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Opiates
Kinds of Opiates Terms modified by Opiates Selected AbstractsRetention in methadone maintenance drug treatment for prescription-type opioid primary users compared to heroin usersADDICTION, Issue 5 2009Caleb J. Banta-Green ABSTRACT Aims To assess retention in methadone maintenance treatment for prescription-type opioid primary (PTOP) users compared to heroin users. Design and participants A retrospective cohort study was carried out to examine the association between opiate types used on 12-month retention. The study population consisted of adults admitted to one of 11 not-for-profit methadone maintenance clinics in 2004 and 2005 throughout Washington State (n = 2308). Logistic regression analyses with fixed effects for treatment agencies were conducted. Measurements Opiate use type in past 30 days: any heroin use or primary prescription opioid without heroin use. Demographics, other drugs used, self-reported medical and psychiatric concerns, social, familial and legal issues, public assistance type and housing stability were documented at intake using a comprehensive biopsychosocial instrument, the Treatment and Assessment Reports Generation Tool. Findings The odds of being retained in treatment for PTOP compared to heroin users not adjusting for other factors was 1.33 (95% confidence interval [CI], 1.03, 1.71). In the final logistic regression model the odds of retention for PTOP compared to heroin users was 1.25 (95% CI, 0.93, 1.67), indicating that there was no statistically significant difference in treatment retention by opiate type after adjusting for demographics, treatment agencies, other drug use, public assistance type, medical, psychiatric, social, legal and familial factors. Conclusion The findings of this study suggest that PTOP can be treated at methadone maintenance treatment facilities at least as effectively as heroin users in terms of treatment retention. [source] Opiates and acute pulmonary oedema: Addicted to the wrong therapyEMERGENCY MEDICINE AUSTRALASIA, Issue 5 2008Luke Hermann No abstract is available for this article. [source] HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokinesGLIA, Issue 2 2006Nazira El-Hage Abstract Opiates exacerbate human immunodeficiency virus type 1 (HIV-1) Tat1-72 -induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in particular, is potentiated by opiate,HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP-1 in neuro-acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat1-72 than in vehicle-, ,-opioid receptor (MOR) antagonist-, or inactive, mutant Tat,31-61 -treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1,/, astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen after treatment with Tat alone, or with morphine plus inactive Tat,31-61 or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation. © 2005 Wiley-Liss, Inc. [source] GC-MS analysis of multiply derivatized opioids in urineJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2007Bud-Gen Chen Abstract Opiates such as hydrocodone, hydromorphone, oxycodone, noroxycodone, and oxymorphone reportedly may interfere with the analysis of morphine and codeine. The analysis of these compounds themselves also is an important issue. Thus, double derivatization approaches utilizing methoxyamine and hydroxylamine to first form oxime products with keto-opiates, followed by the derivatization with trimethylsilyl (TMS) or propionyl groups, have been developed for the simultaneous analysis of these compounds. However, these studies have not included all compounds of interest and resulted in inadequate chromatographic resolution or significant intensity cross-contribution between the ions designating the analyte and its deuterated internal standard for certain compounds. By exploring three-step derivatization approaches with the combination of various derivatization groups and orders, this study concluded that application of methoxyimino/propionyl/TMS groups, in the order listed, facilitated the simultaneous analysis of eight opiates (morphine, 6-acetylmorphine, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone and noroxycodone) in urine samples, achieving satisfactory limits of quantitation and detection. In addition, the adapted approach resulted in two usable products for morphine and codeine providing alternatives, should interferences render any of these products non-usable. Copyright © 2007 John Wiley & Sons, Ltd. [source] Opiate-induced oesophageal dysmotilityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010R. E. KRAICHELY Aliment Pharmacol Ther,31, 601,606 Summary Background, Opiates have well characterized (troublesome) untoward effects on the gastrointestinal tract. Opioid bowel dysfunction has been a subject of research and even drug design, but surprisingly little is known with regard to clinical effects of opiates on the oesophagus. Aim, To characterize opiate effects on motor function of the oesophagus in patients presenting with dysphagia. Methods, Retrospective review of 15 patients with dysphagia referred for oesophageal manometry while on chronic opiates. Manometry was completed during opiate use and in three cases, after opiates were