Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
Opioid Abuse [keywords]
- HIV-1 and morphine regulation of autophagy in microglia: Limited interactions in the context of HIV-1 infection and opioid abuse. [JOURNAL ARTICLE]
- J Virol 2014 Oct 29.
Microglia are the predominant resident central nervous system (CNS) cell type productively infected by human immunodeficiency virus (HIV) type-1, and play a key role in the progression of HIV-associated dementia (HAD). Moreover, neural dysfunction and progression to HAD are accelerated in opiate drug abusers. In the present study, we examined the role of the autophagy pathway in the neuropathogenesis of HIV-1 using primary human microglial cells and determined whether opiates converge at this point. Infection of microglia with the HIV-1SF162 macrophage (M)-tropic strain resulted in increased Beclin1 expression, accompanied by an increase of LC3 protein levels and accumulation of LC3 reporter RFP(+)GFP(+) (yellow) punctae, suggesting that HIV-1 infection triggers autophagosome formation without promoting protein degradation by the lysosome. Conversely, co-exposure with HIV-1 and morphine significantly decreased viral-induced Beclin1 expression and autophagosome formation. Exploration of the possible mechanism(s) used by morphine to disrupt the autophagic process unveiled a significant increase in intracellular pH, which coincided with a reduction in the formation of acidic vesicular organelles and in autophagolysosome formation. Small interfering (si) RNA targeting BECN1, a gene critical for autophagosome formation, significantly reduced viral replication and the viral-induced inflammatory responses. Conversely, morphine-enhanced viral replication and inflammatory responses were not affected by gene silencing with siBeclin1, suggesting that the interactive effect of morphine in HIV-1 pathogenesis is mediated through a Beclin1-independent mechanism. These novel findings may have important implications on the connections between autophagy and HIV-1 pathogenesis mediated by microglial cells in opioid-abusing individuals.About 50% of individuals infected with HIV-1 will develop some sort of neurocognitive impairment that cannot be prevented nor eradicated by antiretroviral therapy. The neuropathogenesis is mostly due to inflammatory responses by infected microglia, the resident immune cells of the brain. Cognitive disorders may also be associated with drugs of abuse. In fact, opioid drug users have an increased risk of developing neurocognitive disorders with increased progression to dementia. While the mechanism(s) by which opioids exacerbate the neuropathogenesis of HIV-1 are not entirely known, it is well accepted that glia are critical to opiate responses. This study gives us new insight into possible autophagic mechanism(s) in microglia that control HIV-1 replication and viral-induced inflammation in the context of opioid abuse and should greatly improve our knowledge in the pathogenesis of HIV-1 resulting from substance abuse to provide a better understanding for the design of candidate antiviral therapies targeting drug-abusing individuals.
- Harms of prescription opioid use in the United States. [JOURNAL ARTICLE]
- Subst Abuse Treat Prev Policy 2014 Oct 27; 9(1):43.
Consumption levels of prescription opioids (POs) have increased substantially worldwide, particularly the United States. An emerging perspective implicates increasing consumption levels of POs as the primary system level driving factor behind the observed PO-related harms. As such, the present study aimed to assess the correlations between consumption levels of POs and PO-related harms, including non-medical prescription opioid use (NMPOU), PO-related morbidity and PO-related mortality.Pearson's product-moment correlations were computed using published data from the United States (2001 - 2010). Consumption levels of POs were extracted from the technical reports published by the International Narcotics Control Board, while data for NMPOU was utilized from the National Survey on Drug Use and Health. Additionally, data for PO-related morbidity (substance abuse treatment admissions per 10,000 people) and PO-related mortality (PO overdose deaths per 100,000 people) were obtained from published studies. Consumption levels of POs were significantly correlated with prevalence of NMPOU in the past month (r =0.741, 95% CI =0.208-0.935), past year (r =0.638, 95% CI =0.014-0.904) and lifetime (r =0.753, 95% CI =0.235-0.938), as well as average number of days per person per year of NMPOU among the general population (r =0.900, 95% CI =0.625-0.976) and NMPOU users (r =0.720, 95% CI =0.165-0.929). Similar results were also obtained for PO-related morbidity and PO-related mortality measures.These findings suggest that reducing consumption levels of POs at the population level may be an effective strategy to limit PO-related harms.
- [Fentanyl tea.] [JOURNAL ARTICLE]
- Ugeskr Laeger 2014 Feb 17; 176(8A)
Fentanyl is a potent synthetic opioid. Abuse of fentanyl patches is rarely occurring, but has been described. In this case a patient had been drinking hot tea mixed with two fentanyl patches. He was found unconscious, with convulsions and respiratory insufficiency. He was intubated and he responded to naloxone treatment, which was repeated several times during the observation. When fentanyl patches are abused this way large quantities of fentanyl are absorbed, giving severe and prolonged effect - exceeding the antidote. The patient must be observed for several hours in an intensive care unit.
