scholarly journals Combination Opioid Analgesics

2008 ◽  
Vol 2;11 (3;2) ◽  
pp. 201-214
Author(s):  
Howard Smith
Keyword(s):  
Adverse Effects ◽  
Opioid Analgesic ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Active Metabolites ◽  
Analgesic Tolerance ◽  
Key Words Pain ◽  
Long Duration ◽  
Wide Range ◽  
Opioid Induced Hyperalgesia

Although there is no “ideal analgesic,” scientists and clinicians alike continue to search for compounds with qualities which may approach the “ideal analgesic.” Characteristics of an “ideal” analgesic may include: the agent is a full agonist providing optimal/maximal analgesia for a wide range/variety of pain states (e.g., broad spectrum analgesic activity), it does not exhibit tolerance, it produces no unwanted effects and minimal adverse effects, it has no addictive potential, it does not facilitate pain/hyperalgesia, it has a long duration, it has high oral bioavailability, it is not vulnerable to important drug interactions, it is not significantly bound to plasma proteins, it has no active metabolites, it has linear kinetics, and it is eliminated partly by hydrolysis to an inactive metabolite (without involvement of oxidative and conjugative enzymes). Investigators have concentrated on ways to alter existing analgesics or to combine existing analgesic compounds with compounds which may improve efficacy over time or minimize adverse effects. The addition of an analgesic with a second agent (which may or may not also be an analgesic) to achieve a “combination analgesic” is a concept which has been exploited for many years. Although there may be many reasons to add 2 agents together in efforts to achieve analgesia, for purposes of this article — reasons for combining an opioid with a second agent to produce a combination opioid analgesic may be classified into 6 major categories: 1.) combinations to prolong analgesic duration; 2.) combinations to enhance or optimize analgesic efficacy (e.g., analgesic synergy); 3.) combinations to diminish or minimize adverse effects; 4.) combinations to diminish opioid effects which are not beneficial (or contrariwise to or enhance beneficial opioid effects); 5.) combinations to reduce opioid tolerance/opioid-induced hyperalgesia; and 6.) combinations to combat dependency issues/addiction potential/craving sensations. Combination opioid analgesics are one avenue which may give rise to “pain pills” with improved analgesic profiles over existing analgesic medications. Key words: Pain, combination opioid analgesic, tolerance, opioid-induced hyperalgesia

scholarly journals Peripherally-Acting Opioids

2008 ◽  
Vol 2s;11 (3;2s) ◽  
pp. S121-S132
Author(s):  
Howard Smith
Keyword(s):  
Spinal Cord ◽  
Adverse Effects ◽  
Opioid Receptors ◽  
Opioid Analgesic ◽  
Opioid Analgesics ◽  
Endogenous Opioids ◽  
Term Therapy ◽  
Endogenous Opioid ◽  
Key Words Pain ◽  
The Brain

Opioids are broad-spectrum analgesics with potent pain-relieving qualities but also with potential adverse effects related to both short-term and long-term therapy. Researchers have attempted to alter existing opioid analgesics, utilize different routes/ formulations, or combine opioid analgesics with other compounds in efforts to improve analgesia while minimizing adverse effects. Exogenous opioids, administered in efforts to achieve analgesia, work by mimicking the actions of endogenous opioids. Endogenous opioids and their receptors are located in the brain (supraspinal areas), spinal cord, and periphery. Although opioids and opioid receptors in the brain and spinal cord have received much attention over many years, peripheral endogenous opioid analgesic systems have only been extensively studied during the past decade. It has been known since 1990 that following injection into the rodent hindpaw, d-Ala2 , N-Me-Phe4 , Gly5 -ol-enkephalin (DAMGO) [a muopioid receptor agonist] probably exerts its antinociceptive effects locally, since the doses administered are too low to have an effect in the central nervous system (CNS). This notion has been supported by the observation that the quaternary compound morphine methyliodide, which does not as readily cross the bloodbrain barrier and enter the CNS, produced antinociception following intradermal administration into the hindpaw, but not when the same dose was administered systemically (subcutaneously at a distant site). With a growing appreciation of peripheral endogenous opioids, peripheral endogenous opioid receptors, and peripheral endogenous opioid analgesic systems, investigators began growing hopeful that it may be possible to achieve adequate analgesics while avoiding unwanted central untoward adverse effects (e.g. respiratory depression, somnolence, addiction). Peripherally-acting opioids, which capitalize on peripheral endogenous opioid analgesic systems, may be one potential future strategy which may be utilized in efforts to achieve potent analgesia with minimal side effects. Key words: Pain, opioids, immune cells, peripherally-acting opioids (PAO), leukocytes, inflammatory pain, peripheral analgesia