discontinued. Results, All patients demonstrated motility abnormalities. Incomplete lower oesophageal sphincter (LOS) relaxation (11.5 ± 1.6 mmHg) was seen in most cases. Ten patients demonstrated nonperistaltic contractions in ,3 of 10 swallows. Additional abnormalities included high amplitude contractions; triple peaked contractions; and increased velocity. The average resting lower oesophageal sphincter (LOSP) met criteria for hypertensive LOS in three patients. These features were suggestive of spasm or achalasia. Repeat manometry off opiates was performed in three cases. LOS relaxation was noted to be complete upon repeat manometry in these cases. There was also improved peristalsis and normal velocity. Conclusions, A range of manometric abnormalities were seen in patients with dysphagia in the setting of opiate use: impaired LOS relaxation, high amplitude/velocity and simultaneous oesophageal waves. These data suggest that the oesophagus is susceptible to the effects of opiates and care must be taken before ascribing dysphagia to a primary oesophageal motility disorder in patients taking opiates. [source] Epidural Infusion of Opiates and Local Anesthetics for Complex Regional Pain SyndromePAIN PRACTICE, Issue 2 2002Sami Moufawad MD CRPS-I consists of multiple signs, including autonomic dysfunction, in the form of edema, vasomotor changes, motor dysfunctions, muscle spasms, tremors and dystonia, as well as burning pain, hypersensitivity and allodynia that could present in any combination. The treatment is progressive physical therapy rehabilitation program. Multiple analgesic modalities have been used to facilitate the rehabilitation program with varying rates of success. The most successful treatment is a multi-disciplinary comprehensive approach, where initial pain control allows for physical and psychological interventions that are believed to be the basis for successful treatment.1 The pain in CRPS-I may be mediated through the sympathetic nervous system, sympathetic maintained pain (SMP) or sympathetic independent pain (SIP)2. [source] Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdoseACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2005M. Tournier Objective:, To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). Method:, Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. Results:, Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3,2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. Conclusion:, Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings. [source] Recent development and potential use of µ- and ,-opioid receptor ligands in positron emission tomography studiesDRUG DEVELOPMENT RESEARCH, Issue 12 2006Gjermund Henriksen Abstract Quantitative non-invasive imaging of target structures in the human central nervous system provided by positron emission tomography (PET) permits investigation of the relationship between molecular events and pharmacological effects in living humans. Due to their prominent role in opiate and stimulant drug misuse and dependence, as well as in nociceptive signaling, µ- and ,-opioid receptors are potential targets for advances in neuro(psycho)pharmacological treatment of these illnesses and syndromes. In this review, we describe recent developments in specific positron emitting radiopharmaceuticals for these opioid receptor subclasses. Implications for further advances and clinical applications of the labeled ligands are discussed. Drug Dev. Res. 67:890,904, 2006. © 2007 Wiley-Liss, Inc. [source] Changes and predictors of change in the physical health status of heroin users over 24 monthsADDICTION, Issue 3 2009Anna Williamson ABSTRACT Aims (i) To describe the course of physical health among the ATOS cohort over 24 months; and (ii) to examine the effects of treatment, drug use patterns and social and psychological factors on health status over 24 months. Design Longitudinal cohort. Setting Sydney, Australia. Participants A total of 615 heroin users recruited for the Australian Treatment Outcome Study (ATOS). Findings The general health of the cohort improved significantly over 24 months. Significant predictors of poor health over 24 months were: being older, being female, past month heroin, other opiate and tobacco use, past month unemployment and current major depression. Spending a greater proportion of time in residential rehabilitation (RR) was associated with better health over 24 months. No other treatment factors demonstrated a significant, independent relationship with health. Conclusions The physical health of dependent heroin users is affected by drug use and psychosocial problems. RR treatment appears to be particularly beneficial to the health of heroin users, suggesting the importance of a comprehensive approach to improving health among this group. [source] The impact of a social network intervention on retention in Belgian therapeutic communities: a quasi-experimental studyADDICTION, Issue 7 2006Veerle Soyez ABSTRACT Background Although numerous studies recognize the importance of social network support in engaging substance abusers into treatment, there is only limited knowledge of the impact of network involvement and support during treatment. The primary objective of this research