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CNS Drugs Oct 2019Opioids are very potent and efficacious drugs, traditionally used for both acute and chronic pain conditions. However, the use of opioids is frequently associated with... (Review)
Review
Opioids are very potent and efficacious drugs, traditionally used for both acute and chronic pain conditions. However, the use of opioids is frequently associated with the occurrence of adverse effects or clinical problems. Other than adverse effects and dependence, the development of tolerance is a significant problem, as it requires increased opioid drug doses to achieve the same effect. Mechanisms of opioid tolerance include drug-induced adaptations or allostatic changes at the cellular, circuitry, and system levels. Dose escalation in long-term opioid therapy might cause opioid-induced hyperalgesia (OIH), which is a state of hypersensitivity to painful stimuli associated with opioid therapy, resulting in exacerbation of pain sensation rather than relief of pain. Various strategies may provide extra-opioid analgesia. There are drugs that may produce independent analgesic effects. A tailored treatment provided by skilled personnel, in accordance with the individual condition, is mandatory. Any treatment aimed at reducing opioid consumption may be indicated in these circumstances. Interventional techniques able to decrease the pain input may allow a decrease in the opioid dose, thus reverting the mechanisms producing tolerance of OIH. Intrathecal therapy with local anesthetics and a sympathetic block are the most common techniques utilized in these circumstances.
Topics: Analgesics, Opioid; Chronic Pain; Drug Tolerance; Humans; Hyperalgesia
PubMed: 31578704
DOI: 10.1007/s40263-019-00660-0 -
Journal of Psychiatric Practice Jan 2020
Topics: Analgesics, Opioid; Humans; Opioid Epidemic; Pain; Prescription Drug Misuse
PubMed: 31913964
DOI: 10.1097/PRA.0000000000000444 -
Cell Nov 2023Opioids are used for pain management despite the side effects that contribute to the opioid crisis. The pursuit of non-addictive opioid analgesics remains unattained due... (Review)
Review
Opioids are used for pain management despite the side effects that contribute to the opioid crisis. The pursuit of non-addictive opioid analgesics remains unattained due to the unresolved intricacies of opioid actions, receptor signaling cascades, and neuronal plasticity. Advancements in structural, molecular, and computational tools illuminate the dynamic interplay between opioids and opioid receptors, as well as the molecular determinants of signaling pathways, which are potentially interlinked with pharmacological responses. Here, we review the molecular basis of opioid receptor signaling with a focus on the structures of opioid receptors bound to endogenous peptides or pharmacological agents. These insights unveil specific interactions that dictate ligand selectivity and likely their distinctive pharmacological profiles. Biochemical analysis further unveils molecular features governing opioid receptor signaling. Simultaneously, the synergy between computational biology and medicinal chemistry continues to expedite the discovery of novel chemotypes with the promise of yielding more efficacious and safer opioid compounds.
