WorldWideScience

Sample records for codeine

  1. 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 ...

  2. To prescribe codeine or not to prescribe codeine?

    Science.gov (United States)

    Fleming, Marc L; Wanat, Matthew A

    2014-09-01

    A recently published study in Pediatrics by Kaiser et al. (2014; Epub April 21, DOI: 10.1542/peds.2013-3171) reported that on average, over the past decade, children aged 3 to 17 were prescribed approximately 700,000 prescriptions for codeine-containing products each year in association with emergency department (ED) visits. Although, guidelines from the American Academy of Pediatrics issued warnings in 1997 and reaffirmed their concerns regarding the safety and effectiveness of codeine in 2006, it is still often prescribed for pain and cough associated with upper respiratory infection. With the impending rescheduling of hydrocodone combination products to Schedule II, physicians and mid-level prescribers may be compelled to prescribe codeine-containing products (e.g., with acetaminophen) due to reduced administrative burden and limits on Schedule II prescriptive authority for nurse practitioners and physician assistants in some states. This commentary expounds on the safety and effectiveness concerns of codeine, with a primary focus on patients in the ED setting.

  3. Codeine

    Science.gov (United States)

    ... blood pressure; Addison's disease (condition in which the body does not make enough of certain natural substances); or thyroid, pancreatic, intestinal, gallbladder, liver, or kidney disease.you should know that this medication may decrease fertility in men and women. Talk to your doctor ...

  4. Codeine misuse and dependence in South Africa – learning from ...

    African Journals Online (AJOL)

    Background. Misuse of prescription and over-the-counter codeine-containing products is a global public health issue. Objectives. To investigate the extent of treatment demand related to the misuse of codeine or codeine dependence in South Africa (SA) and the profile of patients seeking treatment, so as to understand the ...

  5. "Codeine Is My Helper": Misuse of and Dependence on Codeine-Containing Medicines in South Africa.

    Science.gov (United States)

    Van Hout, Marie Claire; Rich, Eileen; Dada, Siphokazi; Bergin, Michael

    2017-02-01

    Misuse of codeine-containing medicines is an emerging global public health concern. The majority of research has been conducted in developed countries (European Members States, Australia, the United States). This study aimed to gain an understanding of unique individual and collective experiences of trajectories of codeine misuse and dependence in South Africa. In-depth interviews were conducted with a purposive sample of adult codeine misusers and dependents ( n = 25). Narratives were analyzed using the empirical phenomenological psychological five-step method. Nine themes with 63 categories emerged, with two additional high levels of abstraction. Findings are illustrated: participant profile and product preferences, motives for use, transitioning to misuse and dependence, pharmacy purchasing and alternative sourcing routes, effects and withdrawal experiences, help-seeking and treatment experiences, and strategies for prevention. The study underscores the need for continued support for enhanced patient awareness of risk of habit forming use and related health consequences and professional pharmacovigilance.

  6. Biotransformation of codeine to 14-OH-codeine derivatives by Rhizobium radiobacter R89-1

    Czech Academy of Sciences Publication Activity Database

    Kyslíková, Eva; Babiak, Petr; Štěpánek, Václav; Zahradník, Jiří; Palyzová, Andrea; Marešová, Helena; Valešová, Renata; Hájíček, J.; Kyslík, Pavel

    2013-01-01

    Roč. 87, MAR 2013 (2013), s. 1-5 ISSN 1381-1177 R&D Projects: GA MŠk 2B08064 Institutional support: RVO:61388971 Keywords : Biotransformation * codeine * morphine Subject RIV: CE - Biochemistry Impact factor: 2.745, year: 2013

  7. Representations of Codeine Misuse on Instagram: Content Analysis

    Science.gov (United States)

    Cherian, Roy; Westbrook, Marisa; Ramo, Danielle

    2018-01-01

    Background Prescription opioid misuse has doubled over the past 10 years and is now a public health epidemic. Analysis of social media data may provide additional insights into opioid misuse to supplement the traditional approaches of data collection (eg, self-report on surveys). Objective The aim of this study was to characterize representations of codeine misuse through analysis of public posts on Instagram to understand text phrases related to misuse. Methods We identified hashtags and searchable text phrases associated with codeine misuse by analyzing 1156 sequential Instagram posts over the course of 2 weeks from May 2016 to July 2016. Content analysis of posts associated with these hashtags identified the most common themes arising in images, as well as culture around misuse, including how misuse is happening and being perpetuated through social media. Results A majority of images (50/100; 50.0%) depicted codeine in its commonly misused form, combined with soda (lean). Codeine misuse was commonly represented with the ingestion of alcohol, cannabis, and benzodiazepines. Some images highlighted the previously noted affinity between codeine misuse and hip-hop culture or mainstream popular culture images. Conclusions The prevalence of codeine misuse images, glamorizing of ingestion with soda and alcohol, and their integration with mainstream, popular culture imagery holds the potential to normalize and increase codeine misuse and overdose. To reduce harm and prevent misuse, immediate public health efforts are needed to better understand the relationship between the potential normalization, ritualization, and commercialization of codeine misuse. PMID:29559422

  8. CHANGING PRESCRIBING CULTURE - A FOCUS ON CODEINE POSTPARTUM.

    Science.gov (United States)

    Al-Adhami, Noor; Whitfield, Karen; North, Angela

    2016-09-01

    To eliminate the prescribing of codeine and codeine combination products postpartum to improve safety in breast fed infants.Concerns have been raised over the use of codeine and codeine combination products during breast feeding after the death of a neonate whose mother had been prescribed codeine postpartum. High concentrations of morphine were found in the infant's blood and this was attributed to the mother being a CYP2D6 ultrafast metaboliser.1 METHODS: The evidence surrounding the safety of codeine and codeine combination products in children, during the postpartum period and specifically for breast fed infants was collated. The evidence was presented to key stakeholders including obstetricians, midwives, safety and quality representatives, nurse unit managers and acute pain team representatives. Postpartum analgesia was discussed and an agreed protocol developed. Training and education sessions were undertaken to obstetric medical and nursing staff. The evidence that was presented to key stakeholders included:▸ Reports over the safety concerns surrounding the use of codeine and codeine combination products during breast feeding▸ Guidelines and contraindications about the use of codeine in children that had been issued by international regulatory bodies (US Food and Drug Administration and European Medicines Agency).▸ Recommendations from the Australian Medicines Handbook to avoid in breast feeding2 ▸ Recommendations from Hale's Medications and Mothers Milk that reported limited data and had made a recent re-classification from L3 (limited data-probably compatible) to L4 (limited data-possibly hazardous).3 Before presenting the evidence to key stakeholders and undertaking training to nursing and medical staff, more than 90% of postpartum women were prescribed a codeine containing product as part of their 'as required' analgesic regimen.Since the intervention, codeine combination products have now been almost completely eliminated on medication

  9. Morphine and Codeine in Biological Fluids: Approaches to Source Differentiation.

    Science.gov (United States)

    ElSohly, M A; Jones, A B

    1989-06-01

    Heroin, morphine, and codeine are among the most abused opiate analgesics today. Analysis of individuals' urines for morphine and codeine is sued as an indication of prior ingestion of these dugs. Poppy seeds and products containing poppy seeds are found to have small amounts of morphine and codeine (usually less than 200 µg morphine/g seeds and much less codeine), which is enough to produce a positive urine test for opiates. This manuscript reviews current data on the analysis of various poppy seed products and urine specimens from individuals ingesting these products. A brief review of the metabolism and elimination of these drugs is presented, with general guidelines for differentiation of poppy seed use versus condone, morphine, or heroin abuse. Copyright © 1989 Central Police University.

  10. Representations of Codeine Misuse on Instagram: Content Analysis.

    Science.gov (United States)

    Cherian, Roy; Westbrook, Marisa; Ramo, Danielle; Sarkar, Urmimala

    2018-03-20

    Prescription opioid misuse has doubled over the past 10 years and is now a public health epidemic. Analysis of social media data may provide additional insights into opioid misuse to supplement the traditional approaches of data collection (eg, self-report on surveys). The aim of this study was to characterize representations of codeine misuse through analysis of public posts on Instagram to understand text phrases related to misuse. We identified hashtags and searchable text phrases associated with codeine misuse by analyzing 1156 sequential Instagram posts over the course of 2 weeks from May 2016 to July 2016. Content analysis of posts associated with these hashtags identified the most common themes arising in images, as well as culture around misuse, including how misuse is happening and being perpetuated through social media. A majority of images (50/100; 50.0%) depicted codeine in its commonly misused form, combined with soda (lean). Codeine misuse was commonly represented with the ingestion of alcohol, cannabis, and benzodiazepines. Some images highlighted the previously noted affinity between codeine misuse and hip-hop culture or mainstream popular culture images. The prevalence of codeine misuse images, glamorizing of ingestion with soda and alcohol, and their integration with mainstream, popular culture imagery holds the potential to normalize and increase codeine misuse and overdose. To reduce harm and prevent misuse, immediate public health efforts are needed to better understand the relationship between the potential normalization, ritualization, and commercialization of codeine misuse. ©Roy Cherian, Marisa Westbrook, Danielle Ramo, Urmimala Sarkar. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 20.03.2018.

  11. Best Practices and Innovations for Managing Codeine Misuse and Dependence

    OpenAIRE

    Norman, Ian J; Bergin, Michael; Parry, Charles D; Van Hout, Marie Claire

    2016-01-01

    PURPOSE: Promoting and ensuring safe use of codeine containing medicines remains a public health issue given the rise in reporting of misuse and dependence particularly in countries where available over-the-counter (OTC). The aim of this unique study was to identify best practices in management of opioid abuse and dependence, particularly codeine, and innovations to meet challenges surrounding safe and compliant use, patient awareness-raising, reducing health harms and enhancing successful tr...

  12. Over-the-counter codeine use in Iceland

    DEFF Research Database (Denmark)

    Almarsdóttir, A B; Grimsson, A

    2000-01-01

    BACKGROUND: The objective of this study was to test the assumption that liberalizing community pharmacy ownership in Iceland would lead to increased irrational use of over-the-counter pain relievers containing codeine. METHODS: Based on this assumption we built and tested a model using an interru......BACKGROUND: The objective of this study was to test the assumption that liberalizing community pharmacy ownership in Iceland would lead to increased irrational use of over-the-counter pain relievers containing codeine. METHODS: Based on this assumption we built and tested a model using...... an interrupted time series design that contrasts the monthly sales data for over-the-counter pain relievers containing codeine before and after the legislation took effect. RESULTS: The total use of over-the-counter pain relievers containing codeine as well as those containing paracetamol and codeine has risen...... leads to irrational use of over-the-counter medicines is not substantiated in the case of over-the-counter pain relievers containing codeine....

  13. Practice implications and recommendations for managing codeine misuse and dependence

    Directory of Open Access Journals (Sweden)

    Bergin Michael

    2015-12-01

    Full Text Available Codeine, a weak opiate, requires increased pharmacovigilance relating to availability, heterogeneous nature of misuse, dependence and associated harm. A scoping review of literature on codeine was conducted using Arksey & O’Malley’s framework (1. Databases searched included PubMed, EBSCO Host, Science Direct, EMBASE, PsycINFO, Cochrane library and Medline from 1994 to 2014. Follow-up search strategies involved hand searching and searching of pharmaceutical, health, medical and drug related websites. Initial zscreening identified 3,105 articles with 475 meeting the inclusion criteria. Eight broad categories organised the literature, data charting and qualitative synthesis. This paper presents implications for practice and makes recommendations to address these issues. Themes identified relate to raising public and practitioner awareness, risk management, dispensing practices and monitoring and surveillance of codeine. Evidence to inform law enforcement, drug surveillance, public health initiatives, harm reduction approaches, pharmacy, clinical and treatment practices is warranted.

  14. Codeine misuse and dependence in South Africa: Perspectives of ...

    African Journals Online (AJOL)

    1 Alcohol, Tobacco and Other Drug Research Unit, South African Medical ... A semi-structured interview comprising 20 questions (8 qualitative ... report on OTC and prescription-only medicines produced by the .... [17] Codeine misusers in rural areas in particular face many ... patients in SA, compared with 30% for Ireland.

  15. Over-the-counter codeine use in Iceland

    DEFF Research Database (Denmark)

    Almarsdóttir, Anna Birna; Grímsson, Almar

    2000-01-01

    Background: The objective of this study was to test the assumption that liberalizing community pharmacy ownership in Iceland would lead to increased irrational use of over-the-counter pain relievers containing codeine. Methods: Based on this assumption we built and tested a model using an interru...

  16. 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

  17. 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.

  18. Codeine, alone and with paracetamol (acetaminophen), for cancer pain.

    Science.gov (United States)

    Straube, Carmen; Derry, Sheena; Jackson, Kenneth C; Wiffen, Philip J; Bell, Rae F; Strassels, Scott; Straube, Sebastian

    2014-09-19

    Pain is very common in patients with cancer. Opioid analgesics, including codeine, play a significant role in major guidelines on the management of cancer pain, particularly for mild to moderate pain. Codeine is widely available and inexpensive, which may make it a good choice, especially in low-resource settings. Its use is controversial, in part because codeine is not effective in a minority of patients who cannot convert it to its active metabolite (morphine), and also because of concerns about potential abuse, and safety in children. To determine the efficacy and safety of codeine used alone or in combination with paracetamol for relieving cancer pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2014, Issue 2), MEDLINE and EMBASE from inception to 5 March 2014, supplemented by searches of clinical trial registries and screening of the reference lists of the identified studies and reviews in the field. We sought randomised, double-blind, controlled trials using single or multiple doses of codeine, with or without paracetamol, for the treatment of cancer pain. Trials could have either parallel or cross-over design, with at least 10 participants per treatment group. Studies in children or adults reporting on any type, grade, and stage of cancer were eligible. We accepted any formulation, dosage regimen, and route of administration of codeine, and both placebo and active controls. Two review authors independently read the titles and abstracts of all studies identified by the searches and excluded those that clearly did not meet the inclusion criteria. For the remaining studies, two authors read the full manuscripts and assessed them for inclusion. We resolved discrepancies between review authors by discussion. Included studies were described qualitatively, since no meta-analysis was possible because of the small amount of data identified, and clinical and methodological between-study heterogeneity. We included 15

  19. How resistant to tampering are codeine containing analgesics on the market? Assessing the potential for opioid extraction

    OpenAIRE

    Kimergård, Andreas; Deluca, Paolo; Hindersson, Peter; Breindahl, Torben

    2016-01-01

    IntroductionMisuse of opioid analgesics, in combination with diversion, dependence, and fatal overdoses, presents a serious problem for public health, which affects many countries worldwide. Within this context, tampering with opioids has been associated with serious harm. The aim of the present study was to assess the tampering potential of codeine combination analgesics on the market (containing codeine/non-opioid analgesics) by the extraction of codeine.MethodsCodeine was extracted from th...

  20. CODEINE CONTAINING COUGH SYRUP ADDICTION IN ASSAM AND NAGALAND

    OpenAIRE

    Wairagkar, Niteen S.; Das, J.; Kumar, S.; Mahanta, J.; Satyanarayana, K.; Phukan, R.K.; Chetia, M.; Goswami, S.K.

    1994-01-01

    The drug abuse monitoring study of Regional Medical Research Center, Dibrugarh, reported 181 and 395 addicts from the states of Assam and Nagaland respectively in one year. Of these, 48 (26.5%) and 49(12.4%) cases were contributed by the primary abuse of codeine containing cough syrups. A11 addicts were males in their early twenties. Most of the addicts were unmarried and educated up to matriculation. The majority of addicts in Assam were Hindus (85.4%) and in Nagaland Christians (81.63%). Un...

  1. Comparison of the postoperative analgesic effects of paracetamol–codeine phosphate and naproxen sodium–codeine phosphate for lumbar disk surgery

    Directory of Open Access Journals (Sweden)

    Reyhan Polat

    2015-09-01

    Full Text Available The aim of this study was to compared the efficacy of paracetamol–codeine phosphate and naproxen sodium–codeine phosphate on postoperative pain and tramadol consumption during the first 24 hours after a lumbar disk surgery. After Ethics Committee approval and informed consent had been obtained, 64 patients were allocated into three groups. Patients received oral paracetamol–codeine (300 mg + 30 mg; Group P, naproxen sodium–codeine (550 mg + 30 mg; Group N, or placebo tablets (Group C 30 minutes prior to induction of anesthesia. Patient-controlled analgesia was supplied postoperatively using tramadol. Pain intensity, tramadol consumption, and side effects were recorded every 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after surgery. Whole study period pain intensity (visual analogue scale scores was lower in Group P (p = 0.007 and Group N (p = 0.001, compared with Group C, however, there was no statistically significant difference between Group P and Group N regarding pain intensity (p > 0.05. Tramadol consumption was lower in Group P and Group N, compared with Group C (p < 0.001, and in turn the lowest incidence of tramadol consumption was detected in Group P compared with Group N (p < 0.001 and Group C (p < 0.001. Side effects were similar between the groups. Preemptive administration of paracetamol–codeine and naproxen sodium–codeine combination significantly reduced tramadol consumption and provided more effective analgesia compared with placebo. The paracetamol–codeine combination was superior to naproxen sodium–codeine with regard to tramadol consumption.

  2. "Tampering to Death": A Fatal Codeine Intoxication Due to a Homemade Purification of a Medical Formulation.

    Science.gov (United States)

    Fais, Paolo; Pigaiani, Nicola; Cecchetto, Giovanni; Montisci, Massimo; Gottardo, Rossella; Viel, Guido; Pascali, Jennifer Paola; Tagliaro, Franco

    2017-11-01

    Many homemade tamper processes of medical codeine formulations are available on selected "forums" on the Internet, where recreational codeine users claim to be able to purify codeine by removing additives, such as acetaminophen, to avoid or limit adverse effects. In this work, it is reported and discussed a fatal case of codeine intoxication. The findings of objects such as jars, filters, and tablets, and amounts of unknown liquid material at the death scene investigation suggested a fatal codeine intoxication after the tampering procedure called "cold water extraction." Toxicological results obtained from the analysis of both the nonbiological material and the body fluids of the decedent integrated with the information collected at the death scene investigation confirmed the above-mentioned hypothesis. This report underlines the importance of a tight interconnection between criminalistics and legal medicine to strengthen the identification of the cause of death and the reconstruction of the event. © 2017 American Academy of Forensic Sciences.

  3. Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

    Science.gov (United States)

    Chen, Z R; Somogyi, A A; Reynolds, G; Bochner, F

    1991-04-01

    1. The pharmacokinetics, metabolism and partial clearances of codeine to morphine, norcodeine and codeine-6-glucuronide after single (30 mg) and chronic (30 mg 8 h for seven doses) administration of codeine were studied in eight subjects (seven extensive and one poor metaboliser of dextromethorphan). Codeine, codeine-6-glucuronide, morphine and norcodeine were measured by high performance liquid chromatographic assays. 2. After the single dose, the time to achieve maximum plasma codeine concentrations was 0.97 +/- 0.31 h (mean +/- s.d.) and for codeine-6-glucuronide it was 1.28 +/- 0.49 h. The plasma AUC of codeine-6-glucuronide was 15.8 +/- 4.5 times higher than that of codeine. The AUC of codeine in saliva was 3.4 +/- 1.1 times higher than that in plasma. The elimination half-life of codeine was 3.2 +/- 0.3 h and that of codeine-6-glucuronide was 3.2 +/- 0.9 h. 3. The renal clearance of codeine was 183 +/- 59 ml min-1 and was inversely correlated with urine pH (r = 0.81). These data suggest that codeine undergoes filtration at the glomerulus, tubular secretion and passive reabsorption. The renal clearance of codeine-6-glucuronide was 55 +/- 21 ml min-1, and was not correlated with urine pH. Its binding to human plasma was less than 10%. These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in

  4. Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain.

    Science.gov (United States)

    De los Santos, A R; Martí, M I; Espinosa, D; Di Girolamo, G; Vinacur, J C; Casadei, A

    1998-01-01

    This study was conducted to compare the analgesic action of Lysine Clonixinate (LC) vs Paracetamol/Codeine association (PC) in the treatment of postepisiotomy pain in primiparae women: 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and randomly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours. Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale (VAS) and patient's assessment before receiving treatment and after 1, 2, 6 and 24 hours. Intensity of spontaneous pain was reduced in 24 hours from 4.28 +/- 2.11 to 1.73 +/- 1.46 (P < 0.0001) in the LC group and from 4.78 +/- 2.08 to 1.90 +/- 1.72 in the PC-treated group (p < 0.0001); with no significant differences between treatments. 54% of the patients treated with LC and 55% of those receiving PC showed onset of analgesic action 30 minutes following dose administration. Patient's final global assessment revealed that 95% of LC-treated patients and 96% of the PC group showed total or partial pain relief during the first treatment day. No sleep disturbances were seen during the night in 75% of patients. Only one patient receiving LC showed nausea not requiring treatment discontinuation. It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain.

  5. Codeine use, dependence and help-seeking behaviour in the UK and Ireland: an online cross-sectional survey.

    Science.gov (United States)

    Kimergård, A; Foley, M; Davey, Z; Dunne, J; Drummond, C; Deluca, P

    2017-09-01

    Codeine misuse and dependence poses a clinical and public health challenge. However, little is known about dependence and treatment needs in the UK and Ireland. To characterize codeine use, dependence and help-seeking behaviour. An online cross-sectional survey advertised on Facebook, Twitter, health and drug websites and e-mail circulars. The survey collected data on demographics and codeine use amongst adults from the UK and Ireland. The Severity of Dependence Scale measured the level of codeine dependence. The sample of 316 respondents had a mean age of 35.3 years (SD = 12.3) and 67% were women. Of the 316 respondents, 54 scored ≥5 on the Severity of Dependence Scale indicating codeine dependence (17.1%). Our study found that codeine dependence is a problem with both prescribed and 'over-the-counter' codeine. Codeine dependence was associated with daily use of codeine, faking or exaggerating symptoms to get a prescription for codeine and 'pharmacy shopping' ( P addiction treatment demand through increased identification and referrals in primary care. © The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. Radiolabeling of codeine with 131I and its biodistribution in rats

    International Nuclear Information System (INIS)

    Enginar, H.

    2009-01-01

    Codeine which was extracted from dry capsules of the opium poppy (Papaver somniferum) was purified by HPLC (High Performance Liquid Chromatography) and characterized by NMR (Nuclear Magnetic Resonance) and IR (Infrared) spectroscopy techniques. The purified compound was labeled with 131 I and biodistribution studies were performed in rats. Radioiodinated codeine distributed uniformly in the cerebellum, m.pons, striatum and hypothalamus while the other branch of brain and Stomach, urinary bladder, and small intestine uptakes were significantly higher than other tissues. (author)

  7. Codeine misuse and dependence in South Africa: Perspectives of addiction treatment providers

    OpenAIRE

    Parry, Charles; Rich, Eileen; Van Hout, Marie-Claire; Deluca, Paolo

    2017-01-01

    Background. General practitioners are referring patients with codeine-related problems to specialist treatment facilities, but little is known about the addiction treatment providers, the kinds of treatment they provide, and whether training or other interventions are needed to strengthen this sector.\\ud Objectives. To investigate the perspectives of addiction treatment providers regarding treatment for codeine misuse or dependence.\\ud Method. Twenty addiction treatment providers linked to th...

  8. Codeine Shopping Behavior in a Retrospective Cohort of Chronic Noncancer Pain Patients: Incidence and Risk Factors.

    Science.gov (United States)

    Chenaf, Chouki; Kabore, Jean-Luc; Delorme, Jessica; Pereira, Bruno; Mulliez, Aurélien; Roche, Lucie; Eschalier, Alain; Delage, Noémie; Authier, Nicolas

    2016-12-01

    Codeine is a widely used opioid analgesic but studies on its misuse in chronic noncancer pain (CNCP) are still lacking. The aim of this study was to assess the incidence of codeine shopping behavior in CNCP patients and to identify the associated risk factors. This was a population-based retrospective cohort study from the French health insurance claims database from 2004 to 2014. The main outcome was the one-year incidence of codeine shopping behavior defined as ≥1 day of overlapping prescriptions written by ≥2 different prescribers and filled in ≥3 different pharmacies. A total of 1,958 CNCP patients treated with codeine were included, with a mean age of 62.7 ± 16.1 years, 36.8% men. The 1-year incidence rate of codeine shopping behavior was 4.03% (95% confidence interval [CI], 3.07-5.28). In multivariate analysis, risk factors associated with shopping behavior were younger age (≤40 years) (hazard ratio [HR] = 7.29; 95% CI, 4.28-12.42), mental health disorders (HR = 2.25; 95% CI, 1.08-4.67), concurrent use of anxiolytic benzodiazepines (HR = 3.12; 95% CI, 1.55-6.26), and previous use of strong opioids (HR = 2.94; 95% CI, 1.24-6.98). The incidence of codeine shopping behavior in CNCP patients was 4% and risk factors identified were shared with those of opioid abuse. Shopping behavior for codeine was not infrequent in CNCP patients. The risk factors identified in this study are similar to those identified for opioid abuse in other studies. Appropriate use of codeine from the perspectives of patients and healthcare providers should be encouraged. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  9. Photocatalytic mineralization of codeine by UV-A/TiO{sub 2}—Kinetics, intermediates, and pathways

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Chin-Sheng [Graduate Institute of Environmental Engineering, National Taiwan University, Taipei 106, Taiwan, ROC (China); Lin, Cheng-Fang, E-mail: cflin@ntu.edu.tw [Graduate Institute of Environmental Engineering, National Taiwan University, Taipei 106, Taiwan, ROC (China); Hong, Pui-Kwan Andy [Department of Civil and Environmental Engineering, University of Utah, Salt Lake City, UT 84112 (United States)

    2016-01-15

    Highlights: • Codeine was completely removed in 30 min under irradiated UV-A/TiO{sub 2}. • Codeine was mineralized in 90 min with near complete N conversion to NH{sub 4}{sup +} and NO{sub 3}{sup −}. • Morphine was authenticated and four others were identified as intermediates. • Degradation proceeded via ipso-substitution and hydroxylation of the aromatic ring. - Abstract: This study investigated the photocatalytic degradation of codeine by UV-irradiated TiO{sub 2}. The degradation kinetics was determined under varied conditions including the TiO{sub 2} loading, codeine concentration, and pH. Codeine and several reaction intermediates including morphine were identified and tracked during degradation using HPLC/MS–MS technique, along with TOC and IC measurements. Specifically, removal of 100 μg/L of spike codeine was complete in 3 min by contact with a 0.1 g/L suspension of TiO{sub 2} under UV irradiation at pH 7. The degradation kinetics of codeine was first-order with respect to both the catalyst TiO{sub 2} and the reactant codeine, with enhanced reaction rates with increasing pH up to pH 9. Mineralization of codeine was possible upon prolonged contact; near complete mineralization of 10 mg/L of codeine was achieved in 90 min with 0.1 g/L TiO{sub 2} under irradiation at pH 5, during which the organic nitrogen was converted to NH{sub 3}-N (74%) and NO{sub 3}-N (22%). Based on the identified intermediates, two degradation pathways were proposed of which one involved ipso-substitution followed by cleavage of the aromatic ring and another involved repeated hydroxylation of the codeine molecule followed by its fragmentation.

  10. Degradation of morphine and codeine by gamma radiation in methanol solution

    International Nuclear Information System (INIS)

    Kantoglu, Oemer; Ergun, Ece

    2015-01-01

    The high concentrations of opiate and solvent in wastewater are toxic to biological life and affect the aquatic environment. Therefore, it must be treated by an advanced treatment process such as ionizing radiation. Effect of organic media on morphine and codeine during gamma irradiation was determined for the first time in this paper. Samples were irradiated at ambient temperature and in air environment at various doses (0, 10, 20, 30, 40, 50 and 60 kGy). Gamma irradiation-induced changes in the molecular structure of morphine and codeine were monitored by direct infusion electrospray ionization mass spectrometry in positive ion mode. The mass of the by-products were appeared to be more than the mass of the original alkaloids. Molecular structures of the by-products and reaction pathways were proposed. Oxygenated morphine and oxygenated codeine were identified in the presence of oxygen. However, solvent radical addition reactions were observed as the main mechanism for the by-product formation in oxygen-free irradiation. The results indicated that 89% of morphine and 98% of codeine were degraded at dose of 50 kGy. In addition, alkaloids and their by-products were not detected above 50 kGy. Here, we demonstrated that ionizing radiation process is a promising method to remove morphine and codeine in solvent/opiate rich industrial wastewater.

  11. Degradation of morphine and codeine by gamma radiation in methanol solution

    Energy Technology Data Exchange (ETDEWEB)

    Kantoglu, Oemer; Ergun, Ece [TAEA, Saraykoey Nuclear Research and Training Center, Ankara (Turkey)

    2015-05-01

    The high concentrations of opiate and solvent in wastewater are toxic to biological life and affect the aquatic environment. Therefore, it must be treated by an advanced treatment process such as ionizing radiation. Effect of organic media on morphine and codeine during gamma irradiation was determined for the first time in this paper. Samples were irradiated at ambient temperature and in air environment at various doses (0, 10, 20, 30, 40, 50 and 60 kGy). Gamma irradiation-induced changes in the molecular structure of morphine and codeine were monitored by direct infusion electrospray ionization mass spectrometry in positive ion mode. The mass of the by-products were appeared to be more than the mass of the original alkaloids. Molecular structures of the by-products and reaction pathways were proposed. Oxygenated morphine and oxygenated codeine were identified in the presence of oxygen. However, solvent radical addition reactions were observed as the main mechanism for the by-product formation in oxygen-free irradiation. The results indicated that 89% of morphine and 98% of codeine were degraded at dose of 50 kGy. In addition, alkaloids and their by-products were not detected above 50 kGy. Here, we demonstrated that ionizing radiation process is a promising method to remove morphine and codeine in solvent/opiate rich industrial wastewater.

  12. Codeine misuse and dependence in South Africa: Perspectives of addiction treatment providers

    Directory of Open Access Journals (Sweden)

    Charles D H Parry

    2017-05-01

    Full Text Available Background. General practitioners are referring patients with codeine-related problems to specialist treatment facilities, but little is known about the addiction treatment providers, the kinds of treatment they provide, and whether training or other interventions are needed to strengthen this sector. Objectives. To investigate the perspectives of addiction treatment providers regarding treatment for codeine misuse or dependence. Method. Twenty addiction treatment providers linked to the South African Community Epidemiology Network on Drug Use and the South African Addiction Medicine Society were contacted telephonically and asked 20 questions. Results. While many participants had received training in pharmacological management of individuals with opioid dependence, only two had received specific training on codeine management. Between half and two-thirds of the treatment settings they worked in provided detoxification, pharmacotherapy, psychosocial treatment and aftercare. Very few treatment settings offered long-term treatment for codeine misuse and dependence. Participants indicated that over half of their codeine patients entered treatment for intentional misuse for intoxication, and dependence resulting from excessive or long-term use. The main barriers to patients entering treatment were seen as denial of having a problem, not being ready for change, mental health problems, stigma, and affordability of treatment. Participants identified a need for further training in how to manage withdrawal and detoxification, treatment modalities including motivational interviewing, and relapse prevention. Conclusions. Gaps in training among treatment providers need to centre on how to manage withdrawal from codeine use and detoxification, motivational interviewing and relapse prevention. Interventions are needed to address barriers to entering treatment, including user denial.

  13. Tramadol can selectively manage moderate pain in children following European advice limiting codeine use.

    Science.gov (United States)

    Marzuillo, Pierluigi; Calligaris, Lorenzo; Barbi, Egidio

    2014-11-01

    The European Medicine Agency recommendations limiting codeine use in children have created a void in managing moderate pain. We review the evidence on the pharmacokinetic, pharmacodynamic and safety profile of tramadol, a possible substitute for codeine. Tramadol appears to be safe in both paediatric inpatients and outpatients. It may be appropriate to limit the current use of tramadol to monitored settings in children with risk factors for respiratory depression, subject to further safety evidence. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  14. Systemic synergism between codeine and morphine in three pain models in mice.

    Science.gov (United States)

    Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

    2013-01-01

    The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes. This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models. Intrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip). This synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.

  15. Tramadol suppositories are less suitable for post-operative pain relief than rectal acetaminophen/codeine

    NARCIS (Netherlands)

    Pluim, M. A.; Wegener, J. T.; Rupreht, J.; Vulto, A. G.

    1999-01-01

    The suitability of tramadol suppositories for inclusion in our hospital formulary for the treatment of mild to moderate post-operative pain was evaluated. In an open randomized trial, rectal tramadol was compared with our standard treatment acetaminophen/codeine suppositories. We expected tramadol

  16. Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults.

    Science.gov (United States)

    Wiffen, Philip J; Knaggs, Roger; Derry, Sheena; Cole, Peter; Phillips, Tudor; Moore, R Andrew

    2016-12-27

    Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

  17. Dopamine transporter SPECT imaging of the peroral addicts of compound codeine phosphate solution

    International Nuclear Information System (INIS)

    Sun Taotao; Hu Shu; Jia Shaowei; Chen Qing; Fan Rong

    2010-01-01

    Objective: To study the damage to striatum in patients perorally addicted to compound codeine phosphate solution by using the brain dopamine transporter SPECT imaging. Methods: Patients perorally addicted to compound codeine phosphate solution (n = 29) and addicted to heroin (n = 27), as well as healthy volunteers (n = 31) were included in the study. Each of them underwent dopamine transporter (DAT) SPECT imaging with 99 Tc m -2β-[N, N'-bis-( 2- mercaptoethyl ) ethylenediamino] methyl, 3β-(4-chlorophenyl)tropane ( 99 Tc m -TRODAT-1). The striatum volume (V, cm 3 ), mass (m, g) and radioactivity ratio (Ra) of striatum to whole brain were calculated using physio-mathematical modeling method. Results: Bilateral striatum of healthy volunteers showed typical 'panda eyes' pattern and the distribution of DAT was uniform and symmetrical. Bilateral striatum of patients addicted to compound codeine phosphate showed impaired tracer uptake, similar to those addicted to heroin. The V, m and Ra of bilateral striatum of patients addicted to compound codeine phosphate were (23.68±4.94) cm 3 , (24.87±5.19) g and (5.01±0.88) %, respectively, which were significantly lower than those of healthy controls: (35.39 ±4.42) cm 3 ,(37.16±4.64) g and (7.93±0.86)% (t =-9.69, -9.69, - 13.01, all P =0.000), but significantly higher than those addicted to heroin: (18.87±4.66) cm 3 , (19.81±4.90) g and (4.26±1.02) % (t =3.74, 3.74, 2.96, P = 0.000, 0.000, 0.005). Conclusion: Long-term peroral intake of compound codeine phosphate solution may damage the function of cerebral striatum, which is someway similar to though less severe than, the impairment caused by heroin. (authors)

  18. Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair.

    Science.gov (United States)

    Joseph, R E; Höld, K M; Wilkins, D G; Rollins, D E; Cone, E J

    1999-10-01

    A 10-week inpatient study was performed to evaluate cocaine, codeine, and metabolite disposition in biological matrices collected from volunteers. An initial report described drug disposition in plasma, sebum, and stratum corneum collected from five African-American males. This report focuses on drug disposition in hair and sweat collected from the same five subjects. Following a three-week washout period, three doses of cocaine HCl (75 mg/70 kg, subcutaneous) and three doses of codeine SO4 (60 mg/70 kg, oral) were administered on alternating days in week 4 (low-dose week). The same dosing sequence was repeated in week 8 with doubled doses (high-dose week). Hair was collected by shaving the entire scalp once each week. Hair from the anterior vertex was divided into two portions. One portion was washed with isopropanol and phosphate buffer; the other portion was not washed. Hair was enzymatically digested, samples were centrifuged, and the supernatant was collected. Sweat was collected periodically by placing PharmChek sweat patches on the torso. Drugs were extracted from sweat patches with methanol/0.2 M sodium acetate buffer (75:25, v/v). Supernatants from hair digests, hair washes, and sweat patch extracts were processed by solid-phase extraction followed by gas chromatography-mass spectrometry analysis for cocaine, codeine, 6-acetylmorphine, and metabolites. Cocaine and codeine were the primary analytes identified in sweat patches and hair. Drugs were detected in sweat within 8 h after dosing, and drug secretion primarily occurred within 24 h after dosing. No clear relationship was observed between dose and drug concentrations in sweat. Drug incorporation into hair appeared to be dose-dependent. Drugs were detected in hair within 1-3 days after the last drug administration; peak drug concentrations generally occurred in the following 1-2 weeks; thereafter, drug concentrations decreased. Solvent washes removed 50-55% of cocaine and codeine from hair collected 1

  19. Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study.

    Science.gov (United States)

    Qiu, Y-W; Su, H-H; Lv, X-F; Jiang, G-H

    2015-01-01

    Codeine-containing cough syrups have become one of the most popular drugs of abuse in young people in the world. Chronic codeine-containing cough syrup abuse is related to impairments in a broad range of cognitive functions. However, the potential brain white matter impairment caused by chronic codeine-containing cough syrup abuse has not been reported previously. Our aim was to investigate abnormalities in the microstructure of brain white matter in chronic users of codeine-containing syrups and to determine whether these WM abnormalities are related to the duration of the use these syrups and clinical impulsivity. Thirty chronic codeine-containing syrup users and 30 matched controls were evaluated. Diffusion tensor imaging was performed by using a single-shot spin-echo-planar sequence. Whole-brain voxelwise analysis of fractional anisotropy was performed by using tract-based spatial statistics to localize abnormal WM regions. The Barratt Impulsiveness Scale 11 was surveyed to assess participants' impulsivity. Volume-of-interest analysis was used to detect changes of diffusivity indices in regions with fractional anisotropy abnormalities. Abnormal fractional anisotropy was extracted and correlated with clinical impulsivity and the duration of codeine-containing syrup use. Chronic codeine-containing syrup users had significantly lower fractional anisotropy in the inferior fronto-occipital fasciculus of the bilateral temporo-occipital regions, right frontal region, and the right corona radiata WM than controls. There were significant negative correlations among fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the right superior corona radiata WM and Barratt Impulsiveness Scale total scores, and between the right frontal region of the inferior fronto-occipital fasciculus and nonplan impulsivity scores in chronic codeine-containing syrup users. There was also a significant negative correlation between fractional

  20. Simultaneous DPV determination of morphine and codeine using dsDNA modified screen printed electrode strips coupled with electromembrane extraction

    Directory of Open Access Journals (Sweden)

    Rouhollah Feizbakhsh

    2016-01-01

    Full Text Available In this work a sensitive electrochemical sensor for simultaneous determination of morphine and codeine constructed by application of disposable screen printed carbon electrode strips (SPCE modified by double strand (ds calf thymus DNA. According to the results of the modified SPCE strips and experimented parameters, we observed a considerable shift between potentials of morphine and codeine current peaks. Related to these observed shifts, we studied on the effect of the concentration of modifier and pH value on the anodic oxidation pattern of morphine and codeine in the case of optimize the method to get better signals with maximum potential distance. Also to boosting the LODs of this electroanalytical method coupled with an electro-membrane preconcentration (EME step. The calibration curve which was plotted by the variation of differential pulse voltammetry (DPV currents as a function of different morphine and codeine concentration were linear within the range of 0.7– 40 µM and 2.3- 40 µM for morphine and codeine respectively. Also the limits of detection were 0.07 µM and 0.23 µM, respectively. Finally, the proposed method was able to determine morphine and codeine simultaneously and effectively in urinary real samples

  1. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.

    Science.gov (United States)

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

    Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column. These compounds have a very similar chemical structure to morphine. Unlike morphine, which is metabolized chiefly through conjugation reactions with uridine diphosphate glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both through oxidative reactions by the cytochrome P450 (CYP450) enzyme and conjugation by UGT enzymes. There is controversy as to whether codeine, dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes, respectively. Knowledge of this metabolism assists in the understanding for the potential of drug-drug interactions with these drugs. This understanding is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.

  2. LIQUID CHROMATOGRAPHIC / MASS SPECTROMETRIC DETERMINATION OF MORPHINE, CODEINE AND COCAINE IN HUMAN SERA USING A NEW INTERNAL SURFACE REVERSED PHASE COLUMN

    OpenAIRE

    Hattori, Hideki; Arinobu, Tetsuya; Iwai, Masae; Suzuki, Osamu; Seno, Hiroshi

    2003-01-01

    A new internal surface reversed phase column (Shim-pack MAYI-ODS) was used for analysis of morphine, codeine and cocaine in human sera by LC/MS/MS. The column enabled direct injection of crude biological samples without pretreatment realizing a rapid analytical procedure. Therecoveries of morphine, codeine and cocaine spiked into human sera were 50-60 %. The regression equations for morphine, codeine and cocaine in sera, using atropine as internal standard, showed good linearity in the ranges...

  3. Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following inguinal hernioplasty.

    Science.gov (United States)

    de los Santos, A R; Di Girolamo, G; Martí, M L

    1998-01-01

    In this study lysine clonixinate, a nonsteroidal antiinflammatory agent with selective inhibition of cyclooxygenase-2 and 5-lipooxygenase in in vitro and in vivo pharmacodynamic studies, was evaluated in a prospective, randomized, double-blind, double-dummy clinical study versus paracetamol/codeine, in 151 patients with pain following inguinal hernioplasty. Patients were treated with one 125 mg tablet of lysine clonixinate or paracetamol/codeine (500 mg + 30 mg) administered at fixed doses every 4 h during 2 days. Controls were carried out 1, 2 and 4 h after the first intake of day 1 and day 2. Each control included assessment of pain at rest, when coughing, sitting and upon moderate pressure. Both treatment groups (lysine clonixinate, 77 patients and paracetamol/codeine, 74 patients) were comparable in terms of demographic and baseline pain intensities. Spontaneous pain was reduced significantly in both treatment groups from the 1st-h control. The following values were recorded in the lysine clonixinate group during day 1: baseline: 6.86 +/- 1.24; 1st h: 4.49 +/- 1.77; 2nd h: 2.96 +/- 1.74; 4th h: 2.23 +/- 1.51. The following values for the same group during day 2 were: predose: 1.70 +/- 1.64; 1st h: 1.16 +/- 1.17; 2nd h: 0.78 +/- 1.06; 4th h: 0.63 +/- 1.05. The paracetamol/codeine group revealed the following values: day 1: baseline: 6.72 +/- 1.22; 1st h: 4.57 +/- 1.72; 2nd h: 2.97 +/- 1.68; 4th h: 2.47 +/- 1.68 and day 2: predose: 2.02 +/- 1.57; 1st h: 1.32 +/- 1.23; 2nd h: 0.82 +/- 0.99; 4th h: 0.66 +/- 0.89. Reduction of pain induced by coughing, sitting and pressure showed similar behavior patterns. No significant differences between both treatment groups were encountered in terms of analgesic efficacy. Incidence of adverse effects was significantly higher in the paracetamol/codeine group (X2: p lysine clonixinate group four out of 77 patients showed side effects but these did not require treatment discontinuation.

  4. The challenge of complex drug use: Associated use of codeine-containing medicines and new psychoactive substances in a European cross-sectional online population.

    Science.gov (United States)

    Kimergård, Andreas; Foley, Michelle; Davey, Zoe; Wadsworth, Elle; Drummond, Colin; Deluca, Paolo

    2017-05-01

    Misuse of codeine-containing medicines in combination with new psychoactive substances (NPS) is inadequately described. This study characterises codeine consumption amongst NPS users and non-NPS users to provide warning of health issues. Online survey conducted between July 2015 and March 2016. Out of 340 respondents, residing in a country in Europe and using codeine recently, 63.8% were female. Mean age: 34.9 years (SD = 12.4). Substance use included NPS (18.5%) and illicit controlled drugs (55.9%). Factors relating to codeine use found to significantly predict NPS use were consuming codeine extracted from combination tablets (OR = 16.79, 95% CI [8.67, 32.51]), obtaining codeine from friends, family, and acquaintances (OR = 3.98, 95% CI [1.82, 8.7]), use of illicit controlled drugs (OR = 34.99, 95% CI [8.39, 145.94]) and use of codeine to experience euphoria (OR = 6.41, 95% CI [3.42, 12.04]). Amongst NPS users, codeine is less likely to be used daily but more likely to be used for recreational purposes. Smaller populations engaging in high-risk use exist who take multiple drugs in high doses. Combinations of misused codeine and NPS highlight the need for policy to respond to a more complex drug situation. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Comparison of the Effects of Oral Diclofenac Sodium Versus Acetaminophen Codein on Pain During Extracorporeal Shock Wave Lithotrypsy

    Directory of Open Access Journals (Sweden)

    Karkhanehei B

    2017-09-01

    Full Text Available Introduction: Urinary calculi is the second common chronic renal disease. Todays, the extracorporeal shock wave lithotripsy (ESWL is the most common method of treatment of kidney calculi, though this method was invented 30 years ago. This study was conducted to compare the effects of oral diclofenac sodium versus acetaminophen codein on pain during ESWL. Methods: After signing informed consent, 90 patients with urinary calculi were randomly allocated into three equal groups (n = 30. In this study, one hour before the ESWL, 30 patients received the acetaminophen codeine (acetaminophen 650 mg plus codeine 20 mg orally and 30 patients received diclofenac sodium 50 mg orally and 30 patients did not receive any drug. Severity of pain was assessed by the four-point scale during the procedure. Results: The results of our study showed that there was no statistically significant difference among the three groups regarding gender, weight, age, overall satisfaction, and pain severity during ESWL. Although morphine consumption and pain severity in groups of acetaminophen codeine and diclofenac sodium was lower than in the third group, this different was not statistically significant (P = 0.086. Conclusion: Oral prescription of acetaminophen codeine and diclofenac sodium, one hour before ESWL, has a similar effect on pain management.

  6. [Perianal and rectal ulcers due to abuse of paracetamol-codeine suppositories].

    Science.gov (United States)

    Wagner, G; Sand, C; Sachse, M M

    2015-03-01

    A 61-year-old woman presented with a progressive perianal ulcer which had developed 4 months ago. Upon further examination, another ulcer of the rectum was detected. Anorectal malignancies, viral infections or primary inflammatory bowel disease were not found. It could be demonstrated that the ulcers were induced by paracetamol and codeine suppositories. After discontinuation of these suppositories, the perianal ulcers healed almost completely within 3 weeks. The pathogenesis of paracetamol-induced ulcers is unknown. However, dose-dependent vasoconstriction is a possible explanation.

  7. Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods

    Directory of Open Access Journals (Sweden)

    Milovanović Vesna

    2012-01-01

    Full Text Available Background/Aim. Saliva represents an alternative specimen for substances abuse determination in toxicology. Hence, the aim of this study was to optimize a method for saliva specimen preparation for heroin metabolites, morphine and 6-monoacetylmorphine (6-mam, and codeine determination by liquid chromatography-mass spectrometry (LC/MS, and to apply this method on saliva samples taken from the patients. Methods. Saliva specimen was prepared using liqiud/liquid extraction of morphine, codeine and 6- mam by mixture of chloroform and isopropanol (9 : 1; v/v. Extracts were analysed by HPLC/MS technique: separation column Waters Spherisorb® 5 μm, ODS2, 4.6 × 100 mm; mobile phase: ammonium acetate : acetonitile (80 : 20; v/v, mobile phase flow rate 0.3 mL/min; mass detection range: 100-400 m/z. Regression and correlation analyses were performed with the probalility level of 0.05. Concentrations of morphine, codeine and 6-mam were determined in saliva samples of the patients with “opiates” in urine identified by the test strips. Results. Calibration for each analysed substance was done in the concentration range from 0.1 to 1 mg/L and the coefficient of correlation was R2 > 0.99. We obtained following calibration curves: y = 385531x + 14584; y = 398036x + 31542; and y = 524162x - 27105, for morphine, codeine and 6-mam, respectively. Recovery for morphine and codeine determination was 99%, while for 6- mam it was 94%. Limits of detection and quantification of a proposed method were 0.01 mg/L and 0.05 mg/L, respectively. Concentration of morphine in the saliva of the heroin users ranged between 0.54 and 5.82 mg/L, concentration of codeine between 0.05 and 5.33, and 6-mam between 0.01 and 0.68 mg/L. A statistically significant correlation between codeine and 6-mam concentrations was obtained. Conclusion. A proposed HPLC/MS method for morphine, codeine and 6-mam determination in saliva is accurate, simple, cheap and suitable for routine analysis and

  8. Voltammetric Determination of Codeine on Glassy Carbon Electrode Modified with Nafion/MWCNTs

    Directory of Open Access Journals (Sweden)

    Robert Piech

    2015-01-01

    Full Text Available A glassy carbon electrode modified with a Nafion/MWCNTs composite is shown to enable the determination of codeine using differential pulse voltammetry in phosphate buffer of pH 3.0. At a preconcentration time of 15 s, the calibration graph is linear in the 0.5 µM (0.15 mg·L−1 to 15 µM (4.5 mg·L−1 concentration range with a correlation coefficient of 0.998. The detection limit at a preconcentration time of 120 s is as low as 4.5 μg·L−1. The repeatability of the method at a 0.6 μg·L−1 concentration level, expressed as the RSD, is 3.7% (for n=5. The method was successfully applied and validated by analyzing codeine in drug, human plasma, and urine samples.

  9. Separation and determination of impurities in paracetamol, codeine and pitophenone in the presence of fenpiverinium in combined suppository dosage form.

    Science.gov (United States)

    Vojta, Jiří; Hanzlík, Pavel; Jedlička, Aleš; Coufal, Pavel

    2015-01-01

    A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fenpiverinium bromide in combined suppository dosage form was developed and validated. The separation of paracetamol and its impurities 4-aminophenol, 4-nitrophenol, 4-chloracetanilid; codeine and its impurities methylcodeine, morphine, codeine dimer and 10-hydroxycodeine; pitophenone and its impurities 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid, 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl]benzoic acid 2-(1-piperidinyl)-ethyl ester, methyl ester of 2-(4-hydroxybenzoyl) benzoic acid and fenpiverinium was achieved by using ion-pair reversed phase liquid chromatography with UV detection. Validation parameters such as the precision, accuracy, linearity, limit of detection (LOD), limit of quantification (LOQ) and robustness were verified for all the mentioned impurities of codeine phosphate hemihydrate and 4-aminophenol and 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid as the main degradation products of paracetamol and pitophenone hydrochloride, respectively. The described method was found to be useful for analysis of the stability samples and therefore suitable for routine purity testing of the drug product. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. 49 CFR 40.139 - On what basis does the MRO verify test results for codeine and morphine?

    Science.gov (United States)

    2010-10-01

    ... PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the... unauthorized use of any opium, opiate, or opium derivative (i.e., morphine, heroin, or codeine). (1) As an MRO... needle tracks; (ii) Behavioral and psychological signs of acute opiate intoxication or withdrawal; (iii...

  11. Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery

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    Cagla Bali

    2016-04-01

    Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N or naproxen sodium-codeine phosphate (Group NC before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS. Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p 0.05. CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.

  12. A comparative study on Benzydamine HCL 0.5% and Acetaminophen Codeine in pain reduction following periodontal surgery

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    Khoshkhoonejad AA.

    2004-07-01

    Full Text Available Statement of Problem: Systemic analgesics are frequently prescribed for pain reduction following periodontal surgery. This type of treatment, however, brings about some disadvantages due to its late effect and inherent side effects. Benzydamine hydrochloride mouth wash is a non steroidal anti-inflammatory drug with local anaesthetic properties. Side effects of benzydamine are minor such as tissue numbness, burning and stinging. It brings relief to pain and inflammation rapidly. Purpose: The goal of this study was to compare benzydamine HCL 0.15% and Acetaminophen codeine as analgesics following periodontal surgery. Materials and Methods: This clinical study was performed on 18 patients referred to periodontics Department, Faculty of Dentistry, Tehran University of Medical Sciences. All patients were affected with chronic mild or moderate periodontitis and required surgery at least at two oral sites with similar lesions. Each patient received benzdamine HCL after first surgery and Acetaminophen codein following second operation. Pain reduction was evaluated by Visual Analog Scale (VAS. Data were analyzed with Wilcoxon-Signed and Mann-Whitney non-parametric tests. Results: Analgesic effect of Acetaminophene codeine was significantly more than that of benzydamine HCL following Reriodontal surgery (P=0.008. No significant difference was found between analgesic effects of Acetaminophene codeine and benzydamine HCL in patients with chronic mild periodontitis (P=0.9, and in cases that osteoplasty (P=0-31 or no osseous surgery (P=0.18 were performed. Conclusion: In cases with mild post-operative pain following periodontal surgery, Benzydamine HCL and be prescribed as an analgesic. However, in other cases this mouth wash should be prescribed along with Acetaminophene codein to reduce systemic drugs consumption.

  13. Clinical update on benefit versus risks of oral paracetamol alone or with codeine: still a good option?

    Science.gov (United States)

    Kress, Hans Georg; Untersteiner, Gerald

    2017-02-01

    After decades of worldwide use of paracetamol/acetaminophen as a popular and apparently safe prescription and over-the-counter medicine, the future role of this poorly understood analgesic has been seriously questioned by recent concerns about prenatal, cardiovascular (CV) and hepatic safety, and also about its analgesic efficacy. At the same time the usefulness of codeine in combination products has come under debate. Based on a PubMed database literature search on the terms efficacy, safety, paracetamol, acetaminophen, codeine and their combinations up to and including June 2016, this clinical update reviews the current evidence of the benefit and risks of oral paracetamol alone and with codeine for mild-to-moderate pain in adults, and compares the respective efficacy and safety profiles with those of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas there is a clear strong association of NSAID use and gastrointestinal (GI) and CV morbidity and mortality, evidence for paracetamol with and without codeine supports the recommended use even in most vulnerable individuals, such as the elderly, pregnant women, alcoholics, and compromised GI and CV patients. The controversies and widespread misconceptions about the complex hepatic metabolism and potential hepatotoxicity have been corrected by recent reviews, and paracetamol remains the first-line nonopioid analgesic in patients with liver diseases if notes of caution are applied. Due to its safety and tolerability profile paracetamol remained a first-line treatment in many international guidelines. Alone and with codeine it is a safe and effective option in adults, whilst NSAIDs are obviously less safe as alternatives, given the risk of potentially fatal GI and CV adverse effects.

  14. Urinary concentrations of morphine and codeine after consumption of poppy seeds.

    Science.gov (United States)

    Thevis, Mario; Opfermann, Georg; Schänzer, Wilhelm

    2003-01-01

    A quantitative analysis of morphine and codeine in human urine was performed after oral intake of cakes containing commercially available poppy seeds in order to estimate the possibility of positive doping results. Therefore, eight products from different manufacturers (poppy seeds or baking mixtures) and origin were obtained and analyzed by gas chromatography-mass spectrometry for the presence of the alkaloids. One selected batch of poppy seeds was used as an ingredient in a typical cake and was the object of an excretion study with nine volunteers. After application, several urine specimens contained morphine with concentrations higher than 1 microg/mL, and peak values of approximately 10.0 microg/mL were detected. Because the International Olympic Committee set a cutoff limit for morphine at 1 microg/mL, high-performance athletes could possibly test positive in doping control after consumption of products containing poppy seeds.

