scholarly journals Individual variability in clinical effect and tolerability of opioid analgesics – Importance of drug interactions and pharmacogenetics

2017 ◽  
Vol 17 (1) ◽  
pp. 193-200 ◽  
Author(s):  
Vigdis Solhaug ◽  
Espen Molden
Keyword(s):  
Side Effects ◽  
Drug Interactions ◽  
Clinical Effect ◽  
Pain Treatment ◽  
Opioid Analgesics ◽  
Individual Variability ◽  
Comorbid Condition ◽  
Variable Response ◽  
Increased Risk ◽  
Serotonergic Drugs

AbstractBackgroundAs pain is often a comorbid condition, many patients use opioid analgesics in combination with several other drugs. This implies a generally increased risk of drug interactions, which along with inherent pharmacogenetic variability and other factors may cause differences in therapeutic response of opioids.AimTo provide an overview of interactions and pharmacogenetic variability of relevance for individual differences in effect and tolerability of opioid analgesics, which physicians and other healthcare professionals should be aware of in clinical practice.MethodsThe article was based on unsystematic searches in PubMed to identify literature highlighting the clinical impact of drug interactions and pharmacogenetics as sources of variable response of opioid analgesics.ResultsCytochrome P450 (CYP)-mediated metabolism is an important process for both clinically relevant interactions and pharmacogenetic variability of several opioids. Concomitant use of CYP inhibitors (e.g. paroxetine, fluoxetine and bupropion) or inducers (e.g. carbamazepine, phenobarbital and phenytoin) could counteract the clinical effect or trigger side effects of analgesics in the same manner as genetically determined differences in CYP2D6-mediated metabolism of many opioids. Moreover, combination treatment with drugs that inhibit or induce P-glycoprotein (ABCB1), a blood-brain barrier efflux transporter, may alter the amount (‘dose’) of opioids distributed to the brain. At the pharmacodynamic level, it is crucial to be aware of the potential risk of interaction causing serotonergic syndrome when combining opioids and serotonergic drugs, in particular antidepressants inhibiting serotonin reuptake (SSRIs and SNRIs). Regarding pharmacogenetics at the receptor level of pain treatment, the knowledge is currently scarce, but an allelic variant of the μ1 opioid receptor (OPRM1) gene has been associated with higher dosage requirement to achieve analgesia.Conclusions and implicationsDrug interactions and pharmacogenetic differences may lead to therapeutic failure or serious side effects of opioid analgesics. Many interactions involve combinations with antidepressants and antiepileptics, which are highly relevant drugs in patients suffering from pain. To prevent unfavourable drug interactions it is important that clinicians pay close attention and use electronic drug interaction checkers when treatments are initiated or discontinued. For the management of issues related to pharmacogenetic differences, blood-based CYP genotyping is available as routine test at many laboratories, and provide a valuable tool for proper choice of drugs and doses for treatment of pain and other diseases.

Sending out Biased Signals: an Appropriate Proposition for Pain?

2019 ◽  
Vol 32 (2) ◽  
pp. 108-110 ◽  
Author(s):  
E. Besserer-Offroy ◽  
P. Sarret
Keyword(s):  
Side Effects ◽  
Acute Pain ◽  
Gold Standard ◽  
Pain Treatment ◽  
Opioid Analgesics ◽  
Mu Opioid Receptor ◽  
Clinical Development ◽  
Mu Opioid ◽  
Development Stages ◽  
The Past

In the past few years, several biased ligands acting at the mu-opioid receptor were reported in the literature. These agonists are aimed at reducing pain while having fewer side effects than morphine, the gold standard of opioid analgesics. In this mini-review, we describe and discuss the recent advances in mu-biased ligands actually in preclinical and clinical development stages, including the latest U.S. Food and Drug Administration review of oliceridine, a biased mu-agonist for moderate to severe acute pain treatment developed by the company Trevena.