Topics: Humans; Analgesics, Opioid; Receptors, Opioid; Signal Transduction; Animals
PubMed: 37995655
DOI: 10.1016/j.cell.2023.10.029 -
Archives of Toxicology Aug 2021Opioid-induced respiratory depression is potentially life-threatening and often regarded as the main hazard of opioid use. Main cause of death is cardiorespiratory... (Review)
Review
Opioid-induced respiratory depression is potentially life-threatening and often regarded as the main hazard of opioid use. Main cause of death is cardiorespiratory arrest with hypoxia and hypercapnia. Respiratory depression is mediated by opioid μ receptors expressed on respiratory neurons in the CNS. Studies on the major sites in the brainstem mediating respiratory rate suppression, the pre-Bӧtzinger complex and parabrachial complex (including the Kӧlliker Fuse nucleus), have yielded conflicting findings and interpretations but recent investigations involving deletion of μ receptors from neurons have led to greater consensus. Some opioid analgesic drugs are histamine releasers. The range of clinical effects of released histamine include increased cardiac output due to an increase in heart rate, increased force of myocardial contraction, and a dilatatory effect on small blood vessels leading to flushing, decreased vascular resistance and hypotension. Resultant hemodynamic changes do not necessarily relate directly to the concentration of histamine in plasma due to a range of variables including functional differences between mast cells and histamine-induced anaphylactoid reactions may occur less often than commonly believed. Opioid-induced histamine release rarely if ever provokes bronchospasm and histamine released by opioids in normal doses does not lead to anaphylactoid reactions or result in IgE-mediated reactions in normal patients. Hypersensitivities to opioids, mainly some skin reactions and occasional type I hypersensitivities, chiefly anaphylaxis and urticaria, are uncommon. Hypersensitivities to morphine, codeine, heroin, methadone, meperidine, fentanyl, remifentanil, buprenorphine, tramadol, and dextromethorphan are summarized. In 2016, the FDA issued a Drug Safety Communication concerning the association of opioids with serotonin syndrome, a toxicity associated with raised intra-synaptic concentrations of serotonin in the CNS, inhibition of serotonin reuptake, and activation of 5-HT receptors. Opioids may provoke serotonin toxicity especially if administered in conjunction with other serotonergic medications. The increasing use of opioid analgesics and widespread prescribing of antidepressants and psychiatric medicines, indicates the likelihood of an increased incidence of serotonin toxicity in opioid-treated patients.
Topics: Analgesics, Opioid; Animals; Drug Hypersensitivity; Hemodynamics; Histamine Release; Humans; Respiratory Insufficiency; Serotonin Syndrome
PubMed: 33974096
DOI: 10.1007/s00204-021-03068-2 -
Physical Medicine and Rehabilitation... May 2020Opioid receptors and opioid agonists are widespread throughout nature. Endogenous opioids mediate complex functions in animals and in humans. The opioid system in humans... (Review)
Review
Opioid receptors and opioid agonists are widespread throughout nature. Endogenous opioids mediate complex functions in animals and in humans. The opioid system in humans plays a central role in pain control and is a key mediator of hedonic homeostasis, mood, and well-being. This system also regulates responses to stress and several peripheral physiologic functions, including respiratory, gastrointestinal, endocrine, and immune systems. This article provides an overview of the basic physiology of opioids, reviews opioid pharmacology, and attempts to address several issues of current importance in the management of patients with established long-term opioid therapy.
Topics: Analgesics, Opioid; Chronic Pain; Humans; Pain Management; Receptors, Opioid
PubMed: 32279731
DOI: 10.1016/j.pmr.2020.01.007 -
European Journal of Drug Metabolism and... Oct 2019Pain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations... (Review)
Review
Pain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations involving more severe pain often require the use of an opioid, which may be administered by many different routes, depending on clinical necessity. Acute and chronic disease states, as well as the constantly changing maturational process, produce unique challenges at every level of pediatrics in dosing and management of all medications, especially with regard to high-risk opioids. Although there has been significant progress in the understanding of opioid pharmacokinetics and pharmacodynamics in neonates, infants, children, and adolescents, somewhat limited data exist from which necessary information, concerning the safe and effective use of these agents, may be drawn. The evidence here provided is intended to be helpful in directing the practitioner to patient-specific reasons for preferring one opioid over another. As our knowledge of opioids and their effects has grown, it has become clear that older medications like codeine and meperidine (pethidine) have very limited use in pediatrics. This review provides pharmacokinetic and pharmacodynamic evidence on the currently available opioids: morphine, fentanyl (and derivatives), codeine, meperidine, oxycodone, hydrocodone, hydromorphone, methadone, buprenorphine, butorphanol, nalbuphine, pentazocin, ketobemidone, tramadol, piritramide, naloxone and naltrexone. Morphine, being the most studied opioid analgesic, is the standard against which all others are compared. Pharmacokinetic parameters of morphine that have been found in neonates, i.e., higher volume of distribution, immature metabolic processes that develop at various rates, elimination that is variable based on age and weight, as well as treated and untreated disease processes, are an example of all opioids in the population discussed in this review. Outside the premature and neonatal population, the use of opioids in infants, children, and adolescents quickly begins to resemble the established values found in adults. As such, the concerns (risks) of these medications become comparable to those seen in adults.