  15. PREOPERATIVE ORAL CODEINE EFFECT ON POSTOPERATIVE CAUGH CONTROL IN CATARACT SURGERY

    Directory of Open Access Journals (Sweden)

    H SOLTANI NEZHAD

    2003-03-01

    Full Text Available Introduction: cataract surgery is .one of the most common operation in ophthalmology. Post operative caught can lead to anterior chamber hemmorage and dehiscence of suture so we were going to finding a way to overcome to this problem. Method: This study is a clinical trial one which was done on 150 ASA 1, 2 patient that were over 45 years old age. These patient have cataract surgery under GA in Farabi Hospital of Esfahan medical university. All of the patient were intubated under direct laryngoscopy. Patients that have more of one laryngoscope, difficult intubation, thraceal intubation prolonged more than 15 seconds and those which have opiate addiction. We divided the patients into two 75 patient group by randomized selection. This study is double blind and 30mg codeine phosphate and placebo has given to the patient one hour preoperatively. Heart rate and systolic and diastolic, blood pressure has been recorded preoperatively, three minutes after intubation and three minutes after extubation respectively. Caught has been counted and recorded immediately. Five minutes and 30 minutes after extubation and results in contorol group are compared with the results in another group. Discussion: According to the statistical analysis t-student test, chi-square and non parametric test and Pvalue only changes in heart rate after extubation has been different in two groups and other findings make no difference in two groups. There was not any significant difference between two groups about age, sex, duration of surgery, preoperative mean heart rate and blood pressure. There was not any difference about mean number of coughs between two groups and according to this study oral codeine phosphate has administered preoperatively has not any effect on reducing postoperative caught in patients who have GA and tracheal incubation for cataract surgery.

  16. Impact of Safety-Related Regulations on Codeine Use in Children: A Quasi-Experimental Study Using Taiwan's National Health Insurance Research Database.

    Science.gov (United States)

    Lin, Chih-Wan; Wang, Ching-Huan; Huang, Wei-I; Ke, Wei-Ming; Chao, Pi-Hui; Chen, Wen-Wen; Hsiao, Fei-Yuan

    2017-07-01

    Safety concerns regarding potential life-threatening adverse events associated with codeine have resulted in policy decisions to restrict its use in pediatrics. However, whether these drug safety communications have had an immediate and strong impact on codeine use remains in question. We aimed to investigate the impact of the two implemented safety-related regulations (label changes and reimbursement regulations) on the use of codeine for upper respiratory infection (URI) or cough. A quasi-experimental study was performed using Taiwan's National Health Insurance Research Database. Quarterly data of codeine prescription rates for URI/cough visits were reported, and an interrupted time series design was used to assess the impact of the safety regulations on the uses of codeine among children with URI/cough visits. Multivariable logistic regression models were used to explore patient and provider characteristics associated with the use of codeine. The safety-related regulations were associated with a significant reduction in codeine prescription rates of -4.24% (95% confidence interval [CI] -4.78 to -3.70), and the relative reduction compared with predicted rates based on preregulation projections was 60.4, 56.6, and 53.2% in the first, second, and third year after the regulations began, respectively. In the postregulation period, physicians specializing in otolaryngology (odds ratio [OR] 1.47, 95% CI 1.45-1.49), practicing in district hospitals (OR 6.84, 95% CI 5.82-8.04) or clinics (OR 6.50, 95% CI 5.54-7.62), and practicing in the least urbanized areas (OR 1.60, 95% CI 1.55-1.64) were more likely to prescribe codeine to children than their counterparts. Our study provides a successful example of how to effectively reduce the codeine prescriptions in children in the 'real-world' settings, and highlights areas where future effort could be made to improve the safety use of codeine. Future research is warranted to explore whether there was a simultaneous decrease in

  17. A case report of over-the-counter codeine dependence as consequence of self-medication for premature ejaculation

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    Sethulakshmi Sreevalsam Anil

    2017-01-01

    Full Text Available Over-the-counter (OTC opioid abuse, including codeine, has been a growing problem around the world. Although the majority of the abusers use it for recreational purposes, many become dependent on it after having used it a medication for pain or cough. We present a case of codeine dependence where the initial prescribed use had been as a cough medication, but the subsequent abuse of it occurred the following self-medication for premature ejaculation. There is growing need for awareness among doctors and pharmacists of OTC abuse of opioids and for preventive interventions such as restricting supply, audit of pharmacies, training pharmacists, and counter staff and dispensing knowledge about proper use of opioid-containing medications to patients.

  18. Regulatory responses to over-the-counter codeine analgesic misuse in Australia, New Zealand and the United Kingdom.

    Science.gov (United States)

    Tobin, Claire L; Dobbin, Malcolm; McAvoy, Brian

    2013-10-01

    Analysis of the policy response by Australia's National Drugs and Poisons Schedule Committee (NDPSC) and comparison with recommendations by expert advisory committees in New Zealand and the United Kingdom. Analysis of public policy documents of relevant regulatory authorities was conducted. Data were extracted regarding changes to over-the-counter (OTC) codeine analgesic scheduling, indications, maximum unit dose, maximum daily dose, maximum pack size, warning labels, consumer medicine information and advertising. Where available, public submissions and other issues considered by the committees and rationale for their recommendations were recorded and thematically analysed. Expert advisory committees in Australia, NZ and the UK defined the policy problem of OTC codeine misuse and harm as small relative to total use and responded by restricting availability. Pharmacist supervision was required at the point-of-sale and pack sizes were reduced to short-term use. Comparison with recommendations by expert advisory committees in NZ and the UK suggests the NDPSC's actions in response to OTC codeine misuse were appropriate given the available evidence of misuse and harm, but highlights opportunities to utilise additional regulatory levers. Framing policy problems as matters of public health in the context of limited evidence may support decision makers to implement cautionary incremental policy change. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

  19. Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

    Directory of Open Access Journals (Sweden)

    Talita Girio Carnaval

    2013-12-01

    Full Text Available Opioids are central analgesics that act on the CNS (central nervous system and PNS (peripheral nervous system. We investigated the effects of codeine (COD and tramadol (TRAM on local anesthesia of the sciatic nerve. Eighty Wistar male rats received the following SC injections in the popliteal fossa: local anesthetic with epinephrine (LA; local anesthetic without vasoconstrictor (LA WV; COD; TRAM; LA + COD; LA + TRAM; COD 20 minutes prior to LA (COD 20' + LA or TRAM 20 minutes prior to LA (TRAM 20' + LA. As a nociceptive function, the blockade was considered the absence of a paw withdraw reflex. As a motor function, it was the absence of claudication. As a proprioceptive function, it was the absence of hopping and tactile responses. All data were compared using repeated-measures analysis of variance (ANOVA. Opioids showed a significant increase in the level of anesthesia, and the blockade duration of LA + COD was greater than that of the remaining groups (p < 0.05. The associated use of opioids improved anesthesia efficacy. This could lead to a new perspective in controlling dental pain.

  20. Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.

    Science.gov (United States)

    Owczarzak, Vicki; Haddad, Joseph

    2006-08-01

    To examine whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. A prospective, randomized control study. Seventy-five children aged 1 to 5 were recruited for this study. Each child was assigned randomly to receive either rectal or oral postoperative pain medication. A journal with eight questions was kept for 10 days after the operation, and an overall survey of five questions was filled out at the first postoperative visit. Postoperative pain was adequately controlled in those patients receiving suppositories when compared with those patients receiving oral pain medication. Adverse effects and total number of doses given per day were similar. Parents found the suppositories easy to administer, and more parents would switch or consider switching from oral pain medication to suppositories if given the choice. The suppositories achieved equivalent pain control as oral medication with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. If given the choice for future surgeries, many parents would switch or consider switching from oral pain medication to suppositories.

  1. Long-term stability of morphine, codeine, and 6-acetylmorphine in real-life whole blood samples, stored at -20°C.

    Science.gov (United States)

    Høiseth, Gudrun; Fjeld, Bente; Burns, Margrete Larsen; Strand, Dag Helge; Vindenes, Vigdis

    2014-06-01

    Stability of drugs during storage is important in forensic toxicology. For the analytes detected after intake of heroin (6-acetylmorphine (6-AM), morphine and codeine), long-time stability in real life whole blood samples are studied in only a small number of cases. Whole blood post mortem (n=37) and whole blood samples from living persons (n=22) containing morphine and codeine as well as 6-AM in blood or urine were selected. All cases represented intake of heroin. All samples contained fluoride and were initially analysed and stored in normal conditions (-20°C) for 4-9 years. All samples were then reanalysed using the same analytical methods and the results were compared. For samples from living persons, the median change in concentration was -3.7% for morphine and -5.3% for codeine. For post mortem samples, the median change in concentration was -12% for morphine and -11% for codeine. Both for samples from living persons and post mortem samples, the decrease in the concentrations from the original analysis to reanalysis were statistically significant for morphine and codeine. Regarding 6-AM, all living samples were negative at reanalysis. For post mortem samples, four cases still tested positive for 6-AM at reanalysis with a median change in the concentrations of -81%. There was no significant change in the morphine to codeine concentration ratios neither for living nor post mortem samples. This study showed that in real life whole blood samples, the concentrations of morphine and codeine are relatively stable during long-term storage at -20°C. 6-AM on the other hand, shows a considerable decrease in concentrations that is important to consider when interpreting results from reanalyses of forensic cases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Inducing rat brain CYP2D with nicotine increases the rate of codeine tolerance; predicting the rate of tolerance from acute analgesic response.

    Science.gov (United States)

    McMillan, Douglas M; Tyndale, Rachel F

    2017-12-01

    Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC 0-60 min ; pnicotine did not alter acute morphine analgesia (1.03-fold; p>0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Anticodeine aptamer immobilized on a Whatman cellulose paper for thin-film microextraction of codeine from urine followed by electrospray ionization ion mobility spectrometry.

    Science.gov (United States)

    Hashemian, Zahra; Khayamian, Taghi; Saraji, Mohammad

    2015-02-01

    A combination of thin-film microextaction based on an aptamer immobilized on modified Whatman cellulose paper followed by electrospray ionization ion mobility spectrometry has been developed for the analysis of codeine in urine samples. The immobilization is based on the covalent linking of an amino-modified anticodeine aptamer to aldehyde groups of the oxidized cellulose paper. The covalent bonds were examined by infrared spectroscopy and elemental analysis. The effect of the extraction parameters, including the elution conditions (solvent type and volume), extraction time, and extraction temperature, on the extraction efficiency were investigated. Under the optimized conditions, the linear dynamic range was found to be 10-300 ng/mL with a detection limit of 3.4 ng/mL for codeine in urine. The relative standard deviation was 6.8% for three replicate measurements of codeine at 100 ng/mL in urine. Furthermore, the samples were analyzed with a standard method for the analysis of codeine using high-performance liquid chromatography with ultraviolet detection. The comparison of the results validates the accuracy of the proposed method as an alternative method for the analysis of codeine in urine samples.

  4. [The knowledge of students and teachers of selected groups about the OTC drugs containing codeine and pseudoephedrine--an alternative to "legal highs"?].

    Science.gov (United States)

    Sliwińska-Mossoń, Mariola; Marcinkiewicz, Marcin; Marciniak, Katarzyna; Milnerowicz, Halina

    2015-01-01

    Currently the youth to intoxication increasingly used drugs generally available over the counter (OTC, Over-The-Counter drug) containing psychotropic substances. The knowledge on the subject among parents and teachers is inadequate. The aim of the study is to assess the knowledge of students and teachers about OTC drugs containing codeine or pseudoephedrine and their consequences on the use and popularity of these drugs. The study was conducted from December 2014 to March 2015 of 93 respondents. In conducting the study used research tool in the form of an anonymous questionnaire consisting of 21 questions for the students and teachers of 16 questions, the questions relate knowledge of the studied group persons on the OTC drugs containing codeine or pseudoephedrine and the effects of their use. Among the students participating in the study, the majority of respondents are aware that using drugs containing codeine or pseudoephedrine can be addicted to them. Higher knowledge on this subject have demonstrated high school students, but less teachers. Most of the respondents had knowledge about the health effects that result from an overdose of these drugs. Among the students most frequently reported sources of knowledge about OTC drugs containing codeine or pseudoephedrine were friends and the Internet. The general knowledge of high school students and teachers on the effects of OTC medications containing codeine or pseudoephedrine is not sufficient. There is a need to conduct preventive and educational action aimed at increasing knowledge among youth and adults on the health effects of these drugs.

  5. Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects

    Science.gov (United States)

    Gelston, Eloise A; Coller, Janet K; Lopatko, Olga V; James, Heather M; Schmidt, Helmut; White, Jason M; Somogyi, Andrew A

    2012-01-01

    AIMS To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide. RESULTS The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID:22092298

  6. Rapid and sensitive electrochemical determination of codeine in pharmaceutical formulations and human urine using a boron-doped diamond film electrode

    International Nuclear Information System (INIS)

    Švorc, Ľubomír; Sochr, Jozef; Svítková, Jana; Rievaj, Miroslav; Bustin, Dušan

    2013-01-01

    Highlights: ► Novel electrochemical sensor for the determination of codeine is presented. ► Codeine provided a single oxidation peak at +1.0 V vs. Ag/AgCl in BRBS at pH 7. ► Detection limit of 0.08 μM was achieved without electrode surface modification. ► Benefits of method: rapidity, low cost, low elaborateness and high repeatability. ► Possibility for drug quality control and drug analysis of biological samples. - Abstract: An unmodified boron-doped diamond film electrode was used for the first time as a sensitive and selective electrochemical sensor for the determination of codeine by the use of differential pulse voltammetry. Codeine provided a single well-defined oxidation peak at +1.0 V vs. Ag/AgCl in Britton-Robinson buffer solution at pH 7.0. Using the optimal differential pulse voltammetric conditions (modulation amplitude of 50 mV, modulation time of 40 ms and scan rate of 50 mV s −1 ), the detection limit of 0.08 μM, the linear response of peak current on codeine concentration in the range from 0.1 to 60 μM (R 2 = 0.998, n = 6) and relative standard deviation of 0.9% at 10 μM concentration level (n = 10) were achieved without any electrode surface modification. The influence of potential interfering agents on the current response was also studied and the results indicated that the proposed method was sufficiently selective. The method was successfully applied in the determination of codeine in real samples including pharmaceutical tablets and human urine with results similar to those declared by manufacturer and obtained by reference high-performance liquid chromatography method, respectively. The typical benefits of the method may be summarized as: rapidity (20 determinations per hour), sensitivity and selectivity, low cost and elaborateness, simplicity, wide linear concentration range, low detection limit and excellent repeatability. It might also represent the competitive alternative to the existing analytical methods in monitoring of

  7. Simultaneous determination of morphine, codeine and 6-acetyl morphine in human urine and blood samples using direct aqueous derivatisation: validation and application to real cases.

    Science.gov (United States)

    Chericoni, S; Stefanelli, F; Iannella, V; Giusiani, M

    2014-02-15

    Opiates play a relevant role in forensic toxicology and their assay in urine or blood is usually performed for example in workplace drug-testing or toxicological investigation of drug impaired driving. The present work describes two new methods for detecting morphine, codeine and 6-monoacethyl morphine in human urine or blood using a single step derivatisation in aqueous phase. Propyl chloroformate is used as the dramatizing agent followed by liquid-liquid extraction and gas-chromatography-mass spectroscopy to detect the derivatives. The methods have been validated both for hydrolysed and unhydrolysed urine. For hydrolysed urine, the LOD and LOQ were 2.5ng/ml and 8.5ng/ml for codeine, and 5.2ng/ml and 15.1ng/ml for morphine, respectively. For unhydrolysed urine, the LOD and LOQ were 3.0ng/ml and 10.1ng/ml for codeine, 2.7ng/ml and 8.1ng/ml for morphine, 0.8ng/ml and 1.5ng/ml for 6-monoacetyl morphine, respectively. In blood, the LOD and LOQ were 0.44ng/ml and 1.46ng/ml for codeine, 0.29ng/ml and 0.98ng/ml for morphine, 0.15ng/ml and 0.51ng/ml for 6-monoacetyl morphine, respectively. The validated methods have been applied to 50 urine samples and 40 blood samples (both positive and negative) and they can be used in routine analyses. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

    Science.gov (United States)

    Qiu, Ying-Wei; Lv, Xiao-Fei; Jiang, Gui-Hua; Su, Huan-Huan; Ma, Xiao-Fen; Tian, Jun-Zhang; Zhuo, Fu-Zhen

    2017-03-01

    To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

  9. A new electrochemical sensor for the simultaneous determination of acetaminophen and codeine based on porous silicon/palladium nanostructure.

    Science.gov (United States)

    Ensafi, Ali A; Ahmadi, Najmeh; Rezaei, Behzad; Abarghoui, Mehdi Mokhtari

    2015-03-01

    A porous silicon/palladium nanostructure was prepared and used as a new electrode material for the simultaneous determination of acetaminophen (ACT) and codeine (COD). Palladium nanoparticles were assembled on porous silicon (PSi) microparticles by a simple redox reaction between the Pd precursor and PSi in an aqueous solution of hydrofluoric acid. This novel nanostructure was characterized by different spectroscopic and electrochemical techniques including scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, fourier transform infrared spectroscopy and cyclic voltammetry. The high electrochemical activity, fast electron transfer rate, high surface area and good antifouling properties of this nanostructure enhanced the oxidation peak currents and reduced the peak potentials of ACT and COD at the surface of the proposed sensor. Simultaneous determination of ACT and COD was explored using differential pulse voltammetry. A linear range of 1.0-700.0 µmol L(-1) was achieved for ACT and COD with detection limits of 0.4 and 0.3 µmol L(-1), respectively. Finally, the proposed method was used for the determination of ACT and COD in blood serum, urine and pharmaceutical compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Efficacy of Preoperative Administration of Paracetamol-Codeine on Pain following Impacted Mandibular Third Molar Surgery: A Randomized, Split-Mouth, Placebo-Controlled, Double-Blind Clinical Trial

    Directory of Open Access Journals (Sweden)

    Maria Paola Cristalli

    2017-01-01

    Full Text Available Objectives. The aim of this study was to determine the effectiveness of preoperative administration of single-dose of paracetamol-codeine, in the relieving of acute postoperative pain after the surgical removal of an impacted mandibular third molar. Materials and Methods. The study cohort consisted of 32 Caucasian outpatients, giving a total of 64 bilateral symmetrical impacted mandibles. Patients were randomized in two experimental groups to receive a preoperative oral dose of paracetamol-codeine (analgesic group or a placebo (placebo group at the first and second surgeries. Study participants were asked to record pain intensity scores during the operation and the next 2 days, the time of the first request for rescue analgesic, and the total number of postoperative-supplement paracetamol-codeine tablets. Results. The pain intensity score on the first day was significantly lower in the analgesic group than in the placebo group (p<0.001. The time to using rescue therapy was significantly longer in the analgesic group than in the placebo group (p=0.004. The number of paracetamol-codeine tablets used postoperatively did not differ between the analgesic and placebo groups (p=0.104. Conclusions. Preoperative paracetamol-codeine is effective in providing immediate postoperative pain control after third molar surgery and in delaying the initial onset of pain. This trial is registered with ClinicalTrials.gov Identifier (Registration Number: NCT03049878.

  11. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.

    Science.gov (United States)

    Maurer, Hans H; Sauer, Christoph; Theobald, Denis S

    2006-06-01

    This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed.

  12. Salt Solubility Products of Diprenorphine Hydrochloride, Codeine and Lidocaine Hydrochlorides and Phosphates – Novel Method of Data Analysis Not Dependent on Explicit Solubility Equations

    Directory of Open Access Journals (Sweden)

    Gergely Völgyi

    2013-12-01

    Full Text Available A novel general approach was described to address many of the challenges of salt solubility determination of drug substances, with data processing and refinement of equilibrium constants encoded in the computer program pDISOL-XTM. The new approach was illustrated by the determinations of the solubility products of diprenorphine hydrochloride, codeine hydrochloride and phosphate, lidocaine hydrochloride and phosphate at 25 oC, using a recently-optimized saturation shake-flask protocol.  The effects of different buffers (Britton-Robinson universal and Sörensen phosphate were compared. Lidocaine precipitates were characterized by X-ray powder diffraction (XRPD and polarization light microscopy. The ionic strength in the studied systems ranged from 0.25 to 4.3 M. Codeine (and possibly diprenorphine chloride were less soluble than the phosphates for pH > 2. The reverse trend was evident with lidocaine.  Diprenorphine saturated solutions showed departure from the predictions of the Henderson-Hasselbalch equation in alkaline (pH > 9 solutions, consistent with the formation of a mixed-charge anionic dimer.

  13. Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

    Science.gov (United States)

    Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

    2011-12-15

    A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Voltammetric Determination of Acetaminophen in the Presence of Codeine and Ascorbic Acid at Layer-by-Layer MWCNT/Hydroquinone Sulfonic Acid-Overoxidized Polypyrrole Modified Glassy Carbon Electrode

    OpenAIRE

    Shahrokhian, Saeed; Saberi, Reyhaneh-Sadat

    2011-01-01

    A very sensitive electrochemical sensor constructed of a glassy carbon electrode modified with a layer-by-layer MWCNT/doped-overoxidized polypyrrole (oppy/MWCNT /GCE) was used for the determination of acetaminophen (AC) in the presence of codeine and ascorbic acid (AA). In comparison to the bare glassy carbon electrode, a considerable shift in the peak potential together with an increase in the peak current was observed for AC on the surface of oppy/MWCNT/GCE, which can be related to the enla...

  15. Alterations in brain metabolism and function following administration of low-dose codeine phosphate: 1H-magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging studies

    OpenAIRE

    Cao, Zhen; Lin, Pei-Yin; Shen, Zhi-Wei; Wu, Ren-Hua; Xiao, Ye-Yu

    2016-01-01

    The aim of the present study was to identify alterations in brain function following administration of a single, low-dose of codeine phosphate in healthy volunteers using resting-state functional magnetic resonance imaging (fMRI). In addition, the metabolic changes in the two sides of the frontal lobe were identified using 1H-magnetic resonance spectroscopy (1H-MRS). A total of 20 right-handed healthy participants (10 males, 10 females) were evaluated, and a Signa HDx 1.5T MRI scanner was use...

  16. Efficacy of Codeine When Added to Paracetamol (Acetaminophen) and Ibuprofen for Relief of Postoperative Pain After Surgical Removal of Impacted Third Molars: A Double-Blinded Randomized Control Trial.

    Science.gov (United States)

    Best, Adrian D; De Silva, R K; Thomson, W M; Tong, Darryl C; Cameron, Claire M; De Silva, Harsha L

    2017-10-01

    The use of opioids in combination with nonopioids is common practice for acute pain management after third molar surgery. One such combination is paracetamol, ibuprofen, and codeine. The authors assessed the efficacy of codeine when added to a regimen of paracetamol and ibuprofen for pain relief after third molar surgery. This study was a randomized, double-blinded, placebo-controlled trial conducted in patients undergoing the surgical removal of at least 1 impacted mandibular third molar requiring bone removal. Participants were randomly allocated to a control group (paracetamol 1,000 mg and ibuprofen 400 mg) or an intervention group (paracetamol 1,000 mg, ibuprofen 400 mg, and codeine 60 mg). All participants were treated under intravenous sedation and using identical surgical conditions and technique. Postoperative pain was assessed using the visual analog scale (VAS) every 3 hours (while awake) for the first 48 hours after surgery. Pain was globally assessed using a questionnaire on day 3 after surgery. There were 131 participants (36% men; control group, n = 67; intervention group, n = 64). Baseline characteristics were similar for the 2 groups. Data were analyzed using a modified intention-to-treat analysis and, for this, a linear mixed model was used. The model showed that the baseline VAS score was associated with subsequent VAS scores and that, with each 3-hour period, the VAS score increased by an average of 0.08. The treatment effect was not statistically meaningful, indicating there was no difference in recorded pain levels between the 2 groups during the first 48 hours after mandibular third molar surgery. Similarly, the 2 groups did not differ in their global ratings of postoperative pain. Codeine 60 mg added to a regimen of paracetamol 1,000 mg and ibuprofen 400 mg does not improve analgesia after third molar surgery. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights

  17. Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

    Science.gov (United States)

    Cigerim, Levent; Eroglu, Cennet Neslihan

    2018-03-01

    The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Voltammetric Determination of Acetaminophen in the Presence of Codeine and Ascorbic Acid at Layer-by-Layer MWCNT/Hydroquinone Sulfonic Acid-Overoxidized Polypyrrole Modified Glassy Carbon Electrode

    Directory of Open Access Journals (Sweden)

    Saeed Shahrokhian

    2011-01-01

    Full Text Available A very sensitive electrochemical sensor constructed of a glassy carbon electrode modified with a layer-by-layer MWCNT/doped-overoxidized polypyrrole (oppy/MWCNT /GCE was used for the determination of acetaminophen (AC in the presence of codeine and ascorbic acid (AA. In comparison to the bare glassy carbon electrode, a considerable shift in the peak potential together with an increase in the peak current was observed for AC on the surface of oppy/MWCNT/GCE, which can be related to the enlarged microscopic surface area of the electrode. The effect of the experimental conditions on the electrode response, such as types of counter ion, pyrrole and counter ion concentration, potential and number of cycles in the polymerization procedure, amount of MWCNT, and the pH, were investigated. Under the optimized conditions, the calibration curve was obtained over two concentration ranges of 2 × 10−7–6 × 10−6 M and 4 × 10−5–1 × 10−4 M of AC with a linear correlation coefficient (R2 of 0.9959 and 0.9947, respectively. The estimated detection limit (3σ for AC was obtained as 5 × 10−8 M. The developed method was successfully applied to analyze the pharmaceutical preparations of AC, and a recovery of 95% with a relative standard deviation of 0.98% was obtained for AC.

  19. Cough and Cold Medicine (DXM and Codeine Syrup)

    Science.gov (United States)

    ... causing a range of effects from lack of motivation to serious health problems. Repeatedly seeking to experience ... misuse cough and cold medicines. Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  20. Disposable pipette extraction for gas chromatographic determination of codeine, morphine, and 6-monoacetylmorphine in vitreous humor.

    Science.gov (United States)

    Kovatsi, Leda; Rentifis, Konstantinos; Giannakis, Dimitrios; Njau, Samuel; Samanidou, Victoria

    2011-07-01

    The availability of a sensitive and rapid analytical method for the determination of opiates, and other substances of forensic interest, in a variety of biological specimens is of utmost importance to forensic laboratories. Solid-phase extraction is very popular in the pre-treatment of forensic samples. Nevertheless, a new approach, disposable pipette extraction (DPX), is gaining increasing interest in sample preparation. DPX has already been applied to the analysis of drugs of abuse in common biological matrices, such as urine and blood, but has not yet been evaluated on alternative biological samples, such as vitreous humor. The objective of this study was to evaluate the applicability of DPX on the analysis of opiates in vitreous humor. The currently developed method is fast, reliable, and easy to perform. The sensitivity, precision, and accuracy are satisfactory. Recoveries obtained are within the range of 72-91%, whereas the sample volume of vitreous humor required is only 100 μL. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I.

    Science.gov (United States)

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

    Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column. Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver. These enzymes produce an active analgesic metabolite and a potentially toxic metabolite. In vivo drug-drug interaction studies with morphine are few, but they do suggest that inhibition or induction of UGT enzymes could alter morphine and its metabolite levels. These interactions could change analgesic efficacy. Hydromorphone and oxymorphone, close synthetic derivatives of morphine, are also metabolized primarily by UGT enzymes. Hydromorphone may have a toxic metabolite similar to morphine. In vivo drug-drug interaction studies with hydromorphone and oxymorphone have not been done, so it is difficult to make conclusions with these drugs.

  2. 77 FR 55500 - Controlled Substances: Final Adjusted Aggregate Production Quotas for 2012

    Science.gov (United States)

    2012-09-10

    ... (for conversion), amphetamine (for sale), codeine (for conversion), codeine (for sale), desomorphine...), desomorphine, diethyltryptamine, dihydromorphine, gamma hydroxybutyric acid, hydrocodone (for sale... g Codeine-N-oxide 602 g Desomorphine 10 g Diethyltryptamine 18 g Difenoxin 50 g Dihydromorphine 3...

  3. Determination of opium and strychnos alkaloids by radiometric titrations with potassium thallium(I) iodide reagent

    International Nuclear Information System (INIS)

    Rama Rao, V.V.; Singh, N.J.; Tandon, S.N.

    1980-01-01

    The titrations were carried out by the batch method in test tubes, using 204 Tl-labelled potassium thallium(I) iodide as precipitant for alkaloids such as codeine, morphine, narcotine, papaverine, thebaine, strychnine and brucine. Direct and reverse titrations were investigated including sensitivity and accuracy. Codeine and narcotine were determined in some pharmaceutical preparations such as codeine sulfate tablets, codopyrin tablets and coscopin syrup

  4. Synthesis and binding studies of 2-arylapomorphines

    DEFF Research Database (Denmark)

    Søndergaard, Kåre; Kristensen, Jesper Langgaard; Palner, Mikael

    2005-01-01

    From codeine, four different 2-aryl substituted apomorphines were synthesised in 6 steps each. Oxidation of codeine with IBX followed by acid catalysed rearrangement gave morphothebaine, which was selectively triflylated at the 2-position and subsequently O-acetylated at the 11-position. The resu......From codeine, four different 2-aryl substituted apomorphines were synthesised in 6 steps each. Oxidation of codeine with IBX followed by acid catalysed rearrangement gave morphothebaine, which was selectively triflylated at the 2-position and subsequently O-acetylated at the 11-position...

  5. The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

    Science.gov (United States)

    Zur, Moran; Hanson, Allison S; Dahan, Arik

    2014-09-30

    While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. The Risk of Using Poppy Seed Tea Made from Several Varieties Available on the Romanian Market

    OpenAIRE

    Croitoru Mircea Dumitru; Fülöp Ibolya; Irimia-Constantin Maria-Raluca; Varga Erzsébet; Kelemen Hajnal; Fogarasi Erzsébet; Faliboga Luana-Maria

    2017-01-01

    Objective: the number of alkaloids like morphine and codeine found in poppy seeds used in food industry are monitored by a directive given by European Food Safety Authority. Based on this regulation the aim of the study was to determine the quantity of morphine and codeine from several brands of poppy seeds. Methods: an HPLC-UV method (205 nm) was developed to measure the quantity of morphine and codeine. Sample preparation was made using recipes posted on Drugs Forum by some users. Limits of...

  7. 77 FR 34069 - Importer of Controlled Substances; Notice of Application; Research Triangle Institute

    Science.gov (United States)

    2012-06-08

    ... Carfentanil (9743) II Coca Leaves (9040) II Cocaine (9041) II Codeine (9050) II Dextropropoxyphene, bulk (non... substances listed in schedule I or II, which fall under the authority of section 1002(a)(2)(B) of the Act (21...

  8. Single nucleotide polymorphism in genome-wide association of ...

    African Journals Online (AJOL)

    Mohd Fareed

    2012-09-25

    Sep 25, 2012 ... Codeine, Tramadol, Acetaminophen. CYP2C9. Celecoxib .... Pharmacogenet- ics of acute azathioprine toxicity: relationship to thiopurine ... Martinez C, Cueto R,. Garcia-Martin E. Pharmacogenomics in drug induced liver.

  9. Oxazepam

    Science.gov (United States)

    ... you are taking or plan to take certain opiate medications for cough such as codeine (in Triacin- ... Ritary, in Sinemet, in Stalevo); medication for depression, seizures, Parkinson's disease, asthma, colds, or allergies; muscle relaxants; ...

  10. Diet and substance abuse recovery

    Science.gov (United States)

    ... of different drugs on nutrition is described below. OPIATES Opiates (including codeine, oxycodone, heroin, and morphine) affect the ... High blood pressure Permanent liver damage (or cirrhosis ) Seizures Severe malnutrition Shortened life expectancy Laboratory tests for ...

  11. Ten Tips to Prevent an Accidental Overdose

    Science.gov (United States)

    ... always good practice to first, check the outside packaging for such things as cuts, slices, or tears. ... Ingested OTC Liquid Drug Products (PDF - 595KB) Drug Interactions: What You Should Know Related Consumer Updates Codeine ...

  12. Download

    African Journals Online (AJOL)

    ABSTRACT. A conventional-type PVC membrane electrode which responds ... such as aluminium hydroxide and magnesium trisilicate tablets, as well as in codein ... containing stoichiometric proportion (1:4) of zinc acetate and ammonium.

  13. Transformation and sorption of illicit drug biomarkers in sewer biofilms

    DEFF Research Database (Denmark)

    Ramin, Pedram; Brock, Andreas Libonati; Causanilles Llanes, Ana

    2017-01-01

    , 16 drug biomarkers were selected, including the major human metabolites of mephedrone, methadone, cocaine, heroin, codeine and tetrahydrocannabinol (THC). Transformation and sorption of these substances were assessed in targeted batch experiments using laboratory-scale biofilm reactors operated under...

  14. Transformation and sorption of illicit drug biomarkers in sewer systems: understanding the role of suspended solids in raw wastewater

    DEFF Research Database (Denmark)

    Ramin, Pedram; Brock, Andreas Libonati; Polesel, Fabio

    2016-01-01

    substrates (primary metabolic processes) and transformation of illicit drug biomarkers (secondary metabolic processes) by suspended biomass. Sixteen drug biomarkers were targeted, including mephedrone, methadone, cocaine, heroin, codeine and tetrahydrocannabinol (THC) and their major human metabolites. Batch...

  15. Fulltext PDF

    Indian Academy of Sciences (India)

    Admin

    Biochemical Laboratory, Harvard Medical School ... This is the frist step in the isolation of phosphocreatine (C. H. Fiske and Y. Subbarow, J. Biol. Chem. ... intense greenish blue color on applying the Denigès codeine test after oxidation with.

  16. Dispositional study of opioids in mice pretreated with sympathomimetic agents.

    Science.gov (United States)

    Dambisya, Y M; Chan, K; Wong, C L

    1992-08-01

    Brain and plasma levels of morphine and codeine were determined by an assay method involving solid-phase extraction and ion-pair reversed phase HPLC. Detection was by a variable wavelength UV-detector (for codeine) and an amperometric electro-chemical detector (for morphine) coupled in series. Ephedrine or phenylpropanolamine pretreatment did not interfere with the plasma disposition of morphine, evidenced by overlapping plasma concentration-time profiles. Brain opioid levels were equally unaffected by sympathomimetic pretreatment. The relative ratios of brain to plasma concentrations at the time corresponding to the respective peak anti-nociceptive activity for morphine and codeine revealed no significant differences. It is concluded that single doses of ephedrine and phenylpropanolamine do not affect the disposition of morphine and codeine in mice.

  17. Draft genome sequence of Agrobacterium sp. strain R89-1, a morphine alkaloid-biotransforming bacterium

    Czech Academy of Sciences Publication Activity Database

    Zahradník, Jiří; Kyslíková, Eva; Kyslík, Pavel

    2016-01-01

    Roč. 4, č. 2 (2016), e00196-16 ISSN 2169-8287 Institutional support: RVO:61388971 Keywords : Agrobacterium sp. strain R89-1 * codeine/morphine * phylogenetic lineage Subject RIV: EE - Microbiology, Virology

  18. Brompheniramine

    Science.gov (United States)

    Poly-Tussin® AC (as a combination product containing Brompheniramine, Codeine, Phenylephrine) ... and tranylcypromine (Parnate); muscle relaxants; narcotic medications for pain; sedatives; sleeping pills; and tranquilizers.tell your doctor ...

  19. Pharmacogenomics Fact Sheet

    Science.gov (United States)

    ... all prescription drugs. For example, it converts the painkiller codeine into its active form, morphine. There are ... patients by providing guidance on dose, possible side effects, or differences in effectiveness for people with certain ...

  20. Somatic Embryogenesis, Rhizogenesis, and Morphinan Alkaloids Production in Two Species of Opium Poppy

    Directory of Open Access Journals (Sweden)

    My Abdelmajid Kassem

    2001-01-01

    Morphine was only detected in aerial parts of Papaver somniferum album. Codeine and thebaine were detected in the rhizogenous but no embryonic callus. These results suggest that root organogenesis is causally related to alkaloid biosynthesis.

  1. Muscle pain

    African Journals Online (AJOL)

    damage or inflammation, like fibromyalgia, tension headaches .... This group includes the following examples: codeine, morphine, oxycodone ... insufficient evidence to support a preference of one opioid ..... [Homepage on internet]. Available ...

  2. Cavities

    Science.gov (United States)

    ... in protein, vitamins, and minerals, such as meats, poultry, grains, and fresh fruits and vegetables, tend to ... treat dry socket? Antibiotics taken by mouth A dressing soaked with an anesthetic Codeine Ear drops to ...

  3. Antitussives and substance abuse

    Directory of Open Access Journals (Sweden)

    Burns JM

    2013-11-01

    Full Text Available Jarrett M Burns, Edward W Boyer Division of Medical Toxicology, Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, USA Abstract: Abuse of antitussive preparations is a continuing problem in the United States and throughout the world. Illicit, exploratory, or recreational use of dextromethorphan and codeine/promethazine cough syrups is widely described. This review describes the pharmacology, clinical effects, and management of toxicity from commonly abused antitussive formulations. Keywords: dextromethorphan, purple drank, sizzurp, codeine/promethazine

  4. A new analgesia regimen after (adeno) tonsillectomy in children: a pilot study.

    Science.gov (United States)

    Syed, M I; Magos, T A; Singh, J; Montague, M L

    2016-12-01

    The objective was to ascertain the efficacy of a new analgesic regimen introduced in children undergoing (adeno)tonsillectomy in view of the ban on codeine use in children codeine, albeit one should bear in mind that parental concerns and adverse effects of the drug were seen in a minority of patients (n = 11) and anaesthetists were reluctant to prescribe the drug in cases of severe OSA or associated central apnoeas (n = 7). © 2015 John Wiley & Sons Ltd.

  5. The Use of Ibuprofen in Posttonsillectomy Analgesia and Its Effect on Posttonsillectomy Hemorrhage Rate.

    Science.gov (United States)

    Pfaff, Julia A; Hsu, Kevin; Chennupati, Sri Kiran

    2016-09-01

    To determine the effect of ibuprofen on posttonsillectomy bleeding when compared with codeine in posttonsillectomy analgesia. Case series with chart review. Tertiary care children's hospital, Philadelphia, Pennsylvania. On July 1, 2012, our institution transitioned from acetaminophen with codeine to ibuprofen for posttonsillectomy analgesia. Pediatric patients (0-18 years old) who underwent surgery from July 1, 2010, to June 30, 2012, were placed in the codeine cohort, and those who underwent surgery from July 1, 2012, to June 30, 2014, were placed in the ibuprofen cohort. A total of 6014 patients underwent tonsillectomy between July 1, 2010, and June 30, 2014, and 211 patients presented for posttonsillectomy hemorrhage during the same period. The incidence of readmission for posttonsillectomy hemorrhage was 3.4% and 3.6% (P = .63; odds ratio [OR] = 1.07; 95% confidence interval [95% CI]: 0.811-1.410) for the codeine and ibuprofen groups, respectively, and the incidence of second operation for control of posttonsillectomy bleeding for the codeine and ibuprofen groups was 1.9% and 2.2% (P = .54; OR = 1.117; 95% CI: 0.781-1.600), respectively. Patients aged 11 to 18 years demonstrated a higher incidence of posttonsillectomy bleeding events overall. When age is controlled, multivariate logistic regression demonstrated no statistically significant increase in posttonsillectomy bleeding events among pediatric patients treated with ibuprofen versus patients treated with codeine (readmission: P = .617; OR = 0.932; 95% CI: 0.707-1.228; reoperation: P = .513; OR = 0.887; 95% CI: 0.618-1.272). Age is an independent risk factor for posttonsillectomy bleeding. When age is controlled, there is no statistically significant increase in the incidence of posttonsillectomy bleeding events among patients treated with ibuprofen when compared to patients treated with codeine. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  6. The Risk of Using Poppy Seed Tea Made from Several Varieties Available on the Romanian Market

    Directory of Open Access Journals (Sweden)

    Croitoru Mircea Dumitru

    2017-06-01

    Full Text Available Objective: the number of alkaloids like morphine and codeine found in poppy seeds used in food industry are monitored by a directive given by European Food Safety Authority. Based on this regulation the aim of the study was to determine the quantity of morphine and codeine from several brands of poppy seeds. Methods: an HPLC-UV method (205 nm was developed to measure the quantity of morphine and codeine. Sample preparation was made using recipes posted on Drugs Forum by some users. Limits of detection were not determined because the lowest concentration from the reference (0.1 μg/ml detected morphine concentrations that are far lower than a limit of toxicological concern. Results: The concentrations, which were found, ranged between Below the Level of Toxicological Concern (BLTC - 243.26 mg/kg for morphine and BLTC - 88.58 mg/kg for codeine using several methods of preparation. Conclusions: one can observe that there are some brands of poppy seeds which do not respect the regulation about the amount of morphine and codeine. The high amount of morphine in some samples suggests that there are different varieties of poppy seeds, which can be used for an illicit purpose and can lead to addiction or even overdose in some cases.

  7. Adverse events associated with opioid-containing cough and cold medications in children.

    Science.gov (United States)

    Paul, Ian M; Reynolds, Kate M; Green, Jody L

    2018-04-10

    Until recently most of the scrutiny of opioid-containing cough and cold medications (CCMs) by the US Food and Drug Administration (FDA) was focused on codeine, only recently shifting equal focus to those containing hydrocodone. We characterized adverse events (AEs) in children Dictionary for Regulatory Activities with preferred terms reported. One hundred and fourteen of the 7035 (2%) cases reviewed involved an opioid-containing product. Ninety-eight cases involved an AE at least potentially related to the opioid ingredient (38 (39%) codeine; 60 (61%) hydrocodone). All three fatality cases involved hydrocodone with an antihistamine. Among non-fatalities, somnolence, lethargy, and/or respiratory depression were more commonly reported among hydrocodone cases than codeine cases (86% vs. 61%; p = .005). These safety surveillance data support the FDA's expanded label changes limiting opioid CCMs for children.

  8. Tramadol for noncancer pain and the risk of hyponatremia.

    Science.gov (United States)

    Fournier, Jean-Pascal; Yin, Hui; Nessim, Sharon J; Montastruc, Jean-Louis; Azoulay, Laurent

    2015-04-01

    Case reports have signaled a possible association between tramadol, a weak opioid analgesic, and hyponatremia. The objective of this study was to determine whether the use of tramadol is associated with an increased risk of hyponatremia, when compared with codeine. Using the UK Clinical Practice Research Datalink and Hospital Episodes Statistics database, a population-based cohort of 332,880 patients initiating tramadol or codeine was assembled from 1998 through 2012. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of hospitalization for hyponatremia associated with the use of tramadol, compared with codeine, in the first 30 days after initiation. A similar analysis was conducted within a highly restricted sub-cohort, which additionally excluded patients with any serum sodium level abnormality in the year before cohort entry. All models were adjusted for propensity score quintiles. The incidence rates of hospitalization for hyponatremia were 4.6 (95% CI, 2.4-8.0) and 1.9 (95% CI, 1.4-2.5) per 10,000 person-months for tramadol and codeine users, respectively. In the adjusted model, the use of tramadol was associated with a 2-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 2.05; 95% CI, 1.08-3.86). In the highly restricted sub-cohort, the use of tramadol was associated with an over 3-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 3.54; 95% CI, 1.32-9.54). In this first population-based study, the use of tramadol was associated with an increased risk of hyponatremia requiring hospitalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Opiates in poppy seed: effect on urinalysis results after consumption of poppy seed cake-filling.

    Science.gov (United States)

    Pettitt, B C; Dyszel, S M; Hood, L V

    1987-07-01

    We report the analysis of poppy seed filling for morphine and codeine content. Concentrations in the range 17.4 to 18.6 micrograms/g (morphine) and 2.3 to 2.5 micrograms/g (codeine) were found in different lots of the filling, which is widely used in baking. The effect of consumption of poppy seed filling on opiate urinalysis results is discussed. Morphine concentrations as high as 4.5 mg/L are reported, with persistence of concentrations greater than 0.3 mg/L as long as 35 h after consumption.

  10. The usage and efficacy of a combination analgesic preparation ...

    African Journals Online (AJOL)

    Combination analgesics are frequently prescribed for the treatment of a multitude of conditions. Many of these preparations contain agents with no proven analgesic efficacy. We examined 3059 patients using a new combination agent containing only paracetamol, codeine, and ibuprofen. It appears that despite a wide ...

  11. 76 FR 39123 - Importer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-07-05

    ... Carfentanil (9743) II Coca Leaves (9040) II Cocaine (9041) II Codeine (9050) II Dextropropoxyphene, bulk (non... registration or re-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves... such basic classes of controlled substances listed in schedule I or II, which fall under the authority...

  12. Identifying the composition of street drug Nyaope using two different ...

    African Journals Online (AJOL)

    The constituents consistently detected in all samples were caffeine, drugs of abuse such as opiates, codeine, morphine, methyl-dioxy amphetamine (MDA) and heroin. Some samples contained antibiotics (citroflex) and antiretroviral drugs (zidovudine). Central nervous system (CNS) depressants such as phenobarbitone ...

  13. Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs

    NARCIS (Netherlands)

    TSAI, A. C.; THIE, G. M.; Lin, C. R.

    1977-01-01

    The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was

  14. The effect of distant reiki on pain in women after elective Caesarean section: A double-blinded randomised controlled trial

    NARCIS (Netherlands)

    S. van der Vaart (Sondra); H. Berger (Howard); C. Tam (Carolyn); Y.I. Goh (Ingrid); V.M.G.J. Gijsen (Violette); S.N. de Wildt (Saskia); A. Taddio (Anna); G. Koren (Gideon)

    2011-01-01

    textabstractIntroduction: Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine,

  15. Comparison study of two different procedures for the determination of drugs of abuse in postmortem brain samples

    DEFF Research Database (Denmark)

    Holm, Karen Marie Dollerup; Reiter, Birgit; Skov, Louise

    2014-01-01

    from blood to brain and thereby see if we could avoid a time comsuming optimization of the Copenhagen method to accommodate the more complex brain matrix. Comparative analyses and quantification of eight drugs of abuse (methadone, morphine, amphetamine, benzoylecgonine, cocaine, morphine, codeine...

  16. Straightforward analytical method to determine opium alkaloids in poppy seeds and bakery products

    NARCIS (Netherlands)

    Lopez Sanchez, Patricia; Pereboom-de Fauw, Diana P.K.H.; Mulder, Patrick P.J.; Spanjer, Martien; Stoppelaar, de Joyce; Mol, Hans G.J.; Nijs, de Monique

    2018-01-01

    A straightforward method to determine the content of six opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine and narceine) in poppy seeds and bakery products was developed and validated down to a limit of quantification (LOQ) of 0.1 mg/kg. The method was based on extraction with

  17. Abeeb olufemi Salaam Community Reintegration Oyo, Oyo State ...

    African Journals Online (AJOL)

    High rates of cannabis, tobacco (nicotine), rophynol, codeine ... their children in Islamic education, called alm- ajiri (Abdulmalik ... cause there are few resources at the teachers' disposal .... graphic profiles, different types of drug and ..... (1996). Drug use among street in southern. Brazil. Drug and Alcohol Dependence, 43.

  18. Perspectives of addiction treatment providers

    African Journals Online (AJOL)

    Background. General practitioners are referring patients with codeine-related problems to specialist treatment facilities, but little is known about the addiction treatment providers, the kinds of treatment they provide, and whether training or other interventions are needed to strengthen this sector. Objectives. To investigate the ...

  19. Antitussive pharmaceutical drugs administration in complex therapy of acute respiratory infections in children

    OpenAIRE

    Lokshina, E.; Zajtseva, O.

    2009-01-01

    There is considered the problem of treatment of cough in children with acute respiratory infections in article. In particular, the data on an effective administration of the domestic combined medication framed on basis of medicinal grasses with codeine in complex therapy of acute respiratory infections is presented.

  20. Human Rights and Drug Control : Access to Controlled Essential Medicines in Resource-Constrained Countries

    NARCIS (Netherlands)

    Gispen, M.E.C.

    2017-01-01

    Millions of people worldwide suffer a range of health and socio-economic related problems because of inadequate availability and use of controlled essential medicines like morphine and codeine for pain treatment. As a result, millions of people, often living in lesser-advanced conditions, suffer in

  1. Techniques for assesment of opiates in body fluid and plant products

    International Nuclear Information System (INIS)

    Kongtip, Pornpimol

    1982-01-01

    This thesis described the determination of morphine like substances in human milk, poppy seed and rice by radioimmunoassay (RIA) and gas chromatography (GC). The first technique was implemented for human milk using chloroform extracts. Among the various drugs tested only codeine was found to have cross reaction with the antibody used and the method gave a sensitivity of 60 pg/tube or 300 pg/cm 3 . The coefficient of variation for both within and between assays were less than 8% whereas the percentage recovery of 10-25 ng/cm 3 of standard morphine hydrochloride added into human milk was higher than 95%. Study in 4 hill tribe opium addicted women showed that the concentration of morphine like substances in their milk ranged from 0-250 ng/cm 3 . Poppy seed and rice were investigated by both GC and RIA. Poppy seed from four different sources were investigated for morphine and codeine. Over 1,200 ng of the compounds were detected in one gram of all the specimen studied and codeine was present in higher concentration. Determination with RIA gave a range of 2,000-6,200 ng in one gram of the seeds. No detectable amount of morphine or codeine was found with GC in either 4 samples of rice obtained from hill tribe villages or in one sample of low land rice whereas 0.4-2.5 ng/g were detected with RIA

  2. Author Details

    African Journals Online (AJOL)

    Rich, E. Vol 107, No 5 (2017) - Articles Codeine misuse and dependence in South Africa: Perspectives of addiction treatment providers. Abstract PDF. ISSN: 0256-95749. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms ...

  3. Oral fixed drug combination analgesic tramadol/paracetamol: Benefits for patients and budgets

    NARCIS (Netherlands)

    M.J.C. Nuijten (Mark); B.P. Nautrup (Barbara Poulsen); H. Liedgens (Hiltrud)

    2006-01-01

    textabstractAlthough pain can present in many different ways, acute, subacute and chronic pain are frequently used and helpful categories that cover a wide range of pain phenomena. This paper reviews five cost-minimization studies of tramadol/paracetamol compared with codeine/paracetamol,

  4. Proctitis and rectal stenosis induced by nonsteroidal antiinflammatory suppositories

    NARCIS (Netherlands)

    D'Haens, G.; Breysem, Y.; Rutgeerts, P.; van Besien, B.; Geboes, K.; Ponette, E.; Vantrappen, G.

    1993-01-01

    Anorectal ulceration eventually leading to rectal stenosis was observed in 10 patients who abused analgetic suppositories containing acetylsalicylic acid, acetaminophen, and codeine. Most patients were middle-aged women with a neurotic or psychiatric background. Perianal skin lesions were present in

  5. quality evaluation of paracetamol in the bulk, dosage forms

    African Journals Online (AJOL)

    Prince Acheampong

    assay of paracetamol-codeine combination drug as well as estimation of the amount of ... post-market is very essential in the policy and technical guidelines of drug regulatory authorities such as the Food and Drugs Board. ... Pharmaceutical industries may also have simple analytical procedures for both in-process and.

  6. Prevalence and sunlight photolysis of controlled and chemotherapeutic drugs in aqueous environments

    International Nuclear Information System (INIS)

    Lin, Angela Yu-Chen; Lin, Yen-Ching; Lee, Wan-Ning

    2014-01-01

    This study addresses the occurrences and natural fates of chemotherapeutics and controlled drugs when found together in hospital effluents and surface waters. The results revealed the presence of 11 out of 16 drugs in hospital effluents, and the maximum detected concentrations were at the μg L −1 level in the hospital effluents and the ng L −1 level in surface waters. The highest concentrations corresponded to meperidine, morphine, 5-fluorouracil and cyclophosphamide. The sunlight photolysis of the target compounds was investigated, and the results indicated that morphine and codeine can be significantly attenuated, with half-lives of 0.27 and 2.5 h, respectively, in natural waters. Photolysis can lower the detected environmental concentrations, also lowering the estimated environmental risks of the target drugs to human health. Nevertheless, 5-fluorouracil and codeine were found to have a high risk quotient (RQ), demonstrating the high risks of directly releasing hospital wastewater into the environment. - Highlights: • High occurrence of chemotherapeutics and controlled substances in aqueous systems. • Photolysis lowers the detected concentrations of morphine and codeine. • 5-fluorouracil and codeine in hospital effluents have high risk quotients. - Chemotherapeutics and controlled drugs occur at significant levels in hospital effluents and surface waters. Natural sunlight photolysis reduces their environmental occurrence

  7. Managing acute pain in patients who report lactose intolerance: the safety of an old excipient re-examined.

    Science.gov (United States)

    Mill, Deanna; Dawson, Jessica; Johnson, Jacinta Lee

    2018-05-01

    Lactose intolerance is exceedingly common, reportedly affecting up to 70% of the world's population, leading to both abdominal and systemic symptoms. Current treatment focuses predominantly on restricting dietary consumption of lactose. Given lactose is one of the most commonly used excipients in the pharmaceutical industry, consideration must be given to the lactose content and therefore safety of pharmaceutical preparations prescribed for patients with lactose intolerance. This article summarizes the current literature examining the likelihood of inducing adverse effects through the administration of lactose-containing pharmaceutical preparations in patients reporting lactose intolerance, describes how to assess this risk on an individual patient basis and reviews suitable analgesic options for this population. A case study is presented detailing a patient reporting lactose intolerance who insists on treatment with the lactose-free product codeine/ibuprofen (Nurofen Plus) rather than other codeine-free analgesics. It is important to assess the likelihood of lactose as an excipient inducing symptoms in this scenario, as reluctance to cease codeine could suggest codeine dependence, an issue that is becoming increasingly common in countries such as Australia and Canada. Given codeine dependence is associated with serious sequelae including hospitalization and death, the patient must either be reassured the lactose component in their prescribed analgesics will not induce symptoms or an alternative treatment strategy must be confirmed. General recommendations applying theory from the literature to the management of acute pain in lactose-intolerant patients are discussed and specific treatment options are outlined. Although large inter-individual variability is reported, most lactose-intolerant patients can tolerate the small quantities of lactose found in pharmaceutical preparations. Cumulative lactose exposure can be assessed in patients taking multiple medications

  8. Dextromethorphan differentially affects opioid antinociception in rats

    Science.gov (United States)

    Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh

    2005-01-01

    Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510

  9. Pain management of musculoskeletal injuries in children: current state and future directions.

    Science.gov (United States)

    Ali, Samina; Drendel, Amy L; Kircher, Janeva; Beno, Suzanne

    2010-07-01

    Pain is the most common reason for seeking health care in the Western world and is a contributing factor in up to 80% of all emergency department (ED) visits. In the pediatric emergency setting, musculoskeletal injuries are one of the most common painful presentations. Inadequate pain management during medical care, especially among very young children, can have numerous detrimental effects. No standard of care exists for the management of acute musculoskeletal injury-related pain in children. Within the ED setting, pain from such injuries has been repeatedly shown to be undertreated. Upon completion of this CME article, the reader should be better able to (1) distinguish multiple nonpharmacological techniques for minimizing and treating pain and anxiety in children with musculoskeletal injuries, (2) apply recent medical literature in deciding pharmacological strategies for the treatment of children with musculoskeletal injuries, and (3) interpret the basic principles of pharmacogenomics and how they relate to analgesic efficacy. Pediatric musculoskeletal injuries are both common and painful. There is growing evidence that, in addition to pharmacological therapy, nonpharmacological methods can be introduced to improve analgesia in the ED and after discharge. Traditionally, acetaminophen with codeine has been used to treat moderate orthopedic injury-related pain in children. Other oral opioids (hydrocodone, oxycodone) are gaining popularity, as well. Current data suggest that ibuprofen is at least as effective as acetaminophen-codeine and codeine alone. Medication compliance might be improved if adverse effects were minimized, and ibuprofen has been shown to have a similar or better adverse effect profile than the oral opioids to which it has been compared. Pharmacogenomic data show that nearly 50% of individuals have at least 1 reduced functioning allele resulting in suboptimal conversion of codeine to active analgesic, so it is not surprising that codeine

  10. Towards safer use of opioids.

    LENUS (Irish Health Repository)

    Carson, R W R

    2009-09-01

    The main aim of our work was to improve the safety of opioid use in our institution, an acute generalhospital with 620 beds. Initially, all reported opioid errors from 2001 - 2006 were audited. The findings directed a range of multidisciplinary staff educational inputs to improve opioid prescribing and administration practice, and encourage drug error reporting. 448 drug errors were reported, of which 54 (12%) involved opioids; of these, 43 (79%) involved codeine, morphine or oxycodone. 31 of the errors (57%) were associated with administration, followed by 12 (22%) with dispensing and 11 (20%) with prescribing. There were 2 reports of definite patient harm. A subsequent audit examined a 17-month period following the introduction of the above teaching: 17 errors were noted, of which 14 (83%) involved codeine, morphine or oxycodone. Again, drug administration was most error-prone, comprising 11 (65%) of reports. However, just 2 (12%) of the reported errors now involved prescribing, which was a reduction.

