Concomitant use of pre-emptive analgesia with local and general anesthesia in rat uterine pain surgical model.

Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and c-fos expression in the spinal cord of the uterine surgical pain model was evaluated. It was a lab-based experimental study in which 60 female Sprague-Dawley rats; eight to 10 weeks old, weighing 150-300 gm were used. The rats were divided into two main groups: (i) superficial pain group (SG) (with skin incision only), (ii) deep pain group (with skin and uterine incisions). Each group was further divided into three subgroups based on the type of preemptive analgesia administered i.e., "tramadol, buprenorphine, and saline subgroups." Pain behavior was evaluated using the "Rat Grimace Scale" (RGS) at 2, 4, 6, 9 and 24 h post-surgery. Additionally, c-fos immunohistochemistry was performed on sections from spinal dorsal horn (T12-L2), and its expression was evaluated using optical density and mean cell count 2 hours postoperatively. Significant reduction in the RGS was noted in both the superficial and deep pain groups within the tramadol and buprenorphine subgroups when compared to the saline subgroup (p ≤ .05). There was a significant decrease in c-fos expression both in terms of number of c-fos positive cells and the optical density across the superficial laminae and lamina X of the spinal dorsal horn in both SD and DG (p ≤ .05). In contrast, the saline group exhibited c-fos expression primarily in laminae I-II and III-IV for both superficial and deep pain groups and lamina X in the deep pain group only (p ≤ .05). Hence, a preemptive regimen results in significant suppression of both superficial and deep components of pain transmission. These findings provide compelling evidence of the analgesic efficacy of preemptive treatment in alleviating pain response associated with uterine surgery.

Older Adult-Onset of Inflammatory Bowel Diseases Is Associated With Higher Utilization of Analgesics: A Nationwide Cohort Study.

INTRODUCTION: Patients with inflammatory bowel diseases (IBD) commonly require analgesic medications to treat pain, which may be associated with complications. We examined trends of analgesic use according to age at IBD onset. METHODS: This nationwide cohort study included adults diagnosed with IBD between 1996 and 2021 in Denmark. Patients were stratified according to their age at IBD onset: 18-39 years (young adult), 40-59 years (adult), and older than 60 years (older adult). We examined the proportion of patients who received prescriptions for analgesic medications within 1 year after IBD diagnosis: strong opioids, tramadol, codeine, nonsteroidal anti-inflammatory drugs, and paracetamol. Multivariable logistic regression analysis was performed to examine the association between age at IBD onset and strong opioid prescriptions and the composite of strong opioid/tramadol/codeine prescriptions. RESULTS: We identified 54,216 adults with IBD. Among them, 25,184 (46.5%) were young adults, 16,106 (29.7%) were adults, and 12,926 (23.8%) were older adults at IBD onset. Older adults most commonly received analgesic prescriptions of every class. Between 1996 and 2021, strong opioid, tramadol, and codeine prescriptions were stable, while paracetamol prescriptions increased and nonsteroidal anti-inflammatory drug prescriptions decreased. After multivariable logistic regression analysis, older adults had higher adjusted odds of receiving strong opioid prescriptions (adjusted odds ratio 1.95, 95% confidence interval 1.77-2.15) and the composite of strong opioid/tramadol/codeine prescriptions (adjusted odds ratio 1.93, 95% confidence interval 1.81-2.06) within 1 year after IBD diagnosis compared with adults. DISCUSSION: In this nationwide cohort, older adults most commonly received analgesic prescriptions within 1 year after IBD diagnosis. Additional research is needed to examine the etiology and sequelae of increased analgesic prescribing to this demographic.

Effects of medication on dopamine transporter imaging using [123I]I-FP-CIT SPECT in routine practice.

PURPOSE: Dopamine transporter (DAT) imaging is used to support the diagnosis of neurodegenerative parkinsonian disorders. Specific medications have been reported to confound the interpretation of [123I]I-FP-CIT SPECT scans, but there is limited data. The aim of the current study is to identify potential medication effects on the interpretation of [123I]I-FP-CIT SPECT scans in routine practice. MATERIALS AND METHODS: Consecutive patients undergoing a [123I]I-FP-CIT SPECT/CT scan on a 360° CZT camera between September 2019 and December 2022 were included. An exhaustive review of patient medications (antidepressants, antipsychotics, anti-epileptics, anti-parkinsonians, benzodiazepines, lithium, opioids, and stimulants) was performed. Two experienced nuclear physicians, blinded to the medication reports, interpreted the [123I]I-FP-CIT SPECT scans visually and a semi-quantitative analysis was performed using a local normal database. RESULTS: The study included 305 patients (71.0 ± 10.4, 135 women) and 145 (47.5%) visually interpreted normal scans. In normal scans, the striatum/occiput radioligand uptake ratio was decreased by noradrenergic and specific serotonergic antidepressants (NASSAs) (n = 15, z-score of - 0.93) and opioid medication (tramadol, n = 6, z-score of - 0.85) and was associated with a younger age in the multivariate analysis. In the overall population, the striatum/occiput ratio was influenced by NASSAs and associated with consensual visual analysis, age, sex, and anti-parkinsonian medications related to the status of the disease. CONCLUSION: Our study confirms the potential impact of antidepressant (NASSA) and opioid (tramadol) medications on the semi-quantitative analysis of [123I]I-FP-CIT SPECT scans. However, when performing a visual analysis, only NASSAs significantly impacted the interpretation of [123I]I-FP-CIT SPECT scans.

