scholarly journals Full Opioid Agonists and Tramadol: Pharmacological and Clinical Considerations

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Amber N. Edinoff ◽  
Leah A. Kaplan ◽  
Sami Khan ◽  
Murray Petersen ◽  
Emily Sauce ◽  
...  
Keyword(s):  
Pain Treatment ◽  
Opioid Analgesic ◽  
Sphincter Of Oddi ◽  
Opiate Withdrawal ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Mu Receptor ◽  
Mu Receptors ◽  
Withdrawal Syndromes ◽  
Control Pain

: Opioids are mu receptor agonists and have been an important part of pain treatment for thousands of years. In order to use these drugs appropriately and successfully in patients, whether to control pain, to treat opiate-induced side effects, or opiate withdrawal syndromes, a solid understanding of the pharmacology of such drugs is crucial. The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl. Phenanthrenes refer to a naturally occurring plant-based compound that includes three or more fused rings. The opioids derived from the opium plant are phenanthrene derivatives, whereas most synthetic opioids are simpler molecules that do not have multiple rings. Methadone acts as a synthetic opioid analgesic similar to morphine in both quality and quantity; however, methadone lasts longer and in oral form, has higher efficacy, and is considered a diphenylheptane. Fentanyl is a strong synthetic phenylpiperdine derivative that exhibits activity as a mu-selective opioid agonist approximately 50 to 100 times more potent than morphine. Meperidine is another medication which is a phenylpiperdine. Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines. Some of the most common adverse effects shared among all opioids are nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, and miosis (except in the case of meperidine). Chronic opioid usage has also established a relationship to opioid-induced hypogonadism and adrenal suppression. Physicians must be stewards of opioid use and use opioids only when necessary.

scholarly journals Participants with mild, moderate, or severe pain following total hip arthroplasty. A sub-study of the PANSAID trial on paracetamol and ibuprofen for postoperative pain treatment

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Luma Mahmoud Issa ◽  
Kasper Højgaard Thybo ◽  
Daniel Hägi-Pedersen ◽  
Jørn Wetterslev ◽  
Janus Christian Jakobsen ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Severe Pain ◽  
Pain Treatment ◽  
Opioid Analgesic ◽  
Opioid Use ◽  
Mild Pain ◽  
Total Hip ◽  
Pain Scores

AbstractObjectivesIn this sub-study of the ‘Paracetamol and Ibuprofen in Combination’ (PANSAID) trial, in which participants were randomised to one of four different non-opioids analgesic regimen consisting of paracetamol, ibuprofen, or a combination of the two after planned primary total hip arthroplasty, our aims were to investigate the distribution of participants’ pain (mild, moderate or severe), integrate opioid use and pain to a single score (Silverman Integrated Approach (SIA)-score), and identify preoperative risk factors for severe pain.MethodsWe calculated the proportions of participants with mild (VAS 0–30 mm), moderate (VAS 31–60 mm) or severe (VAS 61–100 mm) pain and the SIA-scores (a sum of rank-based percentage differences from the mean rank in pain scores and opioid use, ranging from −200 to 200%). Using logistic regression with backwards elimination, we investigated the association between severe pain and easily obtainable preoperative patient characteristics.ResultsAmong 556 participants from the modified intention-to-treat population, 33% (95% CI: 26–42) (Group Paracetamol + Ibuprofen (PCM + IBU)), 28% (95% CI: 21–37) (Group Paracetamol (PCM)), 23% (95% CI: 17–31) (Group Ibuprofen (IBU)), and 19% (95% CI: 13–27) (Group Half Strength-Paracetamol + Ibuprofen (HS-PCM + IBU)) experienced mild pain 6 h postoperatively during mobilisation. Median SIA-scores during mobilisation were: Group PCM + IBU: −48% (IQR: −112 to 31), Group PCM: 40% (IQR: −31 to 97), Group IBU: −5% (IQR: −57 to 67), and Group HS-PCM + IBU: 6% (IQR: −70 to 74) (overall difference: p=0.0001). Use of analgesics before surgery was the only covariate associated with severe pain (non-opioid: OR 0.50, 95% CI: 0.29–0.82, weak opioid 0.56, 95% CI: 0.28–1.16, reference no analgesics before surgery, p=0.02).ConclusionsOnly one third of participants using paracetamol and ibuprofen experienced mild pain after total hip arthroplasty and even fewer experienced mild pain using each drug alone as basic non-opioid analgesic treatment. We were not able, in any clinically relevant way, to predict severe postoperative pain. A more extensive postoperative pain regimen than paracetamol, ibuprofen and opioids may be needed for a large proportion of patients having total hip arthroplasty. SIA-scores integrate pain scores and opioid use for the individual patient and may add valuable information in acute pain research.