The role of oxycodone/naloxone in pain management

Ból ◽  
2017 ◽  
Vol 17 (4) ◽  
pp. 26-40
Author(s):  
Magdalena Kocot-Kępska ◽  
Renata Zajączkowska ◽  
Anna Przeklasa-Muszyńska ◽  
Jan Dobrogowski
Keyword(s):  
Side Effects ◽  
Pain Treatment ◽  
Treatment Options ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Bowel Dysfunction ◽  
Prolonged Release ◽  
Gastrointestinal Side Effects ◽  
Strong Opioids ◽  
Pain Patients

ABSTRACT: Strong opioid analgesics are essential for pain treatment of moderate to severe intensity, regardless of its etiology. An important factor limiting safety and efficacy of opioids are side effects, particularly gastrointestinal. Constipation as part of opioid induced bowel dysfunction is one of the most common reason for discontinuation of strong opioids. Introduction of novel oxycodone/naloxone formulation is an attempt to resolve the problem of opioid induced gastrointestinal side effects. On the basis of clinical trials from 2008-2016 the authors discuss the applicability of oxycodone/naloxone prolonged release in management of different pain syndromes in humans, in cancer patients, in neuropathic pain patients, in the elderly, in acute post-operative pain and other clinical indications for example restless leg syndrome. Presented data indicate comparable or in some cases even better analgesic efficacy of oxycodone with naloxone and lower risk of gastrointestinal side effects, especially constipation, when compared to other strong opioids. The introduction of oxycodone with naloxone significantly expands treatment options for chronic pain patients, likewise improving safety and thus the effectiveness of treatment with strong opioids.

scholarly journals GD04: A blinded, randomized controlled trial of opioid analgesics for the management of acute fracture pain in older adults discharged from the emergency department

CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S63-S64
Author(s):  
C. Varner ◽  
S. McLeod ◽  
A. Orkin ◽  
D. Melady ◽  
B. Borgundvaag
Keyword(s):  
Older Adults ◽  
Side Effects ◽  
Sample Size ◽  
Acute Pain ◽  
Older Patients ◽  
Controlled Trial ◽  
Opioid Analgesics ◽  
Brief Pain Inventory ◽  
Pain Scores ◽  
Increased Risk

Background: Emergency department (ED) providers are frequently challenged with how best to treat acute pain in older patients, specifically when non-opioid analgesics are ineffective or contraindicated. Studies have documented older patients presenting to the ED with painful conditions are less likely to receive pain medications than younger patients, and this oligoanalgesia has been associated with increased risk of delirium and longer hospital stays. Given the concerns for drug interactions, side effects, over-sedation and addiction, emergency physicians often report uncertainty regarding the ideal choice of opioid analgesic in older adults. There are no guidelines informing best practice for the management of acute pain in this population. Objective: The primary objective is to compare the efficacy of codeine, oxycodone and hydromorphone for acute fracture pain in older patients discharged from the ED. Methods: This will be a blinded, randomized controlled trial of older adults (age>70) discharged home from the ED with acute pain secondary to an upper extremity, lower extremity, rib, pelvic or vertebral compression fracture. Patients will be randomized to receive a 3-day supply of codeine, oxycodone or hydromorphone. Patients will also be given acetaminophen. Patients will be contacted by phone or email 3 days following their ED visit. The primary outcome will be differences in pain scores at 3 days assessed using the validated Brief Pain Inventory (Short Form). Secondary outcomes will include side effects (ie: confusion, constipation), adverse events (ie: falls, healthcare visits) and pain interference with daily activity. Patients, physicians and all research staff will be blinded to group allocation. Data Analysis Plan: The study design assumed three arms (codeine, oxycodone and hydromorphone), therefore the 2-tailed alpha will be set to 0.025 to adjust for the increased risk of type-I error with 3 pairwise comparisons. To test for pairwise equality between groups, a 1-way ANOVA will be employed. Proportional differences will be assessed using Pearson chi-square statistic. Sample size calculation: Assuming a mean (SD) change in pain scores between groups of 2.2 (3.0), a minimum clinically important difference on the Brief Pain Inventory of 2.0, a 2-tailed alpha of 0.025 to adjust for 3 pairwise comparisons and a beta of 0.20, we estimate that 47 patients per group (N=141) will be required. To account for potential loss to follow-up, we will increase our sample size by 25% per group, resulting in a final sample size of 177 patients (59 per group). Importance: All analgesics (including opioids) prescribed to older adults are associated with risk of adverse events. This study seeks to inform ED providers of opioid efficacy, side effects and patient-important, functional outcomes in this growing patient population.