was to enhance retention in Therapeutic Community treatment utilizing a social network intervention. Aims The specific goals of this study were (1) to determine whether different pre-treatment factors predicted treatment retention in a Therapeutic Community; and (2) to determine whether participation of significant others in a social network intervention predicted treatment retention. Design, setting and participants Consecutive admissions to four long-term residential Therapeutic Communities were assessed at intake (n = 207); the study comprised a mainly male (84.9%) sample of polydrug (41.1%) and opiate (20.8%) abusers, of whom 64.4% had ever injected drugs. Assessment involved the European version of the Addiction Severity Index (EuropASI), the Circumstances, Motivation, Readiness scales (CMR), the Dutch version of the family environment scale (GKS/FES) and an in-depth interview on social network structure and perceived social support. Network members of different cohorts were assigned to a social network intervention, which consisted of three elements (a video, participation at an induction day and participation in a discussion session). Findings Hierarchical regression analyses showed that client-perceived social support (F1,198 = 10.9, P = 0.001) and treatment motivation and readiness (F1,198 = 8.8; P = 0.003) explained a significant proportion of the variance in treatment retention (model fit: F7,197 = 4.4; P = 0.000). By including the variable ,significant others' participation in network intervention' (network involvement) in the model, the fit clearly improved (F1,197 = 6.2; P = 0.013). At the same time, the impact of perceived social support decreased (F1,197 = 2.9; P = 0.091). Conclusions Participation in the social network intervention was associated with improved treatment retention controlling for other client characteristics. This suggests that the intervention may be of benefit in the treatment of addicted individuals. [source] Dissociation of food and opiate preference by a genetic mutation in zebrafishGENES, BRAIN AND BEHAVIOR, Issue 7 2006B. Lau Both natural rewards and addictive substances have the ability to reinforce behaviors. It has been unclear whether identical neural pathways mediate the actions of both. In addition, little is known about these behaviors and the underlying neural mechanisms in a genetically tractable vertebrate, the zebrafish Danio rerio. Using a conditioned place preference paradigm, we demonstrate that wildtype zebrafish exhibit a robust preference for food as well as the opiate drug morphine that can be blocked by the opioid receptor antagonist naloxone. Moreover, we show that the too few mutant, which disrupts a conserved zinc finger-containing gene and exhibits a reduction of selective groups of dopaminergic and serotonergic neurons in the basal diencephalon, displays normal food preference but shows no preference for morphine. Pretreatment with dopamine receptor antagonists abolishes morphine preference in the wildtype. These studies demonstrate that zebrafish display measurable preference behavior for reward and show that the preference for natural reward and addictive drug is dissociable by a single-gene mutation that alters subregions of brain monoamine neurotransmitter systems. Future genetic analysis in zebrafish shall uncover further molecular and cellular mechanisms underlying the formation and function of neural circuitry that regulate opiate and food preference behavior. [source] HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokinesGLIA, Issue 2 2006Nazira El-Hage Abstract Opiates exacerbate human immunodeficiency virus type 1 (HIV-1) Tat1-72 -induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in particular, is potentiated by opiate,HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP-1 in neuro-acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat1-72 than in vehicle-, ,-opioid receptor (MOR) antagonist-, or inactive, mutant Tat,31-61 -treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1,/, astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen after treatment with Tat alone, or with morphine plus inactive Tat,31-61 or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation. © 2005 Wiley-Liss, Inc. [source] Opiate Use to Control Bowel Motility May Induce Chronic Daily Headache in Patients With MigraineHEADACHE, Issue 3 2001S.M. Wilkinson MD Objectives.,To investigate whether opiate overuse might cause chronic daily headache in those with migraine, we studied patients who were taking codeine (or other opiates) for control of bowel motility after colectomy for ulcerative colitis. Background.,Analgesic overuse is considered by many to be one factor which can result in the transformation of migraine into a chronic daily headache pattern. Most of the evidence for this comes from patients with migraine who are taking increasing amounts of analgesia for headache. Many of these patients revert to an intermittent migraine pattern once the analgesics are stopped. Methods.,Women who were 1 year postcolectomy for ulcerative colitis were identified in several colorectal surgery practices in Calgary. They were sent a questionnaire designed to determine if they had a history of