-
Anesthesiology May 2014Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration... (Review)
Review
Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.
Topics: Ambulatory Care; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Drug Combinations; Humans; Naloxone; Opioid-Related Disorders; Pain Management; Treatment Outcome
PubMed: 24509068
DOI: 10.1097/ALN.0000000000000170 -
The Cochrane Database of Systematic... Jun 2013The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking.
OBJECTIVES
To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of MEDLINE using 'Narcotic antagonists' and smoking terms in April 2013. We also contacted investigators, when possible, for information on unpublished studies.
SELECTION CRITERIA
We considered randomised controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included in the meta-analysis only those trials which reported data on abstinence for a minimum of six months. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psycho-biological mediating variables associated with nicotine dependence.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on the study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. Abstinence at end of treatment was a secondary outcome. We extracted cotinine- or carbon monoxide-verified abstinence where available. Where appropriate, we performed meta-analysis, pooling risk ratios using a Mantel-Haenszel fixed-effect model.
MAIN RESULTS
Eight trials of naltrexone met inclusion criteria for meta-analysis of long-term cessation. One trial used a factorial design so five trials compared naltrexone versus placebo and four trials compared naltrexone plus nicotine replacement therapy (NRT) versus placebo plus NRT. Results from 250 participants in one long-term trial remain unpublished. No significant difference was detected between naltrexone and placebo (risk ratio (RR) 1.00; 95% confidence interval (CI) 0.66 to 1.51, 445 participants), or between naltrexone and placebo as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30, 768 participants). The estimate was similar when all eight trials were pooled (RR 0.97; 95% CI 0.76 to 1.24, 1213 participants). In a secondary analysis of abstinence at end of treatment, there was also no evidence of any early treatment effect, (RR 1.03; 95% CI 0.88 to 1.22, 1213 participants). No trials of naloxone or buprenorphine reported abstinence outcomes.
AUTHORS' CONCLUSIONS
Based on data from eight trials and over 1200 individuals, there was no evidence of an effect of naltrexone alone or as an adjunct to NRT on long-term smoking abstinence, with a point estimate strongly suggesting no effect and confidence intervals that make a clinically important effect of treatment unlikely. Although further trials might narrow the confidence intervals they are unlikely to be a good use of resources.
Topics: Buprenorphine; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 23744347
DOI: 10.1002/14651858.CD003086.pub3 -
Medicinal Research Reviews Sep 2015Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the... (Review)
Review
Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.
Topics: Alkaloids; Animals; Antineoplastic Agents; Centrosome; Chemistry, Pharmaceutical; Drug Evaluation, Preclinical; Female; Humans; Male; Microtubules; Neoplasms; Noscapine; Papaver; Plant Extracts; Stroke; Warfarin
PubMed: 26179481
DOI: 10.1002/med.21357 -
Medical Science Monitor : International... May 2018Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important... (Review)
Review
Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids. A key aspect of "morphinergic" signaling mediated by μ3 opiate receptor activation is its functional coupling with regulatory pathways utilizing constitutive nitric oxide (NO) as a signaling molecule. Importantly, tonic and phasic intra-mitochondrial NO production exerts profound inhibitory effects on the rate of electron transport, H+ pumping, and O2 consumption. Given the pluripotent role of NO as a selective, temporally-defined chemical regulator of mitochondrial respiration and cellular bioenergetics, the expansion of prokaryotic denitrification systems into mitochondrial NO/nitrite cycling complexes represents a series of evolutionary modifications of existential proportions. Presently, our short review provides selective discussion of evolutionary development of morphine, opiate alkaloids, μ3 opiate receptors, and NO systems, within the perspectives of enhanced mitochondrial function, cellular bioenergetics, and the human microbiome.