scholarly journals Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review

2015 ◽  
Vol 18;4 (4;18) ◽  
pp. 395-400
Author(s):  
Alan David Kaye
Keyword(s):  
Side Effects ◽  
Drug Interactions ◽  
Serotonin Syndrome ◽  
Potential Side Effect ◽  
Serotonergic Activity ◽  
Potential Abuse ◽  
Life Threatening ◽  
The Central Nervous System ◽  
Physician Reviews ◽  
Serotonergic Drugs

Background: Serotonin syndrome is a mild to potentially life-threatening syndrome associated with excessive serotonergic activity within the central nervous system. Serotonin syndrome is associated with medication use, drug interactions, and overdose. While serotonin syndrome is often associated with the use of selective serotonin inhibitors (SSRI), an increasing number of reports are being presented involving the use of tramadol. Methods: This review article contains an overview of serotonin syndrome while specifically looking at tramadol’s pharmacology and risk factors for serotonin syndrome. With tramadol’s increasing popularity, the goal of this article is to make physicians more alert and aware of this potential side effect associated with tramadol. Conclusions: In conclusion, with the increasing incidence of serotonin syndrome, prescribing physicians should be aware of and educate their patients on the potential side effects of tramadol. It is important that the prescribing physician reviews patient medications for concurrent serotonergic drugs and monitors for potential abuse. Key words: Tramadol, serotonin syndrome, drug interactions, analgesics

scholarly journals Clinico-pharmacological characteristics of opioid drug-drug interactions in cancer patients with chronic pain syndrome

2019 ◽  
Vol 17 (6) ◽  
pp. 114-122
Author(s):  
O. P. Bobrova ◽  
N. A. Shnayder ◽  
S. K. Zyryanov ◽  
Yu. A. Dyhno ◽  
M. M. Petrova ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cancer Patients ◽  
Pain Treatment ◽  
Pain Syndrome ◽  
Opioid Analgesics ◽  
Individual Choice ◽  
Analgesic Therapy ◽  
Co Morbidity ◽  
The Impact

The aimof the review was to analyze published studies on the impact of opioid drug-drug interactions on the choice of analgesic therapy regimens.Material and methods.A systematic literature search was conducted using PubMed, Scopus, Web of Science, and E-library databases.Results.The review showed a clinical significance of pharmacokinetic interactions of opioids with other drugs in cancer pain treatment. The problems of individual choice of analgesics from different groups under conditions of co-morbidity and concomitant medication were discussed to ensure the effectiveness/safety of the treatment strategy affecting the quality of life of cancer patients.Conclusion.A comprehensive assessment of factors in patients receiving opioid analgesics is a predictor of effective and safe analgesic therapy.

scholarly journals Management of pain treatment in the early postoperative period. Practice of using ketorolac. A clinical case

Pain medicine ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. 18-26
Author(s):  
Dmytro Dmytriiev ◽  
A Andriiets ◽  
E Andriiets ◽  
V Bankivsky ◽  
S Yatsenko
Keyword(s):  
Side Effects ◽  
Postoperative Period ◽  
Wound Repair ◽  
Pain Treatment ◽  
Opioid Analgesics ◽  
Early Postoperative Period ◽  
The Body ◽  
Perioperative Analgesia ◽  
Opioid Induced Hyperalgesia ◽  
Mechanisms Of Development

The current strategy of rational perioperative analgesia involves reducing the use of opioid analgesics and preventing associated side effects. Today it is known that the use of opioid analgesics can further lead to the development of hyperalgesia. Opioid-induced hyperalgesia is an adaptive response of the body in response to exogenous administration of opioids, the mechanisms of development of which are associated with the activation of the central glutamatergic system and the release of spinal dinorphins. In contrast, gabapentin, NSAIDs, and ketamine have opioid-preserving properties, reducing the number of opioid-associated side effects. Hyperalgesia is a condition that underlies the formation of chronic pain and develops regardless of the degree of postoperative wound repair. For the treatment of pain in the postoperative period, the main group of treatment agents are opioid analgesics, which are prescribed to 60% of patients. However, with severe pain, there is a need for opioids in doses that exceed the standard recommended. It is known that the tactics of increasing the dose of opioid analgesics leads to an increase in the frequency of adverse reactions: severe sedation, respiratory depression, nausea, vomiting, intestinal paresis, dysfunction of the biliary and urinary systems, hallucinations. In order to reduce side effects, the doctor reduces the dose of opioids, which is accompanied by inadequate analgesia. Given the above, clinicians prescribe additional drugs of other drug groups that can enhance the analgesic effect of opioids. An important aspect is the ability to reduce the dose of opioids. Our data and data of other authors. Until recently, NSAIDs were rarely used in intensive care units, mainly in mild to moderate pain.

