditions, whereas CBZ- and OXC-treated channels required longer pulses to recover. CBZ, eslicarbazepine and LCM shifted the voltage dependence of the slow inactivation (V0.5, mV) by -4.6, -31.2 and -53.3, respectively. For eslicarbazepine, LCM, CBZ and OXC, the affinity to the slow inactivated state was 5.9, 10.4, 1.7 and 1.8 times higher than to the channels in the resting state, respectively. In conclusion, eslicarbazepine did not share with CBZ and OXC the ability to alter fast inactivation of VGSC. Both eslicarbazepine and LCM reduce VGSC availability through enhancement of slow inactivation, but LCM demonstrated higher interaction with VGSC in the resting state and with fast inactivation gating. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. N-Doped TiO2-Coated Ceramic Membrane for Carbamazepine Degradation in Different Water Qualities

    Science.gov (United States)

    Luster, Enbal; Avisar, Dror; Horovitz, Inna; Lozzi, Luca; Baker, Mark A.; Grilli, Rossana; Mamane, Hadas

    2017-01-01

    The photocatalytic degradation of the model pollutant carbamazepine (CBZ) was investigated under simulated solar irradiation with an N-doped TiO2-coated Al2O3 photocatalytic membrane, using different water types. The photocatalytic membrane combines photocatalysis and membrane filtration in a single step. The impact of each individual constituent such as acidity, alkalinity, dissolved organic matter (DOM), divalent cations (Mg2+ and Ca2+), and Cl− on the degradation of CBZ was examined. CBZ in water was efficiently degraded by an N-doped TiO2-coated Al2O3 membrane. However, elements added to the water, which simulate the constituents of natural water, had an impact on the CBZ degradation. Water alkalinity inhibited CBZ degradation mostly due to increase in pH while radical scavenging by carbonate was more dominant at higher values (>200 mg/L as CaCO3). A negative effect of Ca2+ addition on photocatalytic degradation was found only in combination with phosphate buffer, probably caused by deposition of CaHPO4 or CaHPO4·2H2O on the catalyst surface. The presence of Cl− and Mg2+ ions had no effect on CBZ degradation. DOM significantly inhibited CBZ degradation for all tested background organic compounds. The photocatalytic activity of N-doped TiO2-coated Al2O3 membranes gradually decreased after continuous use; however, it was successfully regenerated by 0.1% HCl chemical cleaning. Nevertheless, dissolution of metals like Al and Ti should be monitored following acid cleaning. PMID:28758982

  4. Influence of UV dose on the UV/H2O2 process for the degradation of carbamazepine in wastewater.

    Science.gov (United States)

    Somathilake, Purnima; Dominic, John Albino; Achari, Gopal; Langford, Cooper H; Tay, Joo-Hwa

    2018-05-02

    This study evaluates the influence of UV dose on degradation of carbamazepine (CBZ) in wastewater under UV-C (λ = 254 nm) photolysis with and without H 2 O 2 . The rate of degradation of CBZ exhibited a direct dependence on the intensity of incident UV irradiation as the rate of degradation was observed to increase linearly (R 2  = 0.98) with UV intensity between 1.67 and 8.95 × 10 17 photons/s. More than 95% of the CBZ that spiked in wastewater rapidly degraded within 4 min with a first-order rate constant of 1.2 min -1 for an optimum H 2 O 2 dose of 100 mg/L. Bench-scale continuous flow reactor experiments also showed that CBZ degraded with first-order kinetics at a rate constant of 1.02 min -1 . The kinetic parameters obtained for a continuous bench-scale reactor were in good agreement with the relationships developed through batch experiments with only a marginal deviation of ± 6.5%. The relationship between UV intensity and CBZ degradation rate obtained in this study was extrapolated to the UV disinfection unit of a wastewater treatment plant to predict possible degradation of CBZ during UV disinfection. The addition of 100 mg/L of H 2 O 2 to the secondary-treated effluent entering the UV disinfection unit is predicted to achieve over 60% degradation of CBZ.