Topics: Alkaloids; Biological Evolution; Energy Metabolism; Humans; Microbiota; Nitric Oxide; Nitrite Reductases
PubMed: 29756604
DOI: 10.12659/MSM.909409 -
Clinical Gastroenterology and... Oct 2018
Topics: Analgesics, Opioid; England; Humans; Inflammatory Bowel Diseases; Opiate Alkaloids
PubMed: 29909124
DOI: 10.1016/j.cgh.2018.06.006 -
Journal of Analytical Toxicology Feb 2022The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG),...
The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG), oxymorphone-3β-D-glucuronide (NOMG), noroxymorphone (NOM), oxymorphone (OM), 6α-oxycodol (αOCL), 6β-oxycodol (βOCL), noroxycodone (NOC) and oxycodone (OC) in urine by liquid chromatography tandem mass spectrometry to be used in a human study. The method was validated according to the Academy Standards Board Standard Practices for Method Development in Forensic Toxicology. The method was then applied to a single-dose pilot study of a subject. Urine samples were collected from the subject after ingesting 10-mg OC as an immediate-release tablet. Additionally, urine specimens (n = 15) that had previously been confirmed positive for OC were analyzed using the validated method. The calibration range for NOMG and OMG was 0.05-10 μg/mL; for all other analytes, it was 0.015-10 μg/mL. Validation parameters such as bias, precision, carryover and dilution integrity, all met the validation criteria. After the method was validated, urine samples from the first subject in the controlled dose study were analyzed. It was observed that OC, NOC and OMG contained the highest concentrations and were present in either the 0.5 or 1 h void. NOC and OMG were detected until the 48 h collection, while OC was detectable till the 24 h collection. Time to reach maximum concentration (Tmax) in the urine was achieved within 1.5 h for OC and within 3 h for NOC and OMG. Maximum concentration (Cmax) in the urine for OC, NOC and OMG was 3.15, 2.0 and 1.56 μg/mg, respectively. OC concentrations in authentic urines ranged from 0.015 to 12 μg/mL. Ranges for NOMG and OMG were 0.054-9.7 μg/mL and 0.14-67 μg/mL, respectively. A comprehensive method for the quantification of NOMG, OMG, NOM, OM, αOCL, βOCL, NOC and OC in urine was optimized and met the validation criteria. The concentrations of NOMG and OMG presented in this study provide the details needed in the forensic community to better comprehend OC pharmacokinetics.
Topics: Chromatography, Liquid; Humans; Oxycodone; Oxymorphone; Pilot Projects; Tandem Mass Spectrometry
PubMed: 33270113
DOI: 10.1093/jat/bkaa186 -
The Cochrane Database of Systematic... Jun 2015The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers pharmacological interventions aimed at reducing drug use or criminal activity, or both, for illicit drug-using offenders.
OBJECTIVES
To assess the effectiveness of pharmacological interventions for drug-using offenders in reducing criminal activity or drug use, or both.
SEARCH METHODS
We searched Fourteen electronic bibliographic databases up to May 2014 and five additional Web resources (between 2004 and November 2011). We contacted experts in the field for further information.