scholarly journals On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2473 ◽  
Author(s):  
Susanna Fürst ◽  
Zoltán S. Zádori ◽  
Ferenc Zádor ◽  
Kornél Király ◽  
Mihály Balogh ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Molecular Mechanisms ◽  
Opioid Analgesic ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Analgesic Tolerance ◽  
Peripheral Analgesia ◽  
Peripheral Opioid Receptors ◽  
Peripheral Sensory

There is growing evidence on the role of peripheral µ-opioid receptors (MORs) in analgesia and analgesic tolerance. Opioid analgesics are the mainstay in the management of moderate to severe pain, and their efficacy in the alleviation of pain is well recognized. Unfortunately, chronic treatment with opioid analgesics induces central analgesic tolerance, thus limiting their clinical usefulness. Numerous molecular mechanisms, including receptor desensitization, G-protein decoupling, β-arrestin recruitment, and alterations in the expression of peripheral MORs and microbiota have been postulated to contribute to the development of opioid analgesic tolerance. However, these studies are largely focused on central opioid analgesia and tolerance. Accumulated literature supports that peripheral MORs mediate analgesia, but controversial results on the development of peripheral opioid receptors-mediated analgesic tolerance are reported. In this review, we offer evidence on the consequence of the activation of peripheral MORs in analgesia and analgesic tolerance, as well as approaches that enhance analgesic efficacy and decrease the development of tolerance to opioids at the peripheral sites. We have also addressed the advantages and drawbacks of the activation of peripheral MORs on the sensory neurons and gut (leading to dysbiosis) on the development of central and peripheral analgesic tolerance.

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 Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway

2018 ◽  
Vol 115 (9) ◽  
pp. E2085-E2094 ◽  
Author(s):  
Sevasti Gaspari ◽  
Immanuel Purushothaman ◽  
Valeria Cogliani ◽  
Farhana Sakloth ◽  
Rachael L. Neve ◽  
...  
Keyword(s):  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Morphine Tolerance ◽  
Protein Signaling ◽  
Chronic Morphine ◽  
Analgesic Tolerance ◽  
Biochemical Assays ◽  
Morphine Administration ◽  
Promising Target

Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPRs). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrated that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects. Using biochemical assays and next-generation RNA sequencing, we identified a key role of RGSz1 in the periaqueductal gray (PAG) in morphine tolerance. Chronic morphine administration promotes RGSz1 activity in the PAG, which in turn modulates transcription mediated by the Wnt/β-catenin signaling pathway to promote analgesic tolerance to morphine. Conversely, the suppression of RGSz1 function stabilizes Axin2–Gαz complexes near the membrane and promotes β-catenin activation, thereby delaying the development of analgesic tolerance. These data show that the regulation of RGS complexes, particularly those involving RGSz1-Gαz, represents a promising target for optimizing the analgesic actions of opioids without increasing the risk of dependence or addiction.

scholarly journals A Comparative Assessment of Postoperative Analgesic Efficacy of Lornoxicam versus Tramadol after Open Reduction and Internal Fixation of Mandibular Fractures

2017 ◽  
Vol 10 (3) ◽  
pp. 171-174 ◽  
Author(s):  
Ankesh Dilip Jain ◽  
VSM Ravisankar ◽  
KSN Siva Bharani ◽  
KM Sudheesh ◽  
Nisha Tewathia
Keyword(s):  
Adverse Effects ◽  
Internal Fixation ◽  
Pain Intensity ◽  
Pain Control ◽  
Open Reduction ◽  
Opioid Analgesic ◽  
Maxillofacial Surgery ◽  
Analgesic Efficacy ◽  
Mandibular Fractures ◽  
Study Results