  5. Flow injection on-line oxidizing fluorometry coupled to dialysis sampling for the study of carbamazepine-protein binding

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Zhiqi [School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)]. E-mail: zqzhang@snnu.edu.cn; Liang Guoxi [School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)

    2005-04-22

    The mechanism of binding of carbamazepine (CBZ) with bovine serum albumin (BSA) has been investigated in vitro based on a new flow injection fluorometry coupled to the technique of dialysis sampling. The CBZ and BSA were mixed in different molar ratios in 0.050 mol L{sup -1} phosphate buffer (containing 0.9% NaCl), pH 7.4, and incubated at 37 {+-} 0.5 deg. C in a water bath. The dialysis sampler was utilized to sample free CBZ from mixed solution with a relative dialytic efficiency of 7.6%. Then the CBZ in dialysis solution was injected into carrier and on-line oxidized by lead dioxide solid-phase reactor into fluorescent product with a maximum excitation wavelength of 355 nm and a maximum emission wavelength of 478 nm. The fluorescence intensity measured was linear proportional with the concentration of free CBZ in mixed solution over the range of 1 x 10{sup -5} to 2 x 10{sup -4} mol L{sup -1} with the detection limit of 6 x 10{sup -6} mol L{sup -1}. According to the fluorescence measurement results from mixed solution, the association constant (K) estimated for CBZ-BSA binding and the number of the binding site (n) with Scatchard analysis were 1.08 x 10{sup 4} L mol{sup -1} and 0.94, respectively. Stern-Volmer plots indicated the presence of dynamic component in the quenching mechanism. The acting force was suggested to be mainly hydrophobic and the distance between the acceptor and donor was 3.12 nm. The estimated binding parameters agreed well with literature values.

  6. Modeling Raw Sewage Leakage and Transport in the Unsaturated Zone of Carbonate Aquifer Using Carbamazepine as an Indicator

    Science.gov (United States)

    Yakirevich, A.; Kuznetsov, M.; Livshitz, Y.; Gasser, G.; Pankratov, I.; Lev, O.; Adar, E.; Dvory, N. Z.

    2016-12-01

    Fast contamination of groundwater in karstic aquifers can be caused due to leaky sewers, for example, or overflow from sewer networks. When flowing through a karst system, wastewater has the potential to reach the aquifer in a relatively short time. The Western Mountain Aquifer (Yarkon-Taninim) of Israel is one of the country's major water resources. During late winter 2013, maintenance actions were performed on a central sewage pipe that caused raw sewage to leak into the creek located in the study area. The subsequent infiltration of sewage through the thick ( 100 m) fractured/karst unsaturated zone led to a sharp increase in contaminant concentrations in the groundwater, which was monitored in a well located 29 meters from the center of the creek. Carbamazepine (CBZ) was used as an indicator for the presence of untreated raw sewage and its quantification in groundwater. The ultimate research goal was to develop a mathematical model for quantifying flow and contaminant transport processes in the fractured-porous unsaturated zone and karstified groundwater system. A quasi-3D dual permeability numerical model, representing the 'vadose zone - aquifer' system, was developed by a series of 1D equations solved in variably-saturated zone and by 3D-saturated flow and transport equation in groundwater. The 1D and 3D equations were coupled at the moving phreatic surface. The model was calibrated and applied to a simulated water flow scenario and CBZ transport during and after the observed sewage leakage event. The results of simulation showed that after the leakage stopped, significant amounts of CBZ were retained in the porous matrix of the unsaturated zone below the creek. Water redistribution and slow recharge during the dry summer season contributed to elevated CBZ concentrations in the groundwater in the vicinity of the creek and tens of meters downstream. The resumption of autumn rains enhanced flushing of CBZ from the unsaturated zone and led to an increase in

