scholarly journals Opioid Analgesia and Opioid-Induced Adverse Effects: A Review

2021 ◽  
Vol 14 (11) ◽  
pp. 1091
Author(s):  
Alok K. Paul ◽  
Craig M. Smith ◽  
Mohammed Rahmatullah ◽  
Veeranoot Nissapatorn ◽  
Polrat Wilairatana ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Adverse Effects ◽  
Adverse Reactions ◽  
Analgesic Tolerance ◽  
Opioid Ligands ◽  
Effective Therapeutic Strategy ◽  
Μ Opioid Receptor ◽  
Repeated Use ◽  
Opioid Receptor Agonists ◽  
Underlying Pathophysiology

Opioids are widely used as therapeutic agents against moderate to severe acute and chronic pain. Still, these classes of analgesic drugs have many potential limitations as they induce analgesic tolerance, addiction and numerous behavioural adverse effects that often result in patient non-compliance. As opium and opioids have been traditionally used as painkillers, the exact mechanisms of their adverse reactions over repeated use are multifactorial and not fully understood. Older adults suffer from cancer and non-cancer chronic pain more than younger adults, due to the physiological changes related to ageing and their reduced metabolic capabilities and thus show an increased number of adverse reactions to opioid drugs. All clinically used opioids are μ-opioid receptor agonists, and the major adverse effects are directly or potentially connected to this receptor. Multifunctional opioid ligands or peripherally restricted opioids may elicit fewer adverse effects, as shown in preclinical studies, but these results need reproducibility from further extensive clinical trials. The current review aims to overview various mechanisms involved in the adverse effects induced by opioids, to provide a better understanding of the underlying pathophysiology and, ultimately, to help develop an effective therapeutic strategy to better manage pain.

Does co-administration of paroxetine change oxycodone analgesia: An interaction study in chronic pain patients

2010 ◽  
Vol 1 (1) ◽  
pp. 24-33 ◽  
Author(s):  
K.K. Lemberg ◽  
T.E. Heiskanen ◽  
M. Neuvonen ◽  
V.K. Kontinen ◽  
P.J. Neuvonen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Adverse Effects ◽  
Opioid Receptor ◽  
Placebo Administration ◽  
Rescue Analgesia ◽  
Analgesic Effects ◽  
Patient Reported ◽  
Chronic Pain Patients ◽  
Μ Opioid Receptor ◽  
Pain Patients

AbstractOxycodone is a strong opioid and it is increasingly used in the management of acute and chronic pain. The pharmacodynamic effects of oxycodone are mainly mediated by the μ-opioid receptor. However, its affinity for the μ-opioid receptor is significantly lower compared with that of morphine and it has been suggested that active metabolites may play a role in oxycodone analgesia. Oxycodone is mainly metabolized by hepatic cytochrome (CYP) enzymes 2D6 and 3A4. Oxycodone is metabolized to oxymorphone, a potent μ-opioid receptor agonist by CYP2D6. However, CYP3A4 is quantitatively a more important metabolic pathway. Chronic pain patients often use multiple medications. Therefore it is important to understand how blocking or inducing these metabolic pathways may affect oxycodone induced analgesia. The aim of this study was to find out whether blocking CYP2D6 would decrease oxycodone induced analgesia in chronic pain patients.The effects of the antidepressant paroxetine, a potent inhibitor of CYP2D6, on the analgesic effects and pharmacokinetics of oral oxycodone were studied in 20 chronic pain patients using a randomized, double-blind, placebo-controlled cross-over study design. Pain intensity and rescue analgesics were recorded daily, and the pharmacokinetics and pharmacodynamics of oxycodone were studied on the 7th day of concomitant paroxetine (20 mg/day) or placebo administration. The patients were genotyped for CYP2D6, 3A4, 3A5 and ABCB1.Paroxetine had significant effects on the metabolism of oxycodone but it had no statistically significant effect on oxycodone analgesia or use of morphine for rescue analgesia. Paroxetine increased the dose-adjusted mean AUC0–12h of oxycodone by 19% (−23 to 113%; P = 0.003), and that of noroxycodone by 100% (5–280%; P < 0.0001) but decreased the AUC0–12 h of oxymorphone by 67% (−100 to −22%; P < 0.0001) and that of noroxymorphone by 68% (−100 to −16%; P < 0.0001).Adverse effects were also recorded in a pain diary for both 7-day periods (placebo/paroxetine). The most common adverse effects were drowsiness and nausea/vomiting. One patient out of four reported dizziness and headache during paroxetine co-administration, whereas no patient reported these during placebo administration (P = 0.0471) indicating that these adverse effects were due to paroxetine.No statistically significant associations of the CYP2D6 or CYP3A4/5 genotype of the patients and the pharmacokinetics of oxycodone or its metabolites, extent of paroxetine–oxycodone interaction, or analgesic effects were observed probably due to the limited number of patients studied.The results of this study strongly suggest that CYP2D6 inhibition does not significantly change oxycodone analgesia in chronic pain patients and that the analgesic activity of oxycodone is mainly due to the parent compound and that metabolites, e.g. oxymorphone, play an insignificant role. The clinical implication of these results is that induction of the metabolism of oxycodone may lead to inadequate analgesia while increased drug effects can be expected after addition of potent CYP3A4/5 inhibitors particularly if combined with CYP2D6 inhibitors or when administered to poor metabolizers of CYP2D6.