Topics: Analgesics, Opioid; Animals; Child; Humans; Infant; Infant, Newborn; Pain; Pain Management
PubMed: 31006834
DOI: 10.1007/s13318-019-00552-0 -
Current Opinion in Anaesthesiology Jun 2020Over the last 3 years and for the first time in 60 years, life expectancy in the United States has declined across all racial groups primarily because of drug overdoses,... (Review)
Review
PURPOSE OF REVIEW
Over the last 3 years and for the first time in 60 years, life expectancy in the United States has declined across all racial groups primarily because of drug overdoses, alcohol abuse, and suicide. A public health response to the opioid crisis must expand its focus to more broadly include children, adolescents, and young adults while increasing efforts toward preventing new cases of opioid addiction, early identification of individuals with opioid-abuse disorder, and ensuring access to effective opioid addiction treatment, while simultaneously continuing to safely meet the needs of patients experiencing pain.
RECENT FINDINGS
Although a multimodal approach to pain management is fundamental in current practice, opioids remain an essential building block in the management of acute and chronic pain and have been for over 5000 years as they work. Left over, unconsumed opioids that were appropriately prescribed for pain have become the gateway for the development of opioid use disorder, particularly in the vulnerable adolescents and young adult patient populations. How to reduce the amount of opioids dispensed, improve methods of disposal in an environmentally safe way, and proactively make naloxone, particularly nasal spray, readily available to patients (and their families) receiving prescription opioids or who are at risk of opioid use disorder are highlighted in this review.
SUMMARY
We describe the historical use of opioids and the scope of the current opioid crisis, review the differences between dependence and addiction, and the private and public sectors response to pain management and highlight the issue of adolescent vulnerability. We conclude with a proposal for future directions that address both public and patient health needs.
Topics: Adolescent; Analgesics, Opioid; Child; Child, Preschool; Drug Overdose; Humans; Infant; Opioid Epidemic; Opioid-Related Disorders; Pediatrics; United States; Young Adult
PubMed: 32371640
DOI: 10.1097/ACO.0000000000000865 -
Molecules (Basel, Switzerland) Aug 2020Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their... (Review)
Review
Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.
Topics: Analgesics, Opioid; Codeine; Drug Misuse; Humans; Loperamide; Nonprescription Drugs
PubMed: 32867117
DOI: 10.3390/molecules25173905 -
Nature Reviews. Nephrology Feb 2022Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated... (Review)
Review
Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated that 50-80% of adult patients treated with HD report having pain. Half of patients with HD-dependent kidney failure (HDKF) have chronic moderate-to-severe pain, which is similar to the burden of pain in patients with cancer. However, pain management in patients with HDKF is often ineffective as most patients report that their pain is inadequately treated. Opioid analgesics are prescribed more frequently for patients receiving HD than for individuals in the general population with chronic pain, and are associated with increased morbidity, mortality and health-care resource use. Furthermore, current opioid prescribing patterns are frequently inconsistent with guideline-recommended care. Evidence for the effectiveness of opioids in pain management in general, and in patients with HDKF specifically, is lacking. Nonetheless, long-term opioid therapy has a role in the treatment of some patients when used selectively, carefully and combined with an ongoing assessment of risks and benefits. Here, we provide a comprehensive overview of the use of opioid therapy in patients with HDKF and chronic pain, including a discussion of buprenorphine, which has potential as an analgesic option for patients receiving HD owing to its unique pharmacological properties.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Pain Management; Practice Patterns, Physicians'; Renal Dialysis; Renal Insufficiency
PubMed: 34621058
DOI: 10.1038/s41581-021-00484-6 -
Nature Sep 2019
Topics: Analgesics, Opioid; Humans; Opioid Epidemic; Opioid-Related Disorders; Pain
PubMed: 31511676
DOI: 10.1038/d41586-019-02681-7