  7. Carbamazepine behaviour and effects in an urban wastewater MBR working with high sludge and hydraulic retention time.

    Science.gov (United States)

    González-Pérez, Daniel María; Pérez, Jorge Ignacio; Nieto, Miguel Ángel Gómez

    2016-08-23

    The behaviour and fate of carbamazepine (CBZ) in urban wastewater treatment by a membrane bioreactor (MBR) and its possible effects on the system's efficiency, and on mixed microbial communities, has been studied. The experimental microfiltration MBR system, with capacity to treat 10.8 m(3) d(-1) of urban wastewater, operated with a pre-denitrification configuration with high sludge and hydraulic retention time. The CBZ concentration assayed was higher than in the usual urban wastewater, in order to provoke a strong biomass reaction. Influent, effluent, and all bioreactors of the MBR system were analysed in order to calculate a CBZ balance. Bench-scale experiments and respirometric analyses were performed, with and without the presence of CBZ, to evaluate its influence on the bacterial activity. The respirometric assays showed variations in the oxygen uptake rate (OUR) in the presence of CBZ. Negative effects were detected in the MBR bacterial community during the initial period of dosing. However, the effects were not permanent and the biomass spiked with CBZ had behaviour similar to that of the biomass without CBZ after a few hours. Biodegradation was not detected during the MBR treatment. The system showed an inefficient elimination of CBZ (less than 10%) with a high concentration in the effluent. The small percentage of CBZ removal was associated with the sludge retention and eliminated by the purge. All CBZ present in the influent was accounted for, and even an increase in the total amount of CBZ was registered in the permeate. During and after the experimental process, CBZ did not significantly affect the efficiency of the MBR system, and the quality of the effluent was not affected by the dosing of CBZ in terms of COD and nitrogen removal.

  8. Second-order advantage with excitation-emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters.

    Science.gov (United States)

    Lozano, Valeria A; Escandar, Graciela M

    2013-06-11

    A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation-emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and quantification of 0.2 and 0.6 ng mL(-1) were respectively obtained. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Sorption of carbamazepine, 17α-ethinylestradiol, iopromide and trimethoprim to biomass involves interactions with exocellular polymeric substances.

    Science.gov (United States)

    Khunjar, Wendell O; Love, Nancy G

    2011-02-01

    The sorption of carbamazepine (CBZ), iopromide (IOP), trimethoprim (TMP) and 17α-ethinylestradiol (EE2) was evaluated using four biomass types (pure ammonia oxidizing bacterial culture, two heterotrophic enrichment cultures with varying levels of oxygenase activity, and a full-scale nitrifying activated sludge (NAS) culture). CBZ and IOP did not sorb to the four biomass types. EE2 did not sorb to the pure culture but sorbed significantly to the heterotrophic cultures and NAS. TMP sorbed to the heterotrophic cultures and NAS, and was not evaluated for the pure culture. Three floc characteristics (hydrophobicity, median particle size, organic matter content) correlated moderately well with the EE2 organic matter sorption coefficient (KOM,EE2). Zeta potential did not correlate well with KOM,EE2 but did with KOM,TMP, indicating that TMP sorption is more influenced by electrostatic factors than EE2. Once divalent cation-linked exocellular polymeric substances (EPS) were removed from flocs, EE2 and TMP sorption to the non-EPS (cellular) fraction decreased by approximately 50%. The correlation between KOM,EE2 for the non-EPS cellular fraction deteriorated while the correlation between KOM,TMP improved. EE2 seemed to sorb more strongly to EPS protein whereas TMP sorbed equally to polysaccharide and protein EPS. Attempts to develop predictive models were not successful. Pharmaceuticals that sorbed to biomass samples underwent biodegradation whereas those that did not sorb were not biodegraded, suggesting a relationship between sorption and pharmaceutical biotransformation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Few-Layer MoS2 Nanodomains Decorating TiO2 Nanoparticles: A Case Study for the Photodegradation of Carbamazepine