Pain after any surgical procedure is inevitable but can be controlled by administration of analgesics in most cases. Postoperative pain after surgical treatment of mandibular fractures can be treated by nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. The purpose of this study is to critically compare the postoperative analgesic efficacy of small doses of intravenous TRAMADOL (opioid analgesic) versus LORNOXICAM (NSAID) in patients with mandibular trauma undergoing open reduction and internal fixation (ORIF) and to assess the presence of any adverse effects due to NSAID or opioid use. Forty adult ASA grade I–II patients with mandibular trauma, scheduled for ORIF under general anesthesia in the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, were selected for the study. The patients were randomly assigned into a tramadol group (Group T) and a lornoxicam group (Group L) and were administered intravenous tramadol 50 mg and intravenous lornoxicam 8 mg, respectively, at specific postoperative intervals. Pain intensity was quantitatively assessed at the 2nd, 4th, 6th, 12th, and 24th postoperative hours using a visual analog scale of 10 cm. Adverse effects of the analgesics were also recorded and compared. Both the drugs resulted in a significant decrease in pain intensity from 2nd to 24th postoperative hours, but better pain control was observed in Group L at 24th postoperative hour. Only two patients experienced nausea and vomiting in Group T and one patient experienced gastric acidity in Group L. The comparative results clearly demonstrate that pain control by intravenous lornoxicam is significantly better than by intravenous tramadol at 24th postoperative hour after ORIF of mandibular trauma. Side effects produced by both the drugs were minor and had no apparent effect on the study results.

scholarly journals Opioids and Neuropathic Pain

2012 ◽  
Vol 3S;15 (3S;7) ◽  
pp. ES93-ES110
Author(s):  
Howard S. Smith
Keyword(s):  
Neuropathic Pain ◽  
Opioid Therapy ◽  
Chronic Neuropathic Pain ◽  
Analgesic Tolerance ◽  
Key Words Pain ◽  
Analgesic Agents ◽  
Opioid Induced Hyperalgesia ◽  
Third Line ◽  
Effective Analgesia ◽  
Better Than

Opioids are broad spectrum analgesics that may be beneficial to alleviate the intense perception of algesia in patients suffering with pain. They have been one of the most controversial analgesics, in part because of their potential for addiction. Opioids or any currently available analgesic will not provide effective analgesia for every patient with chronic neuropathic pain (NP), but overall opioids are considered to be a second or third line class of analgesics that may provide reasonable analgesia to some patients with chronic NP. Although opioids may alleviate chronic NP, overall, NP tends to be less opioid responsive than nociceptive pain. The mechanisms that may contribute to neuropathic pain may simultaneously also contribute to diminishing the antinociceptive properties of opioids for neuropathic pain. Some of these mechanisms may also contribute to analgesic tolerance and/or opioid-induced hyperalgesia. Hyperalgesia consequently to nerve insult and opioidinduced analgesic tolerance, may both involve the N-methyl-D-aspartate (NMDA) receptor and share part of intracellular events producing a state of neural hyperexcitation. Conversely, opioid therapy may contribute to nociceptive processes that may be involved in neuropathic pain such as opioid-induced cholecystokinin release. Furthermore, within NP, peripheral NP appears to be the most opioid responsive, followed by spinal NP while supraspinal NP tends to be the least responsive to opioids. Although, there is no robust evidence that any specific opioid agent is better than any other opioid at effectively treating NP, it is conceivable that some opioids/opioid-like analgesic agents may be particularly well suited to alleviate NP in certain patients suffering from neuropathic pain. Key words: Pain, neuropathic, opioids, oxycodone, methadone, buprenorphine, tramadol, tapentadol

scholarly journals Oxycodone versus other opioid analgesics after laparoscopic surgery: a meta-analysis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Yan Li ◽  
Zhi Dou ◽  
Liqiang Yang ◽  
Qi Wang ◽  
Jiaxiang Ni ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Laparoscopic Surgery ◽  
Adverse Effects ◽  
Adverse Events ◽  
Systematic Reviews ◽  
Visceral Pain ◽  
Meta Analysis ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Significant Difference

