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Handbook of Experimental Pharmacology 2018Opioid abuse has been a global menace for centuries, but the proliferation of synthetic opioids and their use within this current decade have created epidemic-level... (Review)
Review
Opioid abuse has been a global menace for centuries, but the proliferation of synthetic opioids and their use within this current decade have created epidemic-level harms in some countries. According to the United Nations Office on Drugs and Crime, almost 12 million years were estimated loss of "healthy" life resulting in premature death and disability attributable to global opioid abuse just in 2015. Law enforcement and regulatory authorities have been particularly challenged abating the spread of synthetic opioids because soon after controlling the currently recognized abused opioids, their structures are tweaked, and new entities replace them. Drug racketeers have most often exploited the fentanyl phenylpiperidine structure in this regard, but non-fentanyl-like and classical morphinan-like structures have been pirated as well. A growing number of anecdotal reports identify respiratory depression induced by these newer synthetic opioids to be especially refractive to reversal by antagonists, with consequently high levels of lethality. This review examines three of these synthetic opioids representing three chemical classes (U-47700, MT-45, and acetylfentanyl) that have emerged to be of such menace that they have been brought under international control in recent years and addresses factors that could make synthetic opioids especially untreatable by opioid antagonists.
Topics: Analgesics, Opioid; Benzamides; Fentanyl; Humans; Morphinans; Opioid-Related Disorders; Piperazines
PubMed: 30242482
DOI: 10.1007/164_2018_149 -
Nature Sep 2019
Topics: Analgesics, Opioid; Humans; Opioid Epidemic; Opioid-Related Disorders; Pain
PubMed: 31511676
DOI: 10.1038/d41586-019-02681-7 -
Molecular and Cellular Neurosciences Jun 2023The opioids are potent and widely used pain management medicines despite also possessing severe liabilities that have fueled the opioid crisis. The pharmacological... (Review)
Review
The opioids are potent and widely used pain management medicines despite also possessing severe liabilities that have fueled the opioid crisis. The pharmacological properties of the opioids primarily derive from agonism or antagonism of the opioid receptors, but additional effects may arise from specific compounds, opioid receptors, or independent targets. The study of the opioids, their receptors, and the development of remediation strategies has benefitted from derivatization of the opioids as chemical tools. While these studies have primarily focused on the opioids in the context of the opioid receptors, these chemical tools may also play a role in delineating mechanisms that are independent of the opioid receptors. In this review, we describe recent advances in the development and applications of opioid derivatives as chemical tools and highlight opportunities for the future.
Topics: Humans; Analgesics, Opioid; Receptors, Opioid
PubMed: 36948231
DOI: 10.1016/j.mcn.2023.103845 -
Pain Medicine (Malden, Mass.) Oct 2015Millions of patients continue to require opioid analgesics for control of moderate to severe chronic pain, which is a disease that affects more Americans than cancer,... (Review)
Review
OBJECTIVE
Millions of patients continue to require opioid analgesics for control of moderate to severe chronic pain, which is a disease that affects more Americans than cancer, heart disease, and diabetes combined. Common opioid adverse effects include constipation, sedation, and nausea. A lesser-known sequelae is opioid induced androgen deficiency (OPIAD). The objective of this review was to better characterize the effects of opioids on the endocrine system.
METHODS
Published data were evaluated to identify links between opioid use and hypogonadism, as well as to describe proposed physiological mechanisms.
RESULTS
Chronic opioid use may predispose to hypogonadism through alteration of the hypothalamic-pituitary-gonadal axis as well as the hypothalamic-pituitary-adrenal-axis. The resulting hypogonadism and hypotestosteronism may contribute to impaired sexual function, decreased libido, infertility, and osteoporosis- none of which may be clinically recognized as opioid related.
CONCLUSIONS
OPIAD is a recognized consequence of long-term opioid therapy. Patients initiated or maintained on opioids should be queried about symptoms that might suggest hypogonadism including irregular menses, reduced libido, depression, fatigue, and hot flashes or night sweats. Some clinicians recommend assessment of baseline testosterone levels prior to initiating therapy. Additional data appear necessary to formulate guidelines regarding the diagnosis and management of OPIAD. Options include, rotating, reducing the dose or type, or cessation of opioid therapy or adding hormonal supplementation in the form of androgen replacement therapy. There are multiple formulations of testosterone available for replacement therapy, which is usually guided by laboratory measurements.
Topics: Analgesics, Opioid; Chronic Pain; Endocrine System Diseases; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 26461076
DOI: 10.1111/pme.12926 -
Molecular Pharmacology Oct 2020In the past 50 years, scientists have made considerable strides toward understanding how opioids act. This special issue of celebrates these 50 years of opioid research...
In the past 50 years, scientists have made considerable strides toward understanding how opioids act. This special issue of celebrates these 50 years of opioid research and the role that the International Narcotics Research Conference has played in driving this research, by bringing together review and original research articles that present historical highlights, the current state of the art, and perspectives on the future of opioid research. SIGNIFICANCE STATEMENT: Opioids have been used for thousands of years to manage pain and cause euphoria, but their use has been highly limited due to serious side effects. Deciphering the mechanisms of how opioids mediate beneficial and adverse physiological outcomes is essential for developing better treatments for pain and for opioid addiction.