    Directory of Open Access Journals (Sweden)

    Sara Cravanzola

    2018-03-01

    Full Text Available S-doped TiO2 and hybrid MoS2/TiO2 systems have been synthesized, via the sulfidation with H2S of the bare TiO2 and of MoOx supported on TiO2 systems, with the aim of enhancing the photocatalytic properties of TiO2 for the degradation of carbamazepine, an anticonvulsant drug, whose residues and metabolites are usually inefficiently removed in wastewater treatment plants. The focus of this study is to find a relationship between the morphology/structure/surface properties and photoactivity. The full characterization of samples reveals the strong effects of the H2S action on the properties of TiO2, with the formation of defects at the surface, as shown by transmission electron microscopy (TEM and infrared spectroscopy (IR, while also the optical properties are strongly affected by the sulfidation treatment, with changes in the electronic states of TiO2. Meanwhile, the formation of small and thin few-layer MoS2 domains, decorating the TiO2 surface, is evidenced by both high-resolution transmission electron microscopy (HRTEM and UV-Vis/Raman spectroscopies, while Fourier-transform infrared (FTIR spectra give insights into the nature of Ti and Mo surface sites. The most interesting findings of our research are the enhanced photoactivity of the MoS2/TiO2 hybrid photocatalyst toward the carbamazepine mineralization. Surprisingly, the formation of hazardous compounds (i.e., acridine derivatives, usually obtained from carbamazepine, is precluded when treated with MoS2/TiO2 systems.

  11. The context of illicit drug overdose deaths in British Columbia, 2006

    Directory of Open Access Journals (Sweden)

    Waheed Bilal

    2009-05-01

    Full Text Available Abstract Background Illicit drug overdose deaths (IDD relate to individual drug dose and context of use, including use with other drugs and alcohol. IDD peaked in British Columbia (BC in 1998 with 417 deaths, and continues to be a public health problem. The objective of this study was to examine IDD in 2006 in BC by place of residence, injury and death, decedents' age and sex and substances identified. Methods IDD data was obtained through the BC Coroners Office and entered into SPSS (version 14. Fisher's exact and Pearson's χ2 were used for categorical data; Mann-Whitney U-test for continuous variables. Rates were calculated using 2006 population estimates. Results We identified 223 IDD in BC; 54 (24% occurred in Vancouver. Vancouver decedents (compared to those occurring outside Vancouver were older (mean age 43.9 vs. 39.2 years; p Cocaine was identified in 80.3%, opiates 59.6%, methadone 13.9%, methamphetamine/amphetamine 6.3%, and alcohol in 22.9% of deaths. Poly-substance use was common, 2 substances were identified in 43.8% and 3 or more in 34.5% of deaths. Opiates were more frequently identified in Vancouver compared to outside Vancouver (74.1% vs. 55.0% p = 0.015. Conclusion Collaboration with the Coroner's office allowed us to analyze IDD in detail including place of death; cocaine, opiates and poly-substance use were commonly identified. Poly-substance use should be explored further to inform public health interventions.

  12. Severe hypertriglyceridemia and colchicine intoxication following suicide attempt

    Directory of Open Access Journals (Sweden)