Abstract Background Intravenous opioids are administered for the management of visceral pain after laparoscopic surgery. Whether oxycodone has advantages over other opioids in the treatment of visceral pain is not yet clear. Methods In this study, the analgesic efficiency and adverse events of oxycodone and other opioids, including alfentanil, sufentanil, fentanyl, and morphine, in treating post-laparoscopic surgery visceral pain were evaluated. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase, and Cochrane databases were searched in December 2019. Results Ten studies were included in this review. The sample size was 695 participants. The results showed that compared with morphine and fentanyl, oxycodone had a more potent analgesic efficacy on the first day after laparoscopic surgery, especially during the first 0.5 h. There was no significant difference in sedation between the two groups. Compared to morphine and fentanyl, oxycodone was more likely to lead to dizziness and drowsiness. Overall, patient satisfaction did not differ significantly between oxycodone and other opioids. Conclusions Oxycodone is superior to other analgesics within 24 h after laparoscopic surgery, but its adverse effects should be carefully considered.

scholarly journals A Meta-Analysis of the Analgesic Efficacy of Single-Doses of Ibuprofen Compared to Traditional Non-Opioid Analgesics Following Third Molar Surgery

2021 ◽  
Vol 14 (4) ◽  
pp. 360
Author(s):  
Lorenzo Franco-de la Torre ◽  
Norma Patricia Figueroa-Fernández ◽  
Diana Laura Franco-González ◽  
Ángel Josabad Alonso-Castro ◽  
Federico Rivera-Luna ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Safety Profile ◽  
Meta Analysis ◽  
Third Molar ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Third Molar Surgery ◽  
Number Of Patients ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The purpose of this systematic review was to determine the analgesic efficacy and adverse effects of ibuprofen in comparison with other traditional non-opioid analgesics after third molar surgery. A total of 17 full texts were identified in PubMed and assessed using the Cochrane Collaboration’s risk of bias tool by two independent researchers. The sum of pain intensity differences, total pain relief, the overall evaluation, the number of patients requiring rescue analgesics, and adverse effects were collected. Data were analyzed using the Review Manager Software 5.3. for Windows. A total of 15 articles met the criteria. The qualitative and quantitative analysis showed that ibuprofen is more effective to relieve post-operative dental pain than acetaminophen, meclofenamate, aceclofenac, bromfenac, and aspirin. Moreover, ibuprofen and traditional non-steroidal anti-inflammatory drugs have a similar safety profile. In conclusion, ibuprofen 400 mg appears to have good analgesic efficacy and a safety profile similar to other traditional non-steroidal anti-inflammatory drugs after third molar surgery.

Abhängigkeitspotenzial und andere Risiken von Opioidanalgetika im Alter

2017 ◽  
Vol 63 (2) ◽  
pp. 99-114 ◽  
Author(s):  
Dirk K. Wolter
Keyword(s):  
Adverse Effects ◽  
Psychische Störungen ◽  
Opioid Analgesics ◽  
Alte Menschen ◽  
Dsm 5 ◽  
Icd 10

Zusammenfassung. Zielsetzung: Übersicht über Suchtpotenzial und andere Risiken von Opioidanalgetika im höheren Lebensalter. Methodik: Narrativ review. Literaturrecherche in PubMed (Suchbegriffe: opioid analgesics UND abuse; opioid analgesics UND dependence; opioid analgesics UND addiction; opioid analgesics UND adverse effects; jeweils UND elderly) sowie aktuellen einschlägigen Standardwerken; Auswahl nach altersmedizinischer Relevanz und Aktualität. Ergebnisse: Die Verordnung von Opioidanalgetika (OA) hat in den letzten 25 Jahren massiv zugenommen, die weitaus meisten Verordnungen entfallen auf alte Menschen und Menschen mit chronischen Nicht-Tumorschmerzen (CNTS). Die diagnostischen Kriterien für die Opiatabhängigkeit in ICD-10 und DSM-5 sind für die OA-Behandlung von CNTS ungeeignet. Bei langfristiger OA-Behandlung bei CNTS kann eine spezifische Form von Abhängigkeit entstehen, die nicht mit der illegalen Opiat-(Heroin-)Sucht gleichzusetzen ist. Vorbestehende Suchterkrankungen und andere psychische Störungen sind die wesentlichsten Risikofaktoren. Weitere Nebenwirkungen sind zu beachten. Schmerztherapie bei Suchtkranken stellt eine besondere Herausforderung dar. Schlussfolgerungen: Die Anwendung von OA bei CNTS verlangt eine sorgfältige Indikationsstellung. Die besondere Form der Abhängigkeit von OA ist nicht ausreichend erforscht und wird zu wenig beachtet.

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