The Association Between Opioid-Related Industry Payments and Opioid Prescribing at the Individual and Ecological Level in Pennsylvania

Objective: to understand how industry payments related to opioid products are associated with opioid prescribing in Pennsylvania. Methods: we merged the Open Payments data, Medicare Part D public use file, and Dartmouth Hospital Atlas of Health Care Hospital Service Areas from 2015 to analyze relationships between opioid related payments and opioid prescribing. We used a binomial regression model to investigate individual-level trends and a log-linear model to investigate Hospital Service Area-level trends. We mapped the distribution of opioid-related payments in Pennsylvania using GIS software. Results: One additional payment to a physician was associated with 4.2% higher opioid-prescribing rate (OR = 1.0418, 95% CI 1.0416-1.0420, Chi-Square(1) = 122678, p Conclusions: We found a positive association between opioid-related payments to physicians and opioid prescribing. Policy makers and administrators should consider revising rules related to pharmaceutical company marketing tactics and promote judicious opioid prescribing

Safety of opioid patch initiation in Australian residential aged care

Explores opioid use by aged care facility residents before and after initiation of transdermal opioid patches. Abstract Objective: To explore opioid use by aged care facility residents before and after initiation of transdermal opioid patches. Design: A cross-sectional cohort study, analysing pharmacy data on individual patient supply between 1 July 2008 and 30 September 2013. Setting: Sixty residential aged care facilities in New South Wales. Participants: Residents receiving an initial opioid patch during the study period Main outcome measure: The proportion of residents who were opioid-naive in the 4 weeks prior to patch initiation was determined. In addition, the patch strength at initiation and the daily dose of transdermal patches and of additional opioids 1 month after initiation were determined. Results: An opioid patch was initiated in 596 of 5297 residents (11.3%: 2.6% fentanyl, 8.7% buprenorphine) in the 60 residential aged care facilities. The mean age at initiation was 87 years, and 74% of the recipients were women. The proportion of recipients who were opioid-naive before patch initiation was 34% for fentanyl and 49% for buprenorphine. Most were initiated at the lowest available patch strength, and the dose was up-titrated after initiation. Around 15% of fentanyl users and 10% of buprenorphine users needed additional regular opioids after patch initiation. Conclusions: The results suggest some inappropriate initiation of opioid patches in Australian residential aged care facilities. Contrary to best practice, a third of residents initiated on fentanyl patches were opioid-naive in the 4 weeks before initiation. &nbsp

The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus: A Systematic Review of the Literature.

Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies

The challenge of perioperative pain management in opioid-tolerant patients

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone

The unsolved case of “bone-impairing analgesics”. The endocrine effects of opioids on bone metabolism

The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density

Promoting Awareness of the Opioid Epidemic in Rural Vermont

Vermont is in the middle of an opioid epidemic. Heroin use fatalities are on the rise and the number of people in treatment for opioid use disorder in Rutland County has tripled in recent years. Despite this widespread problem, community members of Rutland County feel that there is reluctance to talk about opioid misuse and lack of awareness. This project aims to bring awareness, provide resources, and encourage people struggling with opioid use disorder to seek treatment.https://scholarworks.uvm.edu/fmclerk/1258/thumbnail.jp

Placenta ingestion by rats enhances d- and k-opioid antinociception, but suppresses m-opioid antinociception

Ingestion of placenta or amniotic fluid produces a dramatic enhancement of centrally mediated opioid antinociception in the rat. The present experiments investigated the role of each opioid receptor type (m, d, k) in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF—presumably the active substance). Antinociception was measured on a 52 C hotplate in adult, female rats after they ingested placenta or control substance (1.0 g) and after they received an intracerebroventricular injection of a d-specific ([D-Pen2,D-Pen5]enkephalin (DPDPE); 0, 30, 50, 62, or 70 nmol), m-specific ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO); 0, 0.21, 0.29, or 0.39 nmol), or k-specific\ud (U-62066; spiradoline; 0, 100, 150, or 200 nmol) opioid receptor agonist. The results showed that ingestion of placenta potentiated d- and k-opioid antinociception, but attenuated m-opioid antinociception. This finding of POEF action as both opioid receptor-specific and complex\ud provides an important basis for understanding the intrinsic pain-suppression mechanisms that are activated during parturition and modified by placentophagia, and important information for the possible use of POEF as an adjunct to opioids in pain management

Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant.

Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem. In particular, in utero opioid exposure can result in neonatal abstinence syndrome (NAS) which is a serious condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the approach to the pregnant mother and neonate with prenatal opiate exposure. Although the cornerstone of prenatal management of opioid dependence is opioid maintenance therapy, the ideal agent has yet to be definitively established. Pharmacologic management of NAS is also highly variable and may include an opioid, barbiturate, and/or α-agonist. Genetic factors appear to be associated with the incidence and severity of NAS. Establishing pharmacogenetic risk factors for the development of NAS has the potential for creating opportunities for personalized genomic medicine and novel, individualized therapeutic interventions

An opioid-like system regulating feeding behavior in C. elegans

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggestC. elegans may be the first genetically tractable invertebrate opioid model

In vitro and in vivo pharmacological activities of 14-o-phenylpropyloxymorphone, a potent mixed mu/delta/kappa-opioid receptor agonist with reduced constipation in mice

Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. However, opioid pain medications also cause detrimental side effects, thus highlighting the need of innovative and safer analgesics. Opioids mediate their actions via the activation of opioid receptors, with the mu-opioid receptor as the primary target for analgesia, but also for side effects. One long-standing focus of drug discovery is the pursuit for new opioids exhibiting a favorable dissociation between analgesia and adverse effects. In this study, we describe the in vitro and in vivo pharmacological profiles of the 14-O-phenylpropyl substituted analog of the mu-opioid agonist 14-O-methyloxymorphone (14-OMO). The consequence of the substitution of the 14-O-methyl in 14-OMO with a 14-O-phenylpropyl group on in vitro binding and functional activity, and in vivo behavioral properties (nociception and gastrointestinal motility) was investigated. In binding studies, 14-O-phenylpropyloxymorphone (POMO) displayed very high affinity at mu-, delta-, and kappa-opioid receptors (Ki values in nM, mu:delta:kappa = 0.073:0.13:0.30) in rodent brain membranes, with complete loss of mu-receptor selectivity compared to 14-OMO. In guinea-pig ileum and mouse vas deferens bioassays, POMO was a highly efficacious and full agonist, being more potent than 14-OMO. In the [35S]GTPγS binding assays with membranes from CHO cells expressing human opioid receptors, POMO was a potent mu/delta-receptor full agonist and a kappa-receptor partial agonist. In vivo, POMO was highly effective in acute thermal nociception (hot-plate test, AD50= 0.7 nmol/kg) in mice after subcutaneous administration, with over 70- and 9000-fold increased potency than 14-OMO and morphine, respectively. POMO-induced antinociception is mediated through the activation of the mu-opioid receptor, and it does not involve delta- and kappa-opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced liability to cause constipation at antinociceptive doses