    Lev S

    2017-11-01

    Full Text Available Shaul Lev,1 David Snyder,2 Carmil Azran,3 Victor Zolotarsky,1 Arik Dahan4 1Intensive Care Unit, Rabin Medical Center, Petah-Tikva, 2Sackler School of Medicine NY/American Program, Tel-Aviv University, Tel Aviv, 3Clinical Pharmacy, Herzliya Medical Center, Herzliya, 4Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract: Colchicine overdose is uncommon but potentially life threatening. Due to its serious adverse systemic effects, overdose must be recognized and treated. We report a case of an 18-year-old female who ingested 18 mg (~0.4 mg/kg of colchicine in a suicide attempt. The patient’s clinical manifestations included abdominal cramps, vomiting, pancytopenia, hypocholesterolemia, and rhabdomyolysis. Two unique manifestations of toxicity in this patient were profound and persistent, severe hypertriglyceridemia and electrolyte imbalance, mainly hypophosphatemia, with no other evident cause except the colchicine intoxication. Following intensive supportive treatment, including ventilator support, N-acetylcysteine, granulocyte colony stimulating factor, electrolyte repletion, and zinc supplementation, the patient made a complete recovery. Colchicine intoxication is a severe, life-threatening situation that should be followed closely in intensive care units. Severe changes in body functions can rapidly develop, as previously described in the literature. To our knowledge, this extremely elevated triglyceride level has never been reported without the administration of propofol, and requires further evaluation. Keywords: colchicine, intoxication, hypophosphatemia, hypertriglyceridemia 

  13. Young people who use drugs engaged in harm reduction programs in New York City: Overdose and other risks.

    Science.gov (United States)

    Calvo, Michele; MacFarlane, Jessica; Zaccaro, Heather; Curtis, Matthew; Cabán, María; Favaro, Jamie; Passannante, Marian R; Frost, Taeko

    2017-09-01

    Little is known about the engagement of young people who use drugs (PWUD) in harm reduction programs (HRPs), and few studies have included non-opioid users and non-injectors. While HRPs have effectively engaged PWUD, young people are under-represented in their services. The Injection Drug Users Health Alliance Citywide Study (IDUCS) is the largest community-based study of PWUD in HRPs in the US. From 2014-2015, 2421 HRP participants across New York City (NYC) completed a cross-sectional survey. We investigated differences in socio-demographics, service utilization, and risk behaviors between young (aged 18-30) and older participants and examined factors associated with overdose among young participants. The study included 257 young participants. They were significantly more likely than older participants to be white, educated, uninsured, unstably housed or homeless, and have a history of incarceration and residential drug treatment. They were more likely to report recent overdose but less likely to report knowledge of naloxone. Young participants also had higher rates of alcohol, marijuana, benzodiazepine, and injection drug use, and related risk behaviors such as public injection. Factors associated with past year overdose among young participants included experiencing symptoms of psychological distress (AOR=9.71), being unstably housed or homeless (AOR=4.39), and utilizing detox (AOR=4.20). Young PWUD who access services at HRPs in NYC differ significantly from their older counterparts. New York City and other urban centers that attract young PWUD should consider implementing harm reduction oriented services tailored to the unique needs of young people. Copyright © 2017. Published by Elsevier B.V.

  14. Lipid profile and atherogenic predictor indices of albino rabbits administered coconut water as antidote to paracetamol overdose

    Directory of Open Access Journals (Sweden)

    Chidi Uzoma Igwe

    2016-11-01

    Full Text Available Objective: To investigate the effects of coconut water intake on lipid profile and atherogenic predictor indices of albino rabbits overdosed with paracetamol using standard methods. Methods: Thirty-five albino rabbits weighing between 800–1200 g and aged between 2 and 3 months, were divided into 7 groups (I–VII of 5 animals each. Groups I, II and III were orally administered distilled water (20 mL/kg body weight, coconut water (20 mL/kg body weight and paracetamol (1000 mg/kg body weight respectively, for 7 days. Groups IV and V were administered coconut water (20 mL/kg body weight and silymarin (35 mg/kg body weight, respectively, for 6 days, then paracetamol (1000 mg/kg body weight on the 7th day. Groups VI and VII were administered distilled water for 6 days, paracetamol on the 7th day, then coconut water and silymarin, respectively, after 3 h. Results: The results showed that paracetamol overdose significantly reduced (P < 0.05 the mean body weight of the animals, increased the concentrations of serum total cholesterol, triacylglycerol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol and the atherogenic predictor indices but reduced the serum high density lipoprotein cholesterol concentration of the animals relative to the control. The observed changes in the lipid profile and atherogenic predictor indices were countered more by post- than pre-treatment with coconut water and silymarin. Conclusions: The results indicated that coconut water acted as an effective antidote to paracetamol overdose-induced lipid abnormality in animals.