scholarly journals Pharmacological and genetic manipulations at the µ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice

2021 ◽  
Author(s):  
Li He ◽  
Sarah W. Gooding ◽  
Elinor Lewis ◽  
Lindsey C. Felth ◽  
Anirudh Gaur ◽  
...  
Keyword(s):  
G Protein ◽  
Respiratory Depression ◽  
Opioid Receptor ◽  
Analgesic Tolerance ◽  
Genetic Manipulations ◽  
Opioid Ligands ◽  
Analgesic Effects ◽  
Opioid Drugs ◽  
Opioid Receptor Agonists ◽  
G Protein Coupled

AbstractOpioid drugs are widely used analgesics that activate the G protein-coupled µ-opioid receptor, whose endogenous neuropeptide agonists, endorphins and enkephalins, are potent pain relievers. The therapeutic utility of opioid drugs is hindered by development of tolerance to the analgesic effects, requiring dose escalation for persistent pain control and leading to overdose and fatal respiratory distress. The prevailing hypothesis is that the intended analgesic effects of opioid drugs are mediated by µ-opioid receptor signaling to G protein, while the side-effects of respiratory depression and analgesic tolerance are caused by engagement of the receptor with the arrestin-3 protein. Consequently, opioid drug development has focused exclusively on identifying agonists devoid of arrestin-3 engagement. Here, we challenge the prevailing hypothesis with a panel of six clinically relevant opioid drugs and mice of three distinct genotypes with varying abilities to promote morphine-mediated arrestin-3 engagement. With this genetic and pharmacological approach, we demonstrate that arrestin-3 recruitment does not impact respiratory depression, and effective arrestin-3 engagement reduces, rather than exacerbates, the development of analgesic tolerance. These studies suggest that future development of safer opioids should focus on identifying opioid ligands that recruit both G protein and arrestin-3, thereby mimicking the signaling profile of most endogenous µ-opioid receptor agonists.

scholarly journals Lidocaine: A Local Anesthetic, Its Adverse Effects and Management

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 782
Author(s):  
Entaz Bahar ◽  
Hyonok Yoon
Keyword(s):  
Adverse Effects ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Adverse Reactions ◽  
Rapid Diagnosis ◽  
Diagnosis And Treatment ◽  
Allergic Reactions ◽  
Life Threatening

The most widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded adverse allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate to life-threatening, requiring rapid diagnosis and treatment. This article serves as a review to provide information on LA, their adverse reactions, causes, and management.

scholarly journals AB0864 DO CORTICOSTEROIDS AND HYALURONIC ACID INJECTIONS CAUSE INFECTIONS? A SYSTEMATIC REVIEW OF LITERATURE ON ADVERSE EFFECTS AND INFECTION RATES OF INTRA-ARTICULAR CORTICOSTEROID AND HYALURONIC ACID INJECTIONS IN PATIENTS WITH KNEE OSTEOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1739.2-1739
Author(s):  
C. Hatzantonis
Keyword(s):  
Systematic Review ◽  
Hyaluronic Acid ◽  
Adverse Effects ◽  
Adverse Events ◽  
Knee Osteoarthritis ◽  
Adverse Reactions ◽  
Infection Rates ◽  
Management Options ◽  
Cochrane Reviews ◽  
Number Of Patients