  11. Fate of psychoactive compounds in wastewater treatment plant and the possibility of their degradation using aquatic plants.

    Science.gov (United States)

    Mackuľak, Tomáš; Mosný, Michal; Škubák, Jaroslav; Grabic, Roman; Birošová, Lucia

    2015-03-01

    In this study we analyzed and characterized 29 psychoactive remedies, illicit drugs and their metabolites in single stages of wastewater treatment plants in the capital city of Slovakia. Psychoactive compounds were present within all stages, and tramadol was detected at a very high concentration (706 ng/L). Significant decreases of codeine, THC-COOH, cocaine and buprenorphine concentration were observed in the biological stage. Consequently, we were interested in the possibility of alternative tertiary post-treatment of effluent water with the following aquatic plants: Cabomba caroliniana, Limnophila sessiliflora, Egeria najas and Iris pseudacorus. The most effective plant for tertiary cleansing was I. pseudacorus which demonstrated the best pharmaceutical removal capacity. After 48 h codeine and citalopram was removed with 87% efficiency. After 96 h were all analyzed compounds were eliminated with efficiencies above 58%. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Recovery of thebaine and cryptopine from Indian opium.

    Science.gov (United States)

    Ramanathan, V S; Chandra, P

    1980-01-01

    The thebaine content of the opium collected in the Madhya Pradesh region of India has been estimated and reported to range from 1.5 to 2.0 per cent. A technological process for the recovery of thebaine from the mother liquor remaining after the separation of natural codeine in the Government Opium and Alkaloid Works, Neemuch, has been developed in the laboratory and stepped up to an industrial scale. A method for the recovery to thebaine from the waste slaked-lime residues obtained from crude alkaloid cake mother liquor in the Government Opium and Alkaloid Works at Ghazipur has been worked out and the technical details of the process described. The recovery of thebaine would help to increase the production of codeine, and thebaine can also be used as a raw material for the manufacture of other drugs. Cryptopine has also been recovered from the mother liquor after the separation of thebaine.

  13. Analgetikaforbrug, -overdosering og -dødsfald i Danmark 1979-1986

    DEFF Research Database (Denmark)

    Ott, P; Hansen, P B; Dalhoff, K P

    1990-01-01

    During 1978-1987 the annual sale of analgetics increased by 28% to 164 millions defined daily doses (mDDD) per year. Paracetamol changed status to over-the-counter drug by 1.1.1984 as did combinations of acetylicsalicylic acid and codein 14.5.1984. The consumption of paracetamol increased rapidly...... to 47 mDDD/-year, the mortality steadily decreasing to 0.07 deaths/mDDD in 1986. The consumption of salicylics decreased from 113 to 94 mDDD, of which the salicylic/codein combination constituted an increasing fraction. The mortality of salicylics increased from 0.05 death/mDDD in 1983 to 0.27/m...

  14. Biosynthetic conversion of thebaine to codeinone. Mechanism of ketone formation from enol ether in vivo

    International Nuclear Information System (INIS)

    Horn, J.S.; Paul, A.G.; Rapoport, H.

    1978-01-01

    Biosynthesis of the morphinan alkaloids proceeds by conversion of the enol ether or thebaine to the keto group of neopinone and thence to codeinone. To determine the mechanism of this transformation, [G- 14 C,6- 18 O]thebaine was fed to Papaver somniferum and the codeine and morphine were isolated. Comparison of the 18 O/ 14 C ratios in the codeine and morphine isolated with that of the thebaine fed showed that approximately 34% of the 18 O had been retained. Parallel feedings with [G- 14 C,6- 18 O]-codeinone demonstrated that the loss was due to nonenzymic exchange. Thus, the mechanism of enol ether cleavage in thebaine is established as cleavage of the 6-O-methyl group with retention of the 6-oxygen in the codeinone

  15. Early Discontinuation of Metformin in Individuals Treated with Inhibitors of Transporters of Metformin

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Lee, Moa P; Hallas, Jesper

    2016-01-01

    The aim of this study was to examine the risk of early discontinuation of metformin as a proxy for intolerance, associated with use of drugs known to inhibit transporters involved in metformin distribution. We analysed all incident users of metformin in Denmark between 2000 and 2012 (n = 132......,221) and in a cohort of US patients (n = 296,903). Risk of early discontinuation of metformin was assessed using adjusted logistic regression for 28 drugs putatively inhibiting metformin transporters and four negative controls. Increased odds ratio of early discontinuation of metformin was only associated with codeine...... drugs were associated with a decreased risk. These findings indicate that codeine use may be associated with risk of early discontinuation of metformin and could be used as a basis for further investigation....

  16. Perceived efficacy of analgesic drug regimens used for koalas (Phascolarctos cinereus) in Australia.

    Science.gov (United States)

    de Kauwe, Tyron; Kimble, Benjamin; Govendir, Merran

    2014-06-01

    Recent publications report that some therapeutic drugs used in koalas (Phascolarctos cinereus) have poor oral absorption and are rapidly eliminated. Therefore, information on both the analgesic drug dosage regimens used to treat koalas in Australia and koala caretakers' perceptions of the efficacy of these drugs to control pain was collected for the purpose of identifying the most popular analgesics to prioritize future analgesic pharmacokinetic studies for this species. A one-page, double-sided questionnaire was distributed both electronically and by mail to Australian koala care facilities such as zoos and wildlife hospitals. Information was received from 13 respondents. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently used analgesics, followed by full micro- and partial opioid receptor agonists and acetaminophen with or without codeine. The full micro-opioid receptor agonists and acetaminophen with or without codeine were most consistently considered efficacious, with wider variation in perceived efficacy of the NSAIDs. Analgesic drug combinations were generally thought efficacious.

  17. Cocaine and opiates use in pregnancy: detection of drugs in neonatal meconium and urine.

    Science.gov (United States)

    López, P; Bermejo, A M; Tabernero, M J; Cabarcos, P; Alvarez, I; Fernández, P

    2009-09-01

    In this study, the case of a newborn with symptoms of hyperexcitability was analyzed. After it was confirmed in the hospital that the mother had consumed drugs during pregnancy using an enzyme multiplied immunoassay technique, samples of the newborn's urine and meconium were sent to our laboratory to observe the evolution in the distribution of cocaine and opiates during the days following birth. For urine analysis, screening was done with an immunoassay technique, and the confirmation was done by gas chromatography-mass spectrometry (GC-MS) according to a published method. A GC-MS method for simultaneous analysis of cocaine, benzoylecgonine, codeine, morphine, and 6-acetylmorphine in meconium is described. GC-MS confirmation of urine and meconium results showed consumption of cocaine and codeine during pregnancy and also showed the levels of drugs gradually declined, totally disappearing by the third day.

  18. Material Logistic Support of the Hospital Ships

    Science.gov (United States)

    1986-12-01

    Codeine Sulfate Tablets 6505-00-132-6904 Isoniazid Tablets 6505-00-165-6545 Cephalexin Capsules 6505-00-165-6575 Rifampin Capsules 6505-00-400-2054...35 4. CONSUMPTION RATE FOR MEDICAL CONSUMABLE ITEM FOR SPECIFIC CONDITION UNDER SCENARIO A 38 5. CONTRIBUTION FACTOR FOR BISACODYL TABLETS FOR SCENARIO...probability that patient condition 249 will require Bisacodyl. If the probability was twenty percent, then the amount of Bisacodyl needed would be two tablets

  19. Trace-Level Screening of Chemicals Related to Clandestine Desomorphine Production with Ambient Sampling, Portable Mass Spectrometry

    OpenAIRE

    Hall, Seth E.; O’Leary, Adam E.; Lawton, Zachary E.; Bruno, Alessandra M.; Mulligan, Christopher C.

    2017-01-01

    Desomorphine is a semisynthetic opioid that is responsible for the psychoactive effects of a dangerous homemade injectable mixture that goes by street name “Krokodil.” Desorption electrospray ionization (DESI) and paper spray ionization (PSI) are implemented on a portable mass spectrometer for the direct analysis of desomorphine and precursor reagent codeine from multiple substrates of potential relevance to clandestine drug laboratory synthesis and paraphernalia seizure. Minimal sample prepa...

  20. The synthesis of thebaine-1-3H

    International Nuclear Information System (INIS)

    Choudhry, S.C.; Serico, L.; Cupano, J.; Malarek, D.H.; Liebman, A.A.

    1989-01-01

    A synthesis of thebaine is described where the C-1 position is labelled with tritium to specific activity of 16 Ci/mmole. From codeine, 1-iodocodeine was prepared and converted to 1-iodothebaine in 3 steps. The subsequent key reaction was the selective hydrogenolysis of the carbon-iodine bond in 1-iodothebaine in the presence of the dienic-enol ether system. Using 10% Pd/C as catalyst, the desired reaction occurs in about 80% yield. (author)

  1. Isolation and characterization of latex-specific promoters from Papaver somniferum L.

    OpenAIRE

    Raymond, Michelle Jean

    2004-01-01

    The pharmacologically important alkaloids morphine and codeine are found in latex of opium poppy (Papaver somniferum). Latex is harbored in laticifers, a specialized vascular cell-type. Isolation and characterization of latex-specific genes may provide a useful tool to metabolically engineer increased alkaloid production. Previous research in the Nessler laboratory identified genes that exhibit latex-specific gene expression. Latex-specific genes were an 2-oxoglutarate-dioxygense (DIOX), ...

  2. Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

    OpenAIRE

    Zulak, Katherine G; Weljie, Aalim M; Vogel, Hans J; Facchini, Peter J

    2008-01-01

    Abstract Background Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the al...

  3. When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children

    Directory of Open Access Journals (Sweden)

    Frédérique Rodieux

    2018-03-01

    Full Text Available Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children’s inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults. However, codeine prescription has been restricted for the last 5 years in children because of the risk of fatal overdoses linked to the variable activity of cytochrome P450 (CYP 2D6 which bioactivates codeine. Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity. For this reason, the US Food and Drug Administration recently released a boxed warning regarding the use of tramadol in children. To provide safe and effective tramadol prescription in children, a personalized approach, with dose adaptation according to CYP2D6 activity, would certainly be the safest method. We therefore recommend this approach in children requiring chronic or recurrent nociceptive pain treatment with tramadol. In case of acute inpatients nociceptive pain management, prescribing tramadol at the minimal effective dose, in a child appropriate dosage form and after clear instructions are given to the parents, remains reasonable based on current data. In all other situations, morphine should be preferred for moderate to severe nociceptive pain conditions.

  4. The synthesis of thebaine-1- sup 3 H

    Energy Technology Data Exchange (ETDEWEB)

    Choudhry, S.C.; Serico, L.; Cupano, J.; Malarek, D.H.; Liebman, A.A. (Hoffmann-La Roche, Inc., Nutley, NJ (USA). Chemical Research Dept.)

    1989-12-01

    A synthesis of thebaine is described where the C-1 position is labelled with tritium to specific activity of 16 Ci/mmole. From codeine, 1-iodocodeine was prepared and converted to 1-iodothebaine in 3 steps. The subsequent key reaction was the selective hydrogenolysis of the carbon-iodine bond in 1-iodothebaine in the presence of the dienic-enol ether system. Using 10% Pd/C as catalyst, the desired reaction occurs in about 80% yield. (author).

  5. Hypokalaemia and Renal Tubular Acidosis due to Abuse of Nurofen Plus

    Directory of Open Access Journals (Sweden)

    M. J. Blackstock

    2012-01-01

    Full Text Available Nurofen Plus is a common analgesic containing ibuprofen and codeine. We present a case of a 38-year-old lady who developed renal tubular acidosis with severe hypokalaemia, after chronic abuse of Nurofen Plus tablets. She presented with confusion and profound biochemical abnormalities requiring critical care admission for electrolyte replacement. Ibuprofen causes renal tubular acidosis due to its effects on carbonic anhydrase activity.

  6. An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray

    OpenAIRE

    Ouyang, Handong; Liu, Shue; Zeng, Weian; Levitt, Roy C.; Candiotti, Keith A.; Hao, Shuanglin

    2012-01-01

    The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine) or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors) induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG) ap...

  7. Straightforward analytical method to determine opium alkaloids in poppy seeds and bakery products.

    Science.gov (United States)

    López, Patricia; Pereboom-de Fauw, Diana P K H; Mulder, Patrick P J; Spanjer, Martien; de Stoppelaar, Joyce; Mol, Hans G J; de Nijs, Monique

    2018-03-01

    A straightforward method to determine the content of six opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine and narceine) in poppy seeds and bakery products was developed and validated down to a limit of quantification (LOQ) of 0.1mg/kg. The method was based on extraction with acetonitrile/water/formic acid, ten-fold dilution and analysis by LC-MS/MS using a pH 10 carbonate buffer. The method was applied for the analysis of 41 samples collected in 2015 in the Netherlands and Germany. All samples contained morphine ranging from 0.2 to 240mg/kg. The levels of codeine and thebaine ranged from below LOQ to 348mg/kg and from below LOQ to 106mg/kg, respectively. Sixty percent of the samples exceeded the guidance reference value of 4mg/kg of morphine set by BfR in Germany, whereas 25% of the samples did not comply with the limits set for morphine, codeine, thebaine and noscapine by Hungarian legislation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Thebaine in hair as a marker for chronic use of illegal opium poppy substances.

    Science.gov (United States)

    Lee, Sooyeun; Park, Yonghoon; Han, Eunyoung; Choi, Hwakyung; Chung, Heesun; Oh, Seung Min; Chung, Kyu Hyuck

    2011-01-30

    Opium poppy products are often illegally used for both recreational and medicinal purposes. In order to demonstrate the ingestion of opium poppy substances, morphine, codeine and their metabolites have been identified. However, morphine and codeine also originate from the ingestion of therapeutic drugs. Therefore, thebaine, one of the main opium alkaloids, in hair was suggested as a marker for chronic use of illegal opium poppy substances in the present study. First, thebaine was included in the analyte list of our routine analytical method for the simultaneous quantification of codeine, morphine, norcodeine, normorphine and 6-acetylmorphine (6-AM) in hair, which was fully validated previously. Then, the incorporation of thebaine and other opiates into hair and the effect of hair pigmentation were examined using lean Zucker rats with both dark grey and white hair on the same body. Thebaine was also measured in hair samples from actual cases of opium poppy substance use. Consequently, thebaine in hair was demonstrated as a marker of chronic use of illegal opium poppy substances using an animal study and actual cases. Thebaine and other opiates were successfully measured in pigmented hair from rats that ingested raw opium suspension. Moreover, thebaine identified in hair excluded possibility of ingestion of pharmaceutical opiates in actual cases. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

    Directory of Open Access Journals (Sweden)

    Kazuhisa Sugimura

    2013-02-01

    Full Text Available An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competitive ELISA with M86 and morphine-C-Tg in the absence or presence of varying doses of free morphine and related compounds. IC50 values for opium, morphine, codeine, and heroin were 257 ng/mL, 36.4, 7.3, and 7.4 nM, respectively. Ketamine and cocaine exhibited no competitive binding activity to M86. Thus, we established a phage library-derived scFv, M86, which recognized not only free morphine and codeine as opium components but also heroin. This characteristic of M86 may be useful for developing therapeutic reagents for opiate addiction and as a free morphine-specific antibody probe.

  10. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain.

    Science.gov (United States)

    Fournier, Jean-Pascal; Azoulay, Laurent; Yin, Hui; Montastruc, Jean-Louis; Suissa, Samy

    2015-02-01

    Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia. To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia. A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results. Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score-adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis. The cohort included 334,034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11,019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09-2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56-8.34]) and case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring

  11. Pemberian Ekstrak Benalu Mangga terhadap Perubahan Histologis Hepar Tikus yang Diinduksi Kodein

    Directory of Open Access Journals (Sweden)

    Sekar Maya Wijaya M

    2014-09-01

    Full Text Available Benalu mangga mengandung senyawa kuersetin yang bertindak sebagai hepatoprotektor. Kodein merupakan jenis alkaloid dan banyak digunakan sebagai obat. Oversdosis kodein dapat menyebabkan kerusakan hepar. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian ekstrak benalu mangga terhadap perubahan histologis hepar tikus yang diinduksi kodein. Sebanyak 20 ekor tikus wistar jantan dibagi menjadi 5 kelompok (K0, K, KB1, KB2, dan KB3. Kelompok K0 hanya diberi minum dan pakan standar, kelompok K diberi kodein 12mg/ekor selama 7 hari, selanjutnya hanya diberi pakan dan minum standar. Kelompok KB1 diberi kodein 12mg/ekor selama 7 hari dilanjutkan ekstrak benalu mangga 22mg/ekor sampai hari ke 21, kelompok KB2 diberi kodein 12mg/ekor selama 7 hari dilanjutkan ekstrak benalu mangga 44mg/ekor sampai hari ke 21, dan kelompok KB3 diberi kodein 12mg/ekor selama 7 hari dilanjutkan ekstrak benalu mangga 88mg/ekor sampai hari ke 21.Hari ke-27 semua tikus dibedah, diambil heparnya dan dibuat preparat histologi dengan pengecatan HE.Hasil penelitian kelompok K0 menunjukkan perubahan histologis hepar bermakna (p<0,05 antara K,KB1, KB2, dan KB3, sedangkan kelompok K tetapi tidak menunjukan perubahan bermakna (p>0,05 antara K,KB1, KB2, dan KB3. Pada kelompok K kerusakan struktur hepar meliputi inflamasi perportal dan degenerasi sedangkan pada kelompok KB1, KB2, dan KB3 kerusakan meliputi inflamasi periportal,degenerasi, dan nekrosis.Mango’s mistletoes contain quercetin, a hepatoprotector. Codein is a type of alkaloids widely used as drug. Codein overdose can damage the liver. The objective of the study was know the effect of the administration of extract of mango’s mistletoes on the changes of liver histology of codein-induced rats. As many as 20 male wistar rats were divided into 5 groups (K0, K, KB1, KB2, and KB3. K0 group were given only standard diet and water daily. K group were given codeine at 12mg/rats for 7 days, and afterwards they were given only

  12. Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.

    Science.gov (United States)

    Pellegrini, Manuela; Casá, Adriana; Marchei, Emilia; Pacifici, Roberta; Mayné, Ruth; Barbero, Vanessa; Garcia-Algar, Oscar; Pichini, Simona

    2006-02-24

    A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of opiates (6-monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 degrees C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5-570.0 ng/g for 6-monoacetylmorphine, 8.7-154.8 ng/g for morphine and 7.9-127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

  13. Street-Like Synthesis of Krokodil Results in the Formation of an Enlarged Cluster of Known and New Morphinans.

    Science.gov (United States)

    Soares, José Xavier; Alves, Emanuele Amorim; Silva, André M N; de Figueiredo, Natália Guimarães; Neves, João F; Cravo, Sara Manuela; Rangel, Maria; Netto, Annibal Duarte Pereira; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge; Afonso, Carlos Manuel

    2017-08-21

    "Krokodil" is the street name for a homemade injectable drug that has been used as a cheap substitute for heroin. Codeine is the opioid starting material for krokodil synthesis, and desomorphine is claimed to be the main opioid of krokodil and the main component responsible for its addictive and psychoactive characteristics. However, due to its peculiar manufacture, using cheap raw materials, krokodil is composed of a large and complex mixture of different substances. In order to shed some light upon the chemical complexity of krokodil, its profiling was conducted by reverse phase high performance liquid chromatography coupled to a photodiode array detector (RP-HPLC-DAD) and by liquid chromatography coupled to high resolution tandem mass spectrometry (LC-ESI-IT-Orbitrap-MS). Besides desomorphine, codeine, and morphine, profiting from the high resolution mass spectrometry (HRMS) data, an endeavor to study the morphinans content in krokodil was set for the first time. Considering codeine as the only morphinan precursor and the possible chemical transformations that can occur during krokodil synthesis, the morphinan chemical space was designed, and 95 compounds were defined. By making use of the morphinan chemical space in krokodil, the exact masses featured by HRMS, and the morphinan mass fragmentations patterns, a targeted identification approach was designed and implemented.The proposed 95 morphinans were searched using the full scan chromatogram of krokodil, and findings were validated by mass fragmentation of the correspondent precursor ions (MS 2 spectra). Following this effort, a total of 54 morphinans were detected, highlighting the fact that these additional morphinans may contribute to the psychotropic effects of krokodil.

  14. An exploratory wastewater analysis study of drug use in Auckland, New Zealand.

    Science.gov (United States)

    Lai, Foon Yin; Wilkins, Chris; Thai, Phong; Mueller, Jochen F

    2017-09-01

    New Zealand is considered to have unusual drug use patterns by international standards. However, this understanding has largely been obtained from social surveys where respondents self-report use. The aim of this paper is to conduct the first wastewater study of drug use in Auckland. Wastewater sampling was completed from 2 May to 18 July 2014 at 2 Auckland wastewater treatment plants which service 1.3 million people. Samples were analysed for 17 drug residues by using liquid chromatography-tandem mass spectrometry. Consumption of methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cocaine, codeine and methadone (mg/day/1000 people) was estimated by using a back-calculation formula. Methamphetamine, codeine, morphine and methadone were detected with high frequency (80-100%), followed by amphetamine (~60%), MDMA (~7%, i.e. 8 occasions) and methylone (3 occasions). An overall mean of 360 mg of methamphetamine and 60 mg of MDMA was estimated to have been consumed per day per 1000 people. Methamphetamine consumption was found at similar levels in both catchments (377 and 351 mg/day/1000 people). Cocaine was only detected in 1 catchment and on only 8 occasions. JWH-018 was detected in 1 catchment and only on 1 occasion. Methamphetamine, codeine and other opioids were detected at a consistent level throughout the week. 3,4-Methylenedioxymethamphetamine and methylone were detected only during the weekends. Wastewater analysis confirms that methamphetamine was one of the most commonly detected illegal drugs in Auckland and was detected consistently throughout the week. In contrast, cocaine and MDMA were rarely detected, with detection limited to weekends. [Lai FY, Wilkins C, Thai P, Mueller JF. An exploratory wastewater analysis study of drug use in Auckland, New Zealand. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  15. Improving the prediction of in-sewer transformation of illicit drug biomarkers by identifying a new modelling framework

    DEFF Research Database (Denmark)

    Ramin, Pedram; Brock, Andreas Libonati; Polesel, Fabio

    -3-β-D-glucuronide; codeine and its metabolite norcodeine; methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP); mephedrone; and tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-Δ9-THC (THCOH), and 11-nor-9-carboxy-Δ9-THC (THCCOOH). All the transformation....... Furthermore, abiotic transformation was found to be the main transformation mechanism for THC (aerobic conditions); mephedrone, methadone, cocaine, ecgonine methyl ester, cocaethylene, THCOH and THCCOOH (anaerobic conditions). By use of the proposed model the uncertainty of predicting illicit drug...

  16. Drug eruptions presenting at sites of prior radiation damage (sunlight and electron beam)

    International Nuclear Information System (INIS)

    Shelley, W.B.; Shelley, E.D.; Campbell, A.C.; Weigensberg, I.J.

    1984-01-01

    Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption

  17. Desomorphine goes "crocodile".

    Science.gov (United States)

    Gahr, Maximilian; Freudenmann, Roland W; Hiemke, Christoph; Gunst, Ingo M; Connemann, Bernhard J; Schönfeldt-Lecuona, Carlos

    2012-01-01

    A systematic review was conducted to identify the available data for the term Krokodil, which is a jargon expression for an allegedly new drug. Krokodil seems to be a mixture of several substances and was first used in Russia in 2003, with a tremendous increase in the number of addicted individuals since then. The psychoactive core agent of Krokodil is desomorphine, an opioid-analogon that can be manufactured by boiling tablets containing codeine and other ingredients. The procedure results in a suspension that is used intravenously and regularly causes complications such as abscess, thrombophlebitis, and gangrene.

  18. DOD and VA Health Care: Actions Needed to Help Ensure Appropriate Medication Continuation and Prescribing Practices

    Science.gov (United States)

    2016-01-01

    Hydrocodone ibuprofen 0.1 Oxymorphone 0.1 Meperidinee 0.1 Methadone √ 0.1 Codeine √ 0.1 Tapentadol < 0.1 Oxaprozin < 0.1 Diclofenac misoprostopolf...formulation (e.g., extended or immediate release), salt form (e.g., hydrochloride or sulfate), or strength of the medication. bThis represents the most...form (e.g., liquid or tablet), modified release formulation (e.g., extended or immediate release), salt form (e.g., hydrochloride or sulfate

  19. Quantitative study of controlled substance bedside wasting, disposal and evaluation of potential ecologic effects.

    Science.gov (United States)

    Mankes, Russell F; Silver, Charles D

    2013-02-01

    Drugs in wastewater arise from many sources. For health care, these include excretion and direct disposal (bedside wasting). The present study reports on the dispensing and wasting of 15 controlled substances (CS) at two health care facilities in Albany, NY over a nearly two year period. The study considered measures of ecotoxicity, drug metabolism, excretion and disposal of these CS. Potential alternatives to flushing of CS into wastewaters from healthcare facilities are discussed. Drug medication and waste collection records (12,345) included: numbers of drugs dispensed, returned and wasted. Overall, 8528 g of 15 CS were wasted. Three (midazolam, acetaminophen-codeine and fentanyl) accounted for 87.5% of the total wasted. Wasting varied by hospital, 14 CS at the academic medical center hospital and 8 at the surgical care center were wasted. Liquids were more frequently wasted than tablets or pills. Some combination drugs (acetaminophen (APAP)-codeine) were frequently (50% of drug dispensed) wasted while others were less wasted (APAP-hydrocodone-6.3%; APAP-oxycodone-1.3%). The 8 CS judged more hazardous to aquatic life were: APAP-codeine, APAP-hydrocodone, APAP-oxycodone, alprazolam, diazepam, fentanyl, midazolam, and testosterone. Ketamine, morphine, oxycodone and zolpidem were of lesser acute toxicity based on available LC50 values. These CS might provide a therapeutically equivalent alternative to the more environmentally harmful drugs. In health care facilities, professionals dispose of CS by bedside wasting into water or other receptacles. This can be avoided by returning CS to the hospital's pharmacy department, thence to a licensed distributor. Study of this process of drug wasting can identify opportunities for process improvements. We found 3 CS (APAP-codeine, midazolam and testosterone) where ½ to 1/3 of the drug was wasted and 5 others with 30 to 13% wasted. Knowledge of the adverse impacts from the release of highly toxic drugs into the environment

  20. Synthesis of some 11C-labelled alkaloids

    International Nuclear Information System (INIS)

    Laangstroem, B.; Antoni, G.; Halldin, H.; Svaerd, H.; Bergson, G.

    1982-01-01

    Using ( 11 C)-methyl iodide in N-alkylation reactions in dimethylformamide (DMF), the alkaloids N-( 11 C-methyl)-morphine, N-( 11 C-methyl)-codeine, 6-N(methyl)-9, 10-dihydroergotamine, 6-N-( 11 C-methyl)-bromocriptine and N-( 11 C-methyl)-nicotine have been synthesized in radiochemical yields of 50-95%, within 5-10 min of introducing ( 11 C)-methyl iodide into the reaction vial. ( 11 C)-Methyl iodide was obtained within 4-7 min from ( 11 C)-carbon dioxide prepared by the 14 N(p,α) 11 C reaction. (Authors)

  1. Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

    OpenAIRE

    Matsukizono, Miho; Kamegawa, Mariko; Tanaka, Koichi; Kohra, Shinya; Arizono, Koji; Hamazoe, Yuta; Sugimura, Kazuhisa

    2013-01-01

    An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv) clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg) but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competi...

  2. Rose Hip Powder That Contains the Natural Amount of Shells and Seeds Alleviates Pain in Osteoarthritis of the Dominant Hand—A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial

    DEFF Research Database (Denmark)

    Winther, Kaj; Campbell-Tofte, Joan I A; Hansen, Peter

    2013-01-01

    ), after which they switched to the corresponding treatment for a further three months period (Phase 2). Before entering the study, after 3 weeks and following three months of each of the study phases, scores for pain, stiffness and general feeling of discomfort were evaluated using a 10 step categorical......), showed a reduction in pain, as compared to 36% in the group B initially given placebo (p ... subjects 3 weeks after the switch to placebo. The consumption of rescue medication such as paracetamol, codeine and tramadol also declined significantly in group A when compared to group B (p

  3. The effect of salmeterol and salbutamol on mediator release and skin responses in immediate and late phase allergic cutaneous reactions

    DEFF Research Database (Denmark)

    Petersen, Lars Jelstrup; Skov, P S

    1999-01-01

    on clinical and biochemical EAR and LPR in human skin. METHODS: Measurement of wheal and flare reactions to allergen, codeine, and histamine, and LPR (induration) to allergen. Assessment of histamine and prostaglandin D2 (PGD2) release by microdialysis technique in EAR, and measurement of mediators in LPR......, myeloperoxidase, or eosinophil cationic protein in LPR. CONCLUSIONS: Salmeterol and salbutamol inhibited allergen-induced skin responses, and reduced mediator release in EAR but not LPR. In general, the anti-inflammatory effects of salmeterol did not differ from those induced by salbutamol....

  4. A hybrid FIA/HPLC system incorporating monolithic column chromatography

    International Nuclear Information System (INIS)

    Adcock, Jacqui L.; Francis, Paul S.; Agg, Kent M.; Marshall, Graham D.; Barnett, Neil W.

    2007-01-01

    We have combined the generation of solvent gradients using milliGAT pumps, chromatographic separations with monolithic columns and chemiluminescence detection in an instrument manifold that approaches the automation and separation efficiency of HPLC, whilst maintaining the positive attributes of flow injection analysis (FIA), such as manifold versatility, speed of analysis and portability. As preliminary demonstrations of this hybrid FIA/HPLC system, we have determined six opiate alkaloids (morphine, pseudomorphine, codeine, oripavine, ethylmorphine and thebaine) and four biogenic amines (vanilmandelic acid, serotonin, 5-hydroxyindole-3-acetic acid and homovanillic acid) in human urine, using tris(2,2'-bipyridyl)ruthenium(III) and acidic potassium permanganate chemiluminescence detection

  5. [The antitussive effect of theophylline].

    Science.gov (United States)

    Nemceková, E; Nosál'ová, G; Rybár, A

    1994-08-01

    Theophylline belongs to a group of medicaments used in asthma therapy. It yields an antiinflammatory effect, reduces allergic reactions, and in respiratory airways it improves the mucociliary clearance and eminently dilates smooth muscles. Therefore, the main aim of our interest is its effect on the cough reflex. Cough was evoked by mechanical irritation of the airways in cats with chronic tracheal cannula. It has been discovered that theophylline, when dosed 10 mg per kg of body weight i.p. achieved a more intensive effect than dextromethorphane, namely in evaluation of cough parameters, but it had a lower suppressive effect than codeine. (Fig. 3, Ref. 13.)

  6. Clinging to the Past: The Air Force’s War on Dual-Career Families

    Science.gov (United States)

    2014-06-01

    failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE JUN 2014 2. REPORT...move…to a state where the laws are different…State law can be vastly different, especially with controlled substances…[such as] morphine, codeine...One telecommuter spouse (who is a telecommuter not by choice, but because of her Airman’s career) said she was told “you’ve made it as high as you’re

  7. De fleste anæstesimidler kan bruges uden skadelig påvirkning af barnet ved amning

    DEFF Research Database (Denmark)

    Sønderskov, Michèle Lefort; Albrechtsen, Charlotte Krebs; Bille, Anders Bastholm

    2011-01-01

    physicians. However, individual drugs such as diazepam, morphine, codeine and pethidine should be avoided when possible and otherwise only be administered as single doses with observation of the child. There is an urgent need for high-quality research before sufficient light can be shed on this topic.......Breastfeeding women who undergo general anaesthesia often receive conflicting recommendations regarding the need to discard their milk before resumption of breastfeeding. This narrative review describes the sparse evidence to support the current practice of discarding milk as advocated by many...

  8. Dextromethorphan in Cough Syrup: The Poor Man’s Psychosis

    OpenAIRE

    Martinak, Bridgette; Bolis, Ramy A.; Black, Jeffrey Ryne; Fargason, Rachel E.; Birur, Badari

    2017-01-01

    Dextromethorphan (3-methoxy-N-methylmorphinan), also known as “DXM” and “the poor man’s PCP,” is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psych...

  9. Mu receptor binding of some commonly used opioids and their metabolites

    International Nuclear Information System (INIS)

    Chen, Zhaorong; Irvine, R.J.; Somogyi, A.A.; Bochner, F.

    1991-01-01

    The binding affinity to the μ receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with 3 H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding. Decreasing the length of the alkyl group at position 3 decreased the K i values (morphine < codeine < ethylmorphine < pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, while their O-demethylated metabolites had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites

  10. Mu receptor binding of some commonly used opioids and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhaorong; Irvine, R.J. (Univ. of Adelaide (Australia)); Somogyi, A.A.; Bochner, F. (Univ. of Adelaide (Australia) Royal Adelaide Hospital (Australia))

    1991-01-01

    The binding affinity to the {mu} receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with {sup 3}H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding. Decreasing the length of the alkyl group at position 3 decreased the K{sub i} values (morphine < codeine < ethylmorphine < pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, while their O-demethylated metabolites had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

  11. Very long Detection Times after High and repeated intake of Heroin and Methadone, measured in Oral Fluid

    Directory of Open Access Journals (Sweden)

    Vindenes V.

    2014-12-01

    Full Text Available When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid might lead to negative sanctions, and the knowledge of detection times of these drugs are important to ensure correct interpretation. The aim of this study was to investigate the detection times of opioids in oral fluid. 25 patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid and urine were collected daily and, if the patient gave consent, a blood sample was drawn during the first five days after admission. Morphine, codeine and/or 6-monoacetyl morphine (6-MAM were found in oral fluid and/or urine from 20 patients. The maximum detection times in oral fluid for codeine, morphine and 6-MAM were 1, 3 and 8 days, respectively. Positive oral fluid samples were interspersed with negative samples, mainly for concentrations around cut off. Elimination curves for methadone in oral fluid were found for two subjects, and the detection times were 5 and 8 days. Oral fluid is likely to become a good method for detection of drug abuse in the future

  12. Emerging organic contaminants in coastal waters: anthropogenic impact, environmental release and ecological risk.

    Science.gov (United States)

    Jiang, Jheng-Jie; Lee, Chon-Lin; Fang, Meng-Der

    2014-08-30

    This study provides a first estimate of the sources, distribution, and risk presented by emerging organic contaminants (EOCs) in coastal waters off southwestern Taiwan. Ten illicit drugs, seven nonsteroidal anti-inflammatory drugs (NSAIDs), five antibiotics, two blood lipid regulators, two antiepileptic drugs, two UV filters, caffeine, atenolol, and omeprazole were analyzed by solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (SPE-LC-MS/MS). Thirteen EOCs were detected in coastal waters, including four NSAIDs (acetaminophen, ibuprofen, ketoprofen, and codeine), three antibiotics (ampicillin, erythromycin, and cefalexin), three illicit drugs (ketamine, pseudoephedrine, and MDMA), caffeine, carbamazepine, and gemfibrozil. The median concentrations for the 13 EOCs ranged from 1.47 ng/L to 156 ng/L. Spatial variation in concentration of the 13 EOCs suggests discharge into coastal waters via ocean outfall pipes and rivers. Codeine and ampicillin have significant pollution risk quotients (RQ>1), indicating potentially high risk to aquatic organisms in coastal waters. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Fully automated drug screening of dried blood spots using online LC-MS/MS analysis

    Directory of Open Access Journals (Sweden)

    Stefan Gaugler

    2018-01-01

    Full Text Available A new and fully automated workflow for the cost effective drug screening of large populations based on the dried blood spot (DBS technology was introduced in this study. DBS were prepared by spotting 15 μL of whole blood, previously spiked with alprazolam, amphetamine, cocaine, codeine, diazepam, fentanyl, lysergic acid diethylamide (LSD, 3,4-methylenedioxymethamphet-amine (MDMA, methadone, methamphetamine, morphine and oxycodone onto filter paper cards. The dried spots were scanned, spiked with deuterated standards and directly extracted. The extract was transferred online to an analytical LC column and then to the electrospray ionization tandem mass spectrometry system. All drugs were quantified at their cut-off level and good precision and correlation within the calibration range was obtained. The method was finally applied to DBS samples from two patients with back pain and codeine and oxycodone could be identified and quantified accurately below the level of misuse of 89.6 ng/mL and 39.6 ng/mL respectively.

  14. The economic burden of opioid prescription by dentists: A 12-month survey of consumer expenditure in Brazil.

    Science.gov (United States)

    Nogueira, Tulio Eduardo; Lino, Patrícia Azevedo; Martins, Maria Auxiliadora Parreiras; Silva, Maria Elisa Souza; Leles, Claudio Rodrigues; Abreu, Mauro Henrique Nogueira Guimarães

    2017-09-01

    To describe consumer expenditure on opioids prescribed by dentists in Brazil during a 12-month period. We surveyed individual dispensed prescriptions of opioids in private pharmacies from October 2012 to September 2013. A descriptive analysis of costs included a calculation of the overall and mean maximum price to consumers. Monetary costs were converted from local currency units (Brazilian Real - BRL) to international dollars using purchasing power parity (PPP) exchanging rates. 129,708 prescriptions were retrieved from the database. The overall expenditure on opioids was R$4,316,383.46 BRL or $2,721,315.82 (PPP). The mean cost of an individual prescription was R$33.27 BRL ($20.98 PPP), ranging from 14.19 to 3,255.60 BRL. Codeine was frequently prescribed (87.2 percent). The expenditure on opioids is a significant cost to Brazilian patients, especially given that the Brazilian Public Health System should dispense these drugs free of charge. Codeine was the most prescribed opioid. © 2017 American Association of Public Health Dentistry.

  15. Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial.

    Science.gov (United States)

    Santini, Manuela Favarin; Rosa, Ricardo Abreu da; Ferreira, Maria Beatriz Cardoso; Fischer, Maria Isabel; Souza, Erick Miranda; Só, Marcus Vinícius Reis

    2017-01-01

    Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse effects. In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P0.05), i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

  16. Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children

    Directory of Open Access Journals (Sweden)

    Ida Aka

    2017-11-01

    Full Text Available Cytochrome P450 (CYP enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug–CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC data and surveyed 10 years of electronic health records (EHR data for the number of children exposed to CYP-associated drugs. Subsequently, we performed a focused literature review for drugs commonly used in pediatrics, defined as more than 5000 pediatric patients exposed in the decade-long EHR cohort. There were 48 drug–CYP interactions with a high level of evidence in the CPIC database. Of those, only 10 drugs were commonly used in children (ondansetron, oxycodone, codeine, omeprazole, lansoprazole, sertraline, amitriptyline, citalopram, escitalopram, and risperidone. For these drugs, reports of the drug–CYP interaction in cohorts including children were sparse. There are adequate data for implementation of genotype-guided therapy for children for three of the 10 commonly used drugs (codeine, omeprazole and lansoprazole. For the majority of commonly used drugs with known CYP interactions, more data are required to support pharmacogenomic implementation in children.

  17. Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.

    Science.gov (United States)

    Tang, Magdalene H Y; Ching, C K; Tse, M L; Ng, Carol; Lee, Caroline; Chong, Y K; Wong, Watson; Mak, Tony W L

    2015-04-01

    To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

  18. Hair analysis as evidence in forensic cases.

    Science.gov (United States)

    Moeller, M R; Fey, P; Sachs, H

    1993-12-01

    Because hair analysis can be used for the determination of drug use months after drug consumption, hair analysis data can often act as important and even decisive evidence in the courtroom. More recently developed GC/MS methods offer excellent sensitivity and can make the distinction between chronic heroin and codeine use, which was not possible earlier with radioimmunoassay techniques. From more than a thousand hair analyses, the morphine/codeine ratios necessary to determine heroin use were set at 5:1 for low morphine concentrations (< 1 ng/mg hair) and 2:1 for concentrations above 1 ng/mg hair. The distinction can be further focused with the additional analysis of the metabolite monoacetylmorphine (MAM). As can be seen from several case examples, hair analysis cannot pinpoint an exact date of opiate use, but it can be used to validate or invalidate a subject's statement concerning his/her drug consumption. Interpretations should always be made cautiously. Ranges, means and medians are also listed for amphetamine, cocaine and cannabis and work is under way to draw similar safety guidelines for these drugs.

  19. Estimating population size in wastewater-based epidemiology. Valencia metropolitan area as a case study.

    Science.gov (United States)

    Rico, María; Andrés-Costa, María Jesús; Picó, Yolanda

    2017-02-05

    Wastewater can provide a wealth of epidemiologic data on common drugs consumed and on health and nutritional problems based on the biomarkers excreted into community sewage systems. One of the biggest uncertainties of these studies is the estimation of the number of inhabitants served by the treatment plants. Twelve human urine biomarkers -5-hydroxyindoleacetic acid (5-HIAA), acesulfame, atenolol, caffeine, carbamazepine, codeine, cotinine, creatinine, hydrochlorothiazide (HCTZ), naproxen, salicylic acid (SA) and hydroxycotinine (OHCOT)- were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to estimate population size. The results reveal that populations calculated from cotinine, 5-HIAA and caffeine are commonly in agreement with those calculated by the hydrochemical parameters. Creatinine is too unstable to be applicable. HCTZ, naproxen, codeine, OHCOT and carbamazepine, under or overestimate the population compared to the hydrochemical population estimates but showed constant results through the weekdays. The consumption of cannabis, cocaine, heroin and bufotenine in Valencia was estimated for a week using different population calculations. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The harmful chemistry behind "krokodil": Street-like synthesis and product analysis.

    Science.gov (United States)

    Alves, Emanuele Amorim; Soares, José Xavier; Afonso, Carlos Manuel; Grund, Jean-Paul C; Agonia, Ana Sofia; Cravo, Sara Manuela; Netto, Annibal Duarte Pereira; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2015-12-01

    "Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Recommendations for the proper use of nonprescription cough suppressants and expectorants in solid-organ transplant recipients.

    Science.gov (United States)

    Gabardi, Steven; Carter, Danielle; Martin, Spencer; Roberts, Keri

    2011-03-01

    To describe the pharmacology and safety of oral over-the-counter cough suppressants and expectorants and to present recommendations for the use of these agents in solid-organ transplant recipients based on the potential for adverse drug reactions or drug-disease interactions. Data from journal articles and other sources describing the pharmacology and safety of over-the-counter cough suppressants and expectorants, drug-drug interactions with immunosuppressive agents, and drug-disease state interactions are reviewed. Potential and documented drug-drug interactions between immunosuppressive agents and over-the-counter cough medications guaifenesin, dextromethorphan, diphenhydramine, and codeine were evaluated on the basis of pharmacokinetic and pharmacodynamic principles. Interactions between these cough medications and the physiological changes in the body following transplantation also were examined. Diphenhydramine requires additional monitoring when used to treat cough in transplant recipients owing to its anticholinergic properties and the potential for interactions with cyclosporine. Dextromethorphan can be used in most transplant recipients, although greater caution should be exercised if the patient has undergone liver transplant or has liver impairment. Guaifenesin can be used in transplant recipients but should be used with caution in patients receiving kidney or lung transplants and in patients with renal impairment. Codeine combined with guaifenesin is another option for cough and can be used in most transplant patients although those with reduced renal function should be monitored carefully for adverse events.

  2. Fatal anoxia due to rachacha consumption: Two cases reported.

    Science.gov (United States)

    Monteil-Ganiere, Catherine; Gaulier, Jean-Michel; Chopineaux, Daniel; Barrios, Lucia; Pineau, Alain; Dailly, Éric; Clément, Renaud

    2014-12-01

    Deaths due to ingesting rachacha, which is a homemade paste obtained by decocting poppy heads, are very rare. No fatalities have been recorded in scientific publications. This product is not considered to be very dangerous by its users. We are reporting the first deaths (a 30-year-old man and a 28-year-old woman), after ingesting rachacha balls and alcohol consumption during an evening with a friend. Signs compatible with acute anoxia were observed during autopsy. Toxicological analyses highlighted the presence of morphine and codeine in the blood, urine and bile, with an absence of 6-acetylmorphine. Concomitant consumption of alcohol certainly played a role in the occurrence of death. The black paste found at the scene was identified as rachacha. The mean of consumption (orally) was confirmed by the presence of morphine and codeine in the gastric contents of both victims. The analysis of hair samples was performed to reveal the substance consumption history. Therefore, a possibility of contamination by sweat and/or putrefactive liquids in the post-mortem period must be considered for the interpretation of the results. These two cases show that taking rachacha can be dangerous, especially when combined with the consumption of substances which could potentiate respiratory depression induced by morphine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Enhanced bioavailability of opiates after intratracheal administration

    International Nuclear Information System (INIS)

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-01-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities [codeine (84%), ethylmorphine (100%), and morphine (87%)] of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability

  4. Suppressive effect of pectic polysaccharides from Cucurbita pepo L. var. Styriaca on citric acid-induced cough reflex in guinea pigs.

    Science.gov (United States)

    Nosáľová, Gabriela; Prisenžňáková, Lubica; Košťálová, Zuzana; Ebringerová, Anna; Hromádková, Zdenka

    2011-04-01

    Several water-soluble pectic polysaccharides were isolated from the pumpkin fruit biomass and characterized by composition, structural features and molecular properties. The pectic polysaccharides were tested for antitussive activity by studying the effects of citric acid-induced cough reflex in guinea pigs and reactivity of the airway smooth muscle in vivo conditions in comparison to the narcotic drug codeine. Oral administration of all pectic polysaccharides from pumpkin inhibited the number of coughs induced by citric acid in guinea pigs, but to various extents. The results indicated that the antitussive activity of the pectic polysaccharides is affected by their molecular and structural properties, whereby a synergistic action between the polysaccharide and non-carbohydrate components on the biological response has been suggested as well. The cough depressive efficacy of most of the tested polysaccharides was comparable and even higher than that of codeine. Moreover, the application of these polysaccharides provoked any side effects what is their advantage towards the conventional opioid-derived antitussive agents. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Misleading Drugs with Street Name Temgesic and Norgesic in Hand of Iranian Drug Abusers; What Are Their True Natures?

    Directory of Open Access Journals (Sweden)

    Hassan Solhi

    2015-06-01

    Full Text Available Background: The illicit vials with street name Temgesic and Norgesic has been distributed in black market of Iran in recent years. With reference to their name, one may presume that they contain the opioid Buprenorphine; but there are some reports in opposition to this. True nature of these vials has been shown in the current study. Methods: All of drugs that had been apprehended by law enforcement police in Arak city in center of Iran during March 2010 to September 2010 were included in the study. Totally 31 samples were analyzed. The samples were examined using thin layer chromatography (TLC method. Gas chromatography with mass Spectrophotometry (GC-MS or high performance liquid chromatography (HPLC methods were used to confirm the results. Results: All of the samples contained opioids include Heroin, Morphine, Codeine, Mono acetyl morphine and Acetyl codeine with varying proportions. In addition, pheniramine, amitriptyline and caffeine were found in some samples. There was no Buprenorphine in the samples. Presence of the steroid Dexamethasone in the samples was shown too. Conclusion: When the physicians treat the patients with acute or long-term complications of Temgesic and Norgesic abuse, they should mull over true nature of the vials; not their disingenuous street name.

  6. Qualitative and quantitative determination of yohimbine in authentic yohimbe bark and in commercial aphrodisiacs by HPLC-UV-API/ MS methods.

    Science.gov (United States)

    Zanolari, Boris; Ndjoko, Karine; Ioset, Jean-Robert; Marston, Andrew; Hostettmann, Kurt

    2003-01-01

    The development and validation of a rapid qualitative and quantitative method based on an HPLC-UV-MS technique with atmospheric pressure chemical ionisation and electrospray ionisation for the analysis of yohimbine in a number of commercial aphrodisiac products is reported. HPLC with multiple-stage mass spectrometry experiments allowed the identification of the target compound and increased the selectivity of complex analyses such as those involved with multi-botanical preparations. The precision and the robustness of the method were improved by the use of two internal standards: codeine for UV detection and deuterium-labelled yohimbine for MS detection. Twenty commercial aphrodisiac preparations were analysed and the amount of yohimbine measured and expressed as the maximal dose per day suggested on product labels ranged from 1.32 to 23.16 mg.

  7. Radiation Induced Treatment of Organic Pollutants

    International Nuclear Information System (INIS)

    Ergun, E.; Öztürk, Ş.; Kantoğlu, Ö.

    2012-01-01

    In this period of the research, aerobic and anaerobic digestion, characterization of alkaloids present and radiolysis products formed after irradiation, under different conditions of ambient and additives, optimization of dose to achieve desired end characteristics for discharge of waste water were aimed. In this regard, unirradiated and irradiated wastewaters were subjected to aerobic and anaerobic digestions. Substrate removal efficiencies of unirradiated and irradiated wastewater with various initial COD values were determined with SBR aerobic digestion treatment method. On the other hand Fenton’s advanced oxidation treatment method was also applied for pre-treatment. BMP tests of anaerobic digestion were also completed. LC/MS studies were carried out on unirradiated and irradiated alkaloid standard solutions of morphine, codeine, thebaine, papaverine, and noscapine to determine the degradation mechanisms and byproducts. Dose optimization studies were completed and found to be a lower dose of 5 kGy rather than 40 kGy for ambient irradiation conditions. (author)

  8. Radiation Induced Treatment of Organic Pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Ergun, E.; Öztürk, Ş.; Kantoğlu, Ö. [Turkish Atomic Energy Authority, Sarayköy Nuclear research and Training Center, Ankara (Turkey)

    2012-07-01

    In this period of the research, aerobic and anaerobic digestion, characterization of alkaloids present and radiolysis products formed after irradiation, under different conditions of ambient and additives, optimization of dose to achieve desired end characteristics for discharge of waste water were aimed. In this regard, unirradiated and irradiated wastewaters were subjected to aerobic and anaerobic digestions. Substrate removal efficiencies of unirradiated and irradiated wastewater with various initial COD values were determined with SBR aerobic digestion treatment method. On the other hand Fenton’s advanced oxidation treatment method was also applied for pre-treatment. BMP tests of anaerobic digestion were also completed. LC/MS studies were carried out on unirradiated and irradiated alkaloid standard solutions of morphine, codeine, thebaine, papaverine, and noscapine to determine the degradation mechanisms and byproducts. Dose optimization studies were completed and found to be a lower dose of 5 kGy rather than 40 kGy for ambient irradiation conditions. (author)

  9. Stability of drugs of abuse in urine samples stored at -20 degrees C.

    Science.gov (United States)

    Dugan, S; Bogema, S; Schwartz, R W; Lappas, N T

    1994-01-01

    Isolated studies of the stability of individual drugs of abuse have been reported. However, few have evaluated stability in frozen urine samples stored for 12 months. We have determined the stability of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (9-COOH-THC), amphetamine, methamphetamine, morphine, codeine, cocaine, benzoylecgonine, and phencyclidine in 236 physiological urine samples. Following the initial quantitative analysis, the samples were stored at -20 degrees C for 12 months and then reanalyzed. All drug concentrations were determined by gas chromatographic-mass spectrometric methods with cutoff concentrations of 5 ng/mL for 9-COOH-THC and phencyclidine and 100 ng/mL for each of the other drugs. The average change in the concentrations of these drugs following this long-term storage was not extensive except for an average change of -37% in cocaine concentrations.

  10. The antitussive activity of polysaccharides from Althaea officinalis l., var. Robusta, Arctium lappa L., var. Herkules, and Prunus persica L., Batsch.

    Science.gov (United States)

    Sutovska, M; Nosalova, G; Franova, S; Kardosova, A

    2007-01-01

    The therapy of pathological type of cough presents serious medical problem. The aim of experiments was to investigate polysaccacharide influence on experimentally induced cough. The purified and/or modified polysaccharides from the flowers and plants, characterized by chemical composition and molecular properties were subjected to tests for antitussive activity on cough, induced mechanically in conscious cats of both sexes. The results revealed that the tested polysaccharides exhibited statistically significant cough-suppressing activity, which was noticeably higher than that of the non-narcotic drug used in clinical practice to treat coughing. The most expressive antitussive activity was observed with the polysaccharide from marsh mallow, containing the highest proportion of the uronic acid constituent. Negative influence of the tested compounds on expectoration was negligible when compared to that of codeine. Antitussive activity of various plant polysaccharides was confirmed. These results allow ranging them among prospective antitussive agents (Tab. 2, Fig. 6, Ref. 15) Full Text (Free, PDF) www.bmj.sk.

  11. A 29-Year-Old Man With Nonproductive Cough, Exertional Dyspnea, and Chest Discomfort.

    Science.gov (United States)

    Halpenny, Darragh; Suh, James; Garofano, Suzette; Alpert, Jeffrey

    2015-09-01

    A 29-year-old man presented with a 5-month history of worsening dry cough, exertional dyspnea, chest tightness, and palpitations. He had been treated by his primary care physician with trials of guaifenesin/codeine, azithromycin, albuterol, and omeprazole without improvement. He denied wheezing, fever, sweats, anorexia, joint pain, swelling, or rash. He had no past medical history. He denied a history of tobacco smoking or IV drug use. He kept no pets, worked as a manager in an office environment, and had no history of occupational inhalational exposure. He reported using aerosolized insect spray to eradicate bed bugs in his house shortly before the cough began but did not report any acute symptoms when using the spray.

  12. A systematic model identification method for chemical transformation pathways – the case of heroin biomarkers in wastewater

    DEFF Research Database (Denmark)

    Ramin, Pedram; Valverde Pérez, Borja; Polesel, Fabio

    2017-01-01

    This study presents a novel statistical approach for identifying sequenced chemical transformation pathways in combination with reaction kinetics models. The proposed method relies on sound uncertainty propagation by considering parameter ranges and associated probability distribution obtained...... at any given transformation pathway levels as priors for parameter estimation at any subsequent transformation levels. The method was applied to calibrate a model predicting the transformation in untreated wastewater of six biomarkers, excreted following human metabolism of heroin and codeine. The method....... Results obtained suggest that the method developed has the potential to outperform conventional approaches in terms of prediction accuracy, transformation pathway identification and parameter identifiability. This method can be used in conjunction with optimal experimental designs to effectively identify...

  13. Treatment of depression.

    Science.gov (United States)

    Payk, T R

    1994-10-01

    Depressions are the most common psychiatric diseases. For treatment, plant extracts have been used for thousands of years: examples are extracts from the (sleeping) poppy (opium), deadly nightshade (Atropa belladonna), Indian hemp (hashish), henbane (hyoscyamine), thorn apple (scopolamine), and St. John's wort (hypericum oil). In addition, psychotherapeutic measures, like playing music, dancing, playing theatre, and also the temple sleep, were used. In the 19th century, the introduction of brome (1826), codeine (1832), chloral hydrate (1869), and paraldehyde (1882), as well as the barbiturates (at the turn of the century) introduced significant improvements in pharmacotherapy. The modern thymoleptica therapy started in 1957 with the introduction of imipramine. Now about 40 active antidepressants are marketed. New drug developments should be characterized mainly by an improvement in tolerance.