migraine prior to surgery, if they currently had chronic daily headache, what medications they were taking to control bowel motility, and what medications they were taking for headache. Results.,Twenty-eight patients who met our inclusion criteria returned completed questionnaires. Eight of these exceeded the recommended limits for opiate use in patients with headache. Eight patients met diagnostic criteria for migraine. Two patients had chronic daily headache starting after surgery. Both used daily opiates beginning after their surgery, and both had a history of migraine. The other six patients who used opiates daily did not have a history of migraine and did not have chronic daily headache. All patients with migraine who used daily opiates to control bowel motility following surgery developed chronic daily headache after surgery. Conclusions.,Patients with migraine who use daily opiates for any reason are at high risk of developing transformed migraine with chronic daily headache. This risk appears much lower in patients without a history of migraine who use opiates for nonpain indications. [source] Death of a 10-Month-Old Boy After Exposure to EthylmorphineJOURNAL OF FORENSIC SCIENCES, Issue 2 2010Arne Helland M.D. Abstract:, Ethylmorphine, an opiate that is partially metabolized to morphine, is a common ingredient in antitussive preparations. We present a case where a 10-month-old boy was administered ethylmorphine in the evening and found dead in bed the following morning. Postmortem toxicological analyses of heart blood by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed the presence of ethylmorphine and morphine at concentrations of 0.17 ,M (0.054 mg/L) and 0.090 ,M (0.026 mg/L), respectively. CYP2D6 genotyping showed that the deceased had an extensive metabolizer genotype, signifying a "normal" capacity for metabolizing ethylmorphine to morphine. The autopsy report concluded that death was caused by a combination of opiate-induced sedation and weakening of respiratory drive, a respiratory infection, and a sleeping position that could have impeded breathing. This is the first case report where the death of an infant has been linked to ethylmorphine ingestion. [source] Concurrent Detection of Heroin, Fentanyl, and Xylazine in Seven Drug-related Deaths Reported from the Philadelphia Medical Examiner's OfficeJOURNAL OF FORENSIC SCIENCES, Issue 2 2008Stella C. Wong D.O. Abstract:, Recreational drugs, such as cocaine and heroin, are often adulterated with other pharmacological agents to either enhance or diminish the drug effects. Between April 21, 2006 and August 8, 2006, the Philadelphia Medical Examiner's Office detected xylazine (a veterinary sedative) and fentanyl (a synthetic opioid) in specimens taken from seven cases. Initial immunoassay screening was performed on urine and blood for fentanyl, opiate, cocaine, phencyclidine (PCP), and benzodiazepines. All tests reported positive were confirmed by gas chromatography-mass spectrometry. All seven xylazine positive cases tested positive for fentanyl and six cases tested positive for 6-acetylmorphine (a metabolite and definitive marker for heroin). The seventh case was positive for morphine and had a history of heroin abuse. Xylazine was present in urine in all seven cases and blood levels were detected in three cases. The blood concentrations ranged from trace to 130 ng/mL. Fentanyl was present in the blood and urine in each case and blood concentrations ranged from 4.7 to 47 ng/mL. Adulteration of illicit drugs has become an epidemic health concern for drug users. Healthcare professionals need to be aware of this issue, so the patients can be treated in an effective, timely manner. [source] Neural Circuits Regulating Pulsatile Luteinizing Hormone Release in the Female Guinea-Pig: Opioid, Adrenergic and Serotonergic InteractionsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2001A. C. Gore Abstract We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the ,1 and ,2 but not , receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an ,1 - or ,2 -adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by ,1 and ,2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate,serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems. [source] Opiate-induced oesophageal dysmotilityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010R. E. KRAICHELY Aliment Pharmacol Ther,31, 601,606 Summary Background, Opiates have well characterized (troublesome) untoward effects on the gastrointestinal tract. Opioid bowel dysfunction has been a subject of research and even drug design, but surprisingly little is known with regard to clinical effects of opiates on the oesophagus. Aim, To characterize opiate effects on motor function of the oesophagus in patients presenting with dysphagia. Methods, Retrospective review of 15 patients with dysphagia referred for oesophageal manometry while on chronic opiates. Manometry was completed during opiate use and in three cases, after opiates were discontinued. Results, All patients demonstrated motility abnormalities. Incomplete lower oesophageal sphincter (LOS) relaxation (11.5 ± 1.6 mmHg) was seen in most cases. Ten patients demonstrated nonperistaltic contractions