Background:Knee osteoarthritis has been a leading cause of chronic pain and disability in our increasingly aging population. Conservative management options of physiotherapy and oral analgesics offer some relief, but delivery of intra-articular injections such as corticosteroids or hyaluronic acid has increasingly become the mainstay of pain management of knee osteoarthritis. In a clinical setting, intra-articular injections offer a means to delay a total knee replacement. Despite the abundance of literature on corticosteroids and hyaluronic acid, there is no known percentage of infection rates or adverse effects that clinicians may use to inform patients prior to obtaining consent for the injection.Objectives:To determine a rate of adverse events and infection rates in patients undergoing intra-articular injections of corticosteroids or hyaluronic acid.Methods:A systematic review of current literature including studies involving patients ranging from 45 patients (Carmona L, 2018) to Cochrane reviews of 1767 patients (Campbell Kirk, 2015). From these studies, the number of patients, adverse reactions (i.e. pain, erythema) and serious adverse reactions (infections) were calculated.Results:Within our study, there was a large variation of numbers of adverse effects of hyaluronic acid and corticosteroids amongst studies, with percentages as variable as 0-9.3%. Corticosteroids demonstrated 11-26% reduction of adverse events compared to hyaluronic acid. However, confidence intervals were found to not be statistically significant.Conclusion:Intra-articular injections of corticosteroids and hyaluronic acid, although deemed clinically effective, continue to demonstrate variable rates of adverse effects and infection amongst patients with progressive knee osteoarthritis.Disclosure of Interests:None declared

Transformation of μ-opioid receptor agonists into biologically potent μ-opioid receptor antagonists

2007 ◽  
Vol 15 (3) ◽  
pp. 1237-1251 ◽  
Author(s):  
Tingyou Li ◽  
Yunden Jinsmaa ◽  
Masahiro Nedachi ◽  
Anna Miyazaki ◽  
Yuko Tsuda ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Antagonists ◽  
Receptor Agonists ◽  
Opioid Receptor Antagonists ◽  
Μ Opioid Receptor ◽  
Opioid Receptor Agonists

Deprescribing in mental health: pragmatic steps for a better quality of life

2021 ◽  
Vol 3 (2) ◽  
pp. 60-66
Author(s):  
Nana Tomova ◽  
Ami Hale ◽  
Michelle Kruschandl
Keyword(s):  
Quality Of Life ◽  
Mental Health ◽  
Adverse Effects ◽  
Chronic Conditions ◽  
Adverse Reactions ◽  
Hospital Admissions ◽  
Medication Reviews ◽  
The Uk ◽  
Specialist Pharmacist

Half of the UK population take at least one prescribed medicine, while a quarter take three or more. Polypharmacy has become increasingly common, with the average number of items prescribed per person per year in England having increased by 53.8% in the last decade. Patients are prescribed, and may continue taking, medicines that cause adverse effects and where the harm of the medicine outweighs the benefit. Adverse reactions to medicines are connected to 6.5% of hospital admissions. Patients admitted with one drug side effect are more than twice as likely to be admitted with another. Deprescribing is the optimisation of medication and is a vital part of improving outcomes, managing chronic conditions, and avoiding adverse effects. The goal of deprescribing is to lessen medication burden and enhance quality of life. This article presents case studies from clinical practice in a mental health service, and highlights the merits of specialist pharmacist-led interventions with respects to medication reviews and deprescribing.

Adverse reactions to medication

2019 ◽  
pp. 103-114
Author(s):  
Tomasz Bajorek ◽  
Jonathan Hafferty
Keyword(s):  
Adverse Effect ◽  
Adverse Effects ◽  
Adverse Reactions ◽  
Bleeding Risk ◽  
Inpatient Setting ◽  
Extrapyramidal Side Effects ◽  
Inpatient Psychiatry ◽  
Drug Induced ◽  
Threatening Condition ◽  
Life Threatening

Adverse reactions to medication represent a major issue in inpatient psychiatry. This chapter systematically explores the most relevant, concerning, and problematic adverse effects routinely encountered in an inpatient setting. It describes the typical presentation, pathophysiology, incidence, and practical management of these problems. Extrapyramidal side effects including acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia are considered before the chapter explores the rare but potentially life-threatening condition of neuroleptic malignant syndrome. Other adverse effects common to antipsychotics that are described include hyperprolactinaemia and psychotropic-induced arrhythmias including QTc prolongation. Sexual dysfunction is an under-recognized and undertreated adverse effect common to several classes of psychotropic medication and is also considered. Focusing on antidepressants, the chapter reviews the frequently encountered issue of hyponatraemia as well as serotonin syndrome and selective serotonin reuptake inhibitor-induced bleeding risk. Finally, the chapter addresses perinatal considerations for psychotropic drugs.

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