  14. A "krokodil" emerges from the murky waters of addiction. Abuse trends of an old drug.

    Science.gov (United States)

    Katselou, Maria; Papoutsis, Ioannis; Nikolaou, Panagiota; Spiliopoulou, Chara; Athanaselis, Sotiris

    2014-05-02

    "Krokodil" is the street name for the semi-synthetic opioid derivative desomorphine. Although an old drug, it re-staged on "drug arena" during the last decade causing detrimental effects to its users. Despite the fact that Russia and other former Soviet Republics were the initial plagued countries, "krokodil" arrived in Europe and United States lately, as a substitute of the relative expensive, and in many cases unavailable, heroin. It can be easily manufactured in home-environment from codeine and causes significant health problems, even deaths worldwide. The aim of this review is to summarize the current knowledge about this drug, concerning its chemistry, synthesis, pharmacology and toxicology. Published or reported "krokodil" related cases, fatalities or intoxications, as well as self reports from drug users are reviewed. The existing analytical methodologies for the determination of desomorphine in biological samples as well as its legal status are also presented. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Opioid binding site in EL-4 thymoma cell line

    International Nuclear Information System (INIS)

    Fiorica, E.; Spector, S.

    1988-01-01

    Using EL-4 thymoma cell-line we found a binding site similar to the k opioid receptor of the nervous system. The Scatchard analysis of the binding of [ 3 H] bremazocine indicated a single site with a K/sub D/ = 60 +/- 17 nM and Bmax = 2.7 +/- 0.8 pmols/10 6 cells. To characterize this binding site, competition studies were performed using selective compounds for the various opioid receptors. The k agonist U-50,488H was the most potent displacer of [ 3 H] bremazocine with an IC 50 value = 0.57μM. The two steroisomers levorphanol and dextrorphan showed the same affinity for this site. While morphine, [D-Pen 2 , D-Pen 5 ] enkephalin and β-endorphin failed to displace, except at very high concentrations, codeine demonstrated a IC 50 = 60μM, that was similar to naloxone. 32 references, 3 figures, 2 tables

  16. Perception and knowledge about narcotics among nurses

    Directory of Open Access Journals (Sweden)

    Desai Geetha

    2003-01-01

    Full Text Available Aim: To determine the extent to which nurses are able to correctly identify drugs as narcotics and to ascertain their perception of the addiction potential of opiates when used for pain management. Methods: A questionnaire was administered to 86 nurses who attended palliative care workshops in India. Findings: Only morphine (95%, heroin (71% and codeine (75% were correctly identified as narcotics by the majority of participants. Imipramine (34%, diazepam (20% and phenobarbitone (39% were wrongly classified as narcotics by many nurses. Dextropropoxyphene (11%, pentazocine (21%, buprenorphine (15% were correctly classified as narcotics by fewer than half the participants. Only 14% knew that that the frequency of psychological dependence due to use of morphine for cancer pain was less than 1%.

  17. A Technology-Neutral Role-Based Collaboration Model for Software Ecosystems

    DEFF Research Database (Denmark)

    Stanciulescu, Stefan; Rabiser, Daniela; Seidl, Christoph

    2016-01-01

    by contributing a role-based collaboration model for software ecosystems to make such implicit similarities explicit and to raise awareness among developers during their ongoing efforts. We extract this model based on realization artifacts in a specific programming language located in a particular source code......In large-scale software ecosystems, many developers contribute extensions to a common software platform. Due to the independent development efforts and the lack of a central steering mechanism, similar functionality may be developed multiple times by different developers. We tackle this problem...... efforts and information of ongoing development efforts. Finally, using the collaborations defined in the formalism we model real artifacts from Marlin, a firmware for 3D printers, and we show that for the selected scenarios, the five collaborations were sufficient to raise awareness and make implicit...

  18. Prescription pain medications and chronic headache in Denmark

    DEFF Research Database (Denmark)

    Westergaard, Maria Lurenda; Hansen, Ebba Holme; Glümer, Charlotte

    2015-01-01

    , tramadol, ibuprofen and codeine. CH was associated with osteoarthritis, back pain, and rheumatoid arthritis. Among those with MOH, 32.4 % were dispensed an opioid at least once within 1 year. Only 5.1 % of people with CH were dispensed triptans. CONCLUSIONS: High prevalence of opioid use among people......PURPOSE: The aim of the present paper is to study which prescription pain medications are most commonly dispensed to people with chronic headache (CH), particularly those with medication-overuse headache (MOH). METHODS: This cross-sectional study analysed prescription pain medications dispensed...... within 1 year to 68,518 respondents of a national health survey. Participants with headache ≥15 days per month for 3 months were classified as having CH. Those with CH and over-the-counter analgesic use ≥15 days per month or purchase of ≥20 or ≥30 defined daily doses (DDDs) of prescription pain...

  19. Differentiation of illicit drugs with THz time-domain spectroscopy

    International Nuclear Information System (INIS)

    Liu Guifeng; Ma Shihua; Ji Te; Zhao Hongwei; Wang Wenfeng

    2010-01-01

    The tera hertz time-domain spectroscopy (THz-TDS) was used for sensing and identifying illicit drugs. The absorption spectra of seven illicit drug samples(morphine and its hydrochloride, cocaine hydrochloride, codeine phosphate, papaverine hydrochloride, pethidine hydrochloride, and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature. The geometric structure and vibration frequencies of morphine were calculated by density functional theory. The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes. Each illicit drug has a distinct signature in its THz spectra. The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints. (authors)

  20. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose

    2018-01-01

    analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology......Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug......-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...

  1. The frequency of drugs in randomly selected drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Hels, Tove

    is the Danish legal limit. The percentage of drivers positive for medicinal drugs above the Danish legal concentration limit was 0.4%; while, 0.3% of the drivers tested positive for one or more illicit drug at concentrations exceeding the Danish legal limit. Tetrahydrocannabinol, cocaine, and amphetamine were...... the most frequent illicit drugs detected above the limit of quantitation (LOQ); while, codeine, tramadol, zopiclone, and benzodiazepines were the most frequent legal drugs. Middle aged men (median age 47.5 years) dominated the drunk driving group, while the drivers positive for illegal drugs consisted......Introduction Driving under the influence of alcohol and drugs is a global problem. In Denmark as well as in other countries there is an increasing focus on impaired driving. Little is known about the occurrence of psychoactive drugs in the general traffic. Therefore the European commission...

  2. Simultaneous Screening and Quantification of 29 Drugs of Abuse in Oral Fluid by Solid-Phase Extraction and Ultraperformance LC-MS/MS

    DEFF Research Database (Denmark)

    Linnet, Kristian; Badawi, Nora; Simonsen, Kirsten W.

    2009-01-01

    performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for detection of 29 drugs and illicit compounds in OF. The drugs detected were opioids, amphetamines, cocaine, benzodiazepines, and {Delta}-9-tetrahydrocannabinol. Method: Solid-phase extraction was performed with a Gilson ASPEC XL......4 system equipped with Bond Elut Certify sample cartridges. OF samples (200 mg) diluted with 5 mL of ammonium acetate/methanol (vol/vol 90:10) buffer were applied to the columns and eluted with 3 mL of acetonitrile with aqueous ammonium hydroxide. Target drugs were quantified by use of a Waters...... of amphetamine, cocaine, codeine, {Delta}-9-tetrahydrocannabinol, tramadol, and zopiclone. Conclusions: The UPLC-MS/MS method makes it possible to detect all 29 analytes in 1 chromatographic run (15 min), including {Delta}-9-tetrahydrocannabinol and benzoylecgonine, which previously have been difficult...

  3. Crystallization and preliminary X-ray diffraction analysis of salutaridine reductase from the opium poppy Papaver somniferum

    International Nuclear Information System (INIS)

    Higashi, Yasuhiro; Smith, Thomas J.; Jez, Joseph M.; Kutchan, Toni M.

    2010-01-01

    Recombinant P. somniferum salutaridine reductase (SalR) was purified and crystallized with NADPH using the hanging-drop vapor-diffusion method. Crystals of the SalR–NADPH complex diffracted X-rays to a resolution of 1.9 Å. The opium poppy Papaver somniferum is the source of the narcotic analgesics morphine and codeine. Salutaridine reductase (SalR; EC 1.1.1.248) reduces the C-7 keto group of salutaridine to the C-7 (S)-hydroxyl group of salutaridinol in the biosynthetic pathway that leads to morphine in the opium poppy plant. P. somniferum SalR was overproduced in Escherichia coli and purified using cobalt-affinity and size-exclusion chromatography. Hexagonal crystals belonging to space group P6 4 22 or P6 2 22 were obtained using ammonium sulfate as precipitant and diffracted to a resolution of 1.9 Å

  4. Trace-Level Screening of Chemicals Related to Clandestine Desomorphine Production with Ambient Sampling, Portable Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Seth E. Hall

    2017-01-01

    Full Text Available Desomorphine is a semisynthetic opioid that is responsible for the psychoactive effects of a dangerous homemade injectable mixture that goes by street name “Krokodil.” Desorption electrospray ionization (DESI and paper spray ionization (PSI are implemented on a portable mass spectrometer for the direct analysis of desomorphine and precursor reagent codeine from multiple substrates of potential relevance to clandestine drug laboratory synthesis and paraphernalia seizure. Minimal sample preparation required for analysis and portability of the instrument suggest the potential for rapid, on-site analysis of evidence, a highly desired benefit for forensic science and law enforcement practitioners. Both DESI-MS and PSI-MS can generate spectra consistent with preceding data obtained using traditional ionization methods, while demonstrating detection limits in the low- to sub-ng levels.

  5. Analysis of drugs of forensic interest with capillary zone electrophoresis/time-of-flight mass spectrometry based on the use of non-volatile buffers.

    Science.gov (United States)

    Gottardo, Rossella; Mikšík, Ivan; Aturki, Zeineb; Sorio, Daniela; Seri, Catia; Fanali, Salvatore; Tagliaro, Franco

    2012-02-01

    The present work is aimed at investigating the influence of the background electrolyte composition and concentration on the separation efficiency and resolution and mass spectrometric detection of illicit drugs in a capillary zone electrophoresis-electrospray ionization-time of flight mass spectrometry (CZE-ESI-TOF MS) system. The effect of phosphate, borate and Tris buffers on the separation and mass spectrometry response of a mixture of 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, methadone, cocaine, morphine, codeine and 6-monoacetylmorphine was studied, in comparison with a reference ammonium formate separation buffer. Inorganic non-volatile borate and Tris buffers proved hardly suitable for capillary electrophoresis-mass spectrometry (CE-MS) analysis, but quite unexpectedly ammonium phosphate buffers showed good separation and ionization performances for all the analytes tested. Applications of this method to real samples of hair from drug addicts are also provided. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Stability of opiates in hair fibers after exposure to cosmetic treatment.

    Science.gov (United States)

    Pötsch, L; Skopp, G

    1996-08-15

    The stability of opiates in clipped natural human hair was investigated. Hair fibers were incubated with defined solutions of morphine, codeine and dihydrocodeine (pH 7.4) until saturated. Original opiate-positive hair samples collected from drug addicts also were examined. Commercially available bleaching as well as perming formulas (Poly Blonde Ultra, Poly Lock; Henkel, Düsseldorf, Germany) were applied in vitro to the hair strands of both groups under investigation. After these treatments, the drug concentration had decreased for both bleaching and permanent waving. In the spiked hair, only 2-18% of the starting solution could be found after bleaching. About 20-30% of the drug substances could still be detected after perming. In the authentic hair samples, the drug levels of the formerly opiate positive hair fibers had also been reduced but distinct tendencies could not be observed.

  7. Kitchen chemistry: A scoping review of the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions.

    Science.gov (United States)

    Van Hout, Marie Claire

    2014-01-01

    Misuse of pharmaceuticals is of increasing drug policy and public health concern. A scoping review was conducted on the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions. The research question was broad: What is known from the existing literature about the diversion of pharmaceuticals for non-medicinal use and for home production of drug solutions? The scoping process centred on the systematic selection, collection, and summarization of extant knowledge within this broad thematic remit. One hundred and thirty-four records were grouped into discrete thematic categories namely: non medicinal use and tampering with pharmaceuticals, oral misuse of codeine cough syrups, homemade drug solutions, and home-produced drug-related harms in the narrative review design. Forms of abuse of codeine cough syrup include mixtures with alcohol or soft drinks ('Purple Drank'), with kratom leaves ('Kratom cocktails'), or chemically altered to extract dextromorphan ('Lemon Drop'). Production of homemade opiates ('Cheornaya', 'Kolyosa', Himiya', 'Braun', 'Krokodil'), methamphetamine ('Vint', 'Pervitin'), methcathinone ('Jeff'), and cathinone ('Boltushka') are described. Displacement patterns between the non-medical use of pharmaceuticals, commercial, and homemade drugs appear dependent on availability of opiates, prescribing practices, supervision of substitution drug dosing, availability of cheap ingredients, policing, and awareness of harms. Adverse health and social consequences relate to the use of unknown and contaminated (end) substances, injecting practices, redosing, medical complications, and death. The review highlights a public health imperative requiring a multidisciplinary approach to quantify potential impact and required integrated policy responses incorporating international regulation, enforcement, health surveillance and service delivery. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Evaluation of intravenous fluorescein in intradermal allergy testing in psittacines.

    Science.gov (United States)

    Nett, Claudia S; Hosgood, Giselle; Heatley, J Jill; Foil, Carol S; Tully, Thomas N

    2003-12-01

    This study was designed to improve the clinical feasibility of intradermal skin testing of psittacine birds using intravenous fluorescein stain. Twenty-five healthy, anaesthetized Hispaniolan Amazon parrots (Amazona ventralis) were injected intravenously with 10 mg kg-1 fluorescein-sodium 1% followed by intradermal injections of 0.02 mL phosphate-buffered saline, histamine phosphate (1:100,000 w/v) and codeine phosphate (1:100,000 w/v) at the sternal apteria. Wheal diameters of reaction sites were measured grossly and under illumination with a Wood's lamp after 5 and 10 min. Fluorescence-enhanced injection sites were scored between 0 and 2, with 0 equivalent to normal skin and 2 equivalent to a plucked feather follicle. The presence of a fluorescent halo around intradermal injections was also recorded. Under Wood's light illumination at 10 min, histamine and saline were evaluated as positive and negative controls, respectively, based on a positive test having a halo and a score of 2. Sensitivity and specificity were each 76% for halo, 84 and 42% for score and 64 and 77% for combination of score and halo, respectively. Further, mean histamine reactions were significantly larger than codeine phosphate and saline (8.8 +/- 0.4 mm; 7.2 +/- 0.3 mm; 5.9 +/- 0.6 mm); however, this finding was not consistent in individual birds. Wheal size, halo presence and score were affected by site location independent from the injected compound. Intravenous fluorescein improved the readability of avian skin tests; however, the compounds tested raised inconsistent reactions in wheal size, score or halo presence. The compound-independent site effect raises concern on the validity of avian skin testing and warrants investigation of other techniques such as in vitro allergy testing. Based on our findings, intradermal allergy testing in psittacines with or without fluorescein is unreliable and cannot be recommended for practical clinical use.

  9. Spinal cord stimulation for FBSS and CRPS: A review of 80 cases with on-table trial of stimulation.

    Science.gov (United States)

    Gopal, Hari; Fitzgerald, Joseph; McCrory, Connail

    2016-01-01

    Spinal cord stimulation (SCS) is used for the treatment of chronic neuropathic pain, a notoriously difficult condition to treat. Failed Back Surgery Syndrome (FBSS) and Complex Regional Pain syndrome (CRPS) remain the strongest indications. Funding remains a difficult issue and the use of trial of stimulation is the traditional method of ensuring best outcomes from implantation. A retrospective and consecutive review of 80 cases of spinal cord stimulation for patients with a diagnosis of FBSS and CRPS having undergone prior comprehensive medical management and interventional treatment with no sustained benefit. Trial of stimulation was performed on-table and if acceptable coverage was achieved, the case proceeded to full implantation. The mean patient age was 50.08 years (range 28-80 years). At 12 months follow-up, thirty two patients (40%) no longer required analgesic medication. Thirty patients (37.5%) reported their pain was manageable with first line analgesics. Fourteen (17.5%) reported their pain was manageable first line analgesic and occasional tramadol or codeine. Four (5%) reported that their pain was manageable with NSAID's, paracetamol, amitriptyline, and regular codeine or tramadol. Seventeen out of eighty patients (21.25%) were unemployed before SCS implant, and at 12 months follow up eight of these patients (47.05%) had returned to work. There was no infective complications or explants. Two patients (2.53%) required one lead revision, which was successful. SCS is the most effective treatment for FBSS and CRPS, which is proven resistant to medical management. On-table trial and implantation is easy to perform with good success rate and low morbidity and if successful will reduce complication rates, especially infection.

  10. Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.

    Science.gov (United States)

    Jedinger, N; Schrank, S; Mohr, S; Feichtinger, A; Khinast, J; Roblegg, E

    2015-05-01

    The objective of the present study was to investigate interactions between alcohol and hot-melt extruded pellets and the resulting drug release behavior. The pellets were composed of vegetable calcium stearate as matrix carrier and paracetamol or codeine phosphate as model drugs. Two solid lipids (Compritol® and Precirol®) were incorporated into the matrix to form robust/compact pellets. The drug release characteristics were a strong function of the API solubility, the addition of solid lipids, the dissolution media composition (i.e., alcohol concentration) and correspondingly, the pellet wettability. Pellets comprising paracetamol, which is highly soluble in ethanol, showed alcohol dose dumping regardless of the matrix composition. The wettability increased with increasing ethanol concentrations due to higher paracetamol solubilities yielding increased dissolution rates. For pellets containing codeine phosphate, which has a lower solubility in ethanol than in acidic media, the wettability was a function of the matrix composition. Dose dumping occurred for formulations comprising solid lipids as they showed increased wettabilities with increasing ethanol concentrations. In contrast, pellets comprising calcium stearate as single matrix component showed robustness in alcoholic media due to wettabilities that were not affected by the addition of ethanol. The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms. Moreover, hydrophobic calcium stearate can be considered a suitable matrix system that minimizes the risk of ethanol-induced dose dumping for certain API's. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Musculoskeletal pain: prescription of NSAID and weak opioid by primary health care physicians in Sweden 2004–2008 – a retrospective patient record review

    Directory of Open Access Journals (Sweden)

    Metha Brattwall

    2010-08-01

    Full Text Available Metha Brattwall1, Ibrahim Turan2, Jan Jakobsson31Department of Anaesthesia, Institute for Clinical Sciences at Sahlgrenska Academy, Mölndal Hospital, Gothenburg, Sweden; 2Foot and Ankle Surgical Centre, Stockholm, Sweden; 3Karolinska Institutet, Institution for Physiology and Pharmacology, Department of Anaesthesia, Stockholm, SwedenPurpose: To study the prescription of oral analgesics for musculoskeletal pain by primary care physicians over a 5-year period in Sweden.Design: A retrospective automatic database review of patient records at four primary health care centers. All prescriptions of NSAIDs, weak opioids, and coprescriptions of gastroprotecting medications to patients with musculoskeletal were retrieved for the period January 1, 2004 to November 11, 2008.Results: A total of 27,067 prescriptions prescribed to 23,457 patients with musculoskeletal pain were analyzed. Of all prescriptions, NSAIDs were the most commonly prescribed analgesic comprising 79%, tramadol was the second most commonly prescribed analgesic comprising 9%, codeine the third most (7%, and dextropropoxyphene the fourth (5%. The proportion of NSAIDs and weak opioids and the proportion of the different weak opioids prescribed showed no change over time. The proportion of nonselective and selective NSAIDs prescribed changed; Coxib prescriptions decreased from 9% to 4% of all analgesics prescribed in 2004–2007 with no change in 2008.Conclusion: NSAIDs were found to be the dominant class of analgesic prescribed by primary care physicians to patients diagnosed as musculoskeletal pain. No change was observed in the proportion of NSAID and weak opioid prescription over the period studied. Prescription of selective Coxibs decreased and was less than 4% in 2008. The impact on gastrointestinal and cardiovascular adverse effects associated with the extensive prescription of NSAIDS for musculoskeletal pain warrants further analysis.Keywords: nonsteroidal anti-inflammatory drugs

  12. Full validation of a method for the determination of drugs of abuse in non-mineralized dental biofilm using liquid chromatography-tandem mass spectrometry and application to postmortem samples.

    Science.gov (United States)

    Henkel, Kerstin; Altenburger, Markus J; Auwärter, Volker; Neukamm, Merja A

    2018-01-01

    Alternative matrices play a major role in postmortem forensic toxicology, especially if common matrices (like body fluids or hair) are not available. Incorporation of illicit and medicinal drugs into non-mineralized dental biofilm (plaque) seems likely but has not been investigated so far. Analysis of plaque could therefore extend the spectrum of potentially used matrices in postmortem toxicology. For this reason, a rapid, simple and sensitive method for the extraction, determination and quantification of ten drugs of abuse from plaque using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and fully validated. Amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxyamphetamine (MDA), cocaine, benzoylecgonine, morphine, codeine and 6-acetylmorphine were extracted from 2mg of dried and powdered plaque via ultrasonication with acetonitrile. The extracts were analyzed on a triple-quadrupole linear ion trap mass spectrometer in scheduled multiple reaction monitoring mode (sMRM). The method was fully validated and proved accurate, precise, selective and specific with satisfactory linearity within the calibrated ranges. The lower limit of quantification was 10-15pgmg -1 for all compounds except for MDA (100pgmg -1 ) and amphetamine (200pgmg -1 ). The method has been successfully applied to three authentic postmortem samples with known drug history. Amphetamine, MDMA, cocaine, benzoylecgonine, morphine and codeine could be detected in these cases in concentrations ranging from 18pgmg -1 for cocaine to 1400pgmg -1 for amphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl.

    Science.gov (United States)

    Lloyd, Renae A; Hotham, Elizabeth; Hall, Catherine; Williams, Marie; Suppiah, Vijayaprakash

    2017-12-01

    Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl. A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review. Studies were included based on a combination of key words: chronic pain and related terms, pharmacogenetics and related terms, and opioids and related terms. Among the 1,408 individual papers retrieved from the search in Medline and Embase, 32 original articles were included in this review, with none related to codeine. The 32 papers reported various study designs, opioids, and polymorphisms being studied for associations with treatment outcomes. This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects. Currently, there are few validated studies to form a strong evidence base to support pharmacogenomics testing when initiating opioid therapy. However, the field of pharmacogenomics in chronic pain is likely to expand over the coming years, with the increasing number of treatment options available and larger cohorts being assembled in order to identify true associations. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  14. Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Manuela Favarin Santini

    Full Text Available Abstract Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. Objective: The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. Material and Methods: This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg plus acetaminophen (500 mg, every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg plus acetaminophen (500 mg on the same schedule. Two factors were evaluated: (1 pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2 the occurrence of adverse effects. Results: In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P0.05, i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. Conclusion: This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

  15. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2008-07-01

    The presence and fate of 56 pharmaceuticals, personal care products, endocrine disruptors and illicit drugs (PPCPs) were investigated in the South Wales region of the UK. Two contrasting rivers: River Taff and River Ely were chosen for this investigation and were monitored for a period of 10 months. The impact of the factors affecting the levels of concentration of PPCPs and illicit drugs in surface water such as surrounding area, proximity to wastewater effluent and weather conditions, mainly rainfall was also investigated. Most PPCPs were frequently found in river water at concentrations reaching single microgL(-1) and their levels depended mainly on the extent of water dilution resulting from rainfall. Discharge of treated wastewater effluent into the river course was found to be the main cause of water contamination with PPCPs. The most frequently detected PPCPs represent the group of pharmaceuticals dispensed at the highest levels in the Welsh community. These were antibacterial drugs (trimethoprim, erythromycin-H(2)O and amoxicillin), anti-inflammatories/analgesics (paracetamol, tramadol, codeine, naproxen, ibuprofen and diclofenac) and antiepileptic drugs (carbamazepine and gabapentin). Only four PPCPs out of 56 (simvastatin, pravastatin, digoxin and digoxigenin) were not quantified over the course of the study. Several PPCPs were found to be both ubiquitous and persistent in the aqueous environment (e.g. erythromycin-H(2)O, codeine, carbamazepine, gabapentin and valsartan). The calculated average daily loads of PPCPs indicated that in total almost 6 kg of studied PPCPs are discharged daily into the studied rivers. The illicit drugs studied were found in rivers at low levels of ng L(-1). Average daily loads of amphetamine, cocaine and its main metabolite benzoylecgonine were as follows: 8, 1.2 and 39 gday(-1), respectively. Their frequent occurrence in surface water is primarily associated with their high illegal usage and is strongly associated with the

  16. Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

    Science.gov (United States)

    Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

    2018-02-17

    Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

  17. Utility of opium seed extract tests in preventing hypersensitivity reactions during surgery.

    Science.gov (United States)

    Armentia, A; Pineda, F; Palacios, R; Martín-Gil, F-J; Miguel, A S; Arenal, J J; Tejedor, J; Tef, B M

    2014-01-01

    Anaphylaxis during anaesthesia is fatal in 3-9% of patients and analgesics, including opioids, and is the second most common medicament-related cause, although the prevalence is underestimated. We recently found that patients may generate IgE antibodies to opium seeds. To determine the diagnostic accuracy of specific antibodies to morphine, codeine, rocuronium and oil body and aqueous fractions of Papaver somniferum seeds in the diagnosis and prevention of allergy to opioids. Patients with hypersensitivity reactions during surgery, and severe clinical allergy (pollen, tobacco), and illicit heroin users were selected. The sensitivity, specificity and predictive values of in vivo and in vitro diagnostic techniques including oil body and aqueous fractions of P. somniferum seeds were measured. We studied 203 patients, with mean age 35.1±17.1 and 200 healthy controls. Patients sensitised to heroin or with hypersensitivity reactions during surgery responded to P. somniferum seed tests. Of patients not known to be sensitised to opioids, the highest positivity was in patients sensitised to tobacco (pOpium seed skin tests and IgE, especially the oil body fraction, were more sensitive (64.2%) and specific (98.4%) than morphine, codeine and rocuronium tests for opioid sensitivity. Pollen allergy was not a risk factor for sensitisation to morphine. Sensitivity to opioids and intraoperative anaphylaxis can be diagnosed by routine tests. IgE and skin tests for the oil body fraction of P. somniferum had the highest sensitivity for sensitisation to opioids. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  18. [The history of heroin].

    Science.gov (United States)

    Hosztafi, S

    2001-08-01

    The discovery of heroin and the development of heroin abuse are introduced. Heroin, the hydrochloride of diacetylmorphine, was discovered by acetylation of morphine. Heroin, in pharmacological studies, proved to be more effective than morphine or codeine. The Bayer Company started the production of heroin in 1898 on a commercial scale. The first clinical results were so promising that heroin was considered a wonder drug. Indeed, heroin was more effective than codeine in respiratory diseases. It has turned out, however, that repeated administration of heroin results in the development of tolerance and the patients become heroin-addicts soon. In the early 1910s morphine addicts "discovered" the euphorising properties of heroin and this effect was enhanced by intravenous administration. Heroin became a narcotic drug and its abuse began to spread quickly. Restrictions on its production, use and distribution were regulated by international treties. The total ban on heroin production was also proposed. As a result of the strict regulations the production and cosumption of heroin showed a significant decrease after 1931. At the same time the underworld recognized the shortage of heroin and started the illicit production and trafficking. The quantity of heroin seized by law enforcement agencies in the past decades rose gradually. As an indicator of the worldwide heroin market, the quantity of confiscated heroin underwent a tenfold increase since 1970. The paper surveys the most important heroin-producing and trafficking countries. Heroin, prepared in clandestine ("kitchen" or "jungle") laboratories, is diluted ("cut") by every member of the illegal heroin distributing chain, i.e. smugglers, traffickers, dealers and vendors.

  19. Review of Opioid Pharmacogenetics and Considerations for Pain Management.

    Science.gov (United States)

    Owusu Obeng, Aniwaa; Hamadeh, Issam; Smith, Michael

    2017-09-01

    Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid-related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1. The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real-world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics. © 2017

  20. Limitations of indirect methods of estimating small bowel transit in man

    International Nuclear Information System (INIS)

    Pressman, J.H.; Hofmann, A.F.; Witztum, K.F.

    1987-01-01

    Experiments were carried out in healthy volunteers to explore the utility of a new [ 14 C]lactulose breath test for measuring small intestinal transit time in man and to use this procedure to test whether two antidiarrheal agents, codeine and clonidine, alter small intestinal transit time during digestion of a liquid meal. In an initial validation study performed in 12 subjects, a liquid test meal containing 10 g [ 14 C]lactulose was administered and the colonic entry time estimated from the time course of 14 CO 2 excretion in breath compared with that of H 2 excretion. There was a fair correlation (r = 0.77; P less than 0.001) between results obtained by the two methods; both methods gave similar results, but 14 CO 2 output was delayed when compared to H 2 output and was incomplete. The meal also contained xylose and [ 13 C]glycine, permitting the duodenal entry time of the meal to be estimated by the appearance of xylose in blood and 13 CO 2 in breath, respectively. The same liquid meal was then used to examine the effect on small intestinal transit time (colonic entry time minus duodenal entry time) of codeine or clonidine. 99Tc-sulfur colloid was also added to the meal to permit a comparison of small intestinal transit estimated by imaging with that estimated by the 14 CO 2 -lactulose breath test. 99 Tc radioactivity appeared in the cecum (as assessed using gamma scintigraphy) about 2 hr before 14 CO 2 radioactivity appeared in breath; the correlation between transit time estimated by the two methods was moderate (r = 0.61; P less than 0.05). Based on the [ 14 C]lactulose data, small intestinal transit time ranged from less than 1 to 3 hr for a liquid meal containing 10 g lactulose; within-subject variation was considerably less than between-subject variation

  1. Post-operative pain following coblation or monopolar electrocautery tonsillectomy in children: a prospective, single-blinded, randomised comparison.

    Science.gov (United States)

    Parker, N P; Walner, D L

    2011-10-01

    To compare post-operative pain following tonsillectomy by either coblation or monopolar electrocautery in children. A parallel-designed, prospective, single-blinded, randomised trial. Ambulatory surgical facility. Eighty otherwise healthy paediatric patients undergoing coblation or electrocautery tonsillectomy by a fellowship-trained paediatric otolaryngologist. (i) The number of post-operative days with severe pain based on subjective qualification by the caretaker, (ii) post-operative days with pain rated ≥ 5 on a scale of 1-10, (iii) post-operative days requiring oral paracetamol/acetaminophen with codeine solution and (iv) post-operative days until resumption of a regular diet were assessed and recorded daily using a post-operative pain survey as a form of daily diary that was returned at the 2-week follow-up visit. Patients were consecutively enrolled into two groups of 40 patients. Average ages were 5.2 years for coblation tonsillectomy and 6.0 years for electrocautery tonsillectomy. The average number of post-operative days with severe pain was 4.2 for coblation and 5.9 for electrocautery (P = 0.006), days rating pain ≥ 5 were 3.6 for coblation and 4.8 for electrocautery (P = 0.037), days of codeine use were 2.5 for coblation and 2.9 for electrocautery (P = 0.324), and days until resumption of a regular diet were 5.2 for coblation and 6.2 for electrocautery (0.329). Coblation tonsillectomy may reduce post-operative pain and the time until resumption of a regular diet compared to electrocautery tonsillectomy. © 2011 Blackwell Publishing Ltd.

  2. A prospective study to assess the palatability of analgesic medicines in children.

    Science.gov (United States)

    Smith, Coral June; Sammons, Helen M; Fakis, Apostolos; Conroy, Sharon

    2013-03-01

    This study examined children's opinions on the taste of three analgesic medicines: paracetamol, ibuprofen and codeine. Many medicines for children are unpleasant and unacceptable. Research has shown that children's taste preferences differ to adults, in whom palatability is often tested. Little British research exists on children's opinions on the palatability of medicines. This study aimed to address this gap in knowledge. Prospective observational study. Between May-September 2008, hospital inpatients aged 5-16 years rated the taste of required analgesics on a 100-mm visual analogue scale. This incorporated a 5-point facial hedonic scale. They were also asked their favourite flavour and colour for a medicine. A total of 159 children took part. Eighty-five males (53·5%) and 74 females (46·5%). The median age was 8 years (Inter-quartile range 6-11). The taste of ibuprofen was significantly preferred to paracetamol or codeine. Significant differences were observed depending if the medicine rated was taken first or second (for example pre-medication with paracetamol and ibuprofen). Younger children (5-8 years) were more likely to choose the extremes of the scale when grading than older children were. Preferred flavours on questioning were strawberry 44% and banana 17%. Favourite colours were pink 25·8% and red 20·8%, with girls more likely to choose pink and boys blue. Ibuprofen was the most palatable analgesic medicine tested. Children reported they preferred fruit flavours and colour was sex dependent. Nurses when administering two medicines together should consider giving the least palatable first, for example paracetamol before ibuprofen for pre-medication. © 2012 Blackwell Publishing Ltd.

  3. Optimization and application of an extraction procedure to determine drugs of abuse in solid environmental matrices of Turia River Basin

    Science.gov (United States)

    Andres, Maria Jesus; Alvarez, Rodrigo; Andreu, Vicente; Pico, Yolanda

    2015-04-01

    After their consumption, drug of abuse are excreted through urine or faeces, as parent compound or as secondary metabolites that arrive to wastewater treatment plants. Accordingly, the incomplete removal of these compounds in the treatment plants could release them into environmental compartments [1]. This scenario needs attention from an ecotoxicological perspective because their possible negative effects [2]. The aim of this study is to optimize and apply a solvent extraction and solid phase clean-up methodology to obtain a valid procedure for the extraction of these compounds in different solid matrices. Amphetamine, methamphetamine, ethylamphetamine, ecstasy, ethylone, bk-MMBDB and MBDB belong to phenylethylamine group; codeine and ketamine belong to opioid and phencyclidine group, respectively, and benzoylecgonine is the major excreted metabolite of the alkaloid cocaine. To optimize the method to determinate drugs of abuse in environmental solid matrices, two replicates and one blank were prepared for each sample of sediment. They were prepared by adding 1 g of sediment sample, 5 mL of buffer (methanol-Mc Ilvaine 50:50) and internal standard to obtain a final concentration in the extract of 25 ng/g. Also standards of drugs of abuse were added to the replicates to obtain a final concentration of 100 ng/g. Then all samples were shaken, sonicated and centrifuged and the supernatant was separated and placed in a 250 mL volumetric flask, which was filled the rest with distilled water. SPE was carried out with Strata-X cartridges and 250 mL of sample were passed through them. The extracts were eluted with 6 mL of methanol, evaporated to dryness and reconstituted in 1 mL of methanol-water 1:9. One of the replicates was filtrated through 0.22 μm pore size and the others were not. The samples were determined by liquid chromatography triple quadrupole mass spectrometry (LC-QqQ-MS/MS) using an electrospray ionization source (ESI) in positive ionization mode. The results

  4. Treatment of severe neuropatic pain for patients with the syndrome of Klippel-Trenaunay-Weber: case report

    Directory of Open Access Journals (Sweden)

    Danielle Cristina de Oliveira Soares

    2016-12-01

    Full Text Available Introduction: Klippel-Trenaunay-Weber syndrome is a rare congenital anomaly whose etiology has not yet been elucidated. It is characterized by the triad of vascular malformations, cutaneous hemangiomas and overgrowth of bone and soft tissue adjacent. Pain is a common symptom and can be triggered in the following situations: venous disease, scoliosis by the different members and hemangiomas that affect the body surface, the deep planes or viscera. Case report: A female patient, 17, sent from the SARAH Hospital - Fortaleza to the Institute of Clinic Pain José Frota diagnosed with cerebral palsy type triplegia on right eye and anophthalmia featuring an expansive process of vascular origin extending to the paraspinal region, surpassing sciatic foramen and affecting posterior muscles of the left thigh and leg. There are signs of involvement of the sciatic nerve and deep femoral vessels. He was diagnosed with Klippel-Trenaunay-Weber syndrome. She had continuous pain in shock and burning, EVA 10, extending from the lower back, groin and left leg region. The source of hospital treatment consisted of gabapentin 180mg 12/12h, codeine 10mg 12/12h, ibuprofen 300mg 12/12h, codeine/paracetamol 30mg 12/12h and morphine oral 10mg while in pain, but without pain relief. She also used paroxetine 20mg daily, due to depression. The painful condition prevented sleep, caused irritation and worsened the quality of life of the patient. She continued treatment with gabapentin 300mg 12/12h, dipyrone 500mg 12/12h, Methadone 5mg 12/12h and reassessed two weeks showing significant improvement in pain symptoms and sleep, EVA 2. Conclusion: Pain is a symptom commonly described in the clinical picture of patients with this syndrome. The treatment of this disease is still a challenge. The malformations great gifts made it not always possible embolization or painkillers locks. The therapeutic results with strong opioid were satisfactory and have improved the quality of life of

  5. Role of cytochrome P450 genotype in the steps toward personalized drug therapy

    Directory of Open Access Journals (Sweden)

    Cavallari LH

    2011-11-01

    Full Text Available Larisa H Cavallari1,2, Hyunyoung Jeong1,2, Adam Bress11Department of Pharmacy Practice, 2Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USAAbstract: Genetic polymorphism for cytochrome 450 (P450 enzymes leads to interindividual variability in the plasma concentrations of many drugs. In some cases, P450 genotype results in decreased enzyme activity and an increased risk for adverse drug effects. For example, individuals with the CYP2D6 loss-of-function genotype are at increased risk for ventricular arrhythmia if treated with usual does of thioridazine. In other cases, P450 genotype may influence the dose of a drug required to achieve a desired effect. This is the case with warfarin, with lower doses often necessary in carriers of a variant CYP2C9*2 or *3 allele to avoid supratherapeutic anticoagulation. When a prodrug, such as clopidogrel or codeine, must undergo hepatic biotransformation to its active form, a loss-of-function P450 genotype leads to reduced concentrations of the active drug and decreased drug efficacy. In contrast, patients with multiple CYP2D6 gene copies are at risk for opioid-related toxicity if treated with usual doses of codeine-containing analgesics. At least 25 drugs contain information in their US Food and Drug Administration-approved labeling regarding P450 genotype. The CYP2C9, CYP2C19, and CYP2D6 genes are the P450 genes most often cited. To date, integration of P450 genetic information into clinical decision making is limited. However, some institutions are beginning to embrace routine P450 genotyping to assist in the treatment of their patients. Genotyping for P450 variants may carry less risk for discrimination compared with genotyping for disease-associated variants. As such, P450 genotyping is likely to lead the way in the clinical implementation of pharmacogenomics. This review discusses variability in the CYP2C9, CYP2C19, and CYP2D6 genes and the

  6. Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management

    Directory of Open Access Journals (Sweden)

    Feng XQ

    2017-05-01

    Full Text Available Xiu-qin Feng,1 Ling-ling Zhu,2 Quan Zhou3 1Nursing Administration Office, Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs. Method: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results: Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8% were conducted in healthy volunteers, whereas 10 RCTs (19.2% enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone, quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone, antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol, protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine, grapefruit juice–opioids (oxycodone, fentanyl, methadone, antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol, metoclopramide–morphine, amantadine–morphine, sumatriptan

  7. Limitations of indirect methods of estimating small bowel transit in man

    Energy Technology Data Exchange (ETDEWEB)

    Pressman, J.H.; Hofmann, A.F.; Witztum, K.F.; Gertler, S.L.; Steinbach, J.H.; Stokes, K.; Kelts, D.G.; Stone, D.M.; Jones, B.R.; Dharmsathaphorn, K.

    1987-07-01

    Experiments were carried out in healthy volunteers to explore the utility of a new (/sup 14/C)lactulose breath test for measuring small intestinal transit time in man and to use this procedure to test whether two antidiarrheal agents, codeine and clonidine, alter small intestinal transit time during digestion of a liquid meal. In an initial validation study performed in 12 subjects, a liquid test meal containing 10 g (/sup 14/C)lactulose was administered and the colonic entry time estimated from the time course of /sup 14/CO/sub 2/ excretion in breath compared with that of H/sub 2/ excretion. There was a fair correlation (r = 0.77; P less than 0.001) between results obtained by the two methods; both methods gave similar results, but /sup 14/CO/sub 2/ output was delayed when compared to H/sub 2/ output and was incomplete. The meal also contained xylose and (/sup 13/C)glycine, permitting the duodenal entry time of the meal to be estimated by the appearance of xylose in blood and /sup 13/CO/sub 2/ in breath, respectively. The same liquid meal was then used to examine the effect on small intestinal transit time (colonic entry time minus duodenal entry time) of codeine or clonidine. 99Tc-sulfur colloid was also added to the meal to permit a comparison of small intestinal transit estimated by imaging with that estimated by the /sup 14/CO/sub 2/-lactulose breath test. /sup 99/Tc radioactivity appeared in the cecum (as assessed using gamma scintigraphy) about 2 hr before /sup 14/CO/sub 2/ radioactivity appeared in breath; the correlation between transit time estimated by the two methods was moderate (r = 0.61; P less than 0.05). Based on the (/sup 14/C)lactulose data, small intestinal transit time ranged from less than 1 to 3 hr for a liquid meal containing 10 g lactulose; within-subject variation was considerably less than between-subject variation.

  8. Death in a legal poppy field in Spain.

    Science.gov (United States)

    Martínez, María Antonia; Ballesteros, Salomé; Almarza, Elena; Garijo, Joaquín

    2016-08-01

    Opium is a substance extracted from Papaver somniferum L. Opium latex contains morphine, codeine, and thebaine and non-analgesic alkaloids such as papaverine and noscapine. In Spain opium growing is allowed only for scientific or pharmaceutical purposes and harvest is supervised by the Spanish Health Ministry. This work describes a sudden fatality involving opium consumption in a legal poppy field. The toxicological and autopsy findings, previous disease, paraphernalia, and scenario are discussed in order to clarify cause and manner of death. A 32-year-old white caucasian male was found unresponsive in a legal poppy field in the South of Spain. The emergency medical services responded to the scene where he was pronounced dead. The friends explained that the deceased had presented with about 30min of convulsions; in spite of trying to keep his airway tract open they noted that "he stayed airless". According to them the victim suffered from epilepsy. Tools found beside his body consisted of plain wood sticks with a blade razor, a fabric handle, and paper. A comprehensive toxicological screening for abuse and psychoactive drugs was performed in the deceased samples. This included ethanol and volatile analysis by HS-GC-FID in peripheral blood and urine, enzyme immunoassay in urine by CEDIA, and a basic drug screening in all samples (including paraphernalia) by GC-MS using modes full scan for screening/confirmation and selected ion monitoring for quantitation. The peripheral blood, urine, vitreous, and gastric content contained the following concentrations of opiates expressed in mg/L (gastric content additionally also expressed in mg total): 0.10, 7.12, 0.23, and 14.80 (2.81mg total) of thebaine, 0.13, 4.50, 0.13, and 6.60 (1.25mg total) of morphine (free), 0.48, 0.88, 0.17, and 1.50 (0.28mg total) of codeine. These tree opiates were also detected in the tools (paraphernalia) used by the deceased for opium consumption. Other toxicological findings were metabolites of

  9. High-output stoma after small-bowel resections for Crohn's disease.

    Science.gov (United States)

    Tsao, Stephen K K; Baker, Melanie; Nightingale, Jeremy M D

    2005-12-01

    A 56-year-old Caucasian woman with a history of Crohn's disease and multiple bowel resections resulting in a loop jejunostomy was referred to our Nutritional Unit from a neighboring district general hospital for further management. She was first seen in October 2001, and initial assessment indicated that she was malnourished with fluid depletion, evidenced by the high volume of stomal fluid produced. There had been no sudden change in her medication, her Crohn's disease was quiescent and there was no evidence of any intra-abdominal sepsis. Despite a high calorific intake through her diet, she continued to lose weight. Serum urea and electrolytes; magnesium; C-reactive protein; full blood count; urinary spot sodium; anthropometric measurements. High-output stoma with malabsorption as a consequence of repeated small-bowel surgery. The patient was treated with oral hypotonic fluid restriction (0.5 l/day), 2 l of oral glucose-saline solution per day, high-dose oral antimotility agents (loperamide and codeine phosphate), a proton-pump inhibitor (omeprazole) and oral magnesium replacement. A year later, the patient's loop jejunostomy was closed and an end ileostomy fashioned, bringing an additional 35 cm of small bowel into continuity; macronutrient absorption improved but her problem of dehydration was only slightly reduced. She was stabilized on a twice-weekly subcutaneous magnesium and saline infusion and daily oral 1alpha-hydroxycholecalciferol.

  10. A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study.

    Science.gov (United States)

    Lucenteforte, Ersilia; Vagnoli, Laura; Pugi, Alessandra; Crescioli, Giada; Lombardi, Niccolò; Bonaiuti, Roberto; Aricò, Maurizio; Giglio, Sabrina; Messeri, Andrea; Mugelli, Alessandro; Vannacci, Alfredo; Maggini, Valentina

    2018-05-18

    Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients. We conducted a systematic literature search in EMBASE and PubMed up to the 24th of November 2016 following Cochrane Handbook and PRISMA guidelines. Two independent reviewers screened titles and abstracts along with full-text papers; disagreements were resolved by discussion with two other independent reviewers. We used a data extraction form to provide details of the included studies, and conducted quality assessment using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Young age, lung or gastrointestinal cancer, neuropathic or breakthrough pain and anxiety or sleep disturbance were associated to a worse response to opioid analgesia. No clear association was identified in literature regarding gender, ethnicity, weight, presence of metastases, biochemical or hematological factors. Studies in children were lacking. Between June 2011 and April 2014, the Italian STOP Pain project enrolled 87 paediatric cancer patients under treatment with opioids (morphine, codeine, oxycodone, fentanyl and tramadol). Future studies on cancer pain should be designed with consideration for the highlighted factors to enhance our understanding of opioid non-response and safety. Studies in children are mandatory. CRD42017057740 .

  11. Drug-Excipient Interactions in the Solid State: The Role of Different Stress Factors.

    Science.gov (United States)

    Gressl, Corinna; Brunsteiner, Michael; Davis, Adrian; Landis, Margaret; Pencheva, Klimentina; Scrivens, Garry; Sluggett, Gregory W; Wood, Geoffrey P F; Gruber-Woelfler, Heidrun; Khinast, Johannes G; Paudel, Amrit

    2017-12-04

    Understanding properties and mechanisms that govern drug degradation in the solid state is of high importance to ensure drug stability and safety of solid dosage forms. In this study, we attempt to understand drug-excipient interactions in the solid state using both theoretical and experimental approaches. The model active pharmaceutical ingredients (APIs) under study are carvedilol (CAR) and codeine phosphate (COP), which are known to undergo esterification with citric acid (CA) in the solid state. Starting from the crystal structures of two different polymorphs of each compound, we calculated the exposure and accessibility of reactive hydroxyl groups for a number of relevant crystal surfaces, as well as descriptors that could be associated with surface stabilities using molecular simulations. Accelerated degradation experiments at elevated temperature and controlled humidity were conducted to assess the propensity of different solid forms of the model APIs to undergo chemical reactions with anhydrous CA or CA monohydrate. In addition, for CAR, we studied the solid state degradation at varying humidity levels and also under mechano-activation. Regarding the relative degradation propensities, we found that variations in the exposure and accessibility of molecules on the crystal surface play a minor role compared to the impact of molecular mobility due to different levels of moisture. We further studied drug-excipient interactions under mechano-activation (comilling of API and CA) and found that the reaction proceeded even faster than in physical powder mixtures kept at accelerated storage conditions.

  12. Atomic Structure of Salutaridine Reductase from the Opium Poppy (Papaver somniferum)

    Energy Technology Data Exchange (ETDEWEB)

    Higashi, Yasuhiro; Kutchan, Toni M.; Smith, Thomas J. (Danforth)

    2011-11-18

    The opium poppy (Papaver somniferum L.) is one of the oldest known medicinal plants. In the biosynthetic pathway for morphine and codeine, salutaridine is reduced to salutaridinol by salutaridine reductase (SalR; EC 1.1.1.248) using NADPH as coenzyme. Here, we report the atomic structure of SalR to a resolution of {approx}1.9 {angstrom} in the presence of NADPH. The core structure is highly homologous to other members of the short chain dehydrogenase/reductase family. The major difference is that the nicotinamide moiety and the substrate-binding pocket are covered by a loop (residues 265-279), on top of which lies a large 'flap'-like domain (residues 105-140). This configuration appears to be a combination of the two common structural themes found in other members of the short chain dehydrogenase/reductase family. Previous modeling studies suggested that substrate inhibition is due to mutually exclusive productive and nonproductive modes of substrate binding in the active site. This model was tested via site-directed mutagenesis, and a number of these mutations abrogated substrate inhibition. However, the atomic structure of SalR shows that these mutated residues are instead distributed over a wide area of the enzyme, and many are not in the active site. To explain how residues distal to the active site might affect catalysis, a model is presented whereby SalR may undergo significant conformational changes during catalytic turnover.

  13. Crystal structure of the[mu]-opioid receptor bound to a morphinan antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Mathiesen, Jesper M.; Sunahara, Roger K.; Pardo, Leonardo; Weis, William I.; Kobilka, Brian K.; Granier, Sébastien (Michigan-Med); (Stanford-MED); (UAB, Spain)

    2012-06-27

    Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled {mu}-opioid receptor ({mu}-OR) in the central nervous system. Here we describe the 2.8 {angstrom} crystal structure of the mouse {mu}-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the {mu}-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.

  14. Health-hazard evaluation report HETA 87-311-2087, Penick Corporation, Newark, New Jersey

    Energy Technology Data Exchange (ETDEWEB)

    Klincewicz, S.; Siwinski, G.; Fleeger, A.; Paulozzi, L.

    1990-11-01

    In response to a request from the International Chemical Workers Union to evaluate symptoms of headache, nausea, and respiratory symptoms among workers, an investigation was begun of possible hazardous working conditions at the Penick Corporation (SIC-2833), Newark, New Jersey. The company produced morphine, codeine, synthetic and semisynthetic narcotics from the raw materials gum opium and poppy straw concentrate. Industrial hygiene monitoring detected substantial exposures to alkaloid dusts throughout the building. A concentration as high as 23,564 micrograms/cubic meter was detected in a short term sample collected during the hand scooping of dry powder. Over exposures were detected to toluene (108883), butanol (71363), methanol (67561), and ethanol (64175) during short term episodic jobs. Thirty-two current employees participated in a study of immunologic parameters. A significant decrease in morphine-6-hemisuccinate/human serum albumin immunoglobulin-G antibody levels was noted in 21 workers who submitted blood specimens during both test periods. Narcotic production workers had greater reactivity to most of the compounds on a quantitative skin prick test with opiates. The authors conclude that workers at Penick Corporation developed asthma from occupational exposure to narcotic dusts. The authors recommend that exposures to narcotic dusts and solvents be reduced, and that workers with suspected work related illnesses be evaluated.

  15. Fast quantitation of opioid isomers in human plasma by differential mobility spectrometry/mass spectrometry via SPME/open-port probe sampling interface.

    Science.gov (United States)

    Liu, Chang; Gómez-Ríos, Germán Augusto; Schneider, Bradley B; Le Blanc, J C Yves; Reyes-Garcés, Nathaly; Arnold, Don W; Covey, Thomas R; Pawliszyn, Janusz

    2017-10-23

    Mass spectrometry (MS) based quantitative approaches typically require a thorough sample clean-up and a decent chromatographic step in order to achieve needed figures of merit. However, in most cases, such processes are not optimal for urgent assessments and high-throughput determinations. The direct coupling of solid phase microextraction (SPME) to MS has shown great potential to shorten the total sample analysis time of complex matrices, as well as to diminish potential matrix effects and instrument contamination. In this study, we demonstrate the use of the open-port probe (OPP) as a direct and robust sampling interface to couple biocompatible-SPME (Bio-SPME) fibres to MS for the rapid quantitation of opioid isomers (i.e. codeine and hydrocodone) in human plasma. In place of chromatography, a differential mobility spectrometry (DMS) device was implemented to provide the essential selectivity required to quantify these constitutional isomers. Taking advantage of the simplified sample preparation process based on Bio-SPME and the fast separation with DMS-MS coupling via OPP, a high-throughput assay (10-15 s per sample) with limits of detection in the sub-ng/mL range was developed. Succinctly, we demonstrated that by tuning adequate ion mobility separation conditions, SPME-OPP-MS can be employed to quantify non-resolved compounds or those otherwise hindered by co-extracted isobaric interferences without further need of coupling to other separation platforms. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Improved detection of drugs of abuse using high-performance ion mobility spectrometry with electrospray ionization (ESI-HPIMS) for urine matrices.

    Science.gov (United States)

    Midey, Anthony J; Patel, Aesha; Moraff, Carol; Krueger, Clinton A; Wu, Ching

    2013-11-15

    High-performance ion mobility spectrometry (HPIMS) with electrospray ionization (ESI) has been used to separate drugs of abuse compounds as a function of drift time (ion mobility), which is based on their size, structural shape, and mass-to-charge. HPIMS has also been used to directly detect and identify a variety of the most commonly encountered illegal drugs, as well as a mixture of opiates in a urine matrix without extra sample pretreatment. HPIMS has shown resolving power greater than 65 comparable to that of high-performance liquid chromatography (HPLC) with only 1 mL of solvent and sample required using air as the IMS separation medium. The HPIMS method can achieve two-order of magnitude linear response, precise drift times, and high peak area precision with percent relative standard deviations (%RSD) less than 3% for sample quantitation. The reduced mobilities measured agree very well with other IMS measurements, allowing a simple "dilute-and-shoot" method to be used to detect a mixture of codeine and morphine in urine matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. On-line solid-phase extraction coupled to hydrophilic interaction chromatography-mass spectrometry for the determination of polar drugs.

    Science.gov (United States)

    Fontanals, Núria; Marcé, Rosa M; Borrull, Francesc

    2011-09-02

    The present study describes the first fully automated method based on on-line solid-phase extraction (SPE) coupled to hydrophilic interaction chromatography-electrospray-mass spectrometry (HILIC-(ESI)MS) to determine a group of polar drugs that includes illicit drugs (such as cocaine, morphine, codeine and metabolites) and pharmaceuticals in environmental water samples. The SPE was performed using a highly retentive polymeric sorbent. The HILIC separation was optimised and the initial high organic content of the chromatographic mobile phase, was also suitable for the proper on-line elution of the analytes retained in the SPE column and for enhancing the ESI ionisation efficiency. This method allows the loading of samples of up to 250ml of ultrapure water or 10ml of environmental water samples spiked at low ngl(-1) levels of the analytes. The method yields near 100% recoveries for all the analytes. The method was also validated with environmental water samples with linear ranges from 5 to 1000ngl(-1) and limits of detection ≤2ngl(-1) for most of the compounds. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Twitter-Based Detection of Illegal Online Sale of Prescription Opioid.