Topics: Analgesics, Opioid; Biomedical Research; Congresses as Topic; Drug Design; Humans; Opioid-Related Disorders; Pain
PubMed: 32788221
DOI: 10.1124/molpharm.120.000132 -
Physical Medicine and Rehabilitation... May 2020Numerous guidelines targeting safe use of opioids for chronic pain have been published but substantial challenges persist in clinical application of best practice... (Review)
Review
Numerous guidelines targeting safe use of opioids for chronic pain have been published but substantial challenges persist in clinical application of best practice recommendations. This article describes a pragmatic approach to clinical care of adults with chronic pain receiving long-term opioid therapy. Three components of care are emphasized: (1) medical and mental health assessment before initiating opioid therapy, (2) clinical surveillance during the course of long-term opioid therapy, and (3) clinical considerations and strategies governing opioid tapering. A pressing need exists for ongoing research to further clarify the optimal role that long-term opioid therapy has in treatment of chronic pain.
Topics: Analgesics, Opioid; Chronic Pain; Drug Tapering; Humans; Opioid-Related Disorders; Pain Management
PubMed: 32279729
DOI: 10.1016/j.pmr.2020.01.006 -
Seminars in Nephrology Jan 2021
Topics: Analgesics, Opioid; Humans; Kidney
PubMed: 33896467
DOI: 10.1016/j.semnephrol.2021.03.001 -
Pain Medicine (Malden, Mass.) Oct 2015Opioid-induced constipation (OIC) is common in people treated with opioids and poses risks for physical sequelae, analgesic discontinuation, and decreased quality of... (Review)
Review
INTRODUCTION
Opioid-induced constipation (OIC) is common in people treated with opioids and poses risks for physical sequelae, analgesic discontinuation, and decreased quality of life.
METHODS
Targeted literature review of evidence- and consensus-based data on appropriate diagnosis, concise definition, and conventional and newer management strategies for OIC.
RESULTS
OIC may develop early and need early treatment. To address gaps in consistent definitions and treatment recommendations, a consensus panel organized through the American Academy of Pain Medicine Foundation set diagnostic criteria and endorsed the Bowel Function Index for OIC assessment. The panel further proposed management strategies for OIC, including a proposed threshold for prescriptive therapies.
DISCUSSION
OIC results from action exerted on opioid receptors in the gastrointestinal tract, a mechanism distinct from idiopathic constipation. Lifestyle changes and over-the-counter drugs are first-line treatments but leave refractory constipation in many opioid-treated patients. Newer therapeutic modalities that are available and in development are highlighted.
SUMMARY
Physicians need a better understanding of the negative impacts of OIC for patients and better OIC-specific methods to assess, treat, and monitor it.
Topics: Analgesics, Opioid; Constipation; Humans; Pain; Physician's Role; Quality of Life; Receptors, Opioid
PubMed: 26461071
DOI: 10.1111/pme.12911 -
Annals of Palliative Medicine Mar 2020Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse... (Review)
Review
Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and potentially lethal respiratory depression (RD). Consequently, opioid treatment requires careful evaluation in terms of benefit on the one hand and harm on the other. Considering benefit and harm from an economic perspective, opioid treatment should lead to profit maximization with decision theory defining utility as (profit - loss). We here focus on the most devastating opioid adverse effect, RD and define opioid utility U = P(benefit) - P(harm), where P(benefit) is the probability of opioid-induced analgesia and P(harm) the probability of opioid-induced RD. Other utility functions are also discussed including the utility U = P(benefit AND NOT harm), the most wanted opioid effect, i.e., analgesia without RD, and utility surfaces, which depict the continuum of probabilities of presence or absence of analgesia in combination with the presence or absence of RD. Utility functions are constructed from pharmacokinetic and pharmacodynamic data sets, although pragmatic utility functions may be constructed when pharmacokinetic data are not available. We here discuss utilities of several opioids including the partial mu-opioid-receptor agonist buprenorphine, the full opioid receptor agonists fentanyl and alfentanil, and the bifunctional opioid cebranopadol, which acts at mu-opioid and nociception/orphanin FQ-receptors. We argue that utility functions give clinicians the opportunity to make an informed decision when opioid analgesics are needed for pain relief, in which opioids with a positive utility function are preferred over opioids with negative functions. Furthermore, utility functions of subpopulations will give an extra insight as a utility functions measured in one subgroup (e.g., patients with postoperative pain, good opioid responders) may not be mirrored in other patient subgroups (e.g., neuropathic pain patients, poor opioid responders).
Topics: Analgesics, Opioid; Attitude of Health Personnel; Clinical Decision-Making; Disease Management; Humans; Pain; Pain Management; Pain Measurement
PubMed: 31865743
DOI: 10.21037/apm.2019.10.09 -
Clinical Obstetrics and Gynecology Mar 2019Opioid use for chronic noncancer pain poses a challenge to the gynecologist, and weaning opioids is often a goal for clinicians and patients. In some cases, opioid... (Review)
Review
Opioid use for chronic noncancer pain poses a challenge to the gynecologist, and weaning opioids is often a goal for clinicians and patients. In some cases, opioid cessation can be achieved by weaning a patient's prescribed opioid or with symptomatic management with long-acting opioids or alpha2-adrenergic medications. This review imparts a basic understanding of the physiology of opioid withdrawal, strategies for achieving opioid abstinence, medications for treating the symptoms of withdrawal, and alternatives to opioid taper.
Topics: Analgesics, Opioid; Chronic Pain; Dose-Response Relationship, Drug; Female; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Receptors, Opioid; Substance Withdrawal Syndrome; Systematic Reviews as Topic
PubMed: 30601171
DOI: 10.1097/GRF.0000000000000425