  15. Drug-Induced QT Prolongation as a Result of an Escitalopram Overdose in a Patient with Previously Undiagnosed Congenital Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    Paul Singh

    2014-01-01

    Full Text Available We present a case of drug-induced QT prolongation caused by an escitalopram overdose in a patient with previously undiagnosed congenital LQTS. A 15-year-old Caucasian female presented following a suicide attempt via an escitalopram overdose. The patient was found to have a prolonged QT interval with episodes of torsades de pointes. The patient was admitted to the telemetry unit and treated. Despite the resolution of the torsades de pointes, she continued to demonstrate a persistently prolonged QT interval. She was seen by the cardiology service and diagnosed with congenital long QT syndrome. This case illustrates the potential for an escitalopram overdose to cause an acute QT prolongation in a patient with congenital LQTS and suggests the importance of a screening electrocardiogram prior to the initiation of SSRIs, especially in patients at high risk for QT prolongation.

  16. Exposure to fentanyl-contaminated heroin and overdose risk among illicit opioid users in Rhode Island: A mixed methods study.

    Science.gov (United States)

    Carroll, Jennifer J; Marshall, Brandon D L; Rich, Josiah D; Green, Traci C

    2017-08-01

    Illicit fentanyl use has become wide spread in the US, causing high rates of overdose deaths among people who use drugs. This study describes patterns and perceptions of fentanyl exposure among opioid users in Rhode Island. A mixed methods study was conducted via questionnaire with a convenience sample of 149 individuals using illicit opioids or misusing prescription opioids in Rhode Island between January and November 2016. Of these, 121 knew of fentanyl and reported known or suspected exposure to fentanyl in the past year. Semi-structured interviews were conducted with the first 47 participants. Study participants were predominantly male (64%) and white (61%). Demographic variables were similar across sample strata. Heroin was the most frequently reported drug of choice (72%). Self-reported exposure to illicit fentanyl in the past year was common (50.4%, n=61). In multivariate models, regular (at least weekly) heroin use was independently associated with known or suspected fentanyl exposure in the past year (adjusted prevalence ratio (APR)=4.07, 95% CI: 1.24-13.3, p=0.020). In interviews, users described fentanyl as unpleasant, potentially deadly, and to be avoided. Participants reporting fentanyl exposure routinely experienced or encountered non-fatal overdose. Heroin users reported limited ability to identify fentanyl in their drugs. Harm reduction strategies used to protect themselves from fentanyl exposure and overdose, included test hits, seeking prescription opioids in lieu of heroin, and seeking treatment with combination buprenorphine/naloxone. Participants were often unsuccessful in accessing structured treatment programs. Among illicit opioid users in Rhode Island, known or suspected fentanyl exposure is common, yet demand for fentanyl is low. Fentanyl-contaminated drugs are generating user interest in effective risk mitigation strategies, including treatment. Responses to the fentanyl epidemic should be informed by the perceptions and experiences of

  17. Heroin-related overdose: The unexplored influences of markets, marketing and source-types in the United States

    Science.gov (United States)

    Mars, Sarah G.; Fessel, Jason N.; Bourgois, Philippe; Montero, Fernando; Karandinos, George; Ciccarone, Daniel

    2015-01-01

    Heroin overdose, more accurately termed ‘heroin-related overdose’ due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black ‘tar’ heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007–12) and of users in San Francisco (1994–2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out

  18. Preventing deaths from rising opioid overdose in the US – the promise of naloxone antidote in community-based naloxone take-home programs

    Directory of Open Access Journals (Sweden)