Opioid Pharmacology

2008 ◽  
Vol 2s;11 (3;2s) ◽  
pp. S133-S153 ◽  
Author(s):  
Andrea M. Trescot
Keyword(s):  
Side Effects ◽  
Pain Treatment ◽  
Volume Of Distribution ◽  
Opiate Withdrawal ◽  
Pharmacokinetic Parameters ◽  
Intractable Pain ◽  
Advantages And Disadvantages ◽  
Withdrawal Syndromes ◽  
The Individual ◽  
Mu Agonists

Background: Mu agonists have been an important component of pain treatment for thousands of years. The usual pharmacokinetic parameters (half-life, clearance, volume of distribution) of opioids have been known for some time. However, the metabolism has, until recently, been poorly understood, and there has been recent interest in the role of metabolites in modifying the pharmacodynamic response in patients, in both analgesia and adverse effects. A number of opioids are available for clinical use, including morphine, hydromorphone, levorphanol, oxycodone, and fentanyl. Advantages and disadvantages of various opioids in the management of chronic pain are discussed. Objective: This review looks at the structure, chemistry, and metabolism of opioids in an effort to better understand the side effects, drug interactions, and the individual responses of patients receiving opioids for the treatment of intractable pain. Conclusion: Mu receptor agonists and agonist-antagonists have been used throughout recent medical history for the control of pain and for the treatment of opiate induced side effects and even opiate withdrawal syndromes. Key words: Opioid metabolism, opioid interactions, morphine, codeine, hydrocodone, oxycodone, hydromorphone, methadone, intractable pain, endorphins, enkephalins, dynorphins, narcotics, pharmacology, propoxyphene, fentanyl, oxymorphone, tramadol

scholarly journals Oliceridine as a Novel Selective mu-receptor G-protein Pathway Modulator: A Narrative review

2022 ◽  
Vol 9 (3) ◽  
pp. 3-7
Author(s):  
Uma Advani ◽  
Ravi Prakash ◽  
Parmanand Swami ◽  
Neha Sharma ◽  
Charu Jain ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
G Protein ◽  
English Language ◽  
Opioid Analgesic ◽  
Rapid Onset ◽  
Repeat Dose ◽  
Opioid Agonist ◽  
Onset Of Action ◽  
Previous Response ◽  
Mu Receptor

Abstract Objective: To review the literature on equianalgesic efficacy and better safety(less respiratory depression and gastrointestinal dysfunction) of oliceridine versus opioid analgesic in moderate to severe postoperative pain. Methodology: A comprehensive literature search was conducted in PubMed (January 2021 to March 2021) using keywords as ‘oliceridine’, ‘ligand biased mu receptor agonist’, ‘acute postoperative pain’, ‘conventional opioids’ and ‘morphine’. All English language full text pre-clinical and clinical research articles were searched. In addition, other data source was from ClinicalTrial. Gov. Data Synthesis: Oliceridine is a novel selective µ (mu)-receptor G-protein pathway modulator. G protein biased mu receptor agonists are a new class of opioids exhibiting analgesic properties at par to morphine with less respiratory depressant properties. Oliceridine a first-in-class intravenous (IV) analgesic has received the US FDA approval in August 2020, for management of moderate to severe acute pain in adults. The drug can be administered in cases where the pain is severe enough to require an intravenous opioid and when alternative treatments become inadequate. Oliceridine is an opioid agonist with a rapid onset of action within two to five minutes, was administered via clinician-administered bolus dosing, patient-controlled analgesia (PCA), or a combination of the two. Bolus dosing was initiated at 1 to 2 mg, with supplemental doses of 1 to 3 mg every one to three hours, as needed, based on individual patient need and previous response to oliceridine in management of acute post-operative pain. If oliceridine was administered via PCA, the loading dose was 1.5 mg, the demand dose was 0.5 mg, and the lockout interval (repeat dose)was six minutes. The clinically relevant concentration range of 0 to 35 ng/ml. It is indicated for short-term use only & limited to hospitals or other controlled clinical settings. Oliceridine requires no dosage adjustments in patients with renal impairment as well as in patient with significant medical complications. Therefore, opioids that bias towards G-protein and away from β arrestin signaling should produce analgesia with reduced side effects.

Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-induced Hyperalgesia

2020 ◽  
Vol 9 (3) ◽  
pp. 164-184
Author(s):  
Raymond Brewer ◽  
Kenneth Blum ◽  
Abdalla Bowirrat ◽  
Edward J. Modestino ◽  
David Baron ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Opioid Analgesics ◽  
Well Being ◽  
Deficiency Syndrome ◽  
Pain Tolerance ◽  
Opioid Agonist ◽  
Opioid Agonist Therapy ◽  
Analgesic Agents ◽  
Opioid Induced Hyperalgesia ◽  
Intensive Investigation

Neuroscientists and psychiatrists working in the areas of “pain and addiction” are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, relapse, enhance well-being and attenuate unwanted hyperalgesia. These concepts require intensive investigation. However, based on the rationale provided herein, there is a good chance that combining opioid analgesics with genetically directed pro-dopamine-regulation using KB220 (supported by 43 clinical studies). This prodopamine regulator may become a front-line technology with the potential to overcome, in part, the current heightened rates of chronic opioid-induced hyperalgesia and concomitant Reward Deficiency Syndrome (RDS) behaviors. Current research does support the hypothesis that low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance or hyperalgesia.

scholarly journals The association between initial opioid type and long-term opioid use after hip fracture surgery in elderly opioid-naïve patients

2020 ◽  
Vol 20 (4) ◽  
pp. 755-764
Author(s):  
Amalie H. Simoni ◽  
Lone Nikolajsen ◽  
Anne E. Olesen ◽  
Christian F. Christiansen ◽  
Søren P. Johnsen ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Pain Treatment ◽  
Population Based ◽  
Opioid Use ◽  
Calendar Time ◽  
Opioid Prescription ◽  
Hip Fracture Surgery ◽  
Opioid Users ◽  
Fracture Surgery

AbstractObjectivesLong-term opioid use after hip fracture surgery has been demonstrated in previously opioid-naïve elderly patients. It is unknown if the opioid type redeemed after hip surgery is associated with long-term opioid use. The aim of this study was to examine the association between the opioid type redeemed within the first three months after hip fracture surgery and opioid use 3–12 months after the surgery.MethodsA nationwide population-based cohort study was conducted using data from Danish health registries (2005–2015). Previously opioid-naïve patients registered in the Danish Multidisciplinary Hip Fracture Registry, aged ≥65 years, who redeemed ≥1 opioid prescription within three months after the surgery, were included. Long-term opioid use was defined as ≥1 redeemed prescription within each of three three-month periods within the year after hip fracture surgery. The proportion with long-term opioid use after surgery, conditioned on nine-month survival, was calculated according to opioid types within three months after surgery. Adjusted odds ratios (aOR) for different opioid types were computed by logistic regression analyses with 95% confidence intervals (CI) using morphine as reference. Subgroup analyses were performed according to age, comorbidity and calendar time before and after 2010.ResultsThe study included 26,790 elderly, opioid-naïve patients with opioid use within three months after hip fracture surgery. Of these patients, 21% died within nine months after the surgery. Among the 21,255 patients alive nine months after surgery, 15% became long-term opioid users. Certain opioid types used within the first three months after surgery were associated with long-term opioid use compared to morphine (9%), including oxycodone (14%, aOR; 1.76, 95% CI 1.52–2.03), fentanyl (29%, aOR; 4.37, 95% CI 3.12–6.12), codeine (13%, aOR; 1.55, 95% CI 1.14–2.09), tramadol (13%, aOR; 1.56, 95% CI 1.35–1.80), buprenorphine (33%, aOR; 5.37, 95% CI 4.14–6.94), and >1 opioid type (27%, aOR; 3.83, 95% CI 3.31–4.44). The proportion of long-term opioid users decreased from 18% before 2010 to 13% after 2010.ConclusionsThe findings suggest that use of certain opioid types after hip fracture surgery is more associated with long-term opioid use than morphine and the proportion initiating long-term opioid use decreased after 2010. The findings suggest that some elderly, opioid-naïve patients appear to be presented with untreated pain conditions when seen in the hospital for a hip fracture surgery. Decisions regarding the opioid type prescribed after hospitalization for hip fracture surgery may be linked to different indication for pain treatment, emphasizing the likelihood of careful and conscientious opioid prescribing behavior.