in ,3 of 10 swallows. Additional abnormalities included high amplitude contractions; triple peaked contractions; and increased velocity. The average resting lower oesophageal sphincter (LOSP) met criteria for hypertensive LOS in three patients. These features were suggestive of spasm or achalasia. Repeat manometry off opiates was performed in three cases. LOS relaxation was noted to be complete upon repeat manometry in these cases. There was also improved peristalsis and normal velocity. Conclusions, A range of manometric abnormalities were seen in patients with dysphagia in the setting of opiate use: impaired LOS relaxation, high amplitude/velocity and simultaneous oesophageal waves. These data suggest that the oesophagus is susceptible to the effects of opiates and care must be taken before ascribing dysphagia to a primary oesophageal motility disorder in patients taking opiates. [source] Review article: pain and chronic pancreatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009J. G. LIEB II Summary Background, Pain in chronic pancreatitis chronic pancreatitis is a frustrating and challenging symptom for both the patient and clinician. It is the most frequent and most significant symptom. Many patients fail the currently available conservative options and require opiates or endoscopic/surgical therapy. Aim, To highlight the pathophysiology and management of chronic pancreatitis pain, with an emphasis on recent developments and future directions. Methods, Expert review, utilizing in addition a comprehensive search of PubMed utilizing the search terms chronic pancreatitis and pain, treatment or management and a manual search of recent conference abstracts for articles describing pain and chronic pancreatitis. Results, Pancreatic pain is heterogenous in its manifestations and pathophysiology. First-line medical options include abstinence from alcohol and tobacco, pancreatic enzymes, adjunctive agents, antioxidants, and non-opiate or low potency opiate analgesics. Failure of these options is not unusual. More potent opiates, neurolysis and endoscopic and surgical options can be considered in selected patients, but this requires appropriate expertise. New and better options are needed. Future options could include new types of pancreatic enzymes, novel antinociceptive agents nerve growth factors, mast cell-directed therapy, treatments to limit fibrinogenesis and therapies directed at the central component of pain. Conclusions, Chronic pancreatitis pain remains difficult to treat. An approach utilizing conservative medical therapies is appropriate, with more invasive therapies reserved for failure of this conservative approach. Treatment options will continue to improve with new and novel therapies on the horizon. [source] Plasma profile and pharmacokinetics of dextromethorphan after intravenous and oral administration in healthy dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004B. KuKanich Dextromethorphan is an N -methyl- d -aspartate (NMDA) noncompetitive antagonist which has been used as an antitussive, analgesic adjunct, probe drug, experimentally to attenuate acute opiate and ethanol withdrawal, and as an anticonvulsant. A metabolite of dextromethorphan, dextrorphan, has been shown to behave pharmacodynamically in a similar manner to dextromethorphan. The pharmacokinetics of dextromethorphan were examined in six healthy dogs following intravenous (2.2 mg/kg) and oral (5 mg/kg) administration in a randomized crossover design. Dextromethorphan behaved in a similar manner to other NMDA antagonists upon injection causing muscle rigidity, ataxia to recumbency, sedation, urination, and ptyalism which resolved within 90 min. One dog repeatedly vomited upon oral administration and was excluded from oral analysis. Mean ± SD values for half-life, apparent volume of distribution, and clearance after i.v. administration were 2.0 ±0.6 h, 5.1 ± 2.6 L/kg, and 33.8 ± 16.5 mL/min/kg. Oral bioavailability was 11% as calculated from naïve pooled data. Free dextrorphan was not detected in any plasma sample, however enzymatic treatment of plasma with glucuronidase released both dextromethorphan and dextrorphan indicating that conjugation is a metabolic route. The short half-life, rapid clearance, and poor bioavailability of dextromethorphan limit its potential use as a chronic orally administered therapeutic. [source] Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: A prospective study in methadone, heroin, codeine and morphine addictsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2000M. Hensel Background: In the present study a method of rapid opiate detoxification under general anaesthesia has been evaluated regarding the safety, the efficacy in preventing withdrawal symptoms, and the long-term results. In addition, it was investigated whether the profile and severity of withdrawal symptoms depend on the type of opiate abused (methadone, heroin, codeine, morphine). Methods: Seventy-two opiate addicts were detoxified in an intensive care unit (ICU). Anaesthesia was induced and maintained using propofol infusion. Patients were endotracheally intubated. The opiate receptor antagonist naltrexon was administered into the stomach via a nasogastric tube. Withdrawal