- Prevalence of narcotic bowel syndrome in opioid abusers in iran. [Journal Article]
- Middle East J Dig Dis 2014 Oct; 6(4):208-13.
BACKGROUNDIn spite of the increasing trend in opioid abusers worldwide, the prevalence of narcotic bowel syndrome (NBS) is undetermined. We aimed to estimate the prevalence of NBS and other opioid bowel dysfunction (OBD) in opioid abusers in Kerman, southeast Iran. According to the best of our knowledge, this is the first study to assess the prevalence of NBS in opioid abusers.
METHODSBy referring to addiction treatment centers in Kerman city and in a cross-sectional study, 577 subjects with opium or opioid subtracts abuse were included in our study. A validated questionnaire was used for OBD assessment and diagnosis of NBS was made according to both the presence of chronic abdominal pain despite increasing the opioid dose and ruling out other causes of abdominal pain. SPSS software version 16 was used for data analysis. p value<0.05 was considered as statistically significant.
RESULTSConstipation, regurgitation, and heartburn were the most gastrointestinal complaints that were found in 132(22.9%), 123(21.3%) and 91(15.8%) subjects, respectively. Only 16(2.8%) participants fulfilled all the NBS criteria. Simultaneous use of non-narcotic sedative drugs increased the risk of NBS significantly (the odds ratio 3:1 and p=0.049).
CONCLUSIONNBS is not rare among opioid abusers and should be considered as a cause of chronic abdominal pain in this group.
- Cardiac conduction disturbance after loperamide abuse. [Journal Article]
- Clin Toxicol (Phila) 2014 Nov; 52(9):952-7.
Abstract Context. Prescription opioid abuse is a major public health concern and an ongoing epidemic in the United States. Loperamide is a widely available and inexpensive over-the-counter antidiarrheal with peripheral mu-opioid receptor activity. Online resources discuss the use of loperamide for the amelioration of withdrawal symptoms or recreational abuse. We describe the clinical course of 5 patients abusing loperamide, 3 of whom had life-threatening cardiac arrhythmias. Methods. In this observational case series, patients with cardiac arrhythmias or history of loperamide abuse with cardiac arrhythmias were identified; 5 patients were identified and 4 of the 5 patients were seen directly at the bedside. Clinical profile and outcome of patients is reported.
Results.We report 5 patients with history of loperamide abuse; 3 of the 5 patients had life-threatening cardiac arrhythmias. One of the patients experienced a second life-threatening arrhythmia after he resumed loperamide abuse. Loperamide levels were obtained in 4 of the 5 patients and were at least one order of magnitude greater than therapeutic concentrations. Discontinuation of loperamide resulted in complete resolution of cardiac conduction disturbances.
Conclusion.This case series describes several patients with cardiac conduction abnormalities and life-threatening ventricular arrhythmias temporally related to loperamide abuse. With the recent efforts to restrict the diversion of prescription opioids, increasing abuse of loperamide as an opioid substitute may be seen. Toxicologists should be aware of these risks and we urge all clinicians to report such cases to FDA Medwatch(®).
- Tobacco Smoking, Nicotine Dependence, and Patterns of Prescription Opioid Misuse: Results from a Nationally Representative Sample. [JOURNAL ARTICLE]
- Nicotine Tob Res 2014 Oct 25.
The misuse of prescription opioid medications is a growing public health crisis. Given evidence of complex nicotine-opioid interactions, and initial support for the role of smoking status as a risk factor for prescription opioid misuse, a more detailed analysis of how current and historical patterns of smoking may influence misuse of prescription opioids is warranted.The current study is the first to test whether varying levels of current/historical smoking (current daily, current intermittent, former daily, never) and indices of smoking heaviness/nicotine dependence may be associated with greater likelihood of past-year prescription opioid misuse in the general population. Data were derived from the National Survey on Drug Use and Health (N = 24,348).Consistent with hypotheses, after accounting for sociodemographic factors and major depressive/alcohol use disorders, both daily and intermittent smokers were greater than three times more likely to report past-year non-medical prescription opioid use than were never smokers. In addition, daily smokers were observed to be nearly five times more likely, and intermittent smokers were nearly three times more likely, to have met past-year abuse/dependence criteria, relative to never smokers. Results further revealed positive associations between various indices of smoking heaviness/nicotine dependence and opioid medication misuse, and these findings remained largely consistent when analyses were stratified by gender.These findings indicate that smokers are not a homogeneous group with regard to risk for opioid misuse, and support the utility of comprehensive smoking assessment in the context of opioid-based treatment/tapering.
- Developing and Initiating Validation of a Model Opioid Patient-Prescriber Agreement as a Tool for Patient-Centered Pain Treatment. [JOURNAL ARTICLE]
- Patient 2014 Oct 26.