SELECTION CRITERIA
We included randomised controlled trials assessing the efficacy of any pharmacological intervention a component of which is designed to reduce, eliminate or prevent relapse of drug use or criminal activity, or both, in drug-using offenders. We also report data on the cost and cost-effectiveness of interventions.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
Fourteen trials with 2647 participants met the inclusion criteria. The interventions included in this review report on agonistic pharmacological interventions (buprenorphine, methadone and naltrexone) compared to no intervention, other non-pharmacological treatments (e.g. counselling) and other pharmacological drugs. The methodological trial quality was poorly described, and most studies were rated as 'unclear' by the reviewers. The biggest threats to risk of bias were generated through blinding (performance and detection bias) and incomplete outcome data (attrition bias). Studies could not be combined all together because the comparisons were too different. Only subgroup analysis for type of pharmacological treatment were done. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity, objective results (biological) (two studies, 237 participants (RR 0.72 (95% CI 0.51 to 1.00); subjective (self-report), (three studies, 317 participants (RR 0.61 95% CI 0.31 to 1.18); self-report drug use (three studies, 510 participants (SMD: -0.62 (95% CI -0.85 to -0.39). We found low quality of evidence that antagonist treatment was not effective in reducing drug use (one study, 63 participants (RR 0.69, 95% CI 0.28 to 1.70) but we found moderate quality of evidence that they significantly reduced criminal activity (two studies, 114 participants, (RR 0.40, 95% CI 0.21 to 0.74).Findings on the effects of individual pharmacological interventions on drug use and criminal activity showed mixed results. In the comparison of methadone to buprenorphine, diamorphine and naltrexone, no significant differences were displayed for either treatment for self report dichotomous drug use (two studies, 370 participants (RR 1.04, 95% CI 0.69 to 1.55), continuous measures of drug use (one study, 81 participants, (mean difference (MD) 0.70, 95% CI -5.33 to 6.73); or criminal activity (one study, 116 participants, (RR 1.25, 95% CI 0.83 to 1.88) between methadone and buprenorphine. Similar results were found for comparisons with diamorphine with no significant differences between the drugs for self report dichotomous drug use for arrest (one study, 825 participants, (RR 1.25, 95% CI 1.03 to 1.51) or naltrexone for dichotomous measures of reincarceration (one study, 44 participants, (RR 1.10, 95% CI 0.37 to 3.26), and continuous outcome measure of crime, (MD -0.50, 95% CI -8.04 to 7.04) or self report drug use (MD 4.60, 95% CI -3.54 to 12.74).
AUTHORS' CONCLUSIONS
When compared to non-pharmacological treatment, agonist treatments did not seem effective in reducing drug use or criminal activity. Antagonist treatments were not effective in reducing drug use but significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures. Caution should be taken when interpreting these findings, as the conclusions are based on a small number of trials, and generalisation of these study findings should be limited mainly to male adult offenders. Additionally, many studies were rated at high risk of bias.
Topics: Adult; Buprenorphine; Crime; Criminals; Female; Heroin; Humans; Male; Methadone; Naltrexone; Narcotics; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Substance-Related Disorders
PubMed: 26035084
DOI: 10.1002/14651858.CD010862.pub2 -
Medecine Sciences : M/S 2016Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should... (Review)
Review
Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should however be updated based on recent advances. Thus, the neuroanatomical location of the GABA neurons responsible for this desinhibition has been recently detailed: they belong to a brain structure in continuity with the posterior part of the ventral tegmental area and discovered this past decade. Other data also highlighted the critical role played by glutamatergic transmission in the opioid regulation of dopaminergic neuron activity. During protracted opiate withdrawal, the inhibitory/excitatory balance exerted on dopaminergic neurons is altered. These results are now leading to propose an original hypothesis for explaining the impact of protracted opiate withdrawal on mood.
Topics: Animals; Brain; Dopaminergic Neurons; GABAergic Neurons; Humans; Opiate Alkaloids; Synaptic Transmission; Ventral Tegmental Area
PubMed: 27406773
DOI: 10.1051/medsci/20163206026 -
Molecules (Basel, Switzerland) Feb 2021Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in... (Review)
Review
Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in combination with other drugs for over-the-counter cough relief medication. Due to the psychoactive properties of opioid drugs, the easily obtained codeine often becomes subject to misuse. Codeine misuse has emerged as a concerning public health issue due to its associated adverse effects such as headache, nausea, vomiting, and hemorrhage. Thus, it is very important to develop reliable analytical techniques to detect codeine for both quality control of pharmaceutical formulations and identifying drug misuse in the community. This review aims to provide critical outlooks on analytical methods applicable to the determination of codeine.
Topics: Chemistry Techniques, Analytical; Codeine; Humans
PubMed: 33557168
DOI: 10.3390/molecules26040800 -
Journal of Medical Toxicology :... Apr 2022
Topics: Analgesics, Opioid; Humans; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 34780053
DOI: 10.1007/s13181-021-00864-1