symptoms before and after the detoxification treatment were assessed using an objective and a subjective opiate withdrawal scale (OOWS, SOWS). After detoxification patients entered a long-term naltrexone maintenance programme as well as a supportive psychotherapy programme. Vital organ function was monitored using haemodynamic and respiratory parameters as well as body temperature. Results: Organ function parameters were stable during the whole treatment in all patients and no anaesthetic complications were registered. Minor side effects such as bradycardia or hypotension were observed in 20 patients. Compared to patients with pre-existing heroin, codeine, or morphine abuse respectively, patients from the methadone maintenance programme had significantly higher (P<0.01) OOWS as well as SOWS values after the treatment. Twelve months after the detoxification 49 patients (68%) were abstinent from opiates whereas 17 patients had relapsed during the period of follow-up. Six patients were lost during follow-up. Conclusions: Rapid opiate detoxification under general anaesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms during detoxification and who have failed repeatedly to complete conventional withdrawal. Methadone patients have more withdrawal symptoms than other opiate addicts. [source] New Developments in the Pharmacotherapy of Alcohol DependenceTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 2001Hugh Myrick M.D. Neuroscientific underpinnings and pharmacotherapeutic treatments of sub-stance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. New data on opiate antagonists and acamprosate, an agent that exerts actions through excitatory amino acid systems in relapse prevention, will be reviewed. Finally, there will be a review of new data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy. [source] Substance Dependence and Other Psychiatric Disorders Among Drug Dependent Subjects: Race and Gender CorrelatesTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 2 2000Wilson M. Compton III M.D. Persons in drug treatment with drug dependence were interviewed with the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R disorders. Lifetime prevalence rates were 64% for alcohol dependence, 44% for antisocial personality disorder (ASPD), 39% for phobic disorders, 24% for major depression, 12% for dysthymia, 10% for generalized anxiety disorder, 3% for panic disorder, 3% for mania, 3% for obsessive compulsive disorder, 2% for bulimia, 1% for schizophrenia, and 1% for anorexia. When stratified by race and age, significant main effects were seen, but there were no significant interactions except in "any non-substance disorder" and in the mean number of non-substance use disorders. Caucasians had a higher mean number of drug dependence disorders and higher overall rates of "any other" disorder than African-Americans, and Caucasians and males had higher mean numbers of non-substance use disorders than African-Americans and females, respectively. This was related to rates of alcohol, cannabis, and hallucinogen dependence, and ASPD rates that were higher among men than women and higher among Caucasian respondents than African-American for alcohol, cannabis, hallucinogen, opiate and sedative dependence, major depression, dysthymia, and generalized anxiety disorder. In contrast, women had higher rates than men of amphetamine dependence, phobic disorder, major depression, dysthymia, panic disorder, obsessive compulsive disorder, and mania. African-Americans had higher rates than Caucasians of amphetamine, cocaine, and phencyclidine dependence, but for no comorbid disorders were the rates higher among African-Americans than Caucasians. The differences according to gender in rates of disorders among substance dependent persons are consistent with the results of general population surveys, but the differences in rates according to race are in contrast to these same community surveys. Limitations in the utility of the concept of race as a valid category diminish the generalizability of the findings; however, one possible explanation is differential treatment seeking in African-American and Caucasian populations that would result in the differences seen. [source] Results from the 4th National Clients of Treatment Service Agencies census: changes in clients' substance use and other characteristicsAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2002Fiona Shand Objective: The 2001 Clients of Treatment Service Agencies (COTSA) census, the fourth since 1990, was conducted to enable a comparison of the drug and alcohol-related problems being treated over an 11-year period. Method The 24-hour census was conducted on Wednesday 2 May 2001 in all Australian States and Territories. All agencies providing treatment for drug and alcohol problems in Australia were asked to provide demographic, treatment and substance use information about all clients treated on census day. The data were analysed with frequencies and basic descriptive statistics. Results: Of the agencies surveyed, 90.3% responded. The census suggests that, among the treatment population, the mean age of substance users has decreased and the proportion of clients who are women has increased. Treatment