    Science.gov (United States)

    Mackey, Tim K; Kalyanam, Janani; Katsuki, Takeo; Lanckriet, Gert

    2017-12-01

    To deploy a methodology accurately identifying tweets marketing the illegal online sale of controlled substances. We first collected tweets from the Twitter public application program interface stream filtered for prescription opioid keywords. We then used unsupervised machine learning (specifically, topic modeling) to identify topics associated with illegal online marketing and sales. Finally, we conducted Web forensic analyses to characterize different types of online vendors. We analyzed 619 937 tweets containing the keywords codeine, Percocet, fentanyl, Vicodin, Oxycontin, oxycodone, and hydrocodone over a 5-month period from June to November 2015. A total of 1778 tweets (marketing the sale of controlled substances online; 90% had imbedded hyperlinks, but only 46 were "live" at the time of the evaluation. Seven distinct URLs linked to Web sites marketing or illegally selling controlled substances online. Our methodology can identify illegal online sale of prescription opioids from large volumes of tweets. Our results indicate that controlled substances are trafficked online via different strategies and vendors. Public Health Implications. Our methodology can be used to identify illegal online sellers in criminal violation of the Ryan Haight Online Pharmacy Consumer Protection Act.

  19. Natural products for chronic cough: Text mining the East Asian historical literature for future therapeutics.

    Science.gov (United States)

    Shergis, Johannah Linda; Wu, Lei; May, Brian H; Zhang, Anthony Lin; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie Changli

    2015-08-01

    Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough. © The Author(s) 2015.

  20. Impacts of emerging contaminants on surrounding aquatic environment from a youth festival.

    Science.gov (United States)

    Jiang, Jheng-Jie; Lee, Chon-Lin; Fang, Meng-Der; Tu, Bo-Wen; Liang, Yu-Jen

    2015-01-20

    The youth festival as we refer to Spring Scream, a large-scale pop music festival, is notorious for the problems of drug abuse and addiction. The origin, temporal magnitudes, potential risks and mass inputs of emerging contaminants (ECs) were investigated. Thirty targeted ECs were analyzed by solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (SPE-LC-MS/MS). Sampling strategy was designed to characterize EC behavior in different stages (before and after the youth festival), based on multivariate data analysis to explore the contributions of contaminants from normal condition to the youth festival. Wastewater influents and effluents were collected during the youth festival (approximately 600 000 pop music fans and youth participated). Surrounding river waters are also sampled to illustrate the touristic impacts during peak season and off-season. Seasonal variations were observed, with the highest concentrations in April (Spring Scream) and the lowest in October (off-season). Acetaminophen, diclofenac, codeine, ampicillin, tetracycline, erythromycin-H2O, and gemfibrozil have significant pollution risk quotients (RQs > 1), indicating ecotoxicological concerns. Principal component analysis (PCA) and weekly patterns provide a perspective in assessing the touristic impacts and address the dramatic changes in visitor population and drug consumption. The highest mass loads discharged into the aquatic ecosystem corresponded to illicit drugs/controlled substances such as ketamine and MDMA, indicating the high consumption of ecstasy during Spring Scream.

  1. Emerging contaminants (pharmaceuticals, personal care products, a food additive and pesticides) in waters of Sydney estuary, Australia.

    Science.gov (United States)

    Birch, G F; Drage, D S; Thompson, K; Eaglesham, G; Mueller, J F

    2015-08-15

    The current investigation of marine water from 30 sites adjacent to stormwater outlets across the entire Sydney estuary is the first such research in Australia. The number of analytes detected were: 8/59 pharmaceutical compounds (codeine, paracetamol, tramadol, venlafaxine, propranolol, fluoxetine, iopromide and carbamazepine), 7/38 of the pesticides (2,4-dichlorophenoxyacetic acid (2,4-D), 3,4-dichloroaniline, carbaryl, diuron, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop and simazine) and 0/3 of the personal care products (PCPs) analysed. An artificial sweetener (acesulfame) was detected, however none of the nine antibiotics analysed were identified. Sewage water is not discharged to this estuary, except infrequently as overflow during high-precipitation events. The presence of acesulfame (a recognised marker of domestic wastewater) and pharmaceuticals in water from all parts of the estuary after a dry period, suggests sewage water is leaking into the stormwater system in this catchment. The pesticides are applied to the environment and were discharged via stormwater to the estuary. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Source Apportionment and Risk Assessment of Emerging Contaminants: An Approach of Pharmaco-Signature in Water Systems

    Science.gov (United States)

    Jiang, Jheng Jie; Lee, Chon Lin; Fang, Meng Der; Boyd, Kenneth G.; Gibb, Stuart W.

    2015-01-01

    This paper presents a methodology based on multivariate data analysis for characterizing potential source contributions of emerging contaminants (ECs) detected in 26 river water samples across multi-scape regions during dry and wet seasons. Based on this methodology, we unveil an approach toward potential source contributions of ECs, a concept we refer to as the “Pharmaco-signature.” Exploratory analysis of data points has been carried out by unsupervised pattern recognition (hierarchical cluster analysis, HCA) and receptor model (principal component analysis-multiple linear regression, PCA-MLR) in an attempt to demonstrate significant source contributions of ECs in different land-use zone. Robust cluster solutions grouped the database according to different EC profiles. PCA-MLR identified that 58.9% of the mean summed ECs were contributed by domestic impact, 9.7% by antibiotics application, and 31.4% by drug abuse. Diclofenac, ibuprofen, codeine, ampicillin, tetracycline, and erythromycin-H2O have significant pollution risk quotients (RQ>1), indicating potentially high risk to aquatic organisms in Taiwan. PMID:25874375

  3. Improvements on enzymatic hydrolysis of human hair for illicit drug determination by gas chromatography/mass spectrometry.

    Science.gov (United States)

    Míguez-Framil, Martha; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar; López, Patricia; Tabernero, María Jesús; Bermejo, Ana María

    2007-11-15

    The use of ultrasound energy for accelerating the pronase E enzymatic hydrolysis of human hair for extracting illicit drugs has been novelty tested. The enzymatic extracts obtained after 30 min of sonication in an ultrasonic water bath were subjected to an optimized solid-phase extraction process, which involved a solution of 2.0% (v/v) acetic acid in methanol as eluting solution and concentration by N2 stream evaporation. A gas chromatography/mass spectrometry method was used to separate and determine cocaine, benzoylecgonine, codeine, morphine, and 6-monoacethylmorphine in 20 min. Variables affecting ultrasound-assisted pronase E hydrolysis such as hydrolysis temperature, hydrolysis time, enzyme concentration, catalyzer (1,4-dithiothreitol) concentration, ionic strength, pH, and ultrasound frequency were simultaneously evaluated by a Plackett-Burman design 2(8) PBD of resolution III. The most statistically significant variables were ionic strength and pH, which means that analyte extraction is mainly attributed to pronase E activity. The optimization or evaluation of all the factors has led to an accelerated pronase E hydrolysis of human hair, which can be completed in 30 min. Results have been found to be statistically similar to those obtained with conventional pronase E hydrolysis. The accelerated method was finally applied to several human hair samples from multidrug abusers.

  4. Molecular Imaging on the Cerebral Pathological Damage Target of Ketamine Dependence

    Directory of Open Access Journals (Sweden)

    YANG Hong-jie1,2;HU Shu1;JIA Shao-wei1;GAO Zhou1;WANG Tong3;ZHAO Zheng-qin1

    2014-02-01

    Full Text Available To study the cerebral pathological damage target which result from abusing ketamine through molecular imaging techniques, 20 cases of ketamine dependent patients looking for treatment at the Peking University Shenzhen Hospital and 31 healthy volunteers were included in this study, all of them got brain SPECT DAT imaging. The results were analyzed by SPSS 16.0. The bilateral caudate nucleus and putamen of healthy volunteers were roughly equally large, and the radioactive distribution of DAT in healthy volunteers were uniform and symmetrical. The bilateral corpora striatum showed typical “panda eyes” pattern. But the bilateral corpora striatum of ketamine dependent patients got smaller in shape, got disorders in pattern, and the radioactive distribution of DAT reduced or defected or even got disturbance and with much more non-specific radioactive. The V, m and Ra of bilateral corpora striatum in ketamine dependent patients were (21.03±3.15) cm3, (22.08±3.31) g and (5.37±1.08) %, respectively, which were significantly lower than the healthy volunteers (p<0.01. The cerebral pathological damage target which resulted from abusing ketamine was similar to those of compound codeine phosphate antitussive solution dependence, heroin dependence and MDMA dependence, all of these psychoactive substances damaged the function of DAT.

  5. The effect of intravenous propofol on the incidence of post-dural puncture headache following spinal anesthesia in cesarean section

    Directory of Open Access Journals (Sweden)

    Parisa Golfam

    2016-09-01

    Full Text Available Introduction: Post Dural puncture headache is still a common complication among young women undergone cesarean section, although use of small size spinal needles reduced its prevalence. Several methods have been suggested for prevention and treatment of this side effect; such as complete bed rest, hydration, non-opioid analgesics, caffeine, codeine, which none of them proved to be totally effective. The last option would be epidural blood patch, if headache persist. The aim of this study was evaluation the efficacy of intravenous propofol on post dural puncture headache incidence after cesarean section. Methods: In a randomized clinical trial 120 patients aged 18-45 years old in American Society of Anesthesiologist (ASA class I or II, who had no history of headache, analgesic consumption, substance abuse and drug addiction, candidate for elective cesarean section, were randomly assigned into intervention (propofol and control groups. The anesthesia method for both groups was precisely the same. After spinal anesthesia in the first group 30µg/kg/min of intravenous propofol have been infused slowly. Then at 1, 6, 18, 24 hours and 2nd to 7th days after surgery, anesthesiologist asked groups for presence or absence of headache. The data analyzed with SPSS 16.0 software. Results: Headache incidence rate in the group who receiving propofol was significantly reduced (P.V=0.001. Conclusion: This study showed that 30µg/kg/min of intravenous propofol caused reduced the incidence of post spinal headache in young women undergone elective cesarean section.

  6. Can the use of psychoactive drugs in the general adult population be estimated based on data from a roadside survey of drugs and driving?

    Directory of Open Access Journals (Sweden)

    Hallvard Gjerde

    2011-12-01

    Full Text Available A roadside survey of drugs and driving was performed in south-eastern Norway in 2005-6. Samples of saliva from a total of 10,503 drivers above 20 years of age were analysed, and the results were weighted for under- and over-sampling compared to the population distribution in the study area. Weighted results were compared with data on dispensed prescriptions of zopiclone, codeine and diazepam at Norwegian pharmacies in the same area and with self-reported use of cannabis. When using roadside data to estimate drug use, the use of medicinal drugs was under-estimated by 17-59% compared to amounts dispensed. One of the main reasons for the under-estimation may be that a large proportion of the users of psychoactive medicinal drugs are not frequent drivers. For cannabis, self-reported data corresponded approximately to the estimated prevalence range. The results indicate that roadside surveys cannot be used for accurate estima tions of drug use in the population, but may provide minimum figures.

  7. Palliative Care Development in Mongolia.

    Science.gov (United States)

    Davaasuren, Odontuya; Ferris, Frank D

    2018-02-01

    Since the year 2000, Mongolia has established the foundation measures for a national palliative care program and has made several significant achievements. Systematic reviews and observational studies on palliative care development in Mongolia have taken place over the past 16 years. Mongolia began palliative care development in 2000 with the creation of the Mongolian Palliative Care Society and the Palliative Care Department. Palliative care is included in the Mongolia's Health Law, Health Insurance Law, Social Welfare Law, National Cancer Control Program, and the National Program for Non-Communicable Diseases, and has approved Palliative Care Standards and Pain Management Guidelines. Palliative care education is included in the undergraduate and postgraduate curriculum in all medical universities. Six hospice units in Ulaanbaatar have 50 beds; each of the nine districts and all 21 provinces have up to four to five palliative beds, and there are 36 palliative care units, for a total 190 beds for three million people. In 2014, a pediatric palliative care inpatient unit was established with five beds. Essential drugs for palliative care have been available in Mongolia since 2015. The pharmaceutical company IVCO produces morphine, codeine, pethidine, and oxycodone in Ulaanbaatar. Mongolia has made real progress in integrating palliative care into the health system. Copyright © 2017. Published by Elsevier Inc.

  8. Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum

    Directory of Open Access Journals (Sweden)

    Ashish Srivastava

    2017-07-01

    Full Text Available A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L. plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV and Ageratum leaf curl betasatellite (ALCB, respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch’s postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants.

  9. National All Schedules Prescription Electronic Reporting Act (NASPER): balancing substance abuse and medical necessity.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Brown, Keith R; Singh, Vijay

    2002-07-01

    The National All Schedules Prescription Electronic Reporting Act, or NASPER, is a bill proposed by the American Society of Interventional Pain Physicians to provide and improve patient access with quality care, and protect patients and physicians from deleterious effects of controlled substance misuse, abuse and trafficking. Controlled prescription drugs, including narcotic analgesics, anxiolytics, anti-depressants, stimulants, and sedative-hypnotics play a significant and legitimate role in interventional pain management practices in managing chronic pain and related disorders. Based on the 1997 household survey on drug abuse it is estimated that 76.9 million Americans had used an illicit drug at least once in their life. In 1997, 4.2 million people used analgesics, 2.1 million used tranquillizers, and an additional 2.3 million people used various other drugs, including sedatives, tranquillizers, etc. The non-medical use of prescription drugs exceeds that of all illicit substances except for marijuana and hashish. The report on epidemiology trends in drug abuse, based on community epidemiology work group analysis showed continued increase of abuse of prescription drugs in urban, suburban, and rural areas. The most commonly abused drugs include oxycodone, hydrocodone, hydromorphone, morphine, codeine, clonazepam, alprazolam, lorazepam, diazepam and carisoprodol. The diversion of prescription controlled substances to illicit channels is a public health and safety issue. This review describes the role of controlled substances in chronic pain management, prevalence and economic impact of controlled substance abuse, prescription accountability, effectiveness of prescription monitoring programs, and rationale for national controlled substance electronic reporting system.

  10. Occurrence of emerging contaminants, priority substances (2008/105/CE) and heavy metals in treated wastewater and groundwater at Depurbaix facility (Barcelona, Spain).

    Science.gov (United States)

    Teijon, Gloria; Candela, Lucila; Tamoh, Karim; Molina-Díaz, Antonio; Fernández-Alba, A R

    2010-08-01

    The presence of 170 pharmaceuticals, personal care products, priority substances according to the 2008/105EU Directive and four metals (Cd, Ni, Hg, Pb) have been investigated at the Llobregat delta, south of Barcelona (Spain). In the area, reclaimed water is destined to satisfy environmental uses, irrigation and the construction of a hydraulic barrier against seawater intrusion in the deep aquifer of the delta. A monitoring survey was undertaken of water samples from a tertiary wastewater treatment plant (Depurbaix), treated waste water with an additional treatment of ultrafiltration, reverse osmosis, and UV disinfection (WWATP, for the hydraulic barrier injection). Groundwater samples from the aquifer receiving recharge were also investigated. The pharmaceutical group of substances was detected in sampled waters at concentrations rarely exceeding a few microg/L, among the compounds Caffeine, Nicotine and Galaxolide (musk fragrance) were found to be present in more than 60% of the samples. Diuron was the only priority substance detected. The four metals were always present in a variable concentration. After the WWATP treatment the majority of analytes are removed from tertiary treated wastewater or their concentration is reduced below 0.1 microg/L. Monitoring revealed a widespread occurrence of analysed compounds in groundwater. Among them Codeine (analgesic), Ibuprofen (anti-inflammatory), Iopamidol, Iopromide (contrast agent) and Paraxanthine (metabolite of caffeine) have only been detected in groundwater, and are not present in water currently being injected in the deep aquifer.

  11. Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth.

    Science.gov (United States)

    Pickenpaugh, L; Reader, A; Beck, M; Meyers, W J; Peterson, L J

    2001-01-01

    The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of prophylactic amoxicillin on the occurrence of endodontic flare-up in asymptomatic, necrotic teeth. Seventy patients participated and had a clinical diagnosis of an asymptomatic, necrotic tooth with associated periapical radiolucency. One hour before endodontic treatment, patients randomly received either 3 g of amoxicillin or 3 g of a placebo control in a double-blind manner. After endodontic treatment, each patient received: ibuprofen; acetaminophen with codeine (30 mg); and a 5 1/2-day diary to record pain, swelling, percussion pain, and number and type of pain medication taken. The results demonstrated 10% of the 70 patients had a flare-up characterized by moderate-to-severe postoperative pain or swelling that began approximately 30 h after endodontic treatment and persisted for an average of 74 h. Of the seven patients who had flare-ups, 4 were in the amoxicillin group and 3 were not. Prophylactic amoxicillin did not significantly (p = 0.80) influence the endodontic flare-up. We concluded that a prophylactic dose of amoxicillin before endodontic treatment of asymptomatic, necrotic teeth had no effect on the endodontic flare-up.

  12. Detection of pyrrolizidine alkaloids using flow analysis with both acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence

    International Nuclear Information System (INIS)

    Gorman, Bree A.; Barnett, Neil W.; Bos, Richard

    2005-01-01

    For the first time, analytically useful chemiluminescence was elicited from the reactions of the pyrrolizidine alkaloids. Heliotrine, retronecine, supinine, monocrotaline and echinatine N-oxide yielded chemiluminescence upon reaction with tris(2,2'-bipyridyl)ruthenium(II) whilst lasiocarpine, its N-oxide and supinine elicited light upon reaction with acidic potassium permanganate. Detection limits for heliotrine were 1.25 x 10 -7 M and 9 x 10 -9 M for tris(2,2'-bipyridyl)ruthenium(III) perchlorate with flow injection analysis (FIA) and the silica-immobilised reagent (4-[4-(dichloromethylsilanyl)-butyl]-4'-methyl-2,2'-bipyridine)bis (2,2'-bipyridyl)ruthenium(II) with sequential injection analysis (SIA), respectively. Lasiocarpine was detectable at 1.4 x 10 -7 M using acidic potassium permanganate with FIA. Additionally, the silica-immobilised reagent was optimised with respect to the oxidant (ammonium ceric nitrate) concentration and the aspiration times which afforded a detection limit for codeine of 5 x 10 -10 M using SIA

  13. Opioid binding site in EL-4 thymoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Fiorica, E.; Spector, S.

    1988-01-01

    Using EL-4 thymoma cell-line we found a binding site similar to the k opioid receptor of the nervous system. The Scatchard analysis of the binding of (/sup 3/H) bremazocine indicated a single site with a K/sub D/ = 60 +/- 17 nM and Bmax = 2.7 +/- 0.8 pmols/10/sup 6/ cells. To characterize this binding site, competition studies were performed using selective compounds for the various opioid receptors. The k agonist U-50,488H was the most potent displacer of (/sup 3/H) bremazocine with an IC/sub 50/ value = 0.57..mu..M. The two steroisomers levorphanol and dextrorphan showed the same affinity for this site. While morphine, (D-Pen/sup 2/, D-Pen/sup 5/) enkephalin and ..beta..-endorphin failed to displace, except at very high concentrations, codeine demonstrated a IC/sub 50/ = 60..mu..M, that was similar to naloxone. 32 references, 3 figures, 2 tables.

  14. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

    Science.gov (United States)

    Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

    2018-04-01

    Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. In vivo antitussive activity of Coccinia grandis against irritant aerosol and sulfur dioxide-induced cough model in rodents

    Directory of Open Access Journals (Sweden)

    Shakti Prasad Pattanayak and Priyashree Sunita

    2009-12-01

    Full Text Available Coccinia grandis (Cucurbitaceae has extensively used to get relief from asthma and cough by the indigenous people of India. The antitussive effect of aerosols of two different concentrations (2.5%, 5% w/v of methanol extract of C. grandis fruits were tested by counting the numbers of coughs produced due to aerosols of citric acid, 10 min after exposing the male guinea pigs to aerosols of test solutions for 7 min. In another set of experiment methanol extract was investigated for its therapeutic efficacy on a cough model induced by sulfur dioxide gas in mice. The results showed significant reduction of cough number obtained in the presence of both concentrations of methanol extract as that of the prototype antitussive agent codeine phosphate. Also, methanol extract exhibited significant antitussive effect at 100, 200 and 400 mg/kg, per orally by inhibiting the cough by 20.57, 33.73 and 56.71% within 90 min of performing the experiment respectively.

  16. Desomorphine Screening Using Commercial Enzyme-Linked Immunosorbent Assays.

    Science.gov (United States)

    Winborn, Jessica; Kerrigan, Sarah

    2017-06-01

    Desomorphine ("Krokodil") is a semi-synthetic opioid that has drawn attention as a recreational drug, particularly in Russia, neighboring former Soviet Republics, Eastern and Central Europe. It has no accepted medicinal uses and is currently a schedule I drug in the United States. In clandestine environments, desomorphine is synthesized from codeine using red phosphorous, hydroiodic acid and gasoline. Residual starting materials in illicit preparations have been associated with severe dermatological effects and extensive tissue necrosis. Desomorphine is not well studied, and there are limited reports concerning its pharmacology or detection in biological matrices. Immunoassays are widely relied upon for both antemortem and postmortem toxicology screening. Although desomorphine is an opioid of the phenanthrene-type, its ability to bind to conventional opioid antibodies has not been described. In this report we describe the cross-reactivity of desomorphine using six commercially available enzyme-linked immunosorbent assays (Immunalysis Opiates Direct ELISA, Immunalysis Oxycodone/Oxymorphone Direct ELISA, Randox Opiate ELISA, OraSure Technologies OTI Opiate Micro-plate EIA, Neogen Opiate Group ELISA and Neogen Oxycodone/Oxymorphone ELISA). Cross-reactivites were highly variable between assays, ranging from 77 to desomorphine than those directed towards oxycodone. The Immunalysis Opiates Direct ELISA produced the greatest cross-reactivity, although several of the assays evaluated produced cross-reactivity of a sufficient magnitude to be effective for desomorphine screening. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Desomorphine (Krokodil): An overview of its chemistry, pharmacology, metabolism, toxicology and analysis.

    Science.gov (United States)

    Florez, Diego Hernando Ângulo; Dos Santos Moreira, Ana Maria; da Silva, Pedro Rafael; Brandão, Ricardo; Borges, Marcella Matos Cordeiro; de Santana, Fernando José Malagueño; Borges, Keyller Bastos

    2017-04-01

    "Krokodil" or "Crocodile" is an illegal homemade desomorphine drug obtained from chemical reactions of commercial codeine drugs with several other powerful and highly toxic chemical agents increasing its addiction and hallucinogenic effects when compared with other morphine analogues. This paper summarizes a complete review about an old drug called desomorphine (Krokodil), presenting its chemistry, pharmacology, metabolism, toxicology and analysis. It is of particular interest and concern because this cheaper injectable semisynthetic opioid drug has been largely used in recent years for recreational purposes in several Eastern European as well as North and South American countries, despite known damage to health that continuous use might induce. These injuries are much stronger and more aggressive than morphine's, infecting and rotting skin and soft tissue to the bone of addicts at the point of injection in less than three years, which, in most cases, evolves to death. On this basis, it is imperative that literature reviews focus on the chemistry, pharmacology, toxicology and analysis of dangerous Krokodil to find strategies for rapid and effective determination to mitigate its adverse effects on addicts and prevent consumption. It is crucial to know the symptoms and consequences of the use of Krokodil, as well as METHODS: for identification and quantification of desomorphine, contaminants and metabolites, which can help the forensic work of diagnosis and propose actions to control and eradicate this great danger to public health around the world. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Metabolic fate of desomorphine elucidated using rat urine, pooled human liver preparations, and human hepatocyte cultures as well as its detectability using standard urine screening approaches.

    Science.gov (United States)

    Richter, Lilian H J; Kaminski, Yeda Rumi; Noor, Fozia; Meyer, Markus R; Maurer, Hans H

    2016-09-01

    Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin. It is a crude synthesis product homemade from codeine with toxic byproducts. The aim of the present work was to investigate the metabolic fate of desomorphine in vivo using rat urine and in vitro using pooled human liver microsomes and cytosol as well as human liver cell lines (HepG2 and HepaRG) by Orbitrap-based liquid chromatography-high resolution-tandem mass spectrometry or hydrophilic interaction liquid chromatography. According to the identified metabolites, the following metabolic steps could be proposed: N-demethylation, hydroxylation at various positions, N-oxidation, glucuronidation, and sulfation. The cytochrome P450 (CYP) initial activity screening revealed CYP3A4 to be the only CYP involved in all phase I steps. UDP-glucuronyltransferase (UGT) initial activity screening showed that UGT1A1, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17 formed desomorphine glucuronide. Among the tested in vitro models, HepaRG cells were identified to be the most suitable tool for prediction of human hepatic phase I and II metabolism of drugs of abuse. Finally, desomorphine (crocodile) consumption should be detectable by all standard urine screening approaches mainly via the parent compound and/or its glucuronide assuming similar kinetics in rats and humans.

  19. Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

    Science.gov (United States)

    Sorrentino, Antonella; Trotta, Silvia; Colucci, Anna Pia; Aventaggiato, Lucia; Marzullo, Andrea; Solarino, Biagio

    2018-03-19

    "Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

  20. The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity.

    Science.gov (United States)

    Alves, Emanuele Amorim; Grund, Jean-Paul Cornelis; Afonso, Carlos Manuel; Netto, Annibal Duarte Pereira; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2015-04-01

    "Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis. In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Rapid determination of methadone and its major metabolite in biological fluids by gas-liquid chromatography with thermionic detection for maintenance treatment of opiate addicts.

    Science.gov (United States)

    Chikhi-Chorfi, N; Pham-Huy, C; Galons, H; Manuel, N; Lowenstein, W; Warnet, J M; Claude, J R

    1998-11-06

    A rapid gas-liquid chromatographic assay is developed for the quantification of methadone (Mtd) and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in biological fluids of opiate addicts. After alkaline extraction from samples with lidocaine hydrochloride as internal standard, Mtd and EDDP are separated on SP-2250 column at 220 degrees C and detected with a thermionic detector. The chromatographic time is about 6 min. The relative standard deviations (R.S.D.) of Mtd and EDDP standards are between 1.5 and 5.5%. Most drugs of abuse (morphine, codeine, narcotine, cocaine, benzoylecgonine, cocaethylene, dextropropoxyphene etc) are shown not to interfere with this technique. The method has been applied to study the levels of Mtd and EDDP metabolite in serum, saliva and urine of patients under maintenance treatment for opiate dependence. EDDP levels were found higher than those of Mtd in urine samples from four treated patients, but lower in serum and undetectable in saliva. However, Mtd concentrations were higher in saliva than in serum.

  2. The prevalences of and association between nonmedical prescription opioid use and poor sleep among Chinese high school students.

    Science.gov (United States)

    Tang, Daiting; Li, Pengsheng; Guo, Lan; Xu, Yan; Gao, Xue; Deng, Jianxiong; Huang, Jinghui; Huang, Guoliang; Wu, Hong; Yue, Yue; Lu, Ciyong

    2016-07-28

    The purpose of this study was to investigate the prevalences of and association between nonmedical prescription opioid use (NMPOU) and sleep quality among Chinese high school students. A cross-sectional study was conducted in Chongqing high school students in 2012, and questionnaires from 18,686 students were completed and eligible for this study. Demographic and NMPOU information was collected using a self-administered questionnaire. The Chinese Pittsburgh Sleep Quality index (CPSQI) was used to assess the occurrence of poor sleep. Among the total sample, 18.0% were classified as poor sleepers (27.4% of the subjects with past-month NMPOU), and the prevalences of lifetime, past-year and past-month NMPOU were 14.6, 4.6 and 2.8% across the entire sample, respectively. The most commonly used medicine was licorice tablets with morphine (9.1, 2.5 and 1.5% for lifetime, past-year and past-month, respectively), followed by cough syrup with codeine, Percocet, diphenoxylate and tramadol. After adjustment for potential confounders, the association between past-month NMPOU and poor sleep remained significant (AOR = 1.47, 95% CI 1.17 to 1.85). Programs aimed at decreasing NMPOU should also pay attention to sleep quality among adolescents.

  3. Dolor crónico en el paciente anciano

    Directory of Open Access Journals (Sweden)

    Jorge Hernán López Ramírez

    2001-10-01

    Full Text Available Chronic pain is extremely common among older people. Pain is an unpleasant sensory and emotional experience, but unfortunately, most of primary care physicians take poor attention when their elderly patients complain about it. Several reasons explain this: Patients do not die of pain, pain is subjective, pain management takes time, clinicians are concerned about adverse effects of analgesic medicines etc. Understanding pathophisiology of chronic pain is essential in order to give adequate treatment; in this sense chronic pain can be divided broadly in nociceptive (somatic or visceral for instance osteoarthritis, ischemic disorders etc., neuropathic (peripheral or central, for instance postherpetic neuralgia, post stroke pain etc. and psychogenic. Although older people are more likely to experience adverse reactions, analgesic drugs are safe and effective for use in this population. It is recommended to start with conventional analgesics Iike acetaminophen, sometimes in combination with mild opioids like codeine for moderately severe pain. The use of nonsteroidal anti-inflamatory drugs should be avoided for long time periods in  elderly atients. The use of opioid drugs is controversial but they are probably underused. Fears of addiction are often exaggerated in the elderly. Nonpharmacologic strategies, like physical therapy, exercise programs, TENS, relaxation, etc. used alone or with medications should be an integral part of care for chronic pain patients.

  4. Drug and Solvent Abuse Among Ahwaz\\'s Elderlies

    Directory of Open Access Journals (Sweden)

    Abdolrahim Asadollahi

    2007-10-01

    Full Text Available Objectives: There are researches to point epidemiology of addiction to drugs, chemical and solvent abuse in elderlies. Drug and Solvent abuse is considered as one of these addictions. This study was point to chemical abuse among elderly population of Ahwaz an Iranian city during year of 2007. Methods & Materials: Research method is description-exploration with use to questionnaire, clinical interview and survey of medical and clinical reports among volunteer clients. Statistical community is all elderly population at one of citizen region in Ahwaz city (Iran. Seventy four dossiers were considered via random sampling; with 30 Elder volunteer clients been interviewed and replied to Elderly Drug Abuse Questionnaire (EDAQ. Results: Signification of hypothesis with X2 test was considered significant relation between age and addiction record variables to solvent abuse; this relation is very significant to second value of drug's derivations such as Morphine, Codeine, Tebaine and Heroine. Interview showed psychological dependent due to appeal them to solvent abuse. Kind of abuse among elderly was snuffing and abuse of medicine drugs which were been recommended to them by their physician. Conclusion: Although study of solvent and chemical abuse's epidemiology pointed less average of this addiction in samples, should be considered important and notice in studies. Finally, researchers were suggested to avoid of this new drug abuse and so to control behavior and interaction of these addicted and their behavior development; it's better to control on distribution of solvent and glue materials and recommending of medicine drug via physicians visiting exderlies.

  5. Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters

    Directory of Open Access Journals (Sweden)

    Mrozikiewicz Przemyslaw M.

    2014-06-01

    Full Text Available There are a number of compounds that can modify the activity of ABC (ATP-binding cassette and SLC (solute carrier transporters in the blood-brain barrier (BBB. The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1. Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital and natural (codeine, cyclosporine A, quercetin substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

  6. Use of morphine and 6-monoacetylmorphine in blood for the evaluation of possible risk factors for sudden death in 192 heroin users.

    Science.gov (United States)

    Fugelstad, Anna; Ahlner, Johan; Brandt, Lena; Ceder, Gunnel; Eksborg, Staffan; Rajs, Jovan; Beck, Olof

    2003-04-01

    To detect risk factors for sudden death from heroin injection. Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6-monoacetylmorphine (6-MAM) in blood were included in order to select heroin intoxication cases. Stockholm, Sweden. Autopsy investigation and toxicological analysis of blood and urine; and police reports. In two-thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6-MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one-quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6-MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6-MAM blood concentrations. We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.

  7. Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors

    Directory of Open Access Journals (Sweden)

    Milan Fedurco

    2015-01-01

    Full Text Available The California poppy (Eschscholzia californica Cham. contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABAA receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant α1β2γ2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S-reticuline behaved as positive allosteric modulator at the α3, α5, and α6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S-reticuline at the α3β2γ2 and α5β2γ2 GABAA receptors. Interestingly, α1, α3, and α5 were not significantly affected by (R-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S-reticuline metabolites in the rodent brain.

  8. Consequences of dextropropoxyphene market withdrawal in elderly patients with chronic pain.

    Science.gov (United States)

    Becquemont, Laurent; Delespierre, Tiba; Bauduceau, Bernard; Benattar-Zibi, Linda; Berrut, Gilles; Corruble, Emmanuelle; Danchin, Nicolas; Derumeaux, Geneviève; Doucet, Jean; Falissard, Bruno; Forette, Francoise; Hanon, Olivier; Pasquier, Florence; Pinget, Michel; Ourabah, Rissane; Bucher, Sophie; Lazkani, Aida; Piedvache, Celine; Bertin, Philippe

    2014-10-01

    Describe the consequences of dextropropoxyphene (DXP) market withdrawal on analgesic prescriptions and on the quality of therapeutic management of chronic pain. From a cohort of non-institutionalised elderly patients with chronic pain recruited by general practitioners, we selected patients who were treated with DXP daily for at least 6 months just prior to DXP market withdrawal and who had an evaluation of pain and its impact on daily activities before and after DXP withdrawal. One hundred three patients took DXP daily for chronic pain. Immediately after DXP market withdrawal, 42 (40.8%), 55 (53.4%) and 3 (2.9%) patients were treated with step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9%) were no longer receiving any analgesic medication. Among the 55 patients who continued on step 2 analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain intensity and the impact of pain on daily activities remained stable. DXP market withdrawal had no consequences on the intensity or impact of chronic pain in elderly patients.

  9. Topical lidocaine patch 5% for acute postoperative pain control.

    LENUS (Irish Health Repository)

    Gilhooly, D

    2011-02-01

    A 39-year-old para 3 woman presented for elective caesarean section (lower segment caesarean section (LSCS)) for breech presentation. The patient had a strong history of atopy and anaphylaxis to paracetamol, codeine, penicillin and latex. The patient was asthmatic, triggered by aspirin. Epidural anaesthesia was unsuccessful and LSCS was carried out under spinal anaesthesia. Postoperatively the patient was unwilling to take analgesic medication due to fear of an allergic reaction. Three 5% lidocaine patches were applied to the wound for postoperative analgesia. This reduced the patient\\'s visual analogue scale pain score from 10\\/10 to 5\\/10 at rest and 10\\/10 to 7\\/10 with movement. Transcutaneous electrical nerve stimulation was added and this improved associated back pain, reducing the pain further to 2\\/10. This is the first description of lignocaine patch 5% for postoperative LSCS pain. It is suggested that this method of delivery of local anaesthetic, which is easy to apply and has minimal side effects, should be considered not as a sole agent but as part of a multimodal technique to address postoperative LSCS pain.

  10. Evaluation of the quality consistency of powdered poppy capsule extractive by an averagely linear-quantified fingerprint method in combination with antioxidant activities and two compounds analyses.

    Science.gov (United States)

    Zhang, Yujing; Sun, Guoxiang; Hou, Zhifei; Yan, Bo; Zhang, Jing

    2017-12-01

    A novel averagely linear-quantified fingerprint method was proposed and successfully applied to monitor the quality consistency of alkaloids in powdered poppy capsule extractive. Averagely linear-quantified fingerprint method provided accurate qualitative and quantitative similarities for chromatographic fingerprints of Chinese herbal medicines. The stability and operability of the averagely linear-quantified fingerprint method were verified by the parameter r. The average linear qualitative similarity SL (improved based on conventional qualitative "Similarity") was used as a qualitative criterion in the averagely linear-quantified fingerprint method, and the average linear quantitative similarity PL was introduced as a quantitative one. PL was able to identify the difference in the content of all the chemical components. In addition, PL was found to be highly correlated to the contents of two alkaloid compounds (morphine and codeine). A simple flow injection analysis was developed for the determination of antioxidant capacity in Chinese Herbal Medicines, which was based on the scavenging of 2,2-diphenyl-1-picrylhydrazyl radical by antioxidants. The fingerprint-efficacy relationship linking chromatographic fingerprints and antioxidant activities was investigated utilizing orthogonal projection to latent structures method, which provided important pharmacodynamic information for Chinese herbal medicines quality control. In summary, quantitative fingerprinting based on averagely linear-quantified fingerprint method can be applied for monitoring the quality consistency of Chinese herbal medicines, and the constructed orthogonal projection to latent structures model is particularly suitable for investigating the fingerprint-efficacy relationship. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Amperometric detection of morphine based on poly(3,4-ethylenedioxythiophene) immobilized molecularly imprinted polymer particles prepared by precipitation polymerization

    International Nuclear Information System (INIS)

    Ho, K.-C.; Yeh, W.-M.; Tung, T.-S.; Liao, J.-Y.

    2005-01-01

    Molecular imprinting is a novel technique used for chiral separation, artificial antibodies, sensors, and assays. Typically, molecular imprinted polymers (MIPs) are monoliths with irregular shapes. However, microspherical shapes with more uniform size can be obtained by the method of precipitation polymerization, which offers a higher active surface area by manipulating its compositions. In this study, MIP particles for the target molecule, morphine, were synthesized using a precipitation polymerization method that is more facile than the previous one that produced a thermally polymerized bulk. The conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), was utilized to immobilize the MIP particles onto the indium tin oxide (ITO) glass as a MIP/PEDOT-modified electrode. The sensitivity for the MIP/PEDOT-modified electrode with MIP particles was 41.63 μA/cm 2 mM, which is more sensitive than that with non-MIP particles or that of a single PEDOT film with no incorporated particles in detecting morphine ranging from 0.1 to 2 mM. The detection limit was 0.3 mM (S/N = 3). In addition, we presented that the modified electrode can discriminate codeine that plays an interfering species

  12. Evaluation of hydrophilic interaction liquid chromatography stationary phases for analysis of opium alkaloids.

    Science.gov (United States)

    Bagheri, Mohsen; Taheri, Mohammadreza; Farhadpour, Mohsen; Rezadoost, Hassan; Ghassempour, Alireza; Aboul-Enein, Hassan Y

    2017-08-18

    The separation of a mixture containing five major opium alkaloids, namely morphine, codeine, thebaine, noscapine and papaverine has been investigated in hydrophilic interaction liquid chromatography (HILIC) mode using five different stationary phases: bare silica, zwitterion, aminopropyl, diol and cyanopropyl. In order to propose the appropriate column for separation and purification, retention behaviors of the five natural opioids have been studied on mentioned HILIC stationary phases. The mechanism of separation in diverse HILIC media, based on the formation of water-rich layer on surface of the HILIC stationary phases and the physicochemical properties of opium alkaloids, such as pKa (acidic pK) and the octanol-water distribution coefficient (log Do/w) are discussed. Chromatographic responses including modified limit of detection LOD m , signal to noise ratio (S/N) m , and defined modified R Sm have considered for suggestion of the suitable column for quantitative/qualitative and preparative purposes. According to the obtained results, diol stationary phase is best suited for analytical chromatography, whereas bare silica and zwitterionic stationary phases are appropriate for preparative applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Dioxygenases Catalyze O-Demethylation and O,O-Demethylenation with Widespread Roles in Benzylisoquinoline Alkaloid Metabolism in Opium Poppy*

    Science.gov (United States)

    Farrow, Scott C.; Facchini, Peter J.

    2013-01-01

    In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy. PMID:23928311

  14. Amperometric morphine sensing using a molecularly imprinted polymer-modified electrode

    International Nuclear Information System (INIS)

    Yeh, W.-M.; Ho, K.-C.

    2005-01-01

    This study incorporates morphine into a molecularly imprinted polymer (MIP) for the amperometric detection of morphine. The polymer, poly(3,4-ethylenedioxythiophene), PEDOT, is an electroactive film that catalyzes morphine oxidation and lowers the oxidization potential on an indium tin oxide (ITO) electrode. The MIP-PEDOT modified electrode is prepared by electropolymerizing PEDOT onto an ITO electrode in a 0.1 M LiClO 4 solution with template addition (morphine). After template molecule extraction, the oxidizing current of the MIP-PEDOT modified electrode is measured in a 0.1 M KCl solution (pH = 5.3) at 0.75 V (versus Ag/AgCl/sat'd KCl) with the morphine concentration varying in the 0.1-5 mM range. A linear range, displaying the relationship between steady-state currents and morphine concentrations, from 0.1 to 1 mM, is obtained. The proposed amperometric sensor could be used for morphine detection with a sensitivity of 91.86 μA/cm 2 per mM. A detection limit of 0.2 mM at a signal-to-noise ratio of 3 is achieved. Moreover, the proposed method can discriminate between morphine and its analogs, such as codeine

  15. Benzylisoquinoline alkaloid biosynthesis in opium poppy.

    Science.gov (United States)

    Beaudoin, Guillaume A W; Facchini, Peter J

    2014-07-01

    Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy.

  16. A Tale of Three Cell Types: Alkaloid Biosynthesis Is Localized to Sieve Elements in Opium Poppy

    Science.gov (United States)

    Bird, David A.; Franceschi, Vincent R.; Facchini, Peter J.

    2003-01-01

    Opium poppy produces a diverse array of pharmaceutical alkaloids, including the narcotic analgesics morphine and codeine. The benzylisoquinoline alkaloids of opium poppy accumulate in the cytoplasm, or latex, of specialized laticifers that accompany vascular tissues throughout the plant. However, immunofluorescence labeling using affinity-purified antibodies showed that three key enzymes, (S)-N-methylcoclaurine 3′-hydroxylase (CYP80B1), berberine bridge enzyme (BBE), and codeinone reductase (COR), involved in the biosynthesis of morphine and the related antimicrobial alkaloid sanguinarine, are restricted to the parietal region of sieve elements adjacent or proximal to laticifers. The localization of laticifers was demonstrated using antibodies specific to the major latex protein (MLP), which is characteristic of the cell type. In situ hybridization showed that CYP80B1, BBE, and COR gene transcripts were found in the companion cell paired with each sieve element, whereas MLP transcripts were restricted to laticifers. The biosynthesis and accumulation of alkaloids in opium poppy involves cell types not implicated previously in plant secondary metabolism and dramatically extends the function of sieve elements beyond the transport of solutes and information macromolecules in plants. PMID:14508000

  17. Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy.

    Science.gov (United States)

    Farrow, Scott C; Facchini, Peter J

    2013-10-04

    In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy.

  18. Pattern of quantitative inheritance of yield and component traits in opium poppy (Papaver somniferum L.

    Directory of Open Access Journals (Sweden)

    Maurya Krishna Nand

    2014-01-01

    Full Text Available Generation mean analysis of cross NB-5x58/1 and its reciprocal cross was carried out to understand the nature of gene action in opium poppy. The significance of A, B, C and D scaling tests indicated presence of non-allelic interaction in the inheritance of traits except capsule size and husk yield/plant for reciprocal cross. Additive as well as dominance components of gene action were found in both the crosses. Most of the traits had greater non fixable dominance ‘h’ and dominance x dominance effects ‘l’ than fixable additive (d and additive x additive effects (i except leaves/plant, branches/plant, capsules/plant, stem diameter, capsule weight/plant, husk yield/plant, opium yield/plant, codeine and narcotine content which showed greater importance of additive (d and additive x additive effects (i effects. Inter-mating of the best parents, diallel selective mating or biparental mating in early segregating generations followed by recurrent selections were suggested for genetic improvement of opium poppy.

  19. Literary investigation on the origin of poppy and other narcotics Research Articles

    Directory of Open Access Journals (Sweden)

    Lim Chung San

    2009-06-01

    Full Text Available Objectives : This study was performed to developing orally administered analgesics and locally injected pharmacopuncture analgesics like opioids. Methods : Literary investigation on the origin of poppy (Papaver somniferum L and other narcotics was conducted to examine the potential of developing orally administered analgesics and locally injected pharmacopuncture analgesics. Opium is a gum-like mass derived from air-dried white fluid of immature fruit of the poppy. Opium contains approximately 20 types of alkaloids including morphine, codeine, thebaine, papaverine and others. Natural opioids and synthetic alkaloid derivatives are the constituents of opioid analgesics and their effects and side-effects depend on the peculiarities of receptors. An extreme caution is required in the selection of proper dosage, proper analgesic types, and indications for successful pain management. Results and Discussion : With the enactment of "Narcotic control protocol", herbs such as cannibis and poppy are no longer available for use by Korean medicine doctors, and these doctors are faced with difficulty in managing severe pain in the clinical environment. A systematic consideration is inevitable for overcoming the limitation on these analgesics.

  20. Enhanced prolactin levels in opium smokers.

    Science.gov (United States)

    Moshtaghi-Kashanian, Ghollam-Reza; Esmaeeli, Farzaneh; Dabiri, Shahriar

    2005-12-01

    In Iran, opium is smoked for pleasure or as a medication by some people. It is a complex mixture of 40 different alkaloids, including morphine and codeine along with many impurities. Although it is well established that opioids or tobacco affect many physiological functions in humans, to our knowledge there has been no specific study looking at these effects in opium smokers. To assess that, we investigated the circulating levels of prolactin, TSH, LH, FSH and testosterone in male opium smokers who also smoke cigarettes (n=23, aged 28.4+/- 4.1 years), and comparing this with the corresponding values for nicotine abusers (n=12, 15-25 cigarettes/day) or a healthy control group (n=20) of the same age. Our results showed that 86.96% of the opium-dependent and 41.67 % of the nicotine-dependent group displayed high prolactin values (popium and the plasma prolactin level of opium dependents (p=0.748, popium smokers and 50% of the cigarette smokers (popium smokers was also lower than that of the other two groups (popium and cigarette smoking may synergistically influence pituitary hormone production through the effects on neuropeptides produced either locally or systemic.

  1. Challenges and opportunities in using wastewater analysis to measure drug use in a small prison facility.

    Science.gov (United States)

    van Dyken, Emma; Lai, Foon Yin; Thai, Phong K; Ort, Christoph; Bruno, Raimondo; Hall, Wayne; Kirkbride, K Paul; Mueller, Jochen F; Prichard, Jeremy

    2016-03-01

    Wastewater analysis (WWA) is intended to be a direct and objective method of measuring substance use in large urban populations. It has also been used to measure prison substance use in two previous studies. The application of WWA in this context has raised questions as to how best it might be used to measure illicit drug use in prisons, and whether it can also be used to measure prescription misuse. We applied WWA to a small regional prison to measure the use of 12 licit and illicit substances. We attempted to measure the non-medical use of methadone and buprenorphine and to compare our findings with the results of the prison's mandatory drug testing (MDT). Representative daily composite samples were collected for two periods of 12 consecutive days in May to July 2013 and analysed for 18 drug metabolites. Prescription data and MDT results were obtained from the prison and compared with the substance use estimates calculated from WWA data. Daily use of methamphetamine, methadone, buprenorphine and codeine was detected, while sporadic detection of ketamine and methylone was also observed. Overall buprenorphine misuse appeared to be greater than methadone misuse. Compared with MDT, WWA provides a more comprehensive picture of prison substance use. WWA also has the potential to measure the misuse of medically prescribed substances. However, a great deal of care must be exercised in quantifying the usage of any substance in small populations, such as in prisons. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  2. Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

    Science.gov (United States)

    Koulouris, Andreas I; Banim, Paul; Hart, Andrew R

    2017-04-01

    Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

  3. Comparison between narcotic 'receptors' in the guinea-pig ileum and the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Terenius, L [Uppsala Univ. (Sweden)

    1975-01-01

    The receptors, i.e., specific binding molecules, for narcotic analgesics in the guinea-pig ileum and rat brain have been compared. The relative affinities of a number of narcotics for the two receptors were very similar and discrimination between stereoisomeric agents was identical. The dissociation constants for dihydromorphine binding were 0.78 nM for the ileum and 1.4 nM for the brain receptor, respectively. There was a good correspondance between receptor affinities on the ileum preparation and the literature data on biologic activity on the isolated ileum. Codeine, diphenoxylate, difenoxine and loperamide, which are used clinically for the treatment of diarrhoea showed no selectivity against the ileum receptor. The two latter drugs had a very high receptor affinity and their lack of narcotic activity after oral administration is probably attributable to lack of penetration of the CNS. Receptor binding in both ileum and brain preparations was inhibited by N-ethylmaleimide, Triton X-100, trypsin and phospholipase C. There were small quantitative differences in sensitivity to these agents but it is difficult to assess whether this is because of real differences between the receptor molecules or attributable to secondary effects. As previously described for the brain receptor, the ileum receptor appeared to be present in a fraction enriched in plasma membranes.

  4. Determination of thebaine in water samples, biological fluids, poppy capsule, and narcotic drugs, using electromembrane extraction followed by high-performance liquid chromatography analysis.

    Science.gov (United States)

    Seidi, Shahram; Yamini, Yadollah; Heydari, Akbar; Moradi, Morteza; Esrafili, Ali; Rezazadeh, Maryam

    2011-09-09

    Opium determination is of great importance from toxicological and pharmaceutical standpoints. In present work, electromembrane extraction (EME) coupled with high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection was developed for determination of thebaine as a natural alkaloid, in different matrices containing water, urine, poppy capsule, street heroine, and codeine tablet. Thebaine migrated from 3 mL of sample solutions, through a thin layer of 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. The variables of interest, such as chemical composition of the organic liquid membrane, stirring speed, extraction time and voltage, pH of donor and acceptor phases and salt effect in the EME process were optimized. Under optimal conditions, thebaine was effectively extracted from different matrices with recoveries in the range of 45-55%, which corresponded to preconcentration factors in the range of 90-110. Good linearity was achieved for calibration curves with a coefficient of estimation higher than 0.997. Detection limits and intra-day precision (n=3) were less than 15 μg L(-1) and 8.9%, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. "Detection of Morphine in Opioid Abusers Hair by GC/MS "

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    Khosrou Abdi

    2004-07-01

    Full Text Available Thirty hair samples were collected from the male opioid abusers in which the presence of morphine in their urine samples was confirmed by Thin Layer Chromatography (TLC analyses. The hair samples were washed, cut into small pieces and extracted in a mixture of methanol-triflouroacetic acid (9:1. The methanolic phase was evaporated to dryness under nitrogen stream and derivitized by addition of N-methyl-N-trimethylsilyl triflouroacetamide (MSTFA and 1% trimethyl iodosilane (TMIS with sonication. One micro liter of each derivitized sample was injected into a Gas Chromatograph-Mass Spectrometer (GC/MS system consisting of a capillary column and finnigan MS with selective ion monitoring (SIM mode. The selected mass for ions codeine and morphine were 370 and 429, respectively. The limit of detection (LOD was set at 0.03ng/mg of the hair. By using the above procedure, morphine was detectable in all of the examined samples and this method is capable to detec low levels of morphine in hair for a long period of time following the last intake of the drug

  6. Analgesic properties of the aqueous and ethanol extracts of the leaves of Kalanchoe crenata (Crassulaceae).

    Science.gov (United States)

    Nguelefack, T B; Fotio, A L; Watcho, P; Wansi, S L; Dimo, T; Kamanyi, A

    2004-05-01

    The aqueous and ethanol extracts of the dry leaves of Kalanchoe crenata (300 and 600 mg/kg) were evaluated for their analgesic properties on the pain induced by acetic acid, formalin and heat in mice and by pressure on rats. The ethanol extract of K. crenata at a dose of 600 mg/kg produced an inhibition of 61.13% on pain induced by acetic acid and 50.13% for that induced by formalin. An inhibition of 67.18% was observed on pain induced by heat 45 min after the administration of the extract. The aqueous extract administered at a dose of 600 mg/kg produced a maximum effect of 25% on pain induced by pressure. These activities were similar to those produced by a paracetamol-codeine association, while indomethacin exhibited a protective effect only against the writhing test. Our results suggest that the leaves of K. crenata could be a source of analgesic compounds. Copyright 2004 John Wiley & Sons, Ltd.

  7. Dextromethorphan in Cough Syrup: The Poor Man's Psychosis.

    Science.gov (United States)

    Martinak, Bridgette; Bolis, Ramy A; Black, Jeffrey Ryne; Fargason, Rachel E; Birur, Badari

    2017-09-15

    Dextromethorphan (3-methoxy-N-methylmorphinan), also known as "DXM" and "the poor man's PCP," is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psychosis characterized by Phencyclidine (PCP)-like psychological symptoms, including delusions, hallucinations, and paranoia. We report a noteworthy case of severe dextromethorphan use disorder with dextromethorphan-induced psychotic disorder in a 40-year-old Caucasian female, whose symptoms remitted only following treatment with a combination of an antipsychotic and mood stabilizer. While some states have begun to limit the quantity of DXM sold or restrict sales to individuals over 18-years of age, there is currently no federal ban or restriction on DXM. Abuse of DXM, a readily available and typically inexpensive agent that is not detected on a standard urine drug screen, may be an under-recognized cause of substance-induced psychosis. It is imperative that clinicians are aware of the potential psychiatric sequelae of recreational DXM use.

  8. Dextromethorphan in Cough Syrup: The Poor Man’s Psychosis

    Science.gov (United States)

    Martinak, Bridgette; Bolis, Ramy A.; Black, Jeffrey Ryne; Fargason, Rachel E.; Birur, Badari

    2017-01-01

    Dextromethorphan (3-methoxy-N-methylmorphinan), also known as “DXM” and “the poor man’s PCP,” is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psychosis characterized by Phencyclidine (PCP)-like psychological symptoms, including delusions, hallucinations, and paranoia. We report a noteworthy case of severe dextromethorphan use disorder with dextromethorphan-induced psychotic disorder in a 40-year-old Caucasian female, whose symptoms remitted only following treatment with a combination of an antipsychotic and mood stabilizer. While some states have begun to limit the quantity of DXM sold or restrict sales to individuals over 18-years of age, there is currently no federal ban or restriction on DXM. Abuse of DXM, a readily available and typically inexpensive agent that is not detected on a standard urine drug screen, may be an under-recognized cause of substance-induced psychosis. It is imperative that clinicians are aware of the potential psychiatric sequelae of recreational DXM use. PMID:28936010

  9. Clinical Application of Pharmacogenetics: Where are We Now?

    Science.gov (United States)

    2014-01-01

    Pharmacogenetic (PGx) testing has the potential to improve drug therapy in an individual by informing appropriate drug dosing or drug selection in order to maximize efficacy and safety. Although multiple studies have illustrated the potential benefits of such testing when applied to specific drugs across a broad range of therapy areas, the uptake of PGx testing in routine clinical practice has been relatively limited. Implementation appears to be hampered by the absence of sufficiently strong evidence linking the results of testing with actionable benefits in terms of clinical outcomes. Meanwhile, there are now adequate data to allow dosing recommendations as have been developed by bodies including the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) in several settings, including TPMT/thiopurines, CYP2C19/clopidogrel, CYP2D6/codeine, VKORC1-CYP2C9/warfarin, HLA-B*5701/abacavir, SLCO1B1/simvastatin and HLAB*5801/allopurinol. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) have also recently initiated surveys in order to better understand the extent of, and the role played by, PGx testing in clinical practice. This should help identify where further training and education may be beneficial. To this end, in collaboration with ESPT, the IFCC Pharmacogenetic Laboratory Network has now been formed, with the aim of improving the uptake and quality of PGx testing. PMID:27683445

  10. Detection of pyrrolizidine alkaloids using flow analysis with both acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Gorman, Bree A. [School of Biological and Chemical Sciences, Deakin University, Geelong, Vic. 3217 (Australia); Barnett, Neil W. [School of Biological and Chemical Sciences, Deakin University, Geelong, Vic. 3217 (Australia)]. E-mail: barnie@deakin.edu.au; Bos, Richard [School of Biological and Chemical Sciences, Deakin University, Geelong, Vic. 3217 (Australia)

    2005-06-13

    For the first time, analytically useful chemiluminescence was elicited from the reactions of the pyrrolizidine alkaloids. Heliotrine, retronecine, supinine, monocrotaline and echinatine N-oxide yielded chemiluminescence upon reaction with tris(2,2'-bipyridyl)ruthenium(II) whilst lasiocarpine, its N-oxide and supinine elicited light upon reaction with acidic potassium permanganate. Detection limits for heliotrine were 1.25 x 10{sup -7} M and 9 x 10{sup -9} M for tris(2,2'-bipyridyl)ruthenium(III) perchlorate with flow injection analysis (FIA) and the silica-immobilised reagent (4-[4-(dichloromethylsilanyl)-butyl]-4'-methyl-2,2'-bipyridine)bis (2,2'-bipyridyl)ruthenium(II) with sequential injection analysis (SIA), respectively. Lasiocarpine was detectable at 1.4 x 10{sup -7} M using acidic potassium permanganate with FIA. Additionally, the silica-immobilised reagent was optimised with respect to the oxidant (ammonium ceric nitrate) concentration and the aspiration times which afforded a detection limit for codeine of 5 x 10{sup -10} M using SIA.