    Straus MM

    2013-09-01

    Full Text Available Michele M Straus, Udi E Ghitza, Betty Tai Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, USA Abstract: The opioid overdose epidemic is an alarming and serious public health problem in the United States (US that has been escalating for 11 years. The 2011 National Survey on Drug Use and Health (NSDUH demonstrated that 1 in 20 persons in the US aged 12 or older reported nonmedical use of prescription painkillers in the past year. Prescription drug overdose is now the leading cause of accidental death in the United States – surpassing motor vehicle accidents. Great efforts have been initiated to curb the overdose crisis. Notable examples of these efforts are (1 the Drug Enforcement Administration’s (DEA National Take-Back Initiative instituted in 2010; (2 the Prescription Drug Monitoring Programs (PDMPs implemented in most US states to provide practitioners with point-of-care information regarding a patient's controlled substance use; (3 the naloxone rescue programs initiated in the community to avert mortality resulting from overdose. The use of naloxone rescue strategies has gained traction as an effective measure to prevent fatal opioid overdose. Many US federal-government agencies are working to make these strategies more accessible to first responders and community participants. This new approach faces many challenges, such as accessibility to naloxone and the equipment and training needed to administer it, but none is more challenging than the fear of legal repercussions. US federal-government agencies, local governments, health care institutions, and community-based organizations have begun to tackle these barriers, and naloxone take-home programs have gained recognition as a feasible and sensible preventive strategy to avoid a fatal result from opioid overdose. Although many challenges still need to be overcome

  19. Clinical Validation and Implications of Dried Blood Spot Sampling of Carbamazepine, Valproic Acid and Phenytoin in Patients with Epilepsy

    Science.gov (United States)

    Kong, Sing Teang; Lim, Shih-Hui; Lee, Wee Beng; Kumar, Pasikanthi Kishore; Wang, Hwee Yi Stella; Ng, Yan Lam Shannon; Wong, Pei Shieen; Ho, Paul C.

    2014-01-01

    To facilitate therapeutic monitoring of antiepileptic drugs (AEDs) by healthcare professionals for patients with epilepsy (PWE), we applied a GC-MS assay to measure three AEDs: carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) levels concurrently in one dried blood spot (DBS), and validated the DBS-measured levels to their plasma levels. 169 PWE on either mono- or polytherapy of CBZ, PHT or/and VPA were included. One DBS, containing ∼15 µL of blood, was acquired for the simultaneous measurement of the drug levels using GC-MS. Simple Deming regressions were performed to correlate the DBS levels with the plasma levels determined by the conventional immunoturbimetric assay in clinical practice. Statistical analyses of the results were done using MedCalc Version 12.6.1.0 and SPSS 21. DBS concentrations (Cdbs) were well-correlated to the plasma concentrations (Cplasma): r = 0.8381, 0.9305 and 0.8531 for CBZ, PHT and VPA respectively, The conversion formulas from Cdbs to plasma concentrations were [0.89×CdbsCBZ+1.00]µg/mL, [1.11×CdbsPHT−1.00]µg/mL and [0.92×CdbsVPA+12.48]µg/mL respectively. Inclusion of the red blood cells (RBC)/plasma partition ratio (K) and the individual hematocrit levels in the estimation of the theoretical Cplasma from Cdbs of PHT and VPA further improved the identity between the observed and the estimated theoretical Cplasma. Bland-Altman plots indicated that the theoretical and observed Cplasma of PHT and VPA agreed well, and >93.0% of concentrations was within 95% CI (±2SD); and similar agreement (1∶1) was also found between the observed Cdbs and Cplasma of CBZ. As the Cplasma of CBZ, PHT and VPA can be accurately estimated from their Cdbs, DBS can therefore be used for drug monitoring in PWE on any of these AEDs. PMID:25255292

  20. An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

    Science.gov (United States)

    Mishra, Saurabh M; Rohera, Bhagwan D

    2017-11-01

    The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.