for opiate, cannabis and amphetamine problems increased; treatment for alcohol problems decreased. Substance use patterns differed according to sex, age, size of the population centre, and Indigenous status. Conclusions and implications: Changes among the treatment population reflect changes in demographics and substance use among the broader drug-using community, with the exception of the presentation of alcohol problems for treatment. The reasons for the apparent decline in treatment for alcohol problems are not clear, although a number of factors, such as changes in treatment strategies and facilities and relative increases in other substance use problems, are considered. Any decrease in treatment for a significant health problem such as alcohol use disorder will have considerable public health implications. [source] Study on the antinociceptive action of Tyr-K-MIF-1, a peptide from the MIF familyAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2007R. Zamfirova Summary 1 Tyr-K-MIF-1 is a melanocyte inhibiting factor (MIF) neuropeptide, isolated from the brain. Opposite to other MIFs (Tyr-MIF-1, Tyr-W-MIF-1), it has a very low affinity for opiate , -receptors, but interacts with Tyr-MIF-1 specific binding sites. Tyr-MIF-1 and Tyr-W-MIF-1 evoke antinociception mainly by activating opioid receptors. We investigated the possible antinociceptive effect of Tyr-K-MIF-1 and the involvement of histaminergic system in its mechanism of action. 2 Tested on rats by paw-pressure test, Tyr-K-MIF-1 (0.5, 1 and 2 mg kg,1) was associated with short-lasting analgesia, which was abolished by naloxone (1 mg kg,1). 3 Injected intraperitoneally (i.p.) 15 min before Tyr-K-MIF-1, antagonists of H1 (diphenhydramine, 100 mg kg,1) or H2 (famotidine, 0.3 and 0.6 mg kg,1) histamine receptors diminished peptide antinociceptive effect. Simultaneous H1 - and H2 blockade, as well as pretreatment with 5 mg kg,1 dimaprit (H2 agonist) abolished Tyr-K-MIF-1-induced analgesia. Tyr-K-MIF-1-induced analgesia was also abolished by treatment with R-(,)-methylhistamine (10 mg kg,1, i.p.), an H3 histamine receptor agonist that acts to inhibit histamine release. 4 Our results together with data reported in the literature support the conclusion that activation of the histaminergic system is involved in the mechanism of Tyr-K-MIF-1-induced antinociception. [source] Acoustic cry characteristics of infants exposed to methadone during pregnancyACTA PAEDIATRICA, Issue 1 2009Zoe L Quick Abstract Objective: Infant cry characteristics reflect the neurological and medical status of the infant. This study compared the acoustic cry characteristics of infants born to mothers maintained on methadone during pregnancy with those of infants not exposed to methadone during pregnancy. Methods: At 42 weeks of post-menstrual age, 89 crying episodes ranging in duration from 1.15 to 1.97 sec were collected from 10 methadone-exposed (ME) and 10 non-methadone-exposed (NE) infants. Cry utterances were analysed acoustically using spectrographic displays and measures of cry utterance duration and fine-grained analyses of the fundamental frequency calculated for each cry. Results: No between-group differences were found on measures of cry duration or fundamental frequency. However, analyses of frequency perturbation showed that the cry utterances of ME infants were characterized by significantly higher levels of frequency perturbation than the cries of infants not exposed to methadone. These effects largely persisted after statistical control for the confounding effects of other maternal drug use during pregnancy. Conclusion: The crying behaviour of infants exposed prenatally to the synthetic opiate, methadone, is characterized by higher levels of vocal fold vibratory perturbation than NE infants. These findings suggest the possibility of early, subtle neurological vulnerability in this high-risk group of infants. [source] Pharmacological issues in the management of people with mental illness and problems with alcohol and illicit drug misuseCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 4 2007Trudi Hilton Background,While there is plentiful information on the pharmacological management of detoxification from alcohol and on withdrawal from or maintenance of opiates for people with a principal problem of substance misuse or dependency, the pharmacological management of substance misusers presenting with a mental illness can be more complicated. Mental health and substance misuse services tend to be separate, but there is now a drive to increase effective overlap between them by equipping mental health clinicians with the skills and confidence to manage substance misuse disorders in conjunction with major mental illness. Aims,This paper aims to highlight, for a multi-professional readership, some of the prescribing options and precautions to consider when psychotropic medicines are prescribed for treatment of a mental illness in someone who may continue to use illicit substances or alcohol. It also considers interactions with the completely licit substances, nicotine and caffeine. With recent legislation prohibiting smoking in public places people are likely to reduce or stop smoking, which can have a substantial