  11. NATURAL AND PARTIALLY SYNTETIC ANALGESICS

    Directory of Open Access Journals (Sweden)

    Stevan Glogovac

    2005-12-01

    Full Text Available Humans have a long hystory of stimulating and mind-altering substances use. Depressive drugs, including morphine and other narcotics, barbiturates and ethanol, are strongly addictive for susceptible individuals. The phenomenon is most striking in the case of opiates. Morphine is an alkaloid of opium. Named after the Roman god of dreams, Morpheus, the compound has potent analgesic properties toward all types of pain. By supstitution of two hydroxylic groups of morphine many natural and semysyntetic derivatives with different pharmacological activity and analgesic action are obtained. Determinations and quantifications of narcotic analgesics in drug addicts are important in forensic medicine and clinical toxicology. With development of highly sensitive chromatography technique (HPLC-GC, GH-MS, more and more substances are determined, including opioid drugs: morphine, codeine, dyhydrocodeine, and heroin and 6-monoacetyl morphine. Hair analysys by HPLC/MS spectroscopy is an effective forensic tool for determining the use of abused drugs. The “fingerprint” for heroin in the mixture with the other substances(1-10 components is determined by 1D-TOCSY NMR.

  12. Preoperative oral dextromethorphan does not reduce pain or morphine consumption after open cholecystectomy

    Directory of Open Access Journals (Sweden)

    Mahmoodzadeh Hossein

    2009-01-01

    Full Text Available Background: Dextromethorphan, the D-isomer of the codeine analog levorphanol, is a weak, noncompetitive N-Methyl-D-Aspartate (NMDA receptor antagonist. It has been suggested that NMDA receptor antagonists induce preemptive analgesia when administered before tissue injury occurs, thus decreasing the subsequent sensation of pain. Materials and Methods: The study was conducted in the Dr. Ali Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, between February 2005 and December 2006. In this study, 72 patients scheduled for elective cholesyctectomy were randomized into three groups to receive either oral dextromethorphan 45 mg (Group D45 = 24, dextromethorphan 90 mg (Group D90 = 24, or placebo (Group C, n = 24, as premedication, 120 minutes before surgery. A visual analog scale (VAS for pain of each patient was measured at arrival in the ward and six and 24 hours after surgery. Results: The demographic characteristics of patients, ASA physical status class, duration of surgery, and the basal VAS pain score were similar in the two groups. There was no significant difference in the mean of the VAS pain scores measured over time or morphine consumption among the three groups. Conclusion: Dextromethorphan 45 mg and 90 mg, administrated orally, two hours before surgery, had no effect on postoperative morphine requirement and pain intensity.

  13. Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report.

    Science.gov (United States)

    Lalanne, Laurence; Nicot, Chloe; Lang, Jean-Philippe; Bertschy, Gilles; Salvat, Eric

    2016-11-10

    Opioids are good painkillers, but many patients treated with opioids as painkillers developed a secondary addiction. These patients need to stop misusing opioids, but the mild-to-severe clinical symptoms associated with opioid withdrawal risk increasing their existing pain. In such cases, ketamine, which is used by anaesthetists and pain physicians to reduce opioid medication, may be an effective agent for managing opioid withdrawal. We describe the case of a woman who developed a severe secondary addiction to opioids in the context of lombo-sciatic pain. She presented a severe opioid addiction, and her physicians refused to prescribe such high doses of opioid treatment (oxycontin® extended-release 120 mg daily, oxycodone 60 mg daily, and acetaminophen/codeine 300 mg/25 mg 6 times per day). To assist her with her opioid withdrawal which risked increasing her existing pain, she received 1 mg/kg ketamine oral solution, and two days after ketamine initiation her opioid treatment was gradually reduced. The patient dramatically reduced the dosage of opioid painkillers and ketamine was withdrawn without any withdrawal symptoms. Ketamine displays many interesting qualities for dealing with all symptoms relating to opioid withdrawal. Accordingly, it could be used instead of many psychotropic treatments, which interact with each other, to help with opioid withdrawal. However, the literature describes addiction to ketamine. All in all, although potentially addictive, ketamine could be a good candidate for the pharmacological management of opioid withdrawal.

  14. An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray

    Directory of Open Access Journals (Sweden)

    Handong Ouyang

    2012-01-01

    Full Text Available The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG appears to be critical in regulating the complex signs and symptoms of opioid withdrawal. Numerous neurochemical mechanisms in the PAG have been identified that may contribute to the opioid withdrawal syndrome. Accumulating evidence suggests that glial activation leading to the release of proinflammatory molecules acting on neurons is important in the complex syndrome of opioid dependence and withdrawal. This paper focuses on the recent advances in our understanding of the vital role that glia-neuron interactions play in opioid dependence and withdrawal within the PAG. We summarize those neurochemical mechanisms associated with opioid withdrawal including the recently defined importance of TNFα release from activated glial cells that communicate with TNF receptors on PAG neurons.

  15. A fast ultra high pressure liquid chromatographic method for qualification and quantification of pharmaceutical combination preparations containing paracetamol, acetyl salicylic acid and/or antihistaminics.

    Science.gov (United States)

    Deconinck, E; Sacré, P Y; Baudewyns, S; Courselle, P; De Beer, J

    2011-09-10

    A fully validated UHPLC method for the identification and quantification of pharmaceutical preparations, containing paracetamol and/or acetyl salicylic acid, combined with anti-histaminics (phenylephrine, pheniramine maleate, diphenhydramine, promethazine) and/or other additives as quinine sulphate, caffeine or codeine phosphate, was developed. The proposed method uses a Waters Acquity BEH C18 column (2 mm × 100 mm, 1.7 μm) with a gradient using an ammonium acetate buffer pH 4.0 as aqueous phase and methanol as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 1.5% and 2%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 5% for all of the considered components. A UHPLC method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Evaluation of abalone β-glucuronidase substitution in current urine hydrolysis procedures.

    Science.gov (United States)

    Malik-Wolf, Brittany; Vorce, Shawn; Holler, Justin; Bosy, Thomas

    2014-04-01

    This study examined the potential of abalone β-glucuronidase as a viable and cost effective alternative to current hydrolysis procedures using acid, Helix pomatia β-glucuronidase and Escherichia coli β-glucuronidase. Abalone β-glucuronidase successfully hydrolyzed oxazepam-glucuronide and lorazepam-glucuronide within 5% of the spiked control concentration. Benzodiazepines present in authentic urine specimens were within 20% of the concentrations obtained with the current hydrolysis procedure using H. pomatia β-glucuronidase. JWH 018 N-(5-hydroxypentyl) β-d-glucuronide was hydrolyzed within 10% of the control concentration. Authentic urine specimens showed improved glucuronide cleavage using abalone β-glucuronidase with up to an 85% increase of drug concentration, compared with the results obtained using E. coli β-glucuronidase. The JWH 018 and JWH 073 carboxylic acid metabolites also showed increased drug concentrations of up to 24%. Abalone β-glucuronidase was able to completely hydrolyze a morphine-3-glucuronide control, but only 82% of total morphine was hydrolyzed in authentic urine specimens compared with acid hydrolysis results. Hydrolysis of codeine and hydromorphone varied between specimens, suggesting that abalone β-glucuronidase may not be as efficient in hydrolyzing the glucuronide linkages in opioid compounds compared with acid hydrolysis. Abalone β-glucuronidase demonstrates effectiveness as a low cost option for enzyme hydrolysis of benzodiazepines and synthetic cannabinoids.

  17. Cost-effectiveness analysis of the analgesic therapy of postoperative pain Análisis de costo-efectividad en el tratamiento analgésico para dolor post-operatorio Análise custo-efetividade da terapia analgésica utilizada na dor pós-operatória

    Directory of Open Access Journals (Sweden)

    Silvia Regina Secoli

    2008-02-01

    Full Text Available The study aimed to compare cost-effectiveness of analgesic schemes administered to 89 patients submitted to hemorrhoidectomy, on the 1st postoperative day. The descriptive and retrospective study was carried out in a General Hospital, Sao Paulo, Brazil. In order to carry out the cost-effectiveness analysis, the five most frequently used analgesic schemes were identified in practice. The main outcome was the absence of breakthrough pain episodes. While calculating the costs, analgesics and all devices related to the schemes were taken into consideration. Codeine 120mg+acetaminophen 2000mg was the most effective therapy with the lowest cost per patient with no breakthrough pain episodes ($65.23. Incremental analysis indicated that codeine 120mg+acetaminophen 2000mg+ketoprofen 200mg involved the additional cost of $238.31 in case an extra effectiveness benefit was needed. The analysis showed that the most suitable choice of analgesic therapy should consider the resources available at the institution along with economic and clinical aspects.El presente estudio utilizó el análisis de costo-efectividad para comparar los esquemas analgésicos administrados en 89 pacientes sometidos a hemorroidectomía, durante el 1º día del post-operatorio. Estudio descriptivo y retrospectivo realizado en el Hospital General de São Paulo. Para efectuar este análisis se identificaron los 5 esquemas analgésicos más utilizados por el servicio. El efecto principal fue la ausencia de dolor. Para calcular los costos fueron incluidos los analgésicos y los materiales utilizados para la administración. El esquema codeína 120mg + acetaminofen 2000mg fue más efectivo, siendo de menor costo para el paciente sin dolor ($65,23. Este incremento mostró que la mezcla codeína 120 mg+acetamenofen 2000mg+ cetoprofeno 200mg tuvo un costo adicional de $238,31 para poder obtener un beneficio extra de efectividad. A través del análisis, la selección del esquema analg

  18. Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves.

    Science.gov (United States)

    Hernández, Jehison Jiménez; Ragone, María Inés; Bonazzola, Patricia; Bandoni, Arnaldo L; Consolini, Alicia E

    2018-01-10

    Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca 2+ ) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC 50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca 2+ -CRC, with IC 50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a

  19. Dispersive liquid-liquid microextraction followed by high-performance liquid chromatography-ultraviolet detection to determination of opium alkaloids in human plasma.

    Science.gov (United States)

    Ahmadi-Jouibari, Toraj; Fattahi, Nazir; Shamsipur, Mojtaba; Pirsaheb, Meghdad

    2013-11-01

    A novel, simple, rapid and sensitive dispersive liquid-liquid microextraction method based on the solidification of floating organic drop (DLLME-SFO) combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was used to determine opium alkaloids in human plasma. During the extraction procedure, plasma protein was precipitated by using a mixture of zinc sulfate solution and acetonitrile. Some effective parameters on extraction were studied and optimized. Under the optimum conditions (extraction solvent: 30.0 μl 1-undecanol; disperser solvent: 470 μl acetone; pH: 9; salt addition: 1%(w/v) NaCl and extraction time: 0.5 min), calibration curves are linear in the range of 1.5-1000 μgl(-1) and limit of detections (LODs) are in the range of 0.5-5 μgl(-1). The relative standard deviations (RSDs) for 100 μgl(-1) of morphine and codeine, 10.0 μgl(-1) of papaverine and 20.0 μgl(-1) of noscapine in diluted human plasma are in the range of 4.3-7.4% (n=5). Finally, the method was successfully applied in the determination of opium alkaloids in the actual human plasma samples. The relative recoveries of plasma samples spiked with alkaloids are 88-110.5%. The obtained results show that DLLME-SFO combined with HPLC-UV is a fast and simple method for the determination of opium alkaloids in human plasma. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Management of pediatric tonsillectomy pain: a review of the literature

    Directory of Open Access Journals (Sweden)

    Hansen J

    2016-05-01

    Full Text Available Jennifer Hansen, Ravi D Shah, Hubert A Benzon Department of Pediatric Anesthesiology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Abstract: Tonsillectomy is associated with significant pain and postoperative pain control is often unsatisfactory. We discuss the various strategies that have been investigated to control pain following tonsillectomy. Codeine is a weak analgesic frequently used in children for the treatment of mild-to-moderate pain, however, due to adverse events related to its metabolism, it has been contraindicated for postoperative pain in children since 2013. Intravenous morphine is frequently used for moderate-to-severe pain in children, however, its active metabolite can lead to respiratory depressant and other undesirable side effects. Hydromorphone is a commonly used alternative that has been studied infrequently. Alternatives to narcotic pain strategies have also been studied. Nonsteroidal anti-inflammatory drugs (NSAIDs are effective as analgesics, yet many practitioners avoid their use given the concern for postoperative bleeding. Intraoperative acetaminophen has been shown to improve postoperative pain and decrease recovery room time. Dexamethasone has been shown to improve postoperative pain, vomiting, and decrease airway swelling, and seems to be effective for use during tonsillectomy surgery. Ketamine has been shown to decrease analgesic requirements without adverse affects of hallucinations. Direct injection of local anesthetic into the tonsillar bed has been shown to be effective in improving pain control, however, there is concern that local anesthetic could be erroneously injected into the carotid artery and lead to devastating consequences. Optimal pain control regimens following pediatric tonsillectomy continue to be a challenge for both anesthesiologists and otorhinolaryngologists. Opioids are the most commonly used but are

  1. Can thiolation render a low molecular weight polymer of just 20-kDa mucoadhesive?

    Science.gov (United States)

    Mahmood, Arshad; Bonengel, Sonja; Laffleur, Flavia; Ijaz, Muhammad; Idrees, Muneeb Ahmad; Hussain, Shah; Huck, Christian W; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

    2016-01-01

    The objective was to investigate whether even low-molecular weight polymers (LMWPs) can be rendered mucoadhesive due to thiolation. Interceded by the double catalytic system carbodiimide/N-hydroxysuccinimide, cysteamine was covalently attached to a copolymer, poly(4-styrenesulfonic acid-co-maleic acid) (PSSA-MA) exhibiting a molecular weight of just 20 kDa. Depending on the amount of added N-hydroxysuccinimide and cysteamine, the resulting PSSA-MA-cysteamine (PC) conjugates exhibited increasing degree of thiolation, highest being "PC 2300" exhibiting 2300.16 ± 149.86 μmol thiol groups per gram of polymer (mean ± SD; n = 3). This newly developed thiolated polymer was evaluated regarding mucoadhesive, rheological and drug release properties as well from the toxicological point of view. Swelling behavior in 100 mM phosphate buffer pH 6.8 was improved up to 180-fold. Furthermore, due to thiolation, the mucoadhesive properties of the polymer were 240-fold improved. Rheological measurements of polymer/mucus mixtures confirmed results obtained by mucoadhesion studies. In comparison to unmodified polymer, PC 2300 showed 2.3-, 2.3- and 2.4-fold increase in dynamic viscosity, elastic modulus and viscous modulus, respectively. Sustained release of the model drug codeine HCl out of the thiomer was provided for 2.5 h (p polymer. Moreover, the thiomer was found non-toxic over Caco-2 cells for a period of 6- and 24-h exposure. Findings of the present study provide evidence that due to thiolation LMWPs can be rendered highly mucoadhesive as well as cohesive and that a controlled drug release out of such polymers can be provided.

  2. Characterization and biological activity of Solidago canadensis complex.

    Science.gov (United States)

    Šutovská, M; Capek, P; Kocmálová, M; Fraňová, S; Pawlaczyk, I; Gancarz, R

    2013-01-01

    Polyphenolic-polysaccharide-protein complex has been isolated from flowers of Solidago canadensis L. by hot alkaline extraction procedure. Compositional analyses of S canadensis complex revealed the presence of carbohydrates (43 wt%), protein (27 wt%), phenolics (12 wt%), uronic acids (10 wt%) and inorganic material (8 wt%). The carbohydrate part was rich in neutral sugars (81 wt%) while uronids were determined in lower amount (19 wt%). Monosaccharide analysis of carbohydrate part revealed the presence of five main sugar components, i.e. rhamnose (~23 wt%), arabinose (~20 wt%), uronic acids (~19 wt%), galactose (~17 wt%) and glucose (~14 wt%), and indicated thus the presence of rhamnogalacturonan and arabinogalactan in S. canadensis complex. HPLC analysis of complex showed one single peak of molecule mass at 11.2 kDa. Antitussive activity tests, performed in three doses of Solidago complex, showed the reduction of the number of cough efforts in the dose-dependent manner. Higher doses (50 and 75 mg/kg b.w.) were shown to be by 15 and 20% more effective than that of lower one (25mg/kg b.w.). However, the antitussive effect of the highest dose (75 mg/kg b.w.) was by 10% lower in comparison with that of codeine, the strongest antitussive agent. Besides, the highest dose of the complex (75 mg/kg b.w.) significantly decreased values of specific airways resistance and their effect remained longer as that of salbutamol, a representative of classic antiasthmatic drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. A high-throughput urinalysis of abused drugs based on a SPE-LC-MS/MS method coupled with an in-house developed post-analysis data treatment system.

    Science.gov (United States)

    Cheng, Wing-Chi; Yau, Tsan-Sang; Wong, Ming-Kei; Chan, Lai-Ping; Mok, Vincent King-Kuen

    2006-10-16

    A rapid urinalysis system based on SPE-LC-MS/MS with an in-house post-analysis data management system has been developed for the simultaneous identification and semi-quantitation of opiates (morphine, codeine), methadone, amphetamines (amphetamine, methylamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA)), 11-benzodiazepines or their metabolites and ketamine. The urine samples are subjected to automated solid phase extraction prior to analysis by LC-MS (Finnigan Surveyor LC connected to a Finnigan LCQ Advantage) fitted with an Alltech Rocket Platinum EPS C-18 column. With a single point calibration at the cut-off concentration for each analyte, simultaneous identification and semi-quantitation for the above mentioned drugs can be achieved in a 10 min run per urine sample. A computer macro-program package was developed to automatically retrieve appropriate data from the analytical data files, compare results with preset values (such as cut-off concentrations, MS matching scores) of each drug being analyzed and generate user-defined Excel reports to indicate all positive and negative results in batch-wise manner for ease of checking. The final analytical results are automatically copied into an Access database for report generation purposes. Through the use of automation in sample preparation, simultaneous identification and semi-quantitation by LC-MS/MS and a tailored made post-analysis data management system, this new urinalysis system significantly improves the quality of results, reduces the post-data treatment time, error due to data transfer and is suitable for high-throughput laboratory in batch-wise operation.

  4. Validation of an automated solid-phase extraction method for the analysis of 23 opioids, cocaine, and metabolites in urine with ultra-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Ramírez Fernández, María del Mar; Van Durme, Filip; Wille, Sarah M R; di Fazio, Vincent; Kummer, Natalie; Samyn, Nele

    2014-06-01

    The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers. Moreover, the present configuration included pressure monitoring pipetting increasing pipetting accuracy and detecting sampling errors. The compounds were then separated in a chromatographic run of 9 min using a BEH Phenyl analytical column on a ultra-performance liquid chromatography-tandem mass spectrometry system. Optimization of the SPE was performed with different wash conditions and elution solvents. Intra- and inter-day relative standard deviations (RSDs) were within ±15% and bias was within ±15% for most of the compounds. Recovery was >69% (RSD automated SPE system was observed. The extracted samples were stable for 72 h in the autosampler (4°C). This method was applied to authentic samples (from forensic and toxicology cases) and to proficiency testing schemes containing cocaine, heroin, buprenorphine and methadone, offering fast and reliable results. Automation resulted in improved precision and accuracy, and a minimum operator intervention, leading to safer sample handling and less time-consuming procedures.

  5. EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents.

    Science.gov (United States)

    Loos, Robert; Carvalho, Raquel; António, Diana C; Comero, Sara; Locoro, Giovanni; Tavazzi, Simona; Paracchini, Bruno; Ghiani, Michela; Lettieri, Teresa; Blaha, Ludek; Jarosova, Barbora; Voorspoels, Stefan; Servaes, Kelly; Haglund, Peter; Fick, Jerker; Lindberg, Richard H; Schwesig, David; Gawlik, Bernd M

    2013-11-01

    In the year 2010, effluents from 90 European wastewater treatment plants (WWTPs) were analyzed for 156 polar organic chemical contaminants. The analyses were complemented by effect-based monitoring approaches aiming at estrogenicity and dioxin-like toxicity analyzed by in vitro reporter gene bioassays, and yeast and diatom culture acute toxicity optical bioassays. Analyses of organic substances were performed by solid-phase extraction (SPE) or liquid-liquid extraction (LLE) followed by liquid chromatography tandem mass spectrometry (LC-MS-MS) or gas chromatography high-resolution mass spectrometry (GC-HRMS). Target microcontaminants were pharmaceuticals and personal care products (PPCPs), veterinary (antibiotic) drugs, perfluoroalkyl substances (PFASs), organophosphate ester flame retardants, pesticides (and some metabolites), industrial chemicals such as benzotriazoles (corrosion inhibitors), iodinated x-ray contrast agents, and gadolinium magnetic resonance imaging agents; in addition biological endpoints were measured. The obtained results show the presence of 125 substances (80% of the target compounds) in European wastewater effluents, in concentrations ranging from low nanograms to milligrams per liter. These results allow for an estimation to be made of a European median level for the chemicals investigated in WWTP effluents. The most relevant compounds in the effluent waters with the highest median concentration levels were the artificial sweeteners acesulfame and sucralose, benzotriazoles (corrosion inhibitors), several organophosphate ester flame retardants and plasticizers (e.g. tris(2-chloroisopropyl)phosphate; TCPP), pharmaceutical compounds such as carbamazepine, tramadol, telmisartan, venlafaxine, irbesartan, fluconazole, oxazepam, fexofenadine, diclofenac, citalopram, codeine, bisoprolol, eprosartan, the antibiotics trimethoprim, ciprofloxacine, sulfamethoxazole, and clindamycine, the insect repellent N,N'-diethyltoluamide (DEET), the pesticides

  6. Sample preparation method for the combined extraction of ethyl glucuronide and drugs of abuse in hair.

    Science.gov (United States)

    Meier, Ulf; Briellmann, Thomas; Scheurer, Eva; Dussy, Franz

    2018-04-01

    Often in hair analysis, a small hair sample is available while the analysis of a multitude of structurally diverse substances with different concentration ranges is demanded. The analysis of the different substances often requires different sample preparation methods, increasing the amount of required hair sample. When segmental hair analysis is necessary, the amount of hair sample needed is further increased. Therefore, the required sample amount for a full analysis can quickly exceed what is available. To combat this problem, a method for the combined hair sample preparation using a single extraction procedure for analysis of ethyl glucuronide with liquid chromatography-multistage fragmentation mass spectrometry/multiple reaction monitoring (LC-MS 3 /MRM) and common drugs of abuse with LC-MRM was developed. The combined sample preparation is achieved by separating ethyl glucuronide from the drugs of abuse into separate extracts by fractionation in the solid-phase extraction step during sample clean-up. A full validation for all substances for the parameters selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, and recovery was successfully completed. The following drugs of abuse were included in the method: Amphetamine; methamphetamine; 3,4-methylenedioxy-N-methylamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxy-N-ethylamphetamine (MDE); morphine; 6-monoacetylmorphine; codeine; acetylcodeine; cocaine; benzoylecgonine; norcocaine; cocaethylene; methadone; 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and methylphenidate. In conclusion, as only 1 sample preparation is needed with 1 aliquot of hair, the presented sample preparation allows an optimal analysis of both ethyl glucuronide and of the drugs of abuse, even when the sample amount is a limiting factor. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Assessment of the use of oral fluid as a matrix for drug monitoring in patients undergoing treatment for opioid addiction.

    Science.gov (United States)

    Kunkel, Frank; Fey, Elizabeth; Borg, Damon; Stripp, Richard; Getto, Christine

    2015-01-01

    Drug testing is an important clinical tool that is available to physicians who are assessing the effectiveness of drug treatment as well as patient compliance to the administered program. While urine has traditionally been the matrix of choice for drug monitoring, oral fluid, a filtrate of the blood, has shown great promise as an alternative matrix for such applications. Oral fluid collection can be accomplished without the need for highly trained medical staff through the use of a simple, noninvasive oral fluid collection device, which obtains an adequate sample in only a few minutes. There has been a significant amount of research performed on the use of oral fluid for forensic toxicology application; however, more studies assessing the use of oral fluid drug testing are required to validate its ability to achieve clinical drug monitoring goals. Testing for various drugs in oral fluid may yield a different result when compared to the same drugs in urine, requiring an assessment of the utility of oral fluid for such practices. The purpose of this study was to examine the application of oral fluid drug testing in patients undergoing buprenorphine treatment for opioid dependence. A retrospective analysis of drug testing results obtained from 6,928 patients (4,560 unobserved urine collections and 2,368 observed oral fluid collections) monitored for heroin metabolite, amphetamine, benzodiazepines, buprenorphine, tetrahydrocannabinol, cocaine, codeine, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone was completed. Results of this statistical exercise indicated that patients undergoing observed oral fluid collection tested positive more frequently than those unobserved urine collections for several illicit drugs and prescription medications targeted. Oral fluid was shown to detect illicit drug use as well as noncompliance in this patient population under the studied conditions more often than the urine specimens.

  8. A Survey of the Pain Management of Acute Painful Crisis among Patients with Sickle Cell Disease at Two Centres in Jamaica.

    Science.gov (United States)

    Augier, R; Jenkins, S; Bortolusso Ali, S; Tennant, I; Williams-Johnson, J; Reid, M

    2014-06-01

    The aim of this survey was to establish the pain management approaches to acute painful crisis (APC) in sickle cell patients at two healthcare facilities and to compare with available guidelines. A multi-centre observational survey of the management of APC in sickle cell patients was conducted. Data were collected at the Sickle Cell Unit (SCU), Tropical Medicine Research Institute (TMRI) and Accident and Emergency Department (A&E), University Hospital of the West Indies. One hundred episodes of uncomplicated APC involving 81 patients managed at the SCU clinic and 64 episodes at the A&E in a total of 28 patients were included in the data set. Drugs used at the SCU included oral morphine, codeine and paracetamol and intramuscular diclofenac. At the A&E, parenteral morphine and pethidine were most commonly used. At the SCU, the mean time to initiation of analgesics was 38 minutes (IQR 25 to 50 minutes); at the A&E, this was 111 minutes (IQR 50 to 150 minutes). At the SCU, the mean duration of stay (DOS) was 2.9 hours (IQR 1.9 to 3.8 hours) with 94% of the patients being discharged home. At the A&E, the mean DOS was 13.0 hours (IQR 8.3 to 16.9 hours) with 93% of the patients being discharged home. The A&E patient group contained multiple high frequency presenters. Documentation of pain severity scores was inconsistent. The findings of the survey indicate that the management of APC at the two centres is substantially different. Further study is required to investigate patient satisfaction, centre preference and analgesic therapy efficacy.

  9. Performance of the linear ion trap Orbitrap mass analyzer for qualitative and quantitative analysis of drugs of abuse and relevant metabolites in sewage water.

    Science.gov (United States)

    Bijlsma, Lubertus; Emke, Erik; Hernández, Félix; de Voogt, Pim

    2013-03-20

    This work illustrates the potential of liquid chromatography coupled to a hybrid linear ion trap Fourier Transform Orbitrap mass spectrometer for the simultaneous identification and quantification of 24 drugs of abuse and relevant metabolites in sewage water. The developed methodology consisted of automatic solid-phase extraction using Oasis HLB cartridges, chromatographic separation of the targeted drugs, full-scan accurate mass data acquisition under positive electrospray ionization mode over an m/z range of 50-600Da at a resolution of 30,000 FWHM and simultaneous MS(n) measurements to obtain information of fragment ions generated in the linear ion trap. Accurate mass of the protonated molecule, together with at least one nominal mass product ion and retention time allowed the confident identification of the compounds detected in these complex matrices. In addition to the highly reliable qualitative analysis, Orbitrap analyzer also proved to have satisfactory potential for quantification at sub-ppb analyte levels, a possibility that has been very little explored in the literature until now. The limits of quantification ranged from 4 to 68ngL(-1) in influent sewage water, and from 2 to 35ngL(-1) in effluent, with the exception of MDA, morphine and THC that presented higher values as a consequence of the high ionization suppression in this type of samples. Satisfactory recoveries (70-120%) and precision (abuse could be identified and quantified, mainly MDMA, benzoylecgonine, codeine, oxazepam and temazepam. Orbitrap also showed potential for retrospective investigation of ketamine metabolites in the samples without the need of additional analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine.

    Science.gov (United States)

    Tang, Magdalene H Y; Ching, C K; Poon, Simon; Chan, Suzanne S S; Ng, W Y; Lam, M; Wong, C K; Pao, Ronnie; Lau, Angus; Mak, Tony W L

    2018-05-01

    Rapid oral fluid testing (ROFT) devices have been extensively evaluated for their ability to detect common drugs of abuse; however, the performance of such devices on simultaneous screening for ketamine has been scarcely investigated. The present study evaluated three ROFT devices (DrugWipe ® 6S, Ora-Check ® and SalivaScreen ® ) on the detection of ketamine, opiates, methamphetamine, cannabis, cocaine and MDMA. A liquid chromatography tandem mass spectrometry (LCMS) assay was firstly established and validated for confirmation analysis of the six types of drugs and/or their metabolites. In the field test, the three ROFT devices were tested on subjects recruited from substance abuse clinics/rehabilitation centre. Oral fluid was also collected using Quantisal ® for confirmation analysis. A total of 549 samples were collected in the study. LCMS analysis on 491 samples revealed the following drugs: codeine (55%), morphine (49%), heroin (40%), methamphetamine (35%), THC (8%), ketamine (4%) and cocaine (2%). No MDMA-positive cases were observed. Results showed that the overall specificity and accuracy were satisfactory and met the DRUID standard of >80% for all 3 devices. Ora-Check ® had poor sensitivities (ketamine 36%, methamphetamine 63%, opiates 53%, cocaine 60%, THC 0%). DrugWipe ® 6S showed good sensitivities in the methamphetamine (83%) and opiates (93%) tests but performed relatively poorly for ketamine (41%), cocaine (43%) and THC (22%). SalivaScreen ® also demonstrated good sensitivities in the methamphetamine (83%) and opiates (100%) tests, and had the highest sensitivity for ketamine (76%) and cocaine (71%); however, it failed to detect any of the 28 THC-positive cases. The test completion rate (proportion of tests completed with quality control passed) were: 52% (Ora-Check ® ), 78% (SalivaScreen ® ) and 99% (DrugWipe ® 6S). Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs

    Science.gov (United States)

    Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico

    2016-01-01

    Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID:26837703

  12. Determinants of knowledge and use of psychoactive substance among commercial motorcyclist in Sokoto metropolis, Northwest Nigeria

    Directory of Open Access Journals (Sweden)

    M.O.Raji

    2017-01-01

    Full Text Available Background Substance abuse, also known as drug abuse, is a patterned use of a drug in which the user consumes the substance in amounts or with methods which are harmful to themselves or others, and is a form of substance related disorder. Riding commercial motorcycle entails lot of risk, compounded by abuse of drugs, the scenario can only be worse. This study aimed to assess the determinants of knowledge and use of psychoactive substances among commercial motorcyclist in Sokoto metropolis. Methods The study was a cross sectional descriptive study conducted in Sokoto metropolis, among Commercial motorcyclist, 253 respondents were recruited using multi stage sampling technique. Data was obtained using interviewer administered structured questionnaire containing 47‐item structured questions. Data was analysed using IBM statistical software package version 21, 5% was set as level of significance Result Majority of respondent believed that use of alcohol 214 (84.6, cannabis 147 (58.1 and codeine 171 (67.6 can lead to mental problems. Thirty percent of the respondents reported ever use of psychoactive substances. Most of the respondents (49.3% initiated use of Psychoactive substances between 16‐20 years of age. Respondents who had some formal education had less odds of ever using psychoactive substances (p=0.001, OR= 0.337. Respondents who had ever encouraged fellow commercial motorcyclist to use psychoactive substances had 22 times odds of ever having used psychoactive substances (p=0.000 Conclusion Substance abuse is prevalent among commercial motorcyclist. Despite good knowledge of psychoactive substances and the consequences associated with it, the use was still relatively high. The main predictor of ever use of psychoactive substances was willingness to be friends with someone who use psychoactive substance. There is need for continuous counselling and education of commercial motorcyclist, by road safety workers, on the dangers associated

  13. Human-health pharmaceutical compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

    Science.gov (United States)

    Boyd, Robert A.; Furlong, Edward T.

    2002-01-01

    The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake Mead on the Colorado River and Las Vegas Wash, a waterway used to transport treated wastewater from the Las Vegas metropolitan area to Lake Mead. Current research indicates many of these compounds can bioaccumulate and may adversely affect aquatic organisms by disrupting physiological processes, impairing reproductive functions, increasing cancer rates, contributing to the development of antibiotic-resistant strains of bacteria, and acting in undesirable ways when mixed with other substances. These compounds may be present in effluent because a high percentage of prescription and non-prescription drugs used for human-health purposes are excreted from the body as a mixture of parent compounds and degraded metabolite compounds; also, they can be released to the environment when unused products are discarded by way of toilets, sinks, and trash in landfills. Thirteen of 33 targeted compounds were detected in at least one water sample collected between October 2000 and August 2001. All concentrations were less than or equal to 0.20 micrograms per liter. The most frequently detected compounds in samples from Las Vegas Wash were caffeine, carbamazepine (used to treat epilepsy), cotinine (a metabolite of nicotine), and dehydronifedipine (a metabolite of the antianginal Procardia). Less frequently detected compounds in samples collected from Las Vegas Wash were antibiotics (clarithromycin, erythromycin, sulfamethoxazole, and trimethoprim), acetaminophen (an analgesic and anti-inflammatory), cimetidine (used to treat ulcers), codeine (a narcotic and analgesic), diltiazem (an antihypertensive), and 1,7-dimethylxanthine (a metabolite of caffeine). Fewer compounds were detected in samples collected from Lake Mead than from Las Vegas Wash. Caffeine was detected in all samples

  14. Illicit drugs in alternative biological specimens: a case report.

    Science.gov (United States)

    Margalho, Cláudia; Franco, João; Corte-Real, Francisco; Vieira, Duarte Nuno

    2011-04-01

    Postmortem tissues (e.g. liver, kidney) have been long used in forensic applications especially in those cases where blood is unavailable. The aim of this paper is to demonstrate the importance of the information provided to the forensic toxicologist at the time of carrying out the toxicological analysis, especially in cases where the samples commonly used in forensic toxicology are unavailable. This work describes the toxicological findings in a violent death resulting from a man who was hit by a train. Vitreous humor, liver and kidney were sent for toxicological analysis, once it was not possible to obtain blood and urine. The validated procedures used in the routine casework of Forensic Toxicology Laboratory of the Centre Branch of the National Institute of Legal Medicine, were applied in the analysis of liver, kidney and vitreous humor, using gas chromatography-mass spectrometry after solid-phase extraction and gas chromatography-flame ionization detector for the analysis of drugs of abuse and ethanol, respectively. Morphine, codeine, cocaine, benzoylecgonine and ecgonine methyl ester were found in the liver and in the kidney and no ethanol was found in the vitreous humor. The method validation included the study of specificity, selectivity, limits of detection, recovery and carryover. Although blood and urine are the most common and preferred matrices used for toxicological studies involving drugs of abuse, sometimes the choice of specimen is determined by the case under investigation. The forensic pathologist must be aware that relevant information must be provided so that the toxicological analysis can be conducted in accordance with case history, particularly when the only samples available for analysis are these "unconventional" specimens, since the interpretation of the obtained results is more difficult. Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  15. Profile of diseases prevalent in a tribal locality in Jharkhand, India: A family medicine practitioner′s perspective

    Directory of Open Access Journals (Sweden)

    Sumit Kumar

    2015-01-01

    Full Text Available Background: Majority of Indian population is dependent on general practitioners (GPs for medical services at primary care level in India. They are most preferred and considered to be first contact person for medical services at primary care level. But advances in medical science has put more emphasis on specialist culture and average Bachelor of Medicine and Bachelor of Surgery (MBBS graduates who are working as general physician are gradually feeling themselves less competent because they are less exposed to latest advances in treatment of diseases. Amidst such scenario, Christian Medical College (CMC has come up with an idea: "The refer less and resolve more initiative". It has started a decentralized 2-year family medicine distance diploma course (Postgraduate Diploma in Family Medicine (PGDFM now accredited by Dr. MGR Medical University, Chennai, Tamil Nadu, that trains the GPs to become family medicine specialist. Materials and Methods: As component of PGDFM course, this study was conducted to provide better understanding of prevalent ailments and common treatment provided by the GPs in the community at present giving key insight of current practice in rural area by a registered family medicine practitioner. Results: As part of study, among 500 patients evaluated, three most common diagnosis were upper respiratory infections (URIs; 18%, acute gastroenteritis including water-borne diseases (15.8%, and anemia (10.4%. Treatment given to these patients comprised of mostly of antipyretic, analgesic, and antimicrobial agents. Most common drug prescribed was paracetamol for fever. Other common drugs prescribed were amoxicillin/clavulanic acid, chloroquine, artemisin derivative, doxycycline, co-trimoxazole, miltefosine, cephalexin, ceftriaxone sodium, cefixime, oral rehydration salts, ranitidine, omeprazole, pantoprazole, metronidazole, albendazole, ondansetron, diclofenac sodium, piroxicam, ibuprofen, diphenhydramine, codeine-sulfate, amlodipine

  16. Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method.

    Science.gov (United States)

    Romański, Michał; Kasprzyk, Anna; Teżyk, Artur; Widerowska, Agnieszka; Żaba, Czesław; Główka, Franciszek

    2017-06-05

    A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance. In this paper, a selective and rapid HPLC-ESI-MS/MS method was elaborated and validated for the studies of disposition of TREO and S,S-EBDM in rat plasma, liver, lungs, kidneys, muscle, and brain. The two analytes and codeine, internal standard (IS), were isolated from 50μL of plasma and 100μL of supernatants of the tissues homogenates using ultrafiltration Amicon vials. Chromatographic resolution was accomplished on C18 column with isocratic elution. The limits of quantitation of TREO and S,S-EBDM in the studied matrices ranged from 0.11 to 0.93μM. The HPLC-MS/MS method was adequately precise and accurate within and between runs. The IS-normalized matrix effect differed among the tissues and was the most pronounced in a liver homogenate supernatant (approximately 0.55 for TREO and 0.35 for S,S-EBDM). Stability of the analytes in experimental samples was also established. The validated method for the first time enabled determination of TREO and S,S-EBDM in the six life-important tissues in rats following administration of the prodrug. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Discrete memory impairments in largely pure chronic users of MDMA.

    Science.gov (United States)

    Wunderli, Michael D; Vonmoos, Matthias; Fürst, Marina; Schädelin, Katrin; Kraemer, Thomas; Baumgartner, Markus R; Seifritz, Erich; Quednow, Boris B

    2017-10-01

    Chronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulant-naïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (d primary =.90, d polydrug =1.21), followed by working memory (d primary =.52, d polydrug =.96), executive functions (d primary =.46, d polydrug =.86), and attention (d primary =.23, d polydrug =.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  18. Effects of the summer holiday season on UV filter and illicit drug concentrations in the Korean wastewater system and aquatic environment.

    Science.gov (United States)

    Kim, Ki Yong; Ekpeghere, Kalu Ibe; Jeong, Hee-Jin; Oh, Jeong-Eun

    2017-08-01

    Seasonal variations in the concentrations of eight ultraviolet (UV) filters and 22 illicit drugs including their metabolites in the Korean aquatic environment were investigated. Seawater samples from three beaches, water samples from two rivers, and influents and effluents from three wastewater treatment plants were analyzed. The UV filter concentrations in the seawater, river water, and effluent samples were 39.4-296, 35.4-117, and 6.84-51.1 ng L -1 , respectively. The total UV filter concentrations in the seawater samples were 1.9-4.4 times higher at the peak of the holiday season than outside the peak holiday season. An environmental risk assessment showed that ethylhexyl methoxy cinnamate (EHMC) could cause adverse effects on aquatic organisms in the seawater at the three beaches during the holiday period. Seven of the 22 target illicit drugs including their metabolites were detected in the wastewater influent samples, and the total illicit drug concentrations in the influent samples were 0.08-65.4 ng L -1 . The estimated daily consumption rates for cis-tramadol (Cis-TRM), methamphetamine (MTP), meperidine (MEP), and codeine (COD) were 25.7-118.4, 13.8-36.1, 1.36-12.6, and 1.75-8.64 mg d -1 (1000 people) -1 , respectively. In popular vacation area, the illicit drug consumption rates (Cis-TRM, MTP and MEP) were 1.6-2.6 times higher at the peak of the summer holiday season than at the beginning of the summer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Internet pseudoscience: Testing opioid containing formulations with tampering potential.

    Science.gov (United States)

    Pascali, Jennifer P; Fais, Paolo; Vaiano, Fabio; Pigaiani, Nicola; D'Errico, Stefano; Furlanetto, Sandra; Palumbo, Diego; Bertol, Elisabetta

    2018-05-10

    Drug tampering practices, with the aim to increase availability of drug delivery and/or enhance drug effects, are accessible on Internet and are practiced by some portion of recreational drug users. Not rarely, recreational misuse may result in toxic and even fatal results. The aim of the present study was to assess the tampering risk of medicaments containing different formulations of an opioid in combination with paracetamol or dexketoprofen, following the procedures reported in dedicated forums on the web. Tablets and suppositories containing codeine, tramadol and oxycodone were extracted following the reported "Cold water extraction"; dextromethorphan was extracted from cough syrup following the procedure reported as "Acid/base extraction" and fentanyl was extracted from transdermal patches according the procedure reported in Internet. The tampered products and opportunely prepared calibrators in water were analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The separation of the analytes was carried on Agilent ZORBAX Eclipse Plus C18 (RRHT 2.1 mm × 50 mm, 1.8 μm) by the gradient elution of 0.01% formic acid in water and 0.01% formic acid in methanol. Acquisition was by MRM mode considering at least two transitions for compound. Declared recoveries for these home-made extractions claimed to exceed 99% for the opioid and to complete remove paracetamol, often associated to liver toxicity and thus to obtain a "safer" preparation. In this study, the authors demonstrated that rarely the recoveries for the opioid reached 90% and that up to 60% of the paracetamol amount remained in solution. Thus, high risks for health remained both for the potential lethality of the opioid content, but also for the sub-lethal chronic use of these mixtures, which contained still uncontrolled, ignored, but often important amounts of paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California.

    Science.gov (United States)

    Fram, Miranda S; Belitz, Kenneth

    2011-08-15

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells=61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity>0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of the state with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. Published by Elsevier B.V.

  1. Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank.

    Science.gov (United States)

    Escuder-Vieco, Diana; Garcia-Algar, Óscar; Joya, Xavier; Marchei, Emilia; Pichini, Simona; Pacifici, Roberta; Pallás-Alonso, Carmen Rosa

    2016-08-01

    The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine. © The Author(s) 2016.

  2. Wastewater-based assessment of regional and temporal consumption patterns of illicit drugs and therapeutic opioids in Croatia.

    Science.gov (United States)

    Krizman, Ivona; Senta, Ivan; Ahel, Marijan; Terzic, Senka

    2016-10-01

    A comprehensive study of spatial and temporal consumption patterns of the selected illicit drugs (heroin, cocaine, amphetamine, MDMA, methamphetamine, cannabis) and therapeutic opioids (codeine, methadone) has been performed in six Croatian cities by applying wastewater-based epidemiology. The investigated cities (Bjelovar, Vinkovci, Varazdin, Karlovac, Zadar and Zagreb) varied widely in the population size (27,000-688,000 inhabitants) as well as in the number of registered drug consumers included in compulsory and voluntary medical treatment and rehabilitation programs (30-513 persons/100,000 inhabitants of age 15-64). The most consumed illicit drugs were cannabis (10-70doses/day/1000 inhabitants), heroin (consumption of amphetamine-type drugs was much lower (consumption of illegal drugs was generally associated with larger urban centers (Zagreb and Zadar) however comparatively high consumption rate of cocaine, MDMA and methadone was determined in some smaller cities as well. The overall average dose number of 3 major illegal stimulants (cocaine, MDMA, amphetamine) was rather similar to the number of corresponding heroin doses, which is in disagreement with a comparatively much higher proportion of heroin users in the total number of registered drug users in Croatia. Furthermore, the illicit drug consumption pattern in the large continental city (Zagreb) was characterized by a significant enhancement of the consumption of all stimulants during the weekend, which could not be confirmed neither for the coastal city of Zadar nor for the remaining small continental cities. On the other hand, the city of Zadar exhibited a significant increase of stimulant drug usage during summer vacation period, as a result of pronounced seasonal changes of the population composition and lifestyle in coastal tourist centers. The obtained results represent a valuable complementary data source for the optimisation and implementation of strategies to combat drug abuse in Croatia

  3. Automated solid-phase extraction-liquid chromatography-tandem mass spectrometry analysis of 6-acetylmorphine in human urine specimens: application for a high-throughput urine analysis laboratory.

    Science.gov (United States)

    Robandt, P V; Bui, H M; Scancella, J M; Klette, K L

    2010-10-01

    An automated solid-phase extraction-liquid chromatography- tandem mass spectrometry (SPE-LC-MS-MS) method using the Spark Holland Symbiosis Pharma SPE-LC coupled to a Waters Quattro Micro MS-MS was developed for the analysis of 6-acetylmorphine (6-AM) in human urine specimens. The method was linear (R² = 0.9983) to 100 ng/mL, with no carryover at 200 ng/mL. Limits of quantification and detection were found to be 2 ng/mL. Interrun precision calculated as percent coefficient of variation (%CV) and evaluated by analyzing five specimens at 10 ng/mL over nine batches (n = 45) was 3.6%. Intrarun precision evaluated from 0 to 100 ng/mL ranged from 1.0 to 4.4%CV. Other opioids (codeine, morphine, oxycodone, oxymorphone, hydromorphone, hydrocodone, and norcodeine) did not interfere in the detection, quantification, or chromatography of 6-AM or the deuterated internal standard. The quantified values for 41 authentic human urine specimens previously found to contain 6-AM by a validated gas chromatography (GC)-MS method were compared to those obtained by the SPE-LC-MS-MS method. The SPE-LC-MS-MS procedure eliminates the human factors of specimen handling, extraction, and derivatization, thereby reducing labor costs and rework resulting from human error or technique issues. The time required for extraction and analysis was reduced by approximately 50% when compared to a validated 6-AM procedure using manual SPE and GC-MS analysis.

  4. Breaking worse: the emergence of krokodil and excessive injuries among people who inject drugs in Eurasia.

    Science.gov (United States)

    Grund, Jean-Paul C; Latypov, Alisher; Harris, Magdalena

    2013-07-01

    Krokodil, a homemade injectable opioid, gained its moniker from the excessive harms associated with its use, such as ulcerations, amputations and discolored scale-like skin. While a relatively new phenomenon, krokodil use is prevalent in Russia and the Ukraine, with at least 100,000 and around 20,000 people respectively estimated to have injected the drug in 2011. In this paper we review the existing information on the production and use of krokodil, within the context of the region's recent social history. We searched PubMed, Google Advanced Search, Google Scholar, YouTube and the media search engine www.Mool.com for peer reviewed or media reports, grey literature and video reports. Survey data from HIV prevention and treatment NGOs was consulted, as well as regional experts and NGO representatives. Krokodil production emerged in an atypical homemade drug production and injecting risk environment that predates the fall of communism. Made from codeine, the active ingredient is reportedly desomorphine, but - given the rudimentary 'laboratory' conditions - the solution injected may include various opioid alkaloids as well as high concentrations of processing chemicals, responsible for the localized and systemic injuries reported here. Links between health care and law enforcement, stigma and maltreatment by medical providers are likely to thwart users seeking timely medical help. A comprehensive response to the emergence of krokodil and associated harms should focus both on the substance itself and its rudimentary production methods, as well as on its micro and macro risk environments - that of the on-going syndemic of drug injecting, HIV, HCV, TB and STIs in the region and the recent upheaval in local and international heroin supply. The feasibility of harm reduction strategies for people who inject krokodil may depend more on political will than on the practical implementation of interventions. The legal status of opioid substitution treatment in Russia is a point

  5. Surgical treatment of jaw osteonecrosis in "Krokodil" drug addicted patients.

    Science.gov (United States)

    Poghosyan, Yuri M; Hakobyan, Koryun A; Poghosyan, Anna Yu; Avetisyan, Eduard K

    2014-12-01

    Retrospective study of jaw osteonecrosis treatment in patients using the "Krokodil" drug from 2009 to 2013. On the territory of the former USSR countries there is widespread use of a self-produced drug called "Krokodil". Codeine containing analgesics ("Sedalgin", "Pentalgin" etc), red phosphorus (from match boxes) and other easily acquired chemical components are used for synthesis of this drug, which used intravenously. Jaw osteonecrosis develops as a complication in patients who use "Krokodil". The main feature of this disease is jawbone exposure in the oral cavity. Surgery is the main method for the treatment of jaw osteonecrosis in patients using "Krokodil". 40 "Krokodil" drug addict patients with jaw osteonecrosis were treated. Involvement of maxilla was found in 11 patients (27.5%), mandible in 21 (52.5%), both jaws in 8 (20%) patients. 35 Lesions were found in 29 mandibles and 21 lesions in 19 maxillas. Main factors of treatment success are: cessation of "Krokodil" use in the pre- (minimum 1 month) and postoperative period and osteonecrosis area resection of a minimum of 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues. Surgery was not delayed until sequestrum formation. In the mandible marginal or segmental resection (with or without TMJ exarticulation) was performed. After surgery recurrence of disease was seen in 8 (23%) cases in the mandible, with no cases of recurrence in the maxilla. According to our experience in this case series, surgery is the main method for the treatment of jaw osteonecrosis in patients using "Krokodil". Cessation of drug use and jaw resection minimize the rate of recurrences in such patients. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Development of a new multi-analyte assay for the simultaneous detection of opioids in serum and other body fluids using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Eckart, K; Röhrich, J; Breitmeier, D; Ferner, M; Laufenberg-Feldmann, R; Urban, R

    2015-09-15

    A liquid chromatography-tandem mass spectrometry method using electrospray ionization in positive ionization mode was developed for the simultaneous detection of multiple opioid-type drugs in plasma. The presented assay allows the quantitative determination of alfentanil, buprenorphine, codeine, desomorphine, dextromethorphan, dextrorphan, dihydrocodeine, dihydromorphine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, pholcodine, piritramide, remifentanil, sufentanil, and tramadol as well as the metabolites 6-monoacetylmorphine, bisnortilidine, morphine-3-glucuronide, morphine-6-glucuronide, naltrexol, norbuprenorphine, norfentanyl, norpethidine, nortilidine, and O-desmethyltramadol. Serum and blood samples were purified by solid-phase extraction. The analytes were separated on a phenyl-hexyl (100mm) column by formic acid/acetonitrile gradient elution using an UPLC 1290 Infinity coupled with a 6490 Triple Quadrupole mass spectrometer. The limits of detection ranged from 0.02 to 0.6ng/mL and the lower limits of quantification ranged from 0.1 to 2.0ng/mL. The calibration curves were linear between Calibration Levels 1-6 for all 35 substances. Recovery rates ranged between 51 and 88% for all compounds except alfentanil, bisnortilidine, pethidine, and morphine-3-glucuronide. The matrix effect ranged from 86% for ethylmorphine to 105% for desomorphine. Using the validation procedure proposed by the German Society of Toxicological and Forensic Chemistry, acceptable precision and accuracy data for almost all analytes were obtained. The method was successfully applied to 206 authentic serum samples provided by the palliative and intensive care units of the University Medical Center and the police authorities. Furthermore, a suspected fatal intoxication is demonstrated by an analysis of the sufentanil in post mortem body fluids and tissues. Copyright © 2015 Elsevier B.V. All

  7. The contribution of a clinical pharmacist to the improvement of medication at a geriatric hospital unit in Norway.

    Directory of Open Access Journals (Sweden)

    Veggeland T

    2008-03-01

    Full Text Available The aim of the study was to use a clinical pharmacist in order to improve the medication of patients in a geriatric hospital unit. The hospital had no experience of using a clinical pharmacist before.Methods: A clinical pharmacist participated in the therapeutic team for 27 days during a 4-year period. Drug-related problems were recorded prospectively and discussed before and at the ward round. The results of the physician’s decisions on the current day about potential changes in medication proposed by the pharmacist were continuously recorded.Results: The pharmacist evaluated the medication of 250 patients. At least one drug- related problem was found in 188 (75% of the patients. For these patients, the physician made 606 decisions concerning potential changes in the medication (3.2 per patient. Thirty percent (184/606 of the decisions were connected to further measurements and to the follow-up of laboratory results, mainly (82%, 151/184 for cardiovascular drugs. Forty-two percent (255/606 of the decisions resulted in the discontinuation of drugs, dosage reduction or a decision to revise the assessment at a later stage during hospitalisation. Medicines with anticholinergic adverse effects were to a great extent withdrawn. Twenty-one percent (129/606 of the decisions were made on drugs with an addiction potential: hypnotics, anxiolytics, as well as analgesics containing tramadol and codeine. The result was often (71%, 91/129 dosage reduction, a change from fixed medication to medication on demand or to discontinuation. Conclusion: Even with a modest participation of once a month, the evaluation of a patient’s medication by a clinical pharmacist led to improved changes and the follow-up of the medication of the elderly.

  8. Socio-demographic characteristics of the addicted inmates of Qom and Tabriz prisons in Iran

    Directory of Open Access Journals (Sweden)

    Sattari Mohammadreza

    2012-06-01

    Full Text Available Purpose: The aim of this investigation was to study the factors responsible for drug addiction amongst the inmates of Tabriz and Qom prisons, to further understand the reasons for drug abuse particularly in the young and find improved methods for combating these widespread problems. Methods: A multi-choice questionnaire was provided to inmates to potentially assess the reasons for their drug addiction psychiatric, personal, social, economical, and political factors were thought to be implicated. Two hundred drug addicted prisoners were individually interviewed randomly in both Tabriz and Qom prisons. A questionnaire including questions about the inmates’ demographic characteristics and 49 multiple answers questions, was provided to identify the effects of different reasons for drug addiction for instance: psychiatric, personal, social, economical, and political factors. The collected data were analyzed by Student t-test and chi-squared test using SPSS software. Results: The results showed that the following factors could lead to drug addiction e.g. company with addicted friends and offenders, curiosity, imitation, illiteracy, family problems, crowded family, poverty, unemployment, and lack of self confidence. There were significant differences between Tabriz and Qom prisoners in relation to age, starting age of addiction, job, income, education, class of addiction, marital status, and hobbies. Mean age, mean starting age of addiction, poverty, alcohol drinking before addiction, marital status, heroin addiction, codeine and benzodiazepines abuse were significantly greater for Tabriz prisoners than those of Qom. Conclusion: It is clear that the governmental programs for reducing unemployment, creation of safe hobbies, proper control on drug dispensing in the pharmacies, proper birth control programs, and encouragement to higher education could alleviate addiction problem in Iran.