Opioid treatment agreements generally are used in pain treatment to delineate the terms and consequences of opioid use and abuse.The US Food and Drug Administration (FDA) Safe Use Initiative convened a multi-disciplinary working group with outside experts to draft a patient-centered, model opioid treatment agreement named the Model Patient-Prescriber Agreement (model PPA). The model PPA was evaluated for readability and usability in two tests that sampled both healthcare professional and non-healthcare professional FDA employees. In a survey sent to FDA employees in the Center for Drug Evaluation and Research (CDER), 209 respondents assessed the quality of the content and the level of difficulty in reading and understanding the model PPA. Ten other FDA employees participated in usability testing to assess the effectiveness of the model PPA as an educational and decision-making tool.The majority of the 209 CDER employee survey respondents indicated the model PPA was neutral in tone (67.5 %) and easy or somewhat easy to understand (90.4 %). Usability study participants generally thought the model PPA would facilitate discussion between patient and prescriber and that the content was informative, thorough, and clear.These studies suggest that the working group was able to develop an opioid PPA that may be acceptable and usable among a diverse population of stakeholders. A follow-up pilot study using the model PPA in medical facilities in the USA with patients is underway and will facilitate this determination.
- Effect of mu-opioid agonist DAMGO on surface CXCR4 and HIV-1 replication in TF-1 human bone marrow progenitor cells. [JOURNAL ARTICLE]
- BMC Res Notes 2014 Oct 23; 7(1):752.
Approximately one-third of the AIDS cases in the United States have been attributed to the use of injected drugs, frequently involving the abuse of opioids. Consequently, it is critical to address whether opioid use directly contributes to altered susceptibility to HIV-1 beyond the increased risk of exposure. Previous in vitro and in vivo studies addressing the role of mu-opioid agonists in altering levels of the co-receptor CXCR4 and subsequent HIV-1 replication have yielded contrasting results. The bone marrow is believed to be a potential anatomical sanctuary for HIV-1.The well-characterized CD34+CD38+ human bone marrow-derived hematopoietic progenitor cell line TF-1 was used as a model to investigate the effects of the mu-opioid receptor-specific peptide DAMGO (D-Ala2,N-Me-Phe4,Gly5-ol-enkephalin) on CXCR4 expression as well as infection of undifferentiated human hematopoietic progenitor cells.The results revealed the presence of the mu-opioid receptor-1 isoform (MOR-1) on the surface of TF-1 cells. Furthermore, immunostaining revealed that the majority of TF-1 cells co-express MOR-1 and CXCR4, and a subpopulation of these double-positive cells express the two receptors in overlapping membrane domains. Three subpopulations of TF-1 cells were categorized based on their levels of surface CXCR4 expression, defined as non-, low-, and high-expressing. Flow cytometry indicated that treatment with DAMGO resulted in a shift in the relative proportion of CXCR4+ cells to the low-expressing phenotype. This result correlated with a >3-fold reduction in replication of the X4 HIV-1 strain IIIB, indicating a role for the CXCR4 high-expression subpopulation in sustaining infection within this progenitor cell line.These experiments provide insight into the impact of mu-opioid exposure with respect to inhibition of viral replication in this human TF-1 bone marrow progenitor cell line model.
- Palliative Sedation for Status Epilepticus in a Patient with Progressive Multifocal Leukoencephalopathy. [JOURNAL ARTICLE]
- J Pain Palliat Care Pharmacother 2014 Oct 22.
ABSTRACT Palliative sedation is defined as the use of sedative drugs in order to reduce the patient's consciousness in case of refractory symptoms. The most used drug is midazolam, a benzodiazepine with a short half-life administered either intravenously or subcutaneously. We discuss on a clinical case requiring an exceptionally high dosage of midazolam-up to 160 mg iv daily-to achieve palliative sedation. The patient was an HIV positive 29-year-old male who was suffering from progressive multifocal leukoencephalopathy complicated by a refractory status epilepticus and who was suspected of previous benzodiazepines and opioid abuse. In such situations of a suffering brain doses of midazolam to achieve symptom control may be much higher than expected.
- Sexual dysfunction in patients with alcohol and opioid dependence. [Journal Article, Review]
- Indian J Psychol Med 2014 Oct; 36(4):355-65.
There are limited numbers of studies which have evaluated the sexual dysfunction (SD) in patients with alcohol and opioids dependence. This article reviews the existing literature. Electronic searches were carried out using the PubMed, Google Scholar, and ScienceDirect to locate the relevant literature. Subjects addicted to heroin or on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT) show higher rates of SD in comparison to the general population. SD rates have ranged 34-85% for heroin addicts, 14-81% for MMT, 36-83% for BMT, and 90% for naltrexone maintenance. The rates of SD in alcohol-dependent population have ranged 40-95.2%, with rates being consistently much higher in alcohol-dependent population than in the healthy controls or social drinkers. The common SDs reported have been erectile dysfunction followed by premature ejaculation, retarded ejaculation and decreased sexual desire among men, and dyspareunia and vaginal dryness among women. This review suggests that long-term use of alcohol and opioids are associated with SD in almost all domains of sexual functioning. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse. Further, there is a need to carry out more number of studies to understand the relationship in a better way.