scholarly journals Use of a Consultation Service Following Pharmacogenomic Testing in Psychiatry

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 179-180
Author(s):  
Daniel Dowd ◽  
David S. Krause
Keyword(s):  
Mental Illness ◽  
Drug Interactions ◽  
Metabolic Pathways ◽  
Patient Characteristics ◽  
Healthcare Resource Utilization ◽  
Machine Learning Algorithms ◽  
Mental Illnesses ◽  
Variable Response ◽  
Drug Induced ◽  
Commercial Laboratory

AbstractBackgroundThere is a plethora of drugs available to psychiatrists for treatment of mental illness, which can vary in efficacy, tolerability, metabolic pathways and drug-drug interactions. Psychotropics are the second most commonly listed therapeutic class mentioned in the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling. Pharmacogenomic (PGx) assays are increasingly used in psychiatry to help select safe and appropriate medication for a variety of mental illnesses. Our commercial laboratory offers PGx expert consultations by PharmDs and PhDs to clinician-users. Our database contains valuable information regarding the treatment of a diverse and challenging population.MethodsGenomind offers a PGx assay currently measuring variants of 24 genes relevant for selection of drugs with a mental illness indication. Since 2012 we have analyzed > 250,000 DNA samples. Between 10/18 - 8/20 6,401 reports received a consult. The data contained herein are derived from those consults. Consultants record information on prior meds, reason for failure or intolerability, potential risk-associated or useful drugs based on the genetic variants. Consultants only recommend specific drugs and doses consistent with a published PGx guideline.ResultsThe 5 most commonly discussed genes were SLC6A4, MTHFR, CACNA1C, COMT and BDNF. The 3 most commonly discussed drugs were fluoxetine, lithium and duloxetine. The most common reasons for drug failure were inefficacy and drug induced “agitation, irritability and/or anxiety”. SSRIs were the most common class of discontinued drug; sertraline, escitalopram and fluoxetine were the three most commonly reported discontinuations and were also the 3 most likely to be associated with “no improvement”. Aripiprazole was the most commonly reported discontinued atypical antipsychotic. The providers rated 94% of consultations as extremely or very helpful at the time of consult. An independent validation survey of 128 providers confirmed these ratings, with 96% reporting a rating of “very helpful” or “extremely helpful”. In addition, 94% reported that these consults were superior to PGx consults provided through other laboratories. Patient characteristics captured during consults via a Clinical Global Impressions-Severity (CGI-S) scale revealed that the majority of patients were moderately (54%) or markedly ill (23%). The most frequent symptoms reported were depression, anxiety, insomnia and inattentiveness.DiscussionThe large variety of psychotropic drugs available to providers, and their highly variable response rates, tolerability, capacity for drug-drug interactions and metabolic pathways present a challenge for even expert psychopharmacologists. Consultation with experts in PGx provides additional useful information that may improve outcomes and decrease healthcare resource utilization. This database may provide future opportunities for machine learning algorithms to further inform implications of included gene variants.FundingGenomind, Inc.

The burden of polypharmacy and drug–drug interactions in older cancer patients treated with immunotherapy

2021 ◽  
pp. 107815522110120
Author(s):  
Deniz C Guven ◽  
Gozde Kavgaci ◽  
Oktay H Aktepe ◽  
Hasan C Yildirim ◽  
Taha K Sahin ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cancer Patients ◽  
Injury Risk ◽  
Checkpoint Inhibitors ◽  
High Rate ◽  
Potentially Inappropriate Medications ◽  
Inappropriate Prescription ◽  
Prescription Practices ◽  
Increased Risk ◽  
Older Cancer Patients

Introduction Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. Methods A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. Results The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). Conclusion In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

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