  9. Molecular docking study of Papaver alkaloids to some alkaloid receptors

    Directory of Open Access Journals (Sweden)

    A. Nofallah

    2017-11-01

    Full Text Available Background and objectives: More than 40 different alkaloids have been obtained from opium the most important of which are morphine, codeine, papaverine, noscapine and tabaine. Opioid alkaloids produce analgesia by affecting areas of the brain that have peptides with pharmacological pseudo-opioid properties. These alkaloids show important effects on some intracellular peptides like mu, delta, and kappa receptors. Therefore, studying the effects of these alkaloids on different receptors is essential. Methods: Molecular docking is a well-known method in exploring the protein-ligand interactions. In this research, five important alkaloids were docked to crystal structure of human mu opioid receptor (4DKL, human delta opioid receptor (4EJ4 and human kappa opioid receptor (4DJH which were retrieved from protein databank. The 3D-structures of alkaloids were drawn by chembiooffice2010 and minimized with hyperchem package and submitted to molecular docking utilizing autodock-vina. Flexibility of the proteins was considered. The docking studies were performed to compare the affinity of these five alkaloids to the mentioned receptors. Results: We computationally docked each alkaloid compound onto each receptor structure and estimated their binding affinity based on dock scores. Dock score is a criteria including binding energy which utilized here for prediction and comparison of the binding affinities. Binding interactions of the docked alkaloids in receptor pockets were also visually inspected and compared. Conclusion: In this approach, using docking study as a computational method provided a valuable insight of opioid receptor pocket structures which would be essential to design more efficient drugs in pain managements and addiction treatments.

  10. Comparison of 3 different methods of anesthesia before transrectal prostate biopsy: a prospective randomized trial

    International Nuclear Information System (INIS)

    Oebek, C.; Oezkan, B.; Tunc, B.; Can, G.; Yalcin, V.; Solok, V.

    2004-01-01

    Purpose: Periprostatic nerve block (PNB) is the most common anesthesia technique used before prostate biopsy. However, needle punctures for anesthetic infiltration may be painful and cause higher infectious complications. We assessed whether addition of rectal lidocaine gel would improve its efficacy. We also investigated the efficacy and safety of tramadol, a codeine derivative, as a noninvasive method. Materials and Methods: A total of 300 patients who underwent prostate biopsies were randomized into 4 groups of controls, PNB, perianal/intrarectal lidocaine gel plus PNB and tramadol. Pain was assessed with a numeric analog scale. Results: Each group consisted of 75 patients, and there was a statistically significant difference among pain scores (p = 0.001). Mean pain scores were 4.63 for controls, 2.57 for PNB, 2.03 for infiltration plus gel group and 3.11 for tramadol. Pain and discomfort were least in PNB plus gel arm. The difference of pain score between PNB alone and tramadol group did not reach statistical significance. Infectious complications were higher in the combination group, whereas there were no complications with tramadol. Conclusions: Any form of analgesia/anesthesia was superior to none. The combination of PNB plus gel provided significantly better analgesia compared to PNB alone or tramadol. If this can be duplicated in other trials, the combination may be accepted as the new gold standard of anesthesia for prostate biopsy. The efficacy of tramadol was similar to that of PNB, and was free of complications. Therefore, tramadol may have a role before prostate biopsy, which needs to be explored. (author)

  11. Pain point system scale (PPSS: a method for postoperative pain estimation in retrospective studies

    Directory of Open Access Journals (Sweden)

    Gkotsi A

    2012-11-01

    Full Text Available Anastasia Gkotsi,1 Dimosthenis Petsas,2 Vasilios Sakalis,3 Asterios Fotas,3 Argyrios Triantafyllidis,3 Ioannis Vouros,3 Evangelos Saridakis,2 Georgios Salpiggidis,3 Athanasios Papathanasiou31Department of Experimental Physiology, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Anesthesiology, 3Department of Urology, Hippokration General Hospital, Thessaloniki, GreecePurpose: Pain rating scales are widely used for pain assessment. Nevertheless, a new tool is required for pain assessment needs in retrospective studies.Methods: The postoperative pain episodes, during the first postoperative day, of three patient groups were analyzed. Each pain episode was assessed by a visual analog scale, numerical rating scale, verbal rating scale, and a new tool – pain point system scale (PPSS – based on the analgesics administered. The type of analgesic was defined based on the authors’ clinic protocol, patient comorbidities, pain assessment tool scores, and preadministered medications by an artificial neural network system. At each pain episode, each patient was asked to fill the three pain scales. Bartlett’s test and Kaiser–Meyer–Olkin criterion were used to evaluate sample sufficiency. The proper scoring system was defined by varimax rotation. Spearman’s and Pearson’s coefficients assessed PPSS correlation to the known pain scales.Results: A total of 262 pain episodes were evaluated in 124 patients. The PPSS scored one point for each dose of paracetamol, three points for each nonsteroidal antiinflammatory drug or codeine, and seven points for each dose of opioids. The correlation between the visual analog scale and PPSS was found to be strong and linear (rho: 0.715; P <0.001 and Pearson: 0.631; P < 0.001.Conclusion: PPSS correlated well with the known pain scale and could be used safely in the evaluation of postoperative pain in retrospective studies.Keywords: pain scale, retrospective studies, pain point system

  12. Target screening and confirmation of 35 licit and illicit drugs and metabolites in hair by LC-MSMS.

    Science.gov (United States)

    Lendoiro, Elena; Quintela, Oscar; de Castro, Ana; Cruz, Angelines; López-Rivadulla, Manuel; Concheiro, Marta

    2012-04-10

    A liquid chromatography-tandem mass spectrometry (LC-MSMS) target screening in 50mg hair was developed and fully validated for 35 analytes (Δ9-tetrahidrocannabinol (THC), morphine, 6-acetylmorphine, codeine, methadone, fentanyl, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, benzoylecgonine, cocaine, lysergic acid diethylamide, ketamine, scopolamine, alprazolam, bromazepam, clonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, lormetazepam, nordiazepam, oxazepam, tetrazepam, triazolam, zolpidem, zopiclone, amitriptyline, citalopram, clomipramine, fluoxetine, paroxetine and venlafaxine). Hair decontamination was performed with dichloromethane, and incubation in 2 mL of acetonitrile at 50°C overnight. Extraction procedure was performed in 2 steps, first liquid-liquid extraction, hexane:ethyl acetate (55:45, v:v) at pH 9, followed by solid-phase extraction (Strata-X cartridges). Chromatographic separation was performed in AtlantisT3 (2.1 mm × 100 mm, 3 μm) column, acetonitrile and ammonium formate pH 3 as mobile phase, and 32 min total run time. One transition per analyte was monitored in MRM mode. To confirm a positive result, a second injection monitoring 2 transitions was performed. The method was specific (no endogenous interferences, n=9); LOD was 0.2-50 pg/mg and LOQ 0.5-100 pg/mg; linearity ranged from 0.5-100 to 2000-20,000 pg/mg; imprecision drugs of abuse (THC, cocaine, opiates, amphetamines) and medicines (benzodiazepines, antidepressants) was developed and validated, achieving lower cut-offs than Society of Hair Testing recommendations. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Occurrence and concentrations of pharmaceutical compounds in deep groundwater used for public drinking-water supply in California

    Science.gov (United States)

    Fram, Miranda S.; Belitz, Kenneth

    2011-01-01

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of the state with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping.

  14. Matrix solid-phase dispersion on column clean-up/pre-concentration as a novel approach for fast isolation of abuse drugs from human hair.

    Science.gov (United States)

    Míguez-Framil, Martha; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar; Alvarez-Freire, Iván; Tabernero, María Jesús; Bermejo, Ana María

    2010-10-08

    A simple and fast sample pre-treatment method based on matrix solid-phase dispersion (MSPD) for isolating cocaine, benzoylecgonine (BZE), codeine, morphine and 6-monoacethylmorphine (6-MAM) from human hair has been developed. The MSPD approach consisted of using alumina (1.80 g) as a dispersing agent and 0.6M hydrochloric acid (4 mL) as an extracting solvent. For a fixed hair sample mass of 0.050 g, the alumina mass to sample mass ratio obtained was 36. A previously conditioned Oasis HLB cartridge (2 mL methanol, plus 2 mL ultrapure water, plus 1 mL of 0.2M/0.2M sodium hydroxide/boric acid buffer solution at pH 9.2) was attached to the end of the MSPD syringe for on column clean-up of the hydrochloric acid extract and for transferring the target compounds to a suitable solvent for gas chromatography (GC) analysis. Therefore, the adsorbed analytes were directly eluted from the Oasis HLB cartridges with 2 mL of 2% acetic acid in methanol before concentration by N(2) stream evaporation and dry extract derivatization with N-methyl-tert-butylsilyltrifluoroacetamide (BSTFA) and chlorotrimethylsilane (TMCS). The optimization/evaluation of all the factors affecting the MSPD and on column clean-up procedures has led to a fast sample treatment, and analytes extraction and pre-concentration can be finished in approximately 30 min. The developed method has been applied to eight hair samples from poli-drug abusers and measured analyte concentrations have been found to be statistically similar (95% confidence interval) to those obtained after a conventional enzymatic hydrolysis method (Pronase E). Copyright © 2010. Published by Elsevier B.V.

  15. Effect of morphine on the growth rate of Calliphora stygia (Fabricius) (Diptera: Calliphoridae) and possible implications for forensic entomology.

    Science.gov (United States)

    George, Kelly A; Archer, Melanie S; Green, Lauren M; Conlan, Xavier A; Toop, Tes

    2009-12-15

    Insect specimens collected from decomposing bodies enable forensic entomologists to estimate the minimum post-mortem interval (PMI). Drugs and toxins within a corpse may affect the development rate of insects that feed on them and it is vital to quantify these effects to accurately calculate minimum PMI. This study investigated the effects of morphine on growth rates of the native Australian blowfly, Calliphora stygia (Fabricius) (Diptera: Calliphoridae). Several morphine concentrations were incorporated into pet mince to simulate post-mortem concentrations in morphine, codeine and/or heroin-dosed corpses. There were four treatments for feeding larvae; T 1: control (no morphine); T 2: 2 microg/g morphine; T 3: 10 microg/g morphine; and T 4: 20 microg/g morphine. Ten replicates of 50 larvae were grown at 22 degrees C for each treatment and their development was compared at four comparison intervals; CI 1: 4-day-old larvae; CI 2: 7-day-old larvae; CI 3: pupae; and CI 4: adults. Length and width were measured for larvae and pupae, and costae and tibiae were measured for adults. Additionally, day of pupariation, day of adult eclosion, and survivorship were calculated for each replicate. The continued presence of morphine in meat was qualitatively verified using high-performance liquid chromatography with acidic potassium permanganate chemiluminescence detection. Growth rates of C. stygia fed on morphine-spiked mince did not differ significantly from those fed on control mince for any comparison interval or parameter measured. This suggests that C. stygia is a reliable model to use to accurately age a corpse containing morphine at any of the concentrations investigated.

  16. Socio-demographic characteristics of the addicted inmates of Qom and Tabriz prisons in Iran

    Science.gov (United States)

    Sattari, Mohammadreza; Islambulchilar, Mina; Toluyi, Mohsen; Mashayekhi, Siminozar

    2012-01-01

    Purpose: The aim of this investigation was to study the factors responsible for drug addiction amongst the inmates of Tabriz and Qom prisons, to further understand the reasons for drug abuse particularly in the young and find improved methods for combating these widespread problems. Methods: A multi-choice questionnaire was provided to inmates to potentially assess the reasons for their drug addiction psychiatric, personal, social, economical, and political factors were thought to be implicated. Two hundred drug addicted prisoners were individually interviewed randomly in both Tabriz and Qom prisons. A questionnaire including questions about the inmates’ demographic characteristics and 49 multiple answers questions, was provided to identify the effects of different reasons for drug addiction for instance: psychiatric, personal, social, economical, and political factors. The collected data were analyzed by Student t-test and chi-squared test using SPSS software. Results: The results showed that the following factors could lead to drug addiction e.g. company with addicted friends and offenders, curiosity, imitation, illiteracy, family problems, crowded family, poverty, unemployment, and lack of self confidence. There were significant differences between Tabriz and Qom prisoners in relation to age, starting age of addiction, job, income, education, class of addiction, marital status, and hobbies. Mean age, mean starting age of addiction, poverty, alcohol drinking before addiction, marital status, heroin addiction, codeine and benzodiazepines abuse were significantly greater for Tabriz prisoners than those of Qom. Conclusion: It is clear that the governmental programs for reducing unemployment, creation of safe hobbies, proper control on drug dispensing in the pharmacies, proper birth control programs, and encouragement to higher education could alleviate addiction problem in Iran. PMID:24312772

  17. Misuse of prescription and illicit drugs among high-risk young adults in Los Angeles and New York

    Directory of Open Access Journals (Sweden)

    Stephen E. Lankenau

    2012-02-01

    Full Text Available Background. Prescription drug misuse among young adults is increasingly viewed as a public health concern, yet most research has focused on student populations and excluded high-risk groups. Furthermore, research on populations who report recent prescription drug misuse is limited. This study examined patterns of prescription drug misuse among high-risk young adults in Los Angeles (LA and New York (NY, which represent different local markets for illicit and prescription drugs. Design and Methods. Between 2009 and 2011, 596 young adults (16 to 25 years old who had misused prescription drugs within the past 90 days were interviewed in Los Angeles and New York. Sampling was stratified to enroll three groups of high-risk young adults: injection drug users (IDUs; homeless persons; and polydrug users. Results. In both sites, lifetime history of receiving a prescription for an opioid, tranquilizer, or stimulant was high and commonly preceded misuse. Moreover, initiation of opioids occurred before heroin and initiation of prescription stimulants happened prior to illicit stimulants. NY participants more frequently misused oxycodone, heroin, and cocaine, and LA participants more frequently misused codeine, marijuana, and methamphetamine. Combining prescription and illicit drugs during drug using events was commonly reported in both sites. Opioids and tranquilizers were used as substitutes for other drugs, e.g., heroin, when these drugs were not available. Conclusion. Patterns of drug use among high-risk young adults in Los Angeles and New York appear to be linked to differences in local markets in each city for illicit drugs and diverted prescription drugs.

  18. Clonidine as an adjunct to intravenous regional anesthesia: A randomized, double-blind, placebo-controlled dose ranging study

    Directory of Open Access Journals (Sweden)

    Clarence S Ivie

    2011-01-01

    Full Text Available Background : The addition of clonidine to lidocaine intravenous regional anesthesia (IVRA has been previously reported to improve postoperative analgesia in patients undergoing upper extremity surgery. Our objective was to perform a dose ranging study in order to determine the optimal dose of clonidine used with lidocaine in IVRA. Design & Setting : We performed a double-blinded randomized placebo-controlled study with 60 patients scheduled for elective endoscopic carpal tunnel release under IVRA with 50 ml lidocaine 0.5%. University-affiliated outpatient surgery center. Data collected in operating rooms, recovery room, and by telephone after discharge from surgery center. Materials & Methods : Sixty adult ASA I or II patients undergoing outpatient endoscopic carpal tunnel release under intravenous regional anesthesia.Patients were randomized into five study groups receiving different doses of clonidine in addition to 50 ml 0.5% lidocaine in their IVRA. Group A received 0 mcg/kg, group B 0.25 mcg/kg, group C 0.5 mcg/kg, group D 1.0 mcg/kg and group E 1.5 mcg/kg of clonidine.Intraoperative fentanyl, recovery room pain scores, time to first postsurgical analgesic, total number of acetaminophen/codeine tablets consumed postsurgery, incidence of sedation, hypotension and bradycardia. Results & Conclusions : There was no benefit from any dose of clonidine compared to placebo. There were no clonidine-related side effects seen within the dose range studied. In short duration minor hand surgery, the addition of clonidine to lidocaine-based intravenous regional anesthesia provides no measurable benefit.

  19. Use of cough and cold preparations during breastfeeding.

    Science.gov (United States)

    Mitchell, J L

    1999-12-01

    Adverse reactions in infants from maternal drug ingestion depend largely on the amount of milk consumed by the infant, timing of breastfeeding in relation to dosing, dose of the medication, dosing interval, and duration of therapy. When taking medications, breastfeeding mothers should be instructed to take their medication after breastfeeding, at the lowest effective dose and for the shortest duration. Overall, there are few data from human studies on the use of antihistamines, decongestants, and cough products during breastfeeding. Studies of pseudoephedrine, triprolidine, and loratadine in humans conclude that low levels of each drug would reach a breastfed infant. Since triprolidine and pseudoephedrine are also considered compatible with breastfeeding by the AAP, these 2 drugs should be the first-line choices. Codeine is considered compatible with breastfeeding by the AAP, and would be an acceptable choice for short-term use as a cough suppressant. It is important to note that many of the liquid cough and cold products contain alcohol. In addition, many of the combination products are a mixture of an antihistamine and a decongestant and may also contain aspirin, acetaminophen, ibuprofen, or caffeine. It is preferable for nursing mothers to only take medications that are necessary and to avoid such combination products. The AAP considers alcohol, acetaminophen, ibuprofen, and caffeine compatible with breastfeeding. Aspirin has been associated with significant negative effects on some nursing infants, and the AAP recommends giving aspirin to nursing mothers with caution. Mothers taking cough and cold products should watch for adverse events in their breastfed infants. Infants may experience paradoxical central nervous stimulation from antihistamines and irritability and insomnia from decongestants.

  20. Reimbursement of analgesics for chronic pain.

    Science.gov (United States)

    Pedersen, Line; Hansen, Anneli Borge; Svendsen, Kristian; Skurtveit, Svetlana; Borchgrevink, Petter C; Fredheim, Olav Magnus S

    2012-11-27

    The prevalence of chronic non-malignant pain in Norway is between 24% and 30%. The proportion of the population using opioids for non-malignant pain on a long-term basis is around 1%. The purpose of our study was to investigate how many were prescribed analgesics on reimbursable prescription under reimbursement code -71 (chronic non-malignant pain) in 2009 and 2010, which analgesics were prescribed and whether prescribing practices were in accordance with national guidelines. We retrieved pseudonymised data from the National Prescription Database on all those who received drugs with reimbursement code -71 in 2009 and 2010. The data contain information on drug, dosage, formulation, reimbursement code and date of issue. 90,731 patients received reimbursement for drugs indicated for chronic non-malignant pain in 2010. Of these, 6,875 were given opioids, 33,242 received paracetamol, 25,865 non-steroid inflammatory drugs (NSAIDs), 20,654 amitryptiline and 16,507 gabapentin. Oxycodone was the most frequently prescribed opioid, followed by buprenorphine, tramadol and codeine/paracetamol. Of those who were prescribed opioids, 4,047 (59%) received mainly slow-release opioids, 2,631 (38%) also received benzodiazepines and 2,418 (35%) received benzodiazepine-like sleep medications. The number of patients who received analgesics and opioids on reimbursable prescriptions was low compared to the proportion of the population with chronic pain and the proportion using opioids long-term. 38% of those reimbursed for opioids also used benzodiazepines, which is contrary to official Norwegian guidelines.

  1. Binary Solvents Dispersive Liquid-Liquid Microextraction (BS-DLLME) Method for Determination of Tramadol in Urine Using High-Performance Liquid Chromatography.

    Science.gov (United States)

    Kiarostami, Vahid; Rouini, Mohamad-Reza; Mohammadian, Razieh; Lavasani, Hoda; Ghazaghi, Mehri

    2014-02-03

    Tramadol is an opioid, synthetic analog of codeine and has been used for the treatment of acute or chronic pain may be abused. In this work, a developed Dispersive liquid liquid microextraction (DLLME) as binary solvents-based dispersive liquid-liquid microextraction (BS-DLLME) combined with high performance liquid chromatography (HPLC) with fluorescence detection (FD) was employed for determination of tramadol in the urine samples. This procedure involves the use of an appropriate mixture of binary extraction solvents (70 μL CHCl3 and 30 μL ethyl acetate) and disperser solvent (600 μL acetone) for the formation of cloudy solution in 5 ml urine sample comprising tramadol and NaCl (7.5%, w/v). After centrifuging, the small droplets of extraction solvents were precipitated. In the final step, the HPLC with fluorescence detection was used for determination of tramadol in the precipitated phase. Various factors on the efficiency of the proposed procedure were investigated and optimized. The detection limit (S/N = 3) and quantification limit (S/N = 10) were found 0.2 and 0.9 μg/L, respectively. The relative standard deviations (RSD) for the extraction of 30 μg L of tramadol was found 4.1% (n = 6). The relative recoveries of tramadol from urine samples at spiking levels of 10, 30 and 60 μg/L were in the range of 95.6 - 99.6%. Compared with other methods, this method provides good figures of merit such as good repeatability, high extraction efficiency, short analysis time, simple procedure and can be used as microextraction technique for routine analysis in clinical laboratories.

  2. Tyrosine Aminotransferase Contributes to Benzylisoquinoline Alkaloid Biosynthesis in Opium Poppy1[W

    Science.gov (United States)

    Lee, Eun-Jeong; Facchini, Peter J.

    2011-01-01

    Tyrosine aminotransferase (TyrAT) catalyzes the transamination of l-Tyr and α-ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and l-glutamate. The decarboxylation product of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural products known collectively as benzylisoquinoline alkaloids (BIAs). We have isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum), which remains the only commercial source for several pharmaceutical BIAs, including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5′-phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between PLP and a specific Lys residue. The amino acid sequence of TyrAT showed considerable homology to other putative plant TyrATs, although few of these have been functionally characterized. Purified, recombinant TyrAT displayed a molecular mass of approximately 46 kD and a substrate preference for l-Tyr and α-ketoglutarate, with apparent Km values of 1.82 and 0.35 mm, respectively. No specific requirement for PLP was detected in vitro. Liquid chromatography-tandem mass spectrometry confirmed the conversion of l-Tyr to 4-hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and stems of mature opium poppy plants. Virus-induced gene silencing was used to evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT transcript levels were reduced by at least 80% in silenced plants compared with controls and showed a moderate reduction in total alkaloid content. The modest correlation between transcript levels and BIA accumulation in opium poppy supports a role for TyrAT in the generation of alkaloid precursors, but it also suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde. PMID:21949209

  3. Dwarf mutant of Papaver somniferum with high morphine content

    International Nuclear Information System (INIS)

    Chauhan, S.P.; Patra, N.K.; Srivastava, H.K.

    1987-01-01

    Opium poppy, Papaver somniferum L. is an important medicinal plant known for its morphine, codeine, and thebaine alkaloids. This Institute had earlier released two latex opium yielding poppy varieties, Shyama and Shweta, which are now cultivated by the farmers under the supervision of the Narcotic Department of the Government of India. However, both these varieties became susceptible to downy mildew (Peronospora arborescens). Lodging due to heavy capsule weight is another problem affecting latex yield. With these problems in mind, we undertook mutation breeding on the above mentioned two varieties employing gamma rays (5 kR, 15 kR, 20 kR) and EMS (0.2%, 0.4%, 0.6%) and combined mutagens (5 kR + 0.2% EMS, 5 kR + 0.4% EMS and 5 kR + 0.6% EMS). M 1 from the treated seeds (405 plants) was raised in winter 1984-85. M 2 generation of 13,500 plants (i.e. 270 M 1 progenies x 50 plants) was raised in winter 1985/86. A dwarf mutant with high morphine content was identified in M 2 from the variety Shweta treated with 5 kR + 0.4% EMS. The mutant differs by its dwarf stature, compact leaf arrangements, multilocular capsules, increased capsule number, and small capsule size. The mutant is under testing for its superior morphine production. It may be used as dwarf gene source in hybridization for improving lodging resistance. This mutant is a novel type, which was not available in our germplasm collection

  4. Combination of electrochemistry with chemometrics to introduce an efficient analytical method for simultaneous quantification of five opium alkaloids in complex matrices.

    Science.gov (United States)

    Gholivand, Mohammad-Bagher; Jalalvand, Ali R; Goicoechea, Hector C; Gargallo, Raimundo; Skov, Thomas; Paimard, Giti

    2015-01-01

    For the first time, an analytical methodology based on differential pulse voltammetry (DPV) at a glassy carbon electrode (GCE) and integration of three efficient strategies including variable selection based on ant colony optimization (ACO), mathematical pre-processing selection by genetic algorithm (GA), and sample selection (SS) through a distance-based procedure to improve partial least squares-1 (PLS-1, ACO-GA-SS-PLS-1) multivariate calibration (MVC) for the simultaneous determination of five opium alkaloids including morphine (MOP), noscapine (NOP), thebaine (TEB), codeine (COD), and papaverine (PAP) was used and validated. The baselines of the DPV signals were modeled as a smooth curve, using P-splines, a combination of B-splines and a discrete roughness penalty. After subtraction of the baseline we got a signal with a two-component probability density. One component was for the peaks and it was approximated by a uniform distribution on the potential axis. The other component was for the observed noise around the baseline. Some sources of bi-linearity deviation for electrochemical data were discussed and analyzed. The lack of bi-linearity was tackled by potential shift correction using correlation optimized warping (COW) algorithm. The MVC model was developed as a quinternary calibration model in a blank human serum sample (drug-free) provided by a healthy volunteer to regard the presence of a strong matrix effect which may be caused by the possible interferents present in the serum, and it was validated and tested with two independent sets of analytes mixtures in the blank and actual human serum samples, respectively. Fortunately, the proposed methodology was successful in simultaneous determination of MOP, NOP, TEB, COD, and PAP in both blank and actual human serum samples and its results were satisfactory comparable to those obtained by applying the reference method based on high performance liquid chromatography-ultraviolet detection (HPLC-UV). Copyright

  5. Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy.

    Science.gov (United States)

    Lee, Eun-Jeong; Facchini, Peter J

    2011-11-01

    Tyrosine aminotransferase (TyrAT) catalyzes the transamination of L-Tyr and α-ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and L-glutamate. The decarboxylation product of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural products known collectively as benzylisoquinoline alkaloids (BIAs). We have isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum), which remains the only commercial source for several pharmaceutical BIAs, including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5'-phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between PLP and a specific Lys residue. The amino acid sequence of TyrAT showed considerable homology to other putative plant TyrATs, although few of these have been functionally characterized. Purified, recombinant TyrAT displayed a molecular mass of approximately 46 kD and a substrate preference for L-Tyr and α-ketoglutarate, with apparent K(m) values of 1.82 and 0.35 mm, respectively. No specific requirement for PLP was detected in vitro. Liquid chromatography-tandem mass spectrometry confirmed the conversion of L-Tyr to 4-hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and stems of mature opium poppy plants. Virus-induced gene silencing was used to evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT transcript levels were reduced by at least 80% in silenced plants compared with controls and showed a moderate reduction in total alkaloid content. The modest correlation between transcript levels and BIA accumulation in opium poppy supports a role for TyrAT in the generation of alkaloid precursors, but it also suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde.

  6. [Toxicity of analgesics in the family doctor practice].

    Science.gov (United States)

    Kuźniar-Placek, Justyna; Szponar, Jarosław; Panasiuk, Lech

    2012-01-01

    Analgesic usage without any consultation with a physician is very common in Poland. It increases the risk of occurrence of the harmful effect or harmful interaction with other medicaments taken by the patient. The abuse of painkillers applies not only to opioid but also to nonopioid analgesics. The largest group of commonly available medicaments are NSAIDs. The most frequent undesirable effect of NSAIDs' is dyspepsia. Among the most dangerous, and very often the ones without any symptoms, are gastric and duodenum ulceration for which the bleeding and perforation may be the first manifestation. Each non steroidal anti-inflammatory drug taken in large doses can be a cause of analgesic nephropathy. Its deceitful course can delay the diagnosis leading to chronic kidney failure. A complex supplements, that include central acting substances, increase the risk of kidney damage, as well as physical and psychological addiction. NSAIDs can cause: the heart failure to be more severe, treatment resistant arterial hypertension, increase an effectiveness of anticoagulants or antidiabetic drugs. The problem is also that some medicaments are available without a prescription (acetylsalicylic acid, ibuprofen, acetaminophen), especially that they are ingredients of many complex supplements considered safe. Taking doses larger than therapeutic or simultaneously taking many supplements of the same active substance had many times led to poisoning and even death. Equally dangerous can be an abuse of tramadol, codeine and COX-2 inhibitors. Therefore, prudential prescription of NSAIDs, knowledge of risks related to therapy and informing the patients about their side effects, may decrease the number of patients abusing the analgesics which can lead to lowering the number of deaths caused by serious complications.

  7. Analysis of the phenomenon of over-the-counter drug abuse and not controlled herbs trade by polish adolescents: Part I

    Directory of Open Access Journals (Sweden)

    Daria Suchecka

    2017-06-01

    Full Text Available The phenomenon of stupefying by the use of available over-the-counter drugs (OTC among adolescents is an essential problem in both Poland and throughout the world. Popular analgesics, cold medicine and antihistamines contain psychedelic substances, such as dextromethorphan (DXM, pseudoephedrine/ephedrine, codeine (methylmorphine, dimenhydrinate, paracetamol (acetaminophren and others. Cases of fatal addiction to dextromethorphan, one of the active substances contained in medicines, e.g., the common cold, have been reported. The test results cited by the authors clearly indicate that the use of OTC drugs, whose turnover is not controlled is a domain of females. The extent of use of drugs not prescribed by a doctor has remained for many years at a constant level. The most common poisonings with OTC drugs are caused by those that affect the respiratory system or exert analgesic or antipyretic effects. They are also used in attempted suicides, especially among females. Analyzing poisonings caused by OTC medications their seasonality has been observed. Their number increases during spring–autumn. A territorial differentiation in areas of OTC drug trade in terms of their quantities, with the predominance of southern regions is also noted. Intoxication with psychoactive substances causes the deterioration of relations between young people. In the reviewed studies there is no detailed information on the composition of non-prescription medicines. Moreover, young people have easy access to mushroom fungi, growing in nearby forests and meadows that may have hallucinogenic effects and are available in pharmacies and on the Internet. Med Pr 2017;68(3:413–422

  8. PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

    2015-09-01

    Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

  9. Monitoring of selected priority and emerging contaminants in the Guadalquivir River and other related surface waters in the province of Jaén, South East Spain.

    Science.gov (United States)

    Robles-Molina, José; Gilbert-López, Bienvenida; García-Reyes, Juan F; Molina-Díaz, Antonio

    2014-05-01

    The province of Jaén counts with four natural parks, numerous rivers, reservoirs and wetlands; moreover, it is probably the region with higher olive oil production in the world, which makes this zone a proper target to be studied based on the European Water Framework Directive 2000/60/CE. The aim of this survey is to monitor a total number of 373 compounds belonging to different families (pesticides, PAHs, nitrosamines, drugs of abuse, pharmaceuticals and life-style compounds) in surface waters located at different points of the province of Jaén. Among these compounds some priority organic substances (regulated by the EU Directive 2008/105/EC) and pollutants of emerging concern (not regulated yet) can be found. A liquid chromatography electrospray time-of-flight mass spectrometry (LC-TOFMS) method covering 340 compounds was developed and applied, together with a gas chromatography triple-quadrupole mass spectrometry (GC-MS/MS) method which enabled the analysis of 63 organic contaminants (30 of these compounds are analyzed by LC-TOFMS as well). From April 2009 to November 2010 a total of 83 surface water samples were collected (rivers, reservoirs and wetlands). In this period numerous organic contaminants were detected, most of them at the ng L(-1) level. The most frequently priority substances found were chlorpyrifos ethyl, diuron and hexachlorobenzene. Within the other groups, the most frequently detected compounds were: terbuthylazine, oxyfluorfen, desethyl terbuthylazine, diphenylamine (pesticide family); fluorene, phenanthrene, pyrene (PAHs group), codeine, paracetamol (pharmaceuticals compounds) and caffeine, nicotine (life-style compounds). As is could be expected, the total concentration of emerging contaminants is distinctly larger than that of priority pollutants, highlighting the importance of continuing with the study of their presence, fate and effects in aquatic environments. However, concentration levels (at the ng per liter level) are low in

  10. Pharmacogenomics and pharmacogenetics for the intensive care unit: a narrative review.

    Science.gov (United States)

    MacKenzie, Meghan; Hall, Richard

    2017-01-01

    Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. We selected relevant literature to illustrate the important concepts contained within. Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach. Genetic variability in response to drugs may occur as a result of alterations of drug-metabolizing (cytochrome P [CYP]) enzymes, receptors, and transport proteins leading to enhancement or delay in the therapeutic response. Of relevance to the ICU, genetic variation in CYP-450 isoenzymes results in altered effects of midazolam, fentanyl, morphine, codeine, phenytoin, clopidogrel, warfarin, carvedilol, metoprolol, HMG-CoA reductase inhibitors, calcineurin inhibitors, non-steroidal anti-inflammatory agents, proton pump inhibitors, and ondansetron. Changes in cholinesterase enzyme function may affect the disposition of succinylcholine, benzylisoquinoline muscle relaxants, remifentanil, and hydralazine. Genetic variation in transport proteins leads to differences in the response to opioids and clopidogrel. Polymorphisms in drug receptors result in altered effects of β-blockers, catecholamines, antipsychotic agents, and opioids. Genetic variation also contributes to the diversity and incidence of diseases and conditions such as sepsis, malignant hyperthermia, drug-induced hypersensitivity reactions, cardiac channelopathies, thromboembolic disease, and congestive heart failure. Application of pharmacogenetics and pharmacogenomics has seen improvements in drug therapy. Ongoing study and incorporation of these concepts into clinical decision making in the ICU has the potential to affect patient outcomes.

  11. Prescription opioids for occupational injury: results from workers' compensation claims records.

    Science.gov (United States)

    Berecki-Gisolf, Janneke; Collie, Alex; McClure, Roderick J

    2014-09-01

    The objective of this study is to identify the prevalence of opioid prescription use in an Australian workers' compensation population and assess predictors of long-term use. Retrospective administrative data analysis. WorkSafe Victoria (Australia) workers' compensation. Workers with a workers' compensation claim were included if the injury/illness started in 2008 or 2009 (N = 54,931). Claim payments records dating up to 2 years postinjury were analyzed to determine receipt of prescription opioids. Long-term use was defined as use of any opioid beyond 1 year postinjury. Within the follow-up period, 8,933 (16.3%) workers claimed prescription opioids: 10.0% claimed opioids in the first year only, and 6.3% claimed opioids beyond the first year. The most commonly received opioids were codeine (10.4%), oxycodone (7.5%), and tramadol (5.0%). Dextropropoxyphene, which is considered unsafe in many countries because of potentially fatal side effects, was used by 1.9% of injured workers. Progression to long-term use of opioids was common (N = 3,446; 39%): age (35-64 years; the association with age followed an inverse U-shaped curve), women, laborers, lower socioeconomic status, greater work disability, and greater hospital expense were associated with opioid use beyond the first year postinjury. Prescription opioid use for workplace injury in Australia is common but not as common as reports from U.S. workers' compensation schemes. The type of opioid and number of repeat prescriptions are factors that should be carefully considered by practitioners prescribing opioids to injured workers: progression to long-term use is common and not fully explained by injury severity. Wiley Periodicals, Inc.

  12. Binary Solvents Dispersive Liquid—Liquid Microextraction (BS-DLLME) Method for Determination of Tramadol in Urine Using High-Performance Liquid Chromatography

    Science.gov (United States)

    2014-01-01

    Background Tramadol is an opioid, synthetic analog of codeine and has been used for the treatment of acute or chronic pain may be abused. In this work, a developed Dispersive liquid liquid microextraction (DLLME) as binary solvents-based dispersive liquid-liquid microextraction (BS-DLLME) combined with high performance liquid chromatography (HPLC) with fluorescence detection (FD) was employed for determination of tramadol in the urine samples. This procedure involves the use of an appropriate mixture of binary extraction solvents (70 μL CHCl3 and 30 μL ethyl acetate) and disperser solvent (600 μL acetone) for the formation of cloudy solution in 5 ml urine sample comprising tramadol and NaCl (7.5%, w/v). After centrifuging, the small droplets of extraction solvents were precipitated. In the final step, the HPLC with fluorescence detection was used for determination of tramadol in the precipitated phase. Results Various factors on the efficiency of the proposed procedure were investigated and optimized. The detection limit (S/N = 3) and quantification limit (S/N = 10) were found 0.2 and 0.9 μg/L, respectively. The relative standard deviations (RSD) for the extraction of 30 μg L of tramadol was found 4.1% (n = 6). The relative recoveries of tramadol from urine samples at spiking levels of 10, 30 and 60 μg/L were in the range of 95.6 – 99.6%. Conclusions Compared with other methods, this method provides good figures of merit such as good repeatability, high extraction efficiency, short analysis time, simple procedure and can be used as microextraction technique for routine analysis in clinical laboratories. PMID:24495475

  13. Pharmacy Malpractice: The rate and prevalence of dispensing high-risk prescription-only medications at community pharmacies in Saudi Arabia.

    Science.gov (United States)

    Alshammari, Thamir M; Alhindi, Salman A; Alrashdi, Ahmed M; Benmerzouga, Imaan; Aljofan, Mohamad

    2017-07-01

    To assess the compliance of community pharmacies with the regulations that prohibit the dispensing of prescription-only medications in the absence of a physician prescription in Saudi Arabia. A cross-sectional study was conducted in the period between October 2014 and January 2015. A list of 10 prescription-only medications were selected to be studied. 150 community pharmacies were visited across 6 major regions in Saudi Arabia to assess the prevalence of non-compliance among community pharmacies. Pharmacies were selected in random and researchers (disguised as patients) requested to purchase prescription-only medications in the absence of a prescription. Not all medications were purchased at once. Data were recorded per pharmacy, where pharmacies that approved dispense of the selected drug were scored as non-compliant and the pharmacies that rejected dispense of the selected drug were scored as compliant. Compliance rate was calculated per region per drug. Pharmacies based in governmental hospitals were visited in parallel. A total of 20 were visited. Data and statistical analysis were performed using Statistical Analyses Software (SAS 9.3). A total of 150 pharmacies were visited over a period of 3 months. On average, the percent approved dispense of prescription-only drugs across 6 regions in Saudi Arabia is 63% and the percent rejected dispense is 37% representing a significant non-compliance rate regarding the selected list of medications in this study. The frequency of dispense per medication across 6 major regions in Saudi Arabia is as follows: Isosorbide dinitrate (86%), Enoxaparin (82%), nitroglycerin (74%), Propranolol (73%), Verapamil (70%), Warfarin (65%), Methyldopa (64%), Ciprofloxacin (57%) and Codeine (4%). Non-compliance of community pharmacies with the law of pharmaceutical practice is at an alarming rate in the Kingdom of Saudi Arabia and authoritative figures must intervene to impede and combat such activities .

  14. Impact of solvent conditions on separation and detection of basic drugs by micro liquid chromatography-mass spectrometry under overloading conditions.

    Science.gov (United States)

    Schubert, Birthe; Oberacher, Herbert

    2011-06-03

    In this study the impact of solvent conditions on the performance of μLC/MS for the analysis of basic drugs was investigated. Our aim was to find experimental conditions that enable high-performance chromatographic separation particularly at overloading conditions paired with a minimal loss of mass spectrometric detection sensitivity. A focus was put on the evaluation of the usability of different kinds of acidic modifiers (acetic acid (HOAc), formic acid (FA), methansulfonic acid (CH₃SO₃H), trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA), and heptafluorobutyric acid (HFBA)). The test mixture consisted of eleven compounds (bunitrolol, caffeine, cocaine, codeine, diazepam, doxepin, haloperidol, 3,4-methylendioxyamphetamine, morphine, nicotine, and zolpidem). Best chromatographic performance was obtained with the perfluorinated acids. Particularly, 0.010-0.050% HFBA (v/v) was found to represent a good compromise in terms of chromatographic performance and mass spectrometric detection sensitivity. Compared to HOAc, on average a 50% reduction of the peak widths was observed. The use of HFBA was particularly advantageous for polar compounds such as nicotine; only with such a hydrophobic ion-pairing reagent chromatographic retention of nicotine was observed. Best mass spectrometric performance was obtained with HOAc and FA. Loss of detection sensitivity induced by HFBA, however, was moderate and ranged from 0 to 40%, which clearly demonstrates that improved chromatographic performance is able to compensate to a large extent the negative effect of reduced ionization efficiency on detection sensitivity. Applications of μLC/MS for the qualitative and quantitative analysis of clinical and forensic toxicological samples are presented. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots.

    Science.gov (United States)

    Saussereau, E; Lacroix, C; Gaulier, J M; Goulle, J P

    2012-02-15

    A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Studies on Ancylostomiasis: II.Clinical Symptomatology, Effects of Drugs, especially of Iron Compounds, with Relation to the Severity of Artificial Infection

    International Nuclear Information System (INIS)

    Lee, Mun Ho; Kim, Dong Jip; Lee, Jang Kyu; Seo, Byong Sul

    1967-01-01

    This study was aimed; firstly to observe various clinical symptomatology with relation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminics and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology. 1) The most frequently encountered symptoms and signs were general malaise, cough and hoarseness. The tracheal itching and pain, low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2) If the larger number of the larvae was given, the clinical symptomatology was more severe. 3) Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4) In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds. 1) The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from 15-20 days later and a recovery after 2 months. 2) The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3) The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4) The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency

  17. Presence of emerging contaminants in Natural Wetlands: L

    Science.gov (United States)

    Roig, P. V.; Blasco, C.; Andreu, V.; Pascual, J. A.; Rubio, J. L.; Picó, Y.

    2009-04-01

    latter found in 63 of the 65 analyzed samples in concentrations between 0.01 g/L and 248 mg/L. Others pharmaceuticals present in less quantities were: ciprofloxacin, codeine, diazepam, fenofibrate, ibuprofen, norfloxacin, metoprolol, ofloxacin, propanolol, sulfamethoxazole and trimethoprim. These results demonstrate the incidence of these pollutants in the Natural Park of ĹAlbufera, probably because raw sewage flows into the lake from houses and industries nears its shores. Increased pollution is threatening the sustainable use of ĹAlbufera, a vital resource for this touristic area. References: [1] N. Esiobu, L. Armenta, J. Ike, Int. J. Environ. Health 12. (2002), 133. [2] D. Löffler, T. A. Ternes, J. Chromatogr. A. 1021 (2003), 133-144.

  18. Preoperative opioid strength may not affect outcomes of anterior cervical procedures: a post hoc analysis of 2 prospective, randomized trials

    Science.gov (United States)

    Kelly, Michael P.; Anderson, Paul A.; Sasso, Rick C.; Riew, K. Daniel

    2015-01-01

    Object The aim of this study is to evaluate the relationship between preoperative opioid strength and outcomes of anterior cervical decompressive surgery. Methods A retrospective cohort of 1004 patients enrolled in 1 of 2 investigational device exemption studies comparing cervical total disc arthroplasty (TDA) and anterior cervical discectomy and fusion (ACDF) for single-level cervical disease causing radiculopathy or myelopathy was selected. At a preoperative visit, opioid use data, Neck Disability Index (NDI) scores, 36-ltem Short-Form Health Survey (SF-36) scores, and numeric rating scale scores for neck and arm pain were collected. Patients were divided into strong (oxycodone/morphine/meperidine), weak (codeine/propoxyphene/ hydrocodone), and opioid-naïve groups. Preoperative and postoperative (24 months) outcomes scores were compared within and between groups using the paired t-test and ANCOVA, respectively. Results Patients were categorized as follows: 226 strong, 762 weak, and 16 opioid naïve. The strong and weak groups were similar with respect to age, sex, race, marital status, education level, Worker's Compensation status, litigation status, and alcohol use. At 24-month follow-up, no differences in change in arm or neck pain scores (arm: strong –52.3, weak –50.6, naïve –54.0, p = 0.244; neck: strong –52.7, weak –50.8, naïve –44.6, p = 0.355); NDI scores (strong –36.0, weak –33.3, naïve –32.3, p = 0.181); or SF-36 Physical Component Summary scores (strong: 14.1, weak 13.3, naïve 21.7, p = 0.317) were present. Using a 15-point improvement in NDI to determine success, the authors found no between-groups difference in success rates (strong 80.6%, weak 82.7%, naïve 73.3%, p = 0.134). No difference existed between treatment arms (TDA vs ACDF) for any outcome at any time point. Conclusions Preoperative opioid strength did not adversely affect outcomes in this analysis. Careful patient selection can yield good results in this patient

  19. Incidence and interactions of heavy metals and pharmaceutical products in surface waters of a Mediterranean coastal wetland.

    Science.gov (United States)

    Andreu, Vicente; Pascual, Juan Antonio; Gimeno, Eugenia; Picó, Yolanda

    2013-04-01

    Heavy metals have been during decades a result of the human fingerprint on the ecosystems, mainly in waters, soils or vegetation, being considered as a major s threat also on human health. However, the increasing in human population shows other aspect, such as the so called "emerging contaminants". They constitute an increasing group of compounds that includes, among others, personal care products, drugs of abuse and pharmaceuticals. These contaminants have become, in recent years, of great concern for researchers and, even, for the population. Among these substances, the presence of pharmaceuticals in the ecosystems compartments has becoming an increasing problem for environmental sustainability, and also for human health, with consequences very scarcely known. They reach the nature from waste waters treatment plants, industrial waste effluents, uncontrolled landfills, etc. affecting particularly the fauna in its different levels. Some pharmaceuticals have shown toxicity not only to bacteria, algae and invertebrates but also to fish, mollusks, etc. This work is focused on the study of the presence of 17 relevant pharmaceuticals and 7 heavy metals (Cd, Co, Cr, Cu, Ni, Pb and Zn) in surface waters of the irrigation channels and the lagoon of the Pego-Oliva Marsh Natural Park (Valencian Community, Spain), which is characterized by a long history of human pressures, such as marsh transformation for agricultural uses, urbanization, etc. In this area, 34 sampling zones were selected, covering the main land uses. The interactions and possible relationships between both groups of contaminants were studied, together with the influences of the source of water samples, land uses and their spatial distribution. All water samples appeared contaminated with at least with two compounds. Ibuprofen and codeine were the compounds more frequently detected in concentrations between detection limit and a maximum of 59 ng/L and 63 ng/L respectively. Regarding the studied metals, Zn

  20. Kjøring med mistanke om påvirkning av andre rusmidler enn alkohol

    Directory of Open Access Journals (Sweden)

    Asbjørg S. Christophersen

    2009-10-01

    Full Text Available  SAMMENDRAGStatens rettstoksikologiske institutt har i løpet av de siste år registrert en stor økning av prøver fra bilføreremistenkt for kjøring under påvirkning av andre rusmidler enn alkohol. Antall positive saker økte 42% fra1994 til 1995. De hyppigste påviste stoffer er tetrahydrocannabinol, amfetamin, benzodiazepiner og opiater(morfin/kodein. Bruk av tyngre narkotiske stoffer har blitt mer vanlig i trafikksammenheng og antall positivetilfeller har økt betydelig mer enn totalt antall saker. Fra 1994 til 1995 økte antall positive amfetaminprøvermed 75% (fra 533 til 937 og antall positive prøver som følge av heroininntak økte med 87% (fra 92 til 172.Bruk av flere stoffer samtidig er vanlig, over 60 % av sakene i 1995 var positive på mer enn ett stoff, alkoholikke medregnet. De fleste tilfeller var representert av menn i alderen 25-32 år (37%. Kvinner var representerti ca. 11% av sakene.Christophersen AS, Skurtveit S, Mørland J. Drivers suspected to drive under the influence of drugs otherthan alcohol. Nor J Epidemiol 1996; 6 (1: 45-48.ENGLISH SUMMARYThe National Institute of Forensic Toxicology has registered a large increase in the number of samples fromdrivers suspected to drive under influence of drugs other than alcohol. The number of drug positive casesincreased 42% from 1994 to 1995. The most frequent drugs detected are tetrahydrocannabinol, amphetamine,benzodiazepines and opiates (morphine/codeine. The frequency of hard narcotic drug use has increased morethan the total number of cases. From 1994 to 1995, the number of amphetamine positive samples increased75% (from 533 to 937 and the number of samples positive due to heroin use (detection of the metabolite 6-monoacetylmorphine in urine increased 87%. Multi-drug use is common and more than one drug wasdetected in more than 60% of the cases from 1995, alcohol not included. Most of the cases were representedby men 25-32 years old (37%. Women were represented in about

  1. The effect of distant reiki on pain in women after elective Caesarean section: a double-blinded randomised controlled trial

    Science.gov (United States)

    vanderVaart, Sondra; Berger, Howard; Tam, Carolyn; Goh, Y Ingrid; Gijsen, Violette M G J; de Wildt, Saskia N; Taddio, Anna

    2011-01-01

    Introduction Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. Methods In this randomised, double-blinded study, women who underwent an elective C-section were allocated to either usual care (control, n=40) or three distant reiki sessions in addition to usual care (n=40). Pain was assessed using a visual analogue scale (VAS). The primary endpoint was the Area Under the VAS-Time Curve (AUC) for days 1–3. Secondary measures included: the proportion of women who required opioid medications and dose consumed, rate of healing and vital signs. Results AUC for pain was not significantly different in the distant reiki and control groups (mean±SD; 212.1±104.7 vs 223.1±117.8; p=0.96). There were no significant differences in opioid consumption or rate of healing; however, the distant reiki group had a significantly lower heart rate (74.3±8.1 bpm vs 79.8±7.9 bpm, p=0.003) and blood pressure (106.4±9.7 mm Hg vs 111.9±11.0 mm Hg, p=0.02) post surgery. Conclusion Distant reiki had no significant effect on pain following an elective C-section. Clinical Trial Registration

  2. Assessment of the ion-trap mass spectrometer for routine qualitative and quantitative analysis of drugs of abuse extracted from urine.

    Science.gov (United States)

    Vorce, S P; Sklerov, J H; Kalasinsky, K S

    2000-10-01

    The ion-trap mass spectrometer (MS) has been available as a detector for gas chromatography (GC) for nearly two decades. However, it still occupies a minor role in forensic toxicology drug-testing laboratories. Quadrupole MS instruments make up the majority of GC detectors used in drug confirmation. This work addresses the use of these two MS detectors, comparing the ion ratio precision and quantitative accuracy for the analysis of different classes of abused drugs extracted from urine. Urine specimens were prepared at five concentrations each for amphetamine (AMP), methamphetamine (METH), benzoylecgonine (BZE), delta9-carboxy-tetrahydrocannabinol (delta9-THCCOOH), phencyclidine (PCP), morphine (MOR), codeine (COD), and 6-acetylmorphine (6-AM). Concentration ranges for AMP, METH, BZE, delta9-THCCOOH, PCP, MOR, COD, and 6-AM were 50-2500, 50-5000, 15-800, 1.5-65, 1-250, 500-32000, 250-21000, and 1.5-118 ng/mL, respectively. Sample extracts were injected into a GC-quadrupole MS operating in selected ion monitoring (SIM) mode and a GC-ion-trap MS operating in either selected ion storage (SIS) or full scan (FS) mode. Precision was assessed by the evaluation of five ion ratios for n = 15 injections at each concentration using a single-point calibration. Precision measurements for SIM ion ratios provided coefficients of variation (CV) between 2.6 and 9.8% for all drugs. By comparison, the SIS and FS data yielded CV ranges of 4.0-12.8% and 4.0-11.2%, respectively. The total ion ratio failure rates were 0.2% (SIM), 0.7% (SIS), and 1.2% (FS) for the eight drugs analyzed. Overall, the SIS mode produced stable, comparable mean ratios over the concentration ranges examined, but had greater variance within batch runs. Examination of postmortem and quality-control samples produced forensically accurate quantitation by SIS when compared to SIM. Furthermore, sensitivity of FS was equivalent to SIM for all compounds examined except for 6-AM.

  3. Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

    Directory of Open Access Journals (Sweden)

    Vogel Hans J

    2008-01-01

    Full Text Available Abstract Background Opium poppy (Papaver somniferum produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the altered regulation of other metabolic pathways. As a key component of our functional genomics platform for opium poppy we have used proton nuclear magnetic resonance (1H NMR metabolomics to investigate the interplay between primary and secondary metabolism in cultured opium poppy cells treated with a fungal elicitor. Results Metabolite fingerprinting and compound-specific profiling showed the extensive reprogramming of primary metabolic pathways in association with the induction of alkaloid biosynthesis in response to elicitor treatment. Using Chenomx NMR Suite v. 4.6, a software package capable of identifying and quantifying individual compounds based on their respective signature spectra, the levels of 42 diverse metabolites were monitored over a 100-hour time course in control and elicitor-treated opium poppy cell cultures. Overall, detectable and dynamic changes in the metabolome of elicitor-treated cells, especially in cellular pools of carbohydrates, organic acids and non-protein amino acids were detected within 5 hours after elicitor treatment. The metabolome of control cultures also showed substantial modulations 80 hours after the start of the time course, particularly in the levels of amino acids and phospholipid pathway intermediates. Specific flux modulations were detected throughout primary metabolism, including glycolysis, the tricarboxylic acid cycle, nitrogen assimilation, phospholipid/fatty acid synthesis and the shikimate pathway, all of which

  4. Endogenous morphine-6-glucuronide (M6G) is present in the plasma of patients: validation of a specific anti-M6G antibody for clinical and basic research.

    Science.gov (United States)

    Laux-Biehlmann, Alexis; Chung, Hélène; Mouheiche, Jinane; Vérièpe, Julie; Delalande, François; Lamshöft, Marc; Welters, Ingeborg D; Soldevila, Stéphanie; Bazin, Hervé; Lamarque, Laurent; Van Dorsselaer, Alain; Poisbeau, Pierrick; Schneider, Francis; Goumon, Yannick; Garnero, Patrick

    2014-01-01

    Endogenous morphine and its derivatives (morphine-6-glucuronide [M6G]; morphine-3-glucuronide [M3G]) are formed by mammalian cells from dopamine. Changes in the concentrations of endogenous morphine have been demonstrated in several pathologies (sepsis, Parkinson's disease, etc.), and they might be relevant as pathological markers. While endogenous morphine levels are detectable using enzyme-linked immunosorbant assay (ELISA), mass spectrometry (MS) analysis was, so far, the only approach to detect and quantify M6G. This study describes the preparation of a specific anti-M6G rabbit polyclonal antibody and its validation. The specificity of this antibody was assessed against 30 morphine-related compounds. Then, a M6G-specific ELISA-assay was tested to quantify M6G in the plasma of healthy donors, morphine-treated, and critically ill patients. The antibody raised against M6G displays a strong affinity for M6G, codeine-6-glucuronide, and morphine-3-6-glucuronide, whereas only weak cross-reactivities were observed for the other compounds. Both M6G-ELISA and LC-MS/MS approaches revealed the absence of M6G in the plasma of healthy donors (controls, n = 8). In all positive donors treated with morphine-patch (n = 5), M6G was detected using both M6G-ELISA and LC-MS/MS analysis. Finally, in a study on critically ill patients with circulating endogenous morphine (n = 26), LC-MS/MS analysis revealed that 73% of the positive-patients (19 of 26), corresponding to high M6G-levels in M6G-ELISA, contained M6G. In conclusion, we show that endogenous M6G can be found at higher levels than morphine in the blood of morphine-naive patients. With respect to the interest of measuring endogenous M6G in pathologies, we provide evidences that our ELISA procedure represents a powerful tool as it can easily and specifically detect endogenous M6G levels. © 2013 International Union of Biochemistry and Molecular Biology.