scholarly journals One Shot to Control Pain: Decreasing Postoperative Opioid Use in Gynecologic Oncology Patients with Intrathecal Opioid Injection

2021 ◽  
pp. 100858
Author(s):  
Yevgeniya Ioffe ◽  
Ruofan Yao ◽  
Eileen Hou ◽  
Michelle Wheeler ◽  
Mohammed Nour ◽  
...  
Keyword(s):  
Gynecologic Oncology ◽  
Opioid Use ◽  
Oncology Patients ◽  
Control Pain

scholarly journals Scoping review protocol: the use of telemedicine in providing opioid agonist treatment and related psychosocial supports

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040556
Author(s):  
Des Crowley ◽  
Robyn Homeniuk ◽  
Ide Delargy
Keyword(s):  
Scoping Review ◽  
Psychosocial Support ◽  
Descriptive Analysis ◽  
Cochrane Library ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Opioid Agonist Treatment ◽  
Search Terms ◽  
Medical Librarian ◽  
The Cochrane Library

IntroductionThe global opioid-related disease burden is significant. Opioid agonist treatment (OAT) can be effective in reducing illicit opioid use and fatal overdose, and improving multiple health and social outcomes. Despite evidence for its effectiveness, there are significant deficits in OAT globally. COVID-19 has required rapid adaptation of remote models of healthcare. Telemedicine is not used routinely in OAT, and little is known about the current levels of use and effectiveness. The objective of this review is to describe models of telemedicine and their efficacy.Methods and analysisThis scoping review uses the review methodology described by Arksey and O’Malley and adapted by Levac et al. The search strategy developed by the medical librarian at the Irish College of General Practitioners in conjunction with the research team will involve five databases (PubMed, EMBASE, the Cochrane Library, PsycInfo and OpenGrey) and the hand searching of reference lists. A limited initial search of two databases will be completed to refine search terms, followed by a second comprehensive search using newly refined search terms of all databases and finally hand searching references of included studies. To be included, studies must report on remote ways of providing OAT (including assessment, induction and monitoring) or related psychosocial support; be published in English after 2010. Two researchers will independently screen titles, abstracts and full-text articles considered for inclusion. Data will be extracted onto an agreed template and will undergo a descriptive analysis of the contextual or process-oriented data and simple quantitative analysis using descriptive statistics.Ethics and disseminationResearch ethics approval is not required for this scoping review. The results of this scoping review will inform the development of a national remote model of OAT. The results will be published in peer-reviewed journals and presented at relevant conferences.

Opioid receptors in the accessory optic system of the rat: Effects of monocular enucleation

1990 ◽  
Vol 5 (5) ◽  
pp. 497-506 ◽  
Author(s):  
R.A. Giolli ◽  
R.H.I. Blanks ◽  
Y. Torigoe ◽  
R.J. Clarke ◽  
J.H. Fallon ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Binding ◽  
Mu Opioid Receptor ◽  
Mu Opioid Receptors ◽  
Mu Opioid ◽  
Mu Receptor ◽  
Monocular Enucleation ◽  
Mu Receptors ◽  
Opioid Receptor Binding