Comprehensive overview of analytical and bioanalytical methodologies for the opioid analgesics - Tramadol and combinations.

Synthetic opioids like Tramadol are used to treat mild to moderate pain. Its ability to relieve pain is about a tenth that of morphine. Furthermore, Tramadol shares similar effects on serotonin and norepinephrine to several antidepressants known as serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine and duloxetine. The present review paper discusses the recent developments in analytical methods for identifying drugs in pharmaceutical preparations and toxicological materials, such as blood, saliva, urine, and hair. In recent years, a wide variety of analytical instruments, including capillary electrophoresis, NMR, UV-visible spectroscopy, HPTLC, HPLC, LC-MS, GC, GC-MS, and electrochemical sensors, have been used for drug identification in pharmaceutical preparations and toxicological samples. The primary quantification techniques currently employed for its quantification in various matrices are highlighted in this research.

Structural elucidation of tramadol, its derivatives, and metabolites using chemical derivatization and liquid chromatography-high-resolution tandem mass spectrometry.

RATIONALE: Tramadol (T) is a strong painkiller drug that belongs to the opioid analgesic group. Several accidental intoxication cases after oral administration of T have been reported in the past decade. Tramadol, its derivatives, and metabolites present information-limited mass spectra with one prominent peak representing the amine-containing residue; therefore, their structural determination based on both electron impact mass spectrometry (EI-MS) and ESI-MS/MS spectra could be misleading. METHODS: A novel analytical method for the structural elucidation of tramadol, its four homologs, and its two main phase I metabolites (N-desmethyltramadol and O-desmethyltramadol) was developed using chemical modification and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS) with Orbitrap technology. RESULTS: After chemical derivatization, each of the investigated T series exhibited informative mass spectra that enabled better exposition of their structures. The developed method was successfully implemented to explicitly identify the structures of tramadol and its N-desmethyltramadol metabolite in urine samples at low ng/mL levels. CONCLUSIONS: An efficient derivatization-aided strategy was developed for rapidly elucidating the structure of tramadol-like compounds. The method is intended to assist forensic chemists in better diagnosing T and its analogs and metabolites in clinical or forensic toxicology laboratories.

A novel tramadol-polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study.

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

Pharmacobezoar-Related Fatalities: A Case Report and a Review of the Literature.

ABSTRACT: Pharmacobezoars develop after an acute overdose or during routine drug administration. Here, the authors present a case of fatal multidrug overdose involving a 62-year-old woman. Her usual treatment included tramadol extended-release, citalopram, and mirtazapine. Furthermore, she self-medicated and misused her husband's medications. The autopsy revealed the presence of a voluminous medication bezoar in the stomach. No mechanical complication was noted. Toxicologic analyses were performed using gas chromatography with flame ionization detection, liquid chromatography with diode array detection, gas chromatography with mass spectrometry detection, and liquid chromatography coupled to tandem mass spectrometry. Tramadol (34,000 mcg/L), O-desmethyltramadol (2200 mcg/L), propranolol (6000 mcg/L), bromazepam (2500 mcg/L), zopiclone (1200 mcg/L), and citalopram (700 mcg/L) were identified in femoral blood at toxic concentrations. Interestingly, the femoral blood and vitreous humor concentration ratio was approximately 0.7. Furthermore, an English exhaustive literature search was performed using several different electronic databases without any limiting period to identify published pharmacobezoar-related fatalities. Seventeen publications were identified reporting a total of 19 cases. Decedents' mean age was 47.6 years [0.8-79] and a clear female predominance emerged. Several drugs were involved in pharmacobezoar formation. Death was attributed to drug toxicity in 13 cases, and to mechanical complications and/or sepsis in 4 cases. A mixed cause of death was reported in 2 cases. Although rare, pharmacobezoars remain potentially lethal and raise challenges in therapeutic management.

Combined antiallodynic effects of Neurotropin®-tramadol and Neurotropin®-mirogabalin in rats with L5-spinal nerve ligation.

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50-200 NU/kg, p.o.), tramadol (7.5-60 mg/kg, p.o.), and mirogabalin (3-30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100-400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30-100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100-400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10-100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin-tramadol or Neurotropin-mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

The impact of tightened prescribing restrictions for PBS-subsidised opioid medicines and the introduction of half-pack sizes, Australia, 2020-21: an interrupted time series analysis.

OBJECTIVES: To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half-pack size item codes for IR formulations. DESIGN, SETTING: Population-based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS-eligible residents and IQVIA national opioid