  5. Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures

    Directory of Open Access Journals (Sweden)

    Schriemer David C

    2010-11-01

    Full Text Available Abstract Background Papaver somniferum (opium poppy is the source for several pharmaceutical benzylisoquinoline alkaloids including morphine, the codeine and sanguinarine. In response to treatment with a fungal elicitor, the biosynthesis and accumulation of sanguinarine is induced along with other plant defense responses in opium poppy cell cultures. The transcriptional induction of alkaloid metabolism in cultured cells provides an opportunity to identify components of this process via the integration of deep transcriptome and proteome databases generated using next-generation technologies. Results A cDNA library was prepared for opium poppy cell cultures treated with a fungal elicitor for 10 h. Using 454 GS-FLX Titanium pyrosequencing, 427,369 expressed sequence tags (ESTs with an average length of 462 bp were generated. Assembly of these sequences yielded 93,723 unigenes, of which 23,753 were assigned Gene Ontology annotations. Transcripts encoding all known sanguinarine biosynthetic enzymes were identified in the EST database, 5 of which were represented among the 50 most abundant transcripts. Liquid chromatography-tandem mass spectrometry (LC-MS/MS of total protein extracts from cell cultures treated with a fungal elicitor for 50 h facilitated the identification of 1,004 proteins. Proteins were fractionated by one-dimensional SDS-PAGE and digested with trypsin prior to LC-MS/MS analysis. Query of an opium poppy-specific EST database substantially enhanced peptide identification. Eight out of 10 known sanguinarine biosynthetic enzymes and many relevant primary metabolic enzymes were represented in the peptide database. Conclusions The integration of deep transcriptome and proteome analyses provides an effective platform to catalogue the components of secondary metabolism, and to identify genes encoding uncharacterized enzymes. The establishment of corresponding transcript and protein databases generated by next-generation technologies in a

  6. The Effect of Opioid Prescribing Guidelines on Prescriptions by Emergency Physicians in Ohio.

    Science.gov (United States)

    Weiner, Scott G; Baker, Olesya; Poon, Sabrina J; Rodgers, Ann F; Garner, Chad; Nelson, Lewis S; Schuur, Jeremiah D

    2017-12-01

    The objective of our study is to evaluate the association between Ohio's April 2012 emergency physician guidelines aimed at reducing inappropriate opioid prescribing and the number and type of opioid prescriptions dispensed by emergency physicians. We used Ohio's prescription drug monitoring program data from January 1, 2010, to December 31, 2014, and included the 5 most commonly prescribed opioids (hydrocodone, oxycodone, tramadol, codeine, and hydromorphone). The primary outcome was the monthly statewide prescription total of opioids written by emergency physicians in Ohio. We used an interrupted time series analysis to compare pre- and postguideline level and trend in number of opioid prescriptions dispensed by emergency physicians per month, number of prescriptions stratified by 5 commonly prescribed opioids, and number of prescriptions for greater than 3 days' supply of opioids. Beginning in January 2010, the number of prescriptions dispensed by all emergency physicians in Ohio decreased by 0.3% per month (95% confidence interval [CI] -0.49% to -0.15%). The implementation of the guidelines in April 2012 was associated with a 12% reduction (95% CI -17.7% to -6.3%) in the level of statewide total prescriptions per month and an additional decline of 0.9% (95% CI -1.1% to -0.7%) in trend relative to the preguideline trend. The estimated effect of the guidelines on total monthly prescriptions greater than a 3-day supply was an 11.2% reduction in level (95% CI -18.8% to -3.6%) and an additional 0.9% (95% CI -1.3% to -0.5%) decline in trend per month after the guidelines. Guidelines were also associated with a reduction in prescribing for each of the 5 individual opioids, with various effect. In Ohio, emergency physician opioid prescribing guidelines were associated with a decrease in the quantity of opioid prescriptions written by emergency physicians. Although introduction of the guidelines occurred in parallel with other opioid-related interventions, our

  7. Rheumatoid arthritis: A major symptom and symptomatic therapy

    Directory of Open Access Journals (Sweden)

    Yuri Aleskandrovich Olyunin

    2014-01-01

    Full Text Available Pain is a major problem in patients with rheumatoid arthritis (RA. It produces a serious psychological discomfort, causes sleep disorders, and drastically limits physical activity. Pain is one of the main signs of inflammation and its intensity correlates with inflammatory activity. The early use of disease-modifying antirheumatic drugs, regular monitoring, and timely correction of therapy in accordance with the treat-to-target principle make it possible to effectively monitor the activity of RA and to delay its progression. However, despite a marked decrease in RA activity, pain does not go away completely and may increase with time in a number of cases. Pain occurring in patients with RA is always far short of being caused by arthritis. It may be also related to comorbidity, osteoarthritis or fibromyalgia in particular. Pain induced by comorbidity may seriously distort the result of assessment of inflammatory activity and a physician's decision made to correct drug therapy in accordance with the treat-to-target principle.Nonsteroidal antiinflammatory drugs (NSAIDs are in most common use for the symptomatic therapy of RA. In spite of a significant reduction in pain and stiffness during therapy with NSAIDs, they do not affect the progression of X-ray changes. Virtually all NSAIDs may relieve pain when used in doses substantially smaller than those required to suppress inflammation. NSAIDs are an essential component of combination therapy for RA. They are given just at the early stage of the disease, by taking into account the gastrointestinal tract, kidney, and cardiovascular system. The National Institute for Health and Clinical Excellence in the United Kingdom proposes to administer analgesics (paracetamol and codeine to reduce needs for NSAIDs in RA. For the time being, the use of analgesics in RA has, however, a weak evidence base.Different trials have also studied the efficiency of monotherapy with weak opioids, but it has proven to be

  8. Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis.

    Science.gov (United States)

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

    2015-03-01

    In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of

  9. Internet search and krokodil in the Russian Federation: an infoveillance study.

    Science.gov (United States)

    Zheluk, Andrey; Quinn, Casey; Meylakhs, Peter

    2014-09-18

    Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States. This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed. First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries. In the 6 months preceding CCM sales restrictions, 21 of Russia's 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study. Illicit drug use data are generally regarded as difficult to obtain

  10. Studies on Ancylostomiasis: II.Clinical Symptomatology, Effects of Drugs, especially of Iron Compounds, with Relation to the Severity of Artificial Infection

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mun Ho; Kim, Dong Jip; Lee, Jang Kyu; Seo, Byong Sul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1967-09-15

    This study was aimed; firstly to observe various clinical symptomatology with relation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminics and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology. 1) The most frequently encountered symptoms and signs were general malaise, cough and hoarseness. The tracheal itching and pain, low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2) If the larger number of the larvae was given, the clinical symptomatology was more severe. 3) Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4) In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds. 1) The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from 15-20 days later and a recovery after 2 months. 2) The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3) The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4) The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency

  11. Water quality in coastal wetlands: illicit drugs in surface waters of L'Albufera Natural Park (Valencia, Spain)

    Science.gov (United States)

    Vazquez-Roig, P.; Blasco, C.; Andreu, V.; Pascual, J. A.; Rubio, J. L.; Picó, Y.

    2010-05-01

    cocaine, was found in 100% of the samples tested, at concentrations ranging from 0.14 to 78.71 ng/L. Other substances found were nor-9-carboxy-THC, methadone, codeine, cocaine, morphine, ecgonine methyl ester, extasis (MDMA) and amphetamine, while MDA, methamphetamine, heroin, 6-acetylmorphine and THC were undetectable. References: [1] M. Huerta-Fontela,M. T. Galceran, F. Ventura, Anal. Chem. 79 (2007), 3821-3829. [2] E. Zuccato, S. Castiglioni, R. Bagnati, C. Chiabrando, P. Grassi, R. Fanelli, Water Research 42 (2008) 961-968.

  12. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California

    Energy Technology Data Exchange (ETDEWEB)

    Fram, Miranda S., E-mail: mfram@usgs.gov [U.S. Geological Survey California Water Science Center, 6000 J Street, Placer Hall, Sacramento, CA 95819-6129 (United States); Belitz, Kenneth, E-mail: kbelitz@usgs.gov [U.S. Geological Survey California Water Science Center, 4165 Spruance Road, Suite 200, San Diego, CA 95101-0812 (United States)

    2011-08-15

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 {mu}g/L), caffeine (stimulant, 0.24%, 0.29 {mu}g/L), carbamazepine (mood stabilizer, 1.5%, 0.42 {mu}g/L), codeine (opioid analgesic, 0.16%, 0.214 {mu}g/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 {mu}g/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 {mu}g/L), and trimethoprim (antibiotic, 0.08%, 0.018 {mu}g/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of State with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. - Highlights: {yields

  13. Adherence of French GPs to chronic neuropathic pain clinical guidelines: results of a cross-sectional, randomized, "e" case-vignette survey.

    Directory of Open Access Journals (Sweden)

    Valéria Martinez

    Full Text Available BACKGROUND AND AIMS: The French Pain Society published guidelines for neuropathic pain management in 2010. Our aim was to evaluate the compliance of GPs with these guidelines three years later. METHODS: We used "e" case vignette methodology for this non interventional study. A national panel of randomly selected GPs was included. We used eight "e" case-vignettes relating to chronic pain, differing in terms of the type of pain (neuropathic/non neuropathic, etiology (cancer, postoperative pain, low back pain with or without radicular pain, diabetes and symptoms. GPs received two randomly selected consecutive "e" case vignettes (with/without neuropathic pain. We analyzed their ability to recognize neuropathic pain and to prescribe appropriate first-line treatment. RESULTS: From the 1265 GPs in the database, we recruited 443 (35.0%, 334 of whom logged onto the web site (26.4% and 319 (25.2% of whom completed the survey. Among these GPs, 170 (53.3% were aware of the guidelines, 136 (42.6% were able to follow them, and 110 (34.5% used the DN4 diagnostic tool. Sensitivity for neuropathic pain recognition was 87.8% (CI: 84.2%; 91.4%. However, postoperative neuropathic pain was less well diagnosed (77.9%; CI: 69.6%; 86.2% than diabetic pain (95.2%; CI: 90.0%; 100.0%, cancer pain (90.6%; CI: 83.5%; 97.8% and typical radicular pain (90.7%; CI: 84.9%; 96.5%. When neuropathic pain was correctly recognized, the likelihood of appropriate first-line treatment prescription was 90.6% (CI: 87.4%; 93.8%. The treatments proposed were pregabaline (71.8%, gabapentine (43.9%, amiptriptylline (23.2% and duloxetine (18.2%. However, ibuprofen (11%, acetaminophen-codeine (29.5% and clonazepam (10% were still prescribed. CONCLUSIONS: The compliance of GPs with clinical practice guidelines appeared to be satisfactory, but differed between etiologies.

  14. Immunological screening of drugs of abuse and gas chromatographic-mass spectrometric confirmation of opiates and cocaine in hair.

    Science.gov (United States)

    Segura, J; Stramesi, C; Redón, A; Ventura, M; Sanchez, C J; González, G; San, L; Montagna, M

    1999-03-05

    The work presents an analytical strategy to detect drugs of abuse in hair. It involves two sequential steps: a screening by a simple enzyme-linked immunosorbent assay (ELISA) methodology to detect opiates, cocaine and its metabolites, and benzodiacepines, followed by confirmation of opiates and cocaine metabolites in positive samples by gas chromatography coupled to mass spectrometry (GC-MS). In the same GC-MS run other drugs for substitution therapy (e.g. methadone and its main metabolite) can also be detected. After a double washing of hair samples with dichloromethane, hair specimens were cut into small pieces and 10 mg samples were incubated in 2 ml of methanol-trifluoroacetic acid (9:1) mixture, overnight at 37 degrees C. Aliquots of the extract were then evaporated, reconstituted in buffer and analysed according to the ELISA procedure. Confirmation involved solid-phase extraction of another fraction of the extract kept at -20 degrees C, derivatization with heptafluorobutyric anhydride and hexafluoroisopropanol and detection of cocaine, benzoylecgonine, ecgonine methylester, cocaethylene, morphine, codeine, 6-monoacetylmorphine, methadone and 2-ethylidene-1.5-dimethyl-3,3-diphenylpirrolidine (methadone metabolite) by selective ion monitoring after gas chromatographic separation. During the development of the method it was verified that no more than 10% of cocaine, opiates and benzodiacepines were lost when dichloromethane was used to wash real samples. The results also confirmed the increase of extractability power of TFA when it was added to methanol: the recovery for the analytes (cocaine and its metabolites and opiates) added to methanol-TFA alone was of the order of 90% except for benzoylecgonine (75%), and the recovery for the analytes added to methanol-TFA extract of drug-free hair was about 90% for all analytes except for benzoylecgonine and 6-MAM (around 70%). Regarding the stability of labile compounds, only small amounts of ecgonine methylester (2

  15. Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hye Won Shin

    Full Text Available Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB. This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery.We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software.We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004, motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003, and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001 compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001 and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010. In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05 but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies.In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and

  16. Dihydrocodeine Overdoses in a Neonate and in a 14-year-old Girl Who Were Both Genotyped as Cytochrome P450 2D6*1/*10-*36: Comparing Developmental Ages and Drug Monitoring Data With the Results of Pharmacokinetic Modeling.

    Science.gov (United States)

    Shimizu, Makiko; Kondo, Tatsuki; Fukuoka, Tetsuya; Tanaka, Toshihiro; Yamazaki, Hiroshi

    2018-04-01

    A high activity of cytochrome P450 2D6 (CYP2D6) reportedly leads to toxicity of dihydrocodeine/codeine by increasing toxic potential of their metabolite dihydromorphine/morphine, which are further metabolized to highly active dihydromorphine 6-O-glucuronide and the less active morphine 3-O-glucorinide but rapidly excreted into urine as water-soluble forms. A case of acute respiratory depression after administration of prescribed dihydrocodeine phosphate (2.0 mg/d divided twice a day for 2 days) to a 1-month-old baby boy genotyped as CYP2D6*1/*10-*36 is described. The case is compared with that of a 14-year-old girl, also genotyped as CYP2D6*1/*10-*36, presenting in an agitated state after an overdose (37 mg) of dihydrocodeine phosphate taken as simultaneous ingestion of multiple over-the-counter tablets. In contrast to the rapid clearance of dihydrocodeine from blood in the 14-year-old girl (apparent half-life of 3 hours), the 1-month-old baby boy still had high serum concentrations of dihydrocodeine (400 nmol/L) and dihydromorphine (1.9 nmol/L) 21 hours after the last oral administration of dihydrocodeine-containing cough mixture. The rapid clearance in the 14-year-old girl was mainly attributed to dihydrocodeine glucuronidation and partly attributed to dihydromorphine formation, as determined by liquid chromatography-tandem mass spectrometry analyses. However, the conjugation ratios of dihydrocodeine and dihydromorphine in the neonate were low in comparison with those in the 14-year-old girl and with those measured in 3-, 6-, and 13-year-old control subjects, resulting from the poorly developed glucuronidation potential of the neonate. The current observations suggest that the CYP2D6*1/*10-*36 genotype seen in the 2 Japanese patients may not significantly contribute to the likelihood of dihydrocodeine overdose but highlight the importance of considering age when prescribing dihydrocodeine.

  17. Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures.

    Science.gov (United States)

    Desgagné-Penix, Isabel; Khan, Morgan F; Schriemer, David C; Cram, Dustin; Nowak, Jacek; Facchini, Peter J

    2010-11-18

    Papaver somniferum (opium poppy) is the source for several pharmaceutical benzylisoquinoline alkaloids including morphine, the codeine and sanguinarine. In response to treatment with a fungal elicitor, the biosynthesis and accumulation of sanguinarine is induced along with other plant defense responses in opium poppy cell cultures. The transcriptional induction of alkaloid metabolism in cultured cells provides an opportunity to identify components of this process via the integration of deep transcriptome and proteome databases generated using next-generation technologies. A cDNA library was prepared for opium poppy cell cultures treated with a fungal elicitor for 10 h. Using 454 GS-FLX Titanium pyrosequencing, 427,369 expressed sequence tags (ESTs) with an average length of 462 bp were generated. Assembly of these sequences yielded 93,723 unigenes, of which 23,753 were assigned Gene Ontology annotations. Transcripts encoding all known sanguinarine biosynthetic enzymes were identified in the EST database, 5 of which were represented among the 50 most abundant transcripts. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of total protein extracts from cell cultures treated with a fungal elicitor for 50 h facilitated the identification of 1,004 proteins. Proteins were fractionated by one-dimensional SDS-PAGE and digested with trypsin prior to LC-MS/MS analysis. Query of an opium poppy-specific EST database substantially enhanced peptide identification. Eight out of 10 known sanguinarine biosynthetic enzymes and many relevant primary metabolic enzymes were represented in the peptide database. The integration of deep transcriptome and proteome analyses provides an effective platform to catalogue the components of secondary metabolism, and to identify genes encoding uncharacterized enzymes. The establishment of corresponding transcript and protein databases generated by next-generation technologies in a system with a well-defined metabolite profile facilitates

  18. Comparison of Microbial and Chemical Source Tracking Markers To Identify Fecal Contamination Sources in the Humber River (Toronto, Ontario, Canada) and Associated Storm Water Outfalls.

    Science.gov (United States)

    Staley, Zachery R; Grabuski, Josey; Sverko, Ed; Edge, Thomas A

    2016-11-01

    Storm water runoff is a major source of pollution, and understanding the components of storm water discharge is essential to remediation efforts and proper assessment of risks to human and ecosystem health. In this study, culturable Escherichia coli and ampicillin-resistant E. coli levels were quantified and microbial source tracking (MST) markers (including markers for general Bacteroidales spp., human, ruminant/cow, gull, and dog) were detected in storm water outfalls and sites along the Humber River in Toronto, Ontario, Canada, and enumerated via endpoint PCR and quantitative PCR (qPCR). Additionally, chemical source tracking (CST) markers specific for human wastewater (caffeine, carbamazepine, codeine, cotinine, acetaminophen, and acesulfame) were quantified. Human and gull fecal sources were detected at all sites, although concentrations of the human fecal marker were higher, particularly in outfalls (mean outfall concentrations of 4.22 log 10 copies, expressed as copy numbers [CN]/100 milliliters for human and 0.46 log 10 CN/100 milliliters for gull). Higher concentrations of caffeine, acetaminophen, acesulfame, E. coli, and the human fecal marker were indicative of greater raw sewage contamination at several sites (maximum concentrations of 34,800 ng/liter, 5,120 ng/liter, 9,720 ng/liter, 5.26 log 10 CFU/100 ml, and 7.65 log 10 CN/100 ml, respectively). These results indicate pervasive sewage contamination at storm water outfalls and throughout the Humber River, with multiple lines of evidence identifying Black Creek and two storm water outfalls with prominent sewage cross-connection problems requiring remediation. Limited data are available on specific sources of pollution in storm water, though our results indicate the value of using both MST and CST methodologies to more reliably assess sewage contamination in impacted watersheds. Storm water runoff is one of the most prominent non-point sources of biological and chemical contaminants which can

  19. Solution to Detect, Classify, and Report Illicit Online Marketing and Sales of Controlled Substances via Twitter: Using Machine Learning and Web Forensics to Combat Digital Opioid Access

    Science.gov (United States)

    Klugman, Josh; Kuzmenko, Ella; Gupta, Rashmi

    2018-01-01

    Background On December 6 and 7, 2017, the US Department of Health and Human Services (HHS) hosted its first Code-a-Thon event aimed at leveraging technology and data-driven solutions to help combat the opioid epidemic. The authors—an interdisciplinary team from academia, the private sector, and the US Centers for Disease Control and Prevention—participated in the Code-a-Thon as part of the prevention track. Objective The aim of this study was to develop and deploy a methodology using machine learning to accurately detect the marketing and sale of opioids by illicit online sellers via Twitter as part of participation at the HHS Opioid Code-a-Thon event. Methods Tweets were collected from the Twitter public application programming interface stream filtered for common prescription opioid keywords in conjunction with participation in the Code-a-Thon from November 15, 2017 to December 5, 2017. An unsupervised machine learning–based approach was developed and used during the Code-a-Thon competition (24 hours) to obtain a summary of the content of the tweets to isolate those clusters associated with illegal online marketing and sale using a biterm topic model (BTM). After isolating relevant tweets, hyperlinks associated with these tweets were reviewed to assess the characteristics of illegal online sellers. Results We collected and analyzed 213,041 tweets over the course of the Code-a-Thon containing keywords codeine, percocet, vicodin, oxycontin, oxycodone, fentanyl, and hydrocodone. Using BTM, 0.32% (692/213,041) tweets were identified as being associated with illegal online marketing and sale of prescription opioids. After removing duplicates and dead links, we identified 34 unique “live” tweets, with 44% (15/34) directing consumers to illicit online pharmacies, 32% (11/34) linked to individual drug sellers, and 21% (7/34) used by marketing affiliates. In addition to offering the “no prescription” sale of opioids, many of these vendors also sold other

  20. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California

    International Nuclear Information System (INIS)

    Fram, Miranda S.; Belitz, Kenneth

    2011-01-01

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of State with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. - Highlights: → Pharmaceuticals analyzed in

  1. Tramadol with or without paracetamol (acetaminophen) for cancer pain.

    Science.gov (United States)

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2017-05-16

    chronic malignant tumour-related pain who were experiencing pain intensities described as moderate to severe, with most experiencing at least 4/10 with current treatment. The mean ages were 59 to 70 years, with participants aged between 24 and 87 years. Study length ranged from one day to six months. Five studies used a cross-over design. Tramadol doses ranged from 50 mg as single dose to 600 mg per day; doses of 300 mg per day to 400 mg per day were most common.Nine studies were at high risk of bias for one to four criteria (only one high risk of bias for size). We judged all the results to be very low quality evidence because of widespread lack of blinding of outcome assessment, inadequately described sequence generation, allocation concealment, and small numbers of participants and events. Important outcomes were poorly reported. There were eight different active comparators and one comparison with placebo. There was little information available for any comparison and no firm conclusions could be drawn for any outcome.Single comparisons of oral tramadol with codeine plus paracetamol, of dihydrocodeine, and of rectal versus oral tramadol provided no data for key outcomes. One study used tramadol combined with paracetamol; four participants received this intervention. One study compared tramadol with flupirtine - a drug that is no longer available. One study compared tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen, but the dosing schedule poorly explained.Two studies (191 participants) compared tramadol with buprenorphine. One study (131 participants) reported a similar proportion of no or mild pain at 14 days.Three studies (300 participants) compared tramadol with morphine. Only one study, combining tramadol, tramadol plus paracetamol, and paracetamol plus codeine as a single weak-opioid group reported results. Weak opioid produced reduction in pain of at least 30% from baseline in 55/117 (47%) participants, compared with 91/110 (82

  2. Large impacted upper ureteral calculi: A comparative study between retrograde ureterolithotripsy and percutaneous antegrade ureterolithotripsy in the modified lateral position.

    Science.gov (United States)

    Moufid, Kamal; Abbaka, Najib; Touiti, Driss; Adermouch, Latifa; Amine, Mohamed; Lezrek, Mohammed

    2013-07-01

    pts). Ten patients (33%) of group 2 experienced failure: Migration to the kidney (3 pts), ureteral perforation (2 pts), tortuosity of the ureter (2 pts), and epithelial polyps (2 patients). Group 1 patients had an average visual analog (VAS) pain score of 47 mm compared with 31 mm in group 2 patients. The mean hospital stay (days) in group 1 was higher than the group 2 (2.27 ± 0.8 vs. 1.67 ± 0.6, respectively; P = 0.01). The mean analgesia requirement for group 1 (paracetamol chlorhydrate + codeine 12 ± 3 g) was significantly more compared with group B (6.8 ± 2 g) (P 0.05). After 1 month, the stone free-rate remained higher in group 1 (95.5% vs. 66.7%, respectively; P = 0.012). In our series, Perc-URS is a safe and efficient treatment option for proximal ureteral stone, especially when the stone size is superior to 15 mm with the presence of moderate or severe hydronephrosis.

  3. [Analgesic abuse and psychiatric comorbidity in headache patients].

    Science.gov (United States)

    Radat, F; Irachabal, S; Swendsen, J; Henry, P

    2002-01-01

    Headache patients frequently overuse analgesic medications: 20% of the patients from headache centers is concerned by this problem, which has been estimated to occur in four percent of the community migrainers. Frequent use of various types of headache medication may paradoxically cause an increase in headache attack frequency as well as their chronicisation due to potentially complex mechanisms of sensitization. Patients will enter into a self- perpetuating cycle of daily headaches and use of symptomatic medications which can lead to addiction and to social and occupational impairement. Indeed, many patients will experience pharmacological tolerance and dependence but also by some kind of craving. International Headache Society qualify these patients as abusers referring mostly to the amount of substance ingested. Hence patients are labelled analgesic abusers . However, as many of these analgesic medications contained psychotropic substances (i.e. caffeine, codeine.), these patients may fulfill DSM IV criteria of dependance. Nevertheless, the dependance criteria should be adapted to chronic pain patients. Indeed, if pharmacological dependence and tolerance criteria are easy to apply in such patients, it is not the case for the criteria a great deal of time spent to obtain substances, to use substances or to recover from substances effects . As analgesic medications are legally obtained from medical practitioners, drug seeking behaviours are mostly: obtaining medications from multiple providers, repeating episodes of prescription loss and multiplying requests for early refills. Moreover the detrimental effects of analgesic abuse on psychosocial functioning is likely to be related to pain rather than to medication overuse. Finally the best indicator of addictive behaviors in such patients, is the loss of control over the use of analgesic medication despite the adverse consequences over pain. Comorbidity with addiction to other substances has never been specifically

  4. An optimized animal model for partial and total skin thickness burns studies Um modelo animal aperfeiçoado para estudo de queimaduras superficiais e profundas da pele

    Directory of Open Access Journals (Sweden)

    Ana Paula Bomfim Soares Campelo

    2011-01-01

    Full Text Available PURPOSE: Development of an improved animal model for studying skin burns in rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6: G1-Control, G2- T100°C, G3-T150°C and G4-T200°C. Two 10 x 10 mm squares were outlined with a sterile surgical marker on each side and along the vertebral column using a prepared template positioned between the anterior and posterior limbs. G2-G4 rats were subjected to 100°C, 150°C and 200ºC thermal burns, respectively. G1 rats served as controls. Burns were inflicted by applying a copper plate connected to an electronic temperature controlling device to the dorsal skin of anesthetized rats. Four burns were produced on each animal (total area: 4 cm²/animal leaving about 1 cm of undamaged skin between burn areas. Analgesia was administered during 24 h after burn injury by adding 30 mg codeine phosphate hemihydrate to 500 ml tap water. RESULTS: The application of 100°C and 150ºC resulted in partial thickness skin burns with central reepithelialization of the burned area only at 100°C. In G4 group the whole thickness of the skin was injured without central reepithelialization. However, there was marginal reepithelialization in all groups. CONCLUSION: The model studied is inexpensive and easily reproducible, enabling the achievement of controlled burns with partial or total impairment of the skin in experimental animals.OBJETIVO: Desenvolvimento de um modelo animal aperfeiçoado para estudo de queimaduras cutâneas em ratos. MÉTODOS: Vinte e quatro ratos Wistar, machos, foram distribuídos aleatoriamente em quatro grupos (n=6: G1-Controle, G2-T100°C, G3-T150°C e G4-T200°C. Dois quadrados medindo 10x10 mm foram delineados com um marcador cirúrgico estéril em cada lado e ao longo da coluna vertebral e posicionados entre os membros anteriores e posteriores, utilizando um molde previamente preparado. Os ratos dos grupos G2-G4 foram submetidos a queimaduras térmicas de 100

  5. [Use of Emerging Drugs in Medellín, Colombia].

    Science.gov (United States)

    Castaño Pérez, Guillermo A; Calderón Vallejo, Gustavo A; Berbesi Fernández, Dedsy Yajaira

    2013-09-01

    .5%; LYP, 44.5%, and LMP, 23.5%. Then there was smokable cocaine (Crack and Free-Base), with LP, 80%, LYP, 52.1%, and LYP=31.7%. The opiate derivatives (heroine, morphine, opium, codeine, dextromethorphan, meperidine, fentanyl) had an LP, 61.4%; LYP, 26.7% and LMP, 16%. The consumption statistics of the hallucinogens such as mushrooms, scopolamine and "yague", had an LP, 73.5%; LYP, 23.2% and LMP, 12.2%. Finally, use of inhalants such as popper and dichloromethane (Dick) had an LP, 87.9%; LYP, 37.6% and LMP, 21.6%. These results are an alert to the need to track the development of these so called emergent drugs due to the risks they pose for public health. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  6. Solution to Detect, Classify, and Report Illicit Online Marketing and Sales of Controlled Substances via Twitter: Using Machine Learning and Web Forensics to Combat Digital Opioid Access.

    Science.gov (United States)

    Mackey, Tim; Kalyanam, Janani; Klugman, Josh; Kuzmenko, Ella; Gupta, Rashmi

    2018-04-27

    On December 6 and 7, 2017, the US Department of Health and Human Services (HHS) hosted its first Code-a-Thon event aimed at leveraging technology and data-driven solutions to help combat the opioid epidemic. The authors—an interdisciplinary team from academia, the private sector, and the US Centers for Disease Control and Prevention—participated in the Code-a-Thon as part of the prevention track. The aim of this study was to develop and deploy a methodology using machine learning to accurately detect the marketing and sale of opioids by illicit online sellers via Twitter as part of participation at the HHS Opioid Code-a-Thon event. Tweets were collected from the Twitter public application programming interface stream filtered for common prescription opioid keywords in conjunction with participation in the Code-a-Thon from November 15, 2017 to December 5, 2017. An unsupervised machine learning–based approach was developed and used during the Code-a-Thon competition (24 hours) to obtain a summary of the content of the tweets to isolate those clusters associated with illegal online marketing and sale using a biterm topic model (BTM). After isolating relevant tweets, hyperlinks associated with these tweets were reviewed to assess the characteristics of illegal online sellers. We collected and analyzed 213,041 tweets over the course of the Code-a-Thon containing keywords codeine, percocet, vicodin, oxycontin, oxycodone, fentanyl, and hydrocodone. Using BTM, 0.32% (692/213,041) tweets were identified as being associated with illegal online marketing and sale of prescription opioids. After removing duplicates and dead links, we identified 34 unique “live” tweets, with 44% (15/34) directing consumers to illicit online pharmacies, 32% (11/34) linked to individual drug sellers, and 21% (7/34) used by marketing affiliates. In addition to offering the “no prescription” sale of opioids, many of these vendors also sold other controlled substances and illicit drugs

  7. Incidence of pharmaceuticals in soils, sediments and waters of Pego-Oliva Marsh by LC-MS/MS.

    Science.gov (United States)

    Vazquez-Roig, P.; Andreu, V.; Blasco, C.; Picó, Y.

    2012-04-01

    The presence of pharmaceutical residues in the environmental compartments is a growing problem that could have unexpected consequences. In recent years, the number of pharmaceuticals detected in the environment had increased spectacularly, reaching a broad number of the most consumed drugs and including virtually all the existing therapeutic classes. These compounds come mainly from human excretions, waste effluents of manufacturing processes and animal farms. In Spain, obsolete sewage treatment plants, and even the absence of those, are the main problem to be solved. Some pharmaceuticals have shown toxicity to bacteria, algae and invertebrates. Besides that reproductive problems in fishes have been observed in "in vitro" studies. By the other hand, synergistic effects of exposure to mixtures of drugs or toxic effects due to accumulation would be expected. A method developed in our laboratory was utilized to monitor the occurrence of 16 relevant pharmaceuticals in the Pego-Oliva Marsh Natural Reserve (Valencian Community, Spain). A total 46 samples of soils (at two different depths), 15 sediments and 34 waters were collected in June 2009. Solid samples were concentrated by pressurized liquid extraction (ASE® 200) using water at 90°C as extracting solvent and three cycles of extraction of 7 minutes. The aqueous extract obtained was passed through two cartridges connected in series: to an Isolute® SAX cartridge (strong anion exchange) on the top and an Oasis® HLB cartridge below. Extraction was carried out with 6mL of methanol. Quantification was performed by a Quattro Micro LC-MS/MS with an ESI interface working in both positive and negative mode. Two transitions were utilized for each compound to obtain an unequivocal confirmation, with the exception of ibuprofen which only gave one transition with adequate sensitivity. All water samples appeared contaminated with at least with two compounds. Ibuprofen and codeine were the compounds more frequently detected in

  8. Antibiotics are not useful to reduce pain associated with irreversible pulpitis.

    Science.gov (United States)

    Hoskin, Eileen; Veitz-Keenan, Analia

    2016-09-01

    Data sourcesCochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Clinical Trials.gov and the WHO International Clinical Trials Registry Platform. There were no language restrictions.Study selectionRandomised controlled trials which compared the relief of pain with systemic antibiotics and analgesics against placebo and analgesics in the preoperative phase of irreversible pulpitis. The primary interest was pain control with an antibiotic or without one in the presence of analgesics. The secondary outcomes were type, dose and frequency of medication for pain relief and any adverse effects related to hypersensitivity or other reactions to either the antibiotic or analgesics.Data extraction and synthesisTwo authors independently assessed the results of the searches. Data extraction and risk bias assessment were also carried out independently. A third reviewer settled any disagreement on inclusion. Since only one study was included a meta-analysis could not be performed.ResultsOnly one double blind randomised clinical trial involving 40 participants with a diagnosis of irreversible pulpitis in one of their teeth was included in this review. This was a low risk, well-constructed double blind study. Half of the participants were treated with penicillin 500 mg, the other with a placebo every six hours over a seven- day period. In addition, all the participants were instructed to initially take one tablet of ibuprofen every 4-6 hours as needed and to take acetaminophen with codeine (two tablets every 4-6 hours) only if the ibuprofen did not relieve the pain.There was no significant difference in the mean total number of ibuprofen tablets over the study period; 9.2(standard deviation (SD) 6.02) in the penicillin group versus, 9.6 (SD 6.34) in the placebo group; mean difference -0.40 (95% CI -4.23 to 3.43); P value = 0.84.The mean total number of Tylenol tablets, 6.9 (SD 6.87), used in the penicillin group versus 4

  9. Consumo de drogas y violencia laboral en mujeres trabajadoras de Monterrey, N. L., México Consumo de drogas e violência ocupacional em mulheres trabalhadoras de Monterrey, N. L. México Drug consumption and occupational violence in working women of Monterrey, N. L., Mexico

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    Maria Magdalena Alonso Castillo

    2005-12-01

    qualitative approach. Results indicated that 37.1% of women consumed alcohol, 29.1% tobacco, 0.4% marihuana, 0.1% inhalants, and, among medical drugs, 5% consumed tranquilizers, and 1% other substances (barbiturates, antidepressive agents, Tylenol/codeine. The c² test found no significant difference between sociodemographic and occupational factors and drug consumption (p<.05, except for the work form (c²=18.08, gl=4, p=.001. However, violence rate showed a positive association with drug consumption (p<.05. This study found 126 cases of violence, 34 of which narrated their experience. Drug consumption and violence perception was identified in 2 categories: Conceptualization of Occupational Violence and Relationship between Violence and Drug Consumption.

  10. Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients.

    Science.gov (United States)

    Coller, Janet K; Michalakas, Jennifer R; James, Heather M; Farquharson, Aaron L; Colvill, Joel; White, Jason M; Somogyi, Andrew A

    2012-11-01

    Management of pain in opioid dependent individuals is problematic due to numerous issues including cross-tolerance to opioids. Hence there is a need to find alternative analgesics to classical opioids and tramadol is potentially one such alternative. Methadone inhibits CYP2D6 in vivo and in vitro. We aimed to investigate the effect of methadone on the pathways of tramadol metabolism: O-demethylation (CYP2D6) to the opioid-active metabolite M1 and N-demethylation (CYP3A4) to M2 in subjects maintained on methadone or buprenorphine as a control. Compared with subjects on buprenorphine, methadone reduced the clearance of tramadol to active O-desmethyl-tramadol (M1) but had no effect on N-desmethyltramadol (M2) formation. Similar to other analgesics whose active metabolites are formed by CYP2D6 such as codeine, reduced formation of O-desmethyltramadol (M1) is likely to result in reduced analgesia for subjects maintained on methadone. Hence alternative analgesics whose metabolism is independent of CYP2D6 should be utilized in this patient population. To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine methadone and seven buprenorphine maintained subjects received a single 100 mg dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites. The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012-0.103)] compared with those taking buprenorphine [0.192 (0.108-0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower

  11. Diretrizes para o tratamento de pacientes com síndrome de dependência de opióides no Brasil Brazilian guideline for the treatment of patients with opioids dependence syndrome

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    Danilo Antonio Baltieri

    2004-12-01

    Full Text Available Existe uma prevalência relativamente baixa do uso de ópioides no Brasil, em particular envolvendo o uso não médico da codeína e de xaropes que contêm opióides. No entanto, a síndrome de dependência apresenta um significativo impacto total na mortalidade e morbidade. Nos últimos 20 anos, o avanço científico tem modificado nosso entendimento sobre a natureza da adição aos opióides e os variados tratamentos possíveis. A adição é uma doença crônica tratável se o tratamento for realizado e adaptado tendo em vista as necessidades do paciente específico. Há, de um fato, um conjunto de tratamentos que podem efetivamente reduzir o uso da droga, ajudar a gerenciar a fissura pela droga, prevenir recaídas e recuperar as pessoas para o funcionamento social produtivo. O tratamento da dependência de drogas será parte de perspectivas de longo prazo do ponto de vista médico, psicológico e social. Esta diretriz almeja fornecer um guia para os psiquiatras e outros profissionais de saúde que tratam de pacientes com Síndrome de Dependência de Opióides. Ela tece comentários sobre o tratamento somático e psicossocial que é utilizado nesses pacientes e revisa as evidências científicas e seu poder. Da mesma forma, os aspectos históricos, epidemiológicos e neurobiológicos da dependência de opióides são revisados.There is a relatively low prevalence of opioid use in Brazil, particularly involving the non-medical use of codeine and opiate-containing syrups. However, opioid dependence syndrome shows a significant total impact on mortality and morbidity. Over the past 20 years, scientific progress has changed our understanding of the nature of opioid addiction and its various possible treatments. Addiction is a chronic illness treatable if the treatment is well-delivered and tailored to the needs of the particular patient. There is indeed an array of treatments that can effectively reduce drug use, help manage drug cravings

  12. CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

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    St Sauver JL

    2017-07-01

    phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95% CI: 1.39, 5.17; p=0.003.Conclusion: Our results suggest that >30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39% of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene–drug interactions could be substantial. Keywords: CYP2D6, opioid, phenotype, adverse effects

  13. Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration

    International Nuclear Information System (INIS)

    Arcangeli, Giorgio; Giovinazzo, Giuseppe; Saracino, Biancamaria; D'Angelo, Luciano; Giannarelli, Diana; Arcangeli, Giancarlo; Micheli, Adriana

    1998-01-01

    Purpose: In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that can assure the highest percentage and the longest duration of pain relief, we performed a prospective, although not randomized, study on patients with bone metastases from various primary sites. Methods and Materials: From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tumors were treated in our radiotherapy center with palliative intent. Irradiation fields were treated with three main fractionation schedules: (1) Conventional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1-4 consecutive fractions. Pain intensity was self-assessed by patients using a visual analogic scale graduated from 0 (no pain) to 10 (the strongest pain one can experience). Analgesic requirement was assessed by using a five-point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 = Nonopioids more than once daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperidine, etc.). Complete pain relief meant the achievement of a score ≤ 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively. Results: Total pain relief (complete + partial) was observed in 195 (76%) sites, in 158 of which (62%) a complete response was obtained. Metastases from NSC lung tumors appeared to be the least responsive among all primary tumors, with 46% complete pain relief in comparison to 65% and 83% complete relief in breast (p = 0.04) and in prostate metastases (p 0.002), respectively. A significant difference in pain relief was detected among

  14. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.

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    Kathleen Hempenstall

    2005-07-01

    receptor antagonists (e.g., oral memantine, oral dextromethorphan, intravenous ketamine, codeine, ibuprofen, lorazepam, certain 5HT1 receptor agonists, and acyclovir. Topical administration of benzydamine, diclofenac/diethyl ether, and vincristine (iontophoresis are similarly not associated with efficacy, nor are intrathecal administration of lidocaine alone or epidural administration of lidocaine and methylprednisolone, intravenous therapy with lidocaine, subcutaneous injection of Cronassial, or acupuncture. However, many of the trials that demonstrated a lack of efficacy represented comparatively low numbers of patient episodes or were single-dose studies, so it may be appropriate to regard such interventions as "not yet adequately tested" rather than demonstrating "no evidence of efficacy." Topical aspirin/diethyl ether has not been adequately tested. CONCLUSION: The evidence base supports the oral use of tricyclic antidepressants, certain opioids, and gabapentinoids in PHN. Topical therapy with lidocaine patches and capsaicin is similarly supported. Intrathecal administration of methylprednisolone appears to be associated with high efficacy, but its safety requires further evaluation.

  15. Analysis of 44 drugs of abuse and metabolites in wastewater and river water using a hybrid quadrupole time-of-flight tandem mass spectrometry

    Science.gov (United States)

    Andres-Costa, M. Jesus; Andreu, Vicente; Picó, Yolanda

    2016-04-01

    morphine derivatives (codeine, EDDP, morphine and methadone) and cannabinoids (THC) were detected in the influent, effluent or river water samples. These compounds were quantified, reaching cocainics and morphine derivates the highest values. Regarding post-target screening approach, more than 120 contaminants, mostly pharmaceuticals, but also mycotoxins and polyphenols were unambiguously identified. This new approach to data evaluation by non-target screening analyses opens the possibility of various other applications, for example in open and groundwater or for monitoring natural attenuation. Acknowledgements This work has been supported by the Spanish Ministry of Economy and Competitiveness trough the project CGL 2011-29703-C02-02. MJ Andrés Costa also acknowledges to this Ministry the FPI grant to perform her PhD. References Castiglioni S, Zuccato E. Chiabrando C., Faneli R., Bagnati R. Spectroscopy Europe (2007), 19, 7-9. Richardson SD. Anal Chem (2011), 84, 747-778. Zuccato E., Castiglioni S. Philos Trans R Soc A (2009), 367, 3965-3978. Zuccato E., Castiglioni S., Bagnati, R., Chiabrando C., Grassi P., Fanelli R. Water Res (2008), 42, 961-968.

  16. [New patterns of substance use and abuse among French adolescents, a knowledge synthesis].

    Science.gov (United States)

    Jeanne, G; Purper-Ouakil, D; Rigole, H; Franc, N

    2017-08-01

    There have been significant changes in adolescent consumption habits over the past fifteen years. New molecules have been synthesized, new devices created and a number of products have increased in popularity; and as a result clinicians sometimes lack information. We chose to focus on this population because of its vulnerability, as adolescents show low sensitivity to long-term outcomes of their actions and may be easily influenced by peers as regards experimentation of new drugs. The most consumed products by adolescents in France are tobacco, alcohol and cannabis with the physiological effects and consumption patterns of these drugs well documented. The purpose of this review is to identify and describe other products that are frequently used by adolescents to get high, to increase performance, for purposes of self-medication or because of peer pressure. We summarized the current scientific evidence regarding drug availability, physical and chemical properties, pharmacodynamics and adverse effects. A literature review was conducted from 2000 to 2015 based on Pudmed, Google Scholar and governmental websites, using the following keyword alone or in combination: "adolescent", "new", "misuse", "abuse", "toxicity", "pharmacology" "cocaine", "MDMA", "inhalant", "poppers", "magic mushroom", "psilocybin", "designer drug", "legal high", "smart drug", "cathinone", "mephedrone", "cannabinoid", "prescription drug", "codeine", "opioid", "methylphenidate", "cough syrup", "purple drank". New products, including synthetic cannabis, cathinone or purple drank seem to be the most dangerous. They are easily accessible and may lead to short-term severe or lethal complications. Other substances do not pose a major short-term health risk by themselves. However, their consumption may be an indication of other unhealthy risk behaviors, such as prescription drug use, which may be related to psychiatric comorbidity. Unfortunately, we do not have enough data to determine the long

  17. Rating the elderly with terminal cancer disease

    International Nuclear Information System (INIS)

    Riveros Rios, M.

    2012-01-01

    with bone metastasis of lung cancer progression and no response to chemotherapeutic treatment • Less than half of older women terminalidad presented some criteria to be among the most frequent relapse breast cancer and breast cancer with widespread metastatic bone and liver and no response to treatment, cancer Systemic relapse colon • The completion of the comprehensive geriatric Ranking in older adults of both sexes in terminal stage was verified that the Rating physical took place in more than half, almost a quarter functional assessment was performed in less than one quarter the mental assessment was performed, psychological and social • In older adults with criteria or terminally ill hospice bring accurate indication bypass had the same in less than half • Symptoms reported in the medical history who presented the elderly with end-stage disease were by frequencies: pain almost half of patients, constipation, anorexia and nausea / vomiting in nearly a quarter of patients, dyspne a, fatigue, and dysphagia in one fifth of patients and insomnia represents just three patients. • The pharmacological management mentioned in the medical history of the symptoms presented was: For pain alone or in combination: use of opioids (morphine, codeine, tramadol)almost a little over a quarter, NSAIDs on a quarter of patients and others (paracetamole, gabapentin)less than a fifth For nausea and / or vomiting: metaclopramide less than a fifth, ondansetron and haloperidol was not used in only two patients For dyspne a or as adjuvant pain: steroids in one quarter of patients For constipation: laxatives in one quarter of patients For anxiety: short-acting benzodiazepine only in 3 patients To stimulate appetite: steroids / medroxyprogesterone or cyproheptadine only two patients • The associated co morbidities, we found a frequency of: Hypertension nearly half of the patients, type 2 Diabetes Mellitus fifth pulmonary emphysema, kidney failure and heart disease in less than one

  18. O Conhecimento de diferenças raciais pode evitar reações idiossincrásicas na anestesia? El conocimiento de diferencias raciales puede evitar reacciones idiosincrásicas en la anestesia? Could the understanding of racial differences prevent idiosyncratic anesthetic reactions?

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    Nilton Bezerra do Vale

    2003-04-01

    . (2 Afro-American: different therapeutic approaches, essential arterial hypertension caused by the poorert response to ACEI anti-hypertensives, AT1 blockers, beta-blockers and clonidine, contrasted with the best anti-hypertensive response of diuretics, calcium channel blockers, claverdilol; attenuated isoproterenol-mediated vasodilatation (beta2 and a better vasodilating response to sublingual nitroglycerine; lower t-PA-induced thrombolytic effect; slower recovery from intravenous anesthesia with propofol and remifentanil; less glycuronide conjugation of paracetamol and less pain relief by codeine in weak metabolizers (CYP2D6; melanin slows onset of epidermal analgesia with EMLA anesthetic cream; less epinephrine-induced mydriasis; major metacholine-induced bronchocospasm in asthmatic children; G-6-PD deficit in erythrocytes increases the risk for hemolysis to oxidative drugs in 10% of the Afro-American population. (3 Asians: toxic kinetic changes of meperidine and codeine; longer diazepam-induced anxiolysis; postpartum intravenous ergonovine-induced coronary artery spasm; inter-relationships of GABA receptor, dehydrogenases and Japanese drinking behavior contribute to their higher sensitivity to alcohol. Cytochrome P450 isoenzymes show genetic polymorphisms in neuropsychotropic drugs metabolism and the slow acetylation of N-acetyltransferase in equatorial populations (95% increases isoniazid and hydrazine toxicity. CONCLUSIONS: This review aimed at answering specific questions in the area of anesthetic idiosyncrasy related to the effect of ethnicity on drugs’ pharmacokinetics and pharmacodynamics, in addition to surgical patients safety by optimizing a more individualized neuropsychopharmacotherapy.

  19. Aspirin for acute treatment of episodic tension-type headache in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2017-01-13

    plus codeine, peppermint oil, or metamizole) at any of the doses tested. A single dose of aspirin between 500 mg and 1000 mg provided some benefit in terms of less frequent use of rescue medication and more participants satisfied with treatment compared with placebo in adults with frequent episodic TTH who have an acute headache of moderate or severe intensity. There was no difference between a single dose of aspirin and placebo for the number of people experiencing adverse events. The amount and quality of the evidence was very limited and should be interpreted with caution.

  20. Phytotherapy of Acute Respiratory Viral Diseases

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    I.B. Ershova

    2016-11-01

    of acute respiratory viral infections the medicinal plants of several pharmacological groups mainly used are: plants with a tonic effect (plants containing vitamins and minerals — rose hips, black currant, sea buckthorn, citrus fruits, adaptogens and immune modulators should be used in pediatric practice with caution (Ginseng, Rhodiola Rosea, Aralia Manchurian, plants containing biogenic stimulators — the aloe latex, kalanchoe, plant with bactericidal and bacteriostatic effect (sage leaves drug, eucalyptus switchgrass, plants with anti-inflammatory effect, containing tannins — oak bark, Potentilla rhizome, rhizome of Polygonum snake, burnet, alder cones, etc; plants containing essential oils, azulene derivatives — Chamomile flowers; plants containing mucus — Farfara leaves, Plantain; Linden flowers; plants with antipyretic and diaphoretic action — plants containing vitamins (fruits of raspberry, black currant fruit, cranberry; plants containing salicylic acid derivatives — Viola tricolor, raspberry fruit; plants with protective, emollient, expectorant action containing mucus — Farfara leaves; Linden flowers, plantain leaves are large; containing alkaloids, with antitussive effect —codeine phosphate; glaucine hydrochloride grass of Thermopsis lancet; bronchodilators plants; plants with anti-allergic effect, containing flavonoids — herb of Viola tricolor, the roots of Licorice. The article presents the re­commendation of professor O.D. Barnaulov, a pediatric phytotherapist O.A. Daniluk on herbal medicine using in children, the rules of the certain medicinal plants use by Y.I. Korshikova, dosage regimen for herbal remedies for children, proposed by N.P. Menshikova, as well as practical advice on drafting phytospecies for the treatment and prophylaxis of acute respiratory viral infections and prescribing proposed by phytotherapist O.V. Kostareva.

  1. CONSIDERAȚII TEORETICE ȘI PRACTICE PRIVIND INFRACȚIUNILE DE PRACTICARE ILEGALĂ A ACTIVITĂȚII DE ÎNTREPRINZĂTOR (art.241 DIN CODUL PENAL

    Directory of Open Access Journals (Sweden)

    Vitalie STATI

    2017-07-01

    Full Text Available În prezentul studiu analizei sunt supuse temeiul real şi temeiul juridic ale răspunderii penale pentru faptele incriminate la art.241 CP RM. Sunt stabilite caracteristicile obiectului juridic şi ale obiectului imaterial în cazul infracţiunilor pre­văzute la art.241 CP RM. Se arată că noţiunea „activitate de întreprinzător”, utilizată în art.241 CP RM, are acelaşi înţeles ca şi noţiunea „activitate de întreprinzător” folosită în art.1 al Legii cu privire la antre­pre­no­riat şi întreprinderi. Se relevă forma şi conţinutul faptei prejudiciabile specificate la art.241 CP RM, prin prisma prevederilor de la lit.a-d art.125 CP RM. Se argumentează că calificarea desfăşurării activităţii de întreprinzător fără licenţă în baza art.241 CP RM (coroborat cu lit.b art.125 CP RM ar însemna nu altceva decât aplicarea prin analogie a legii penale, interzisă de alin.(2 art.3 CP RM. Sunt profilate particularităţile ce caracterizează consumarea infracţiunilor prevăzute la art.241 CP RM. Se stabileşte că scopul infracţiunilor prevăzute la art.241 CP RM este cel de asigurare a unei surse perma­nente de venituri. Sunt relevate ipotezele în care subiectul infracţiunilor prevăzute la art.241 CP RM are o calitate specială. Nu în ultimul rând, sunt elucidate criteriile de delimitare a infracţiunilor specificate la art.241 CP RM de infrac­ţiunile prevăzute la art.190, 2411, 244, 2441 şi altele din Codul penal.SOME THEORETICAL AND PRACTICAL CONSIDERATIONS WITH REGARD TO THE OFFENCE OF ILLEGAL PRACTICE OF ENTREPRENEURIAL ACTIVITY (art.241 OF THE PENAL CODEIn this study there are analyzed both the factual basis and the legal basis of the penal liability for the offences crimi­nalized in art.241 PCRM.There are also established the features of the legal object and the immaterial object of the offenses referred to at art.241 PCRM.It is argued that the concept of "entrepreneurial activity", applied in

  2. Análise clínica e terapêutica dos pacientes oncológicos atendidos no programa de dor e cuidados paliativos do Hospital Universitário Clementino Fraga Filho no ano de 2003 Análisis clínico y terapéutico de los pacientes oncológicos atendidos en el programa de dolor y cuidados paliativos del Hospital Universitario Clementino Fraga Filho en el año 2003 Clinical and therapeutic analysis of oncology patients treated at the pain and palliative care program of the Hospital Universitário Clementino Fraga Filho in 2003

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    Giselane Lacerda Figueredo Salamonde

    2006-12-01

    los pacientes y la humanización en el término de la vida.BACKGROUND AND METHODS: The main goal of palliative care is the control of pain and other symptoms in patients with chronic diseases without possibility of cure, especially advanced cancer. About 75% of patients with advanced cancer experience severe pain, which interferes with quality of life and, according to the WHO, it is considered a worldwide medical emergency. This study evaluated the profile of oncology patients enrolled in the Chronic Pain Treatment and Palliative Care Program of the HUCFF/FM/UFRJ, focusing on the role of the anesthesiologist, medications used, humanization of the treatment, and improvement in patient's quality of life. METHODS: The 2003-oncology patients' charts were analyzed retrospectively. Several parameters were compared: age, race, gender, preexisting conditions organ the cancer originated from, type of pain and other symptoms, medications, hospital routine, and end of treatment. RESULTS: The types of pain included nociceptive, neuropathic, and incidental, which were evaluated using the unidimensional faces pain rating scale. In the first week, patients were treated with home-based patient controlled analgesia (PCA with oral methadone. After this period, the patient returned to the clinic to calculate the regular dose of methadone. Other opioids used included codeine, tramadol, morphine, and oxycodone. Besides pain, patients experienced: constipation, vomiting, delirium, sleep disturbances, and dyspnea. Neuroleptics, corticosteroids, and laxatives were also used as adjuvant therapy. CONCLUSIONS: Patient controlled analgesia with methadone is safe and effective, since there were no significant side effects. The clinical and pharmacological knowledge of the anesthesiologist in the multidisciplinary team provided for better patient care, relief of symptoms, and humanization of the final stages of life.

  3. [Early achievements of the Danish pharmaceutical industry--8. Lundbeck].

    Science.gov (United States)

    Grevsen, Jørgen V; Kirkegaard, Hanne; Kruse, Edith; Kruse, Poul R

    2016-01-01

    to develop a relatively large number of originator products. In this context a product like Lucamid can hardly be regarded as an example of such a compulsory development of an originator product, an acetylsalicylic acid analogue. There were already such products on the market, but the wish to develop a better active ingredient has probably been bigger. From the three first editions of The Tariff of Medicines from 1935, 1937 and 1939 respectively it appears how Lundbeck's business within the area of medicines developed during the last half of the 1930s. In 1935 Lundbeck had placed 36 different medicinal products on the market, and all of them were in-licensing products. 4 years later, in 1939 Lundbeck had placed 40 different medicinal products on the market, and the number of in-licensing products had been reduced to 18 and 22 products were Lundbeck products. However, the increased focus on the development of own new medicinal products as Epicutan and Klianyl did not stop the in-licensing activities. Varex which Lundbeck brought on the market in 1942 came from a German pharmaceutical company with which Lundbeck had not previously collaborated. In Denmark Lundbeck had the intention to market 4 of Goedecke's 6 different medicinal products which all had Gelonida as part of the proprietary name. However, only one of these products got a longer life and with a simplified name, namely Gelonida. The fixed combination with three compounds of acetylsalicylic acid, phenacetin and codeine was without doubt effective, however, already at the end of the 1950s concern was raised about the safety of phenacetin. The Card Index of Medicines is a primary source of knowledge of how Lundbeck marketed the earliest medicinal products to the prescribing physicians. (ABSTRACT TRUNCATED)