effect on the levels of medication in their blood. Copyright © 2007 John Wiley & Sons, Ltd. [source] Regional Fos expression induced by morphine withdrawal in the 7-day-old ratDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2009Anika A. McPhie Abstract Human infants are often exposed to opiates chronically but the mechanisms by which opiates induce dependence in the infant are not well studied. In the adult the brain regions involved in the physical signs of opiate withdrawal include the periaqueductal gray area, the locus coeruleus, amygdala, ventral tegmental area, nucleus accumbens, hypothalamus, and spinal cord. Microinjection studies show that many of these brain regions are involved in opiate withdrawal in the infant rat. Our goal here was to determine if these regions become metabolically active during physical withdrawal from morphine in the infant rat as they do in the adult. Following chronic morphine or saline treatment, withdrawal was precipitated in 7-day-old pups with the opiate antagonist naltrexone. Cells positive for Fos-like immunoreactivity were quantified within select brain regions. Increased Fos-like labeled cells were found in the periaqueductal gray, nucleus accumbens, locus coeruleus, and spinal cord. These are consistent with other studies showing that the neural circuits underlying the physical signs of opiate withdrawal are similar in the infant and adult. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 544,552, 2009. [source] Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdoseACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2005M. Tournier Objective:, To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). Method:, Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. Results:, Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3,2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. Conclusion:, Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings. [source] Lifetime multiple substance use pattern among heroin users before entering methadone maintenance treatment clinic in Yunnan, ChinaDRUG AND ALCOHOL REVIEW, Issue 4 2010LEI LI Abstract Introduction and Aims. Multiple substance use leads to greater levels of psycho-behavioural problems, unsafe sex, and therefore a high risk of contracting sexually transmitted diseases, and is also more difficult to treat. This study aims to determine pattern of lifetime multiple substance use among Chinese heroin users before entering methadone maintenance treatment clinic. Design and Methods. A survey to obtain retrospective longitudinal data on lifetime multiple substance use was conducted among 203 heroin users in two of the biggest methadone maintenance clinics in Kunming City, Yunnan province. Results. All participants used more than one substance in their lifetime. Most of them used four or more substance groups (range two to seven groups). The most common substance patterns in lifetime use were alcohol, tobacco, opiates and depressants. Approximately 80% of them had a history of simultaneous substance use (co-use). The most common combination of co-use pattern was heroin with depressant. Common reasons for co-use were to get high, to experiment, to sleep and to increase the potency of other drugs. Determinants of co-use were education, marital status and family relationship. Discussion and Conclusions. Multiple substance use is highly prevalent among Chinese heroin users. Depressants are the most common substances used in combination with heroin.[Li L, Sangthong R, Chongsuvivatwong V, McNeil E, Li J. Lifetime multiple substance use pattern among heroin users before entering methadone maintenance treatment clinic in Yunnan, China. Drug Alcohol Rev 2010] [source] Poppy seed tea and opiate abuse in New ZealandDRUG AND ALCOHOL REVIEW, Issue 2 2007KLARE BRAYE Abstract The opium poppy Papaver somniferum contains an array of opiates. There is a variety of methods of preparation that can be used by people with opiate dependence, with patterns of use determined by numerous factors including cost, safety, potency and legal status. The objective of this study was to determine the frequency and nature of poppy seed tea (PST) use by opiate-dependent patients in the form of a written questionnaire. The study took place at the Community Alcohol and Drug Clinic, Wellington, New Zealand, and comprised 24 opiate-dependent patients attending the clinic. A total of 11 of 24 (46%) patients reported having used PST. In five patients currently using PST it represented the major source of opiates, and two had managed to withdraw from use of other opiates with regular PST use. Patients reported a median onset of action of 15 minures and an effect lasting a median of 24 hours. The major limitation of PST use was the foul taste. PST is used commonly by opiate-dependent patients attending an alcohol and drug clinic in New Zealand. The use of PST as the major source of opiates could be considered favourably within ,harm reduction' philosophies, because of its low cost, legal availability and oral route of administration. Conversely, there is the potential for PST to act as a ,gateway drug' by inducing opioid dependence and introducing people to the culture of drug abuse. [source] |