AbstractThe presence and concentrations of each of the three subtypes of opioid receptors (mu, kappa, and delta) has been studied in the accessory optic nuclei (dorsal, lateral, and medial terminal nuclei and the interstitial nucleus of the superior fasciculus, posterior fibers: DTN, LTN, MTN, and inSFp) in normal young rats with radioligands directed towards each opioid receptor subtype. The changes in mu opioid receptors have also been investigated in monocularly enucleated rats in which one eye was removed and the rats sacrificed at postoperative day (PO) 2, 3, 5, 7, 14, and 30. As the MTN is the only accessory optic nucleus of the rat large enough for semiquantitative evaluation, the mu receptor population of the MTN has been subjected to optical microdensitometric analysis.All four of the accessory optic nuclei (AOS nuclei) are found to contain exceedingly high levels of mu opioid receptor binding with the selective radioligand [3H]-[D-Ala, MePhe4, Gly-ol5] (DAGO), low levels of kappa opioid receptor binding using the radioligand [3H]-[ethylketocyclazocine] (EKC) together with the competing agents [D-Pro4]-morphiceptin and [D-Ser2, Thr6]-Leu-enkephalin, and an absence of delta opioid receptor binding with the radioligand [3H]-[D-A1a2, D-Leu5]-enkephalin (DADLE) combined with the competing agent [D-Pro4]-morphiceptin. Monocular enucleation, as studied on the mu opioid receptor population with this experimental approach, results in virtually a complete loss of mu opioid receptors throughout all four of the contralaterally located AOS nuclei, including both dorsal and ventral subdivisions of the medial terminal nucleus (MTNd, v). Kappa and delta receptors are very few (kappa receptors) or are lacking (delta receptors) in the AOS nuclei, and for this reason, the effects of monocular enucleation on these two opioid receptor subtypes have not been investigated. Monocular enucleation also produces a significant lowering in mu receptor binding in other primary optic nuclei (the lateral geniculate nuclei, nucleus of the optic tract, and superficial layers of the superior colliculus) and in the pars principalis of the medial geniculate nucleus (description of changes in mu receptors in non-accessory optic primary optic nuclei will be considered elsewhere).Microdensitometric study of the MTNd, v shows that the decreased binding of mu receptors in this nucleus is barely detectable (about 6%) at PO2 and rises to 6–15% at PO3. At PO5 receptor loss reaches approximately 62%, whereas at PO7 it is about 81% complete. At PO14 and PO30, the mu receptor loss is nearly complete at around 93%. Mu receptor loss involves all of the AOS nuclei contralateral, but none ipsilateral, to ocular enucleation, an observation entirely consistent with the overwhelmingly crossed (about 97%) nature of the retinofugal projection to the rat accessory optic nuclei. These opioid receptors represent a prominent feature in the AOS and other primary optic nuclei of the rat. Their role in visuomotor control remains uncertain but probably involves the fine-tuning of information concerned with compensatory eye movements.

Problematic Prescription Opioid Use in a Chronic Pain Treatment Facility: The Role of Emotional Processes

2018 ◽  
Vol 54 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Lindsay M. S. Oberleitner ◽  
Mark A. Lumley ◽  
Emily R. Grekin ◽  
Kathryn M. Z. Smith ◽  
Amy M. Loree ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Treatment ◽  
Prescription Opioid ◽  
Opioid Use ◽  
Treatment Facility ◽  
Emotional Processes ◽  
Chronic Pain Treatment ◽  
Prescription Opioid Use

scholarly journals Exploring the effectiveness of dextroamphetamine for the treatment of stimulant use disorder: a qualitative study with patients receiving injectable opioid agonist treatment

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Heather Palis ◽  
Kirsten Marchand ◽  
Gerald “ Spike” Peachey ◽  
Jordan Westfall ◽  
Kurt Lock ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Research Question ◽  
Substitution Effect ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Opioid Agonist Treatment ◽  
Stimulant Use ◽  
Practice Elements ◽  
Concurrent Use ◽  
Wide Range

Abstract Background A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients. Methods Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question. Results Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants’ perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic). Conclusion In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide “effective” treatment for people with a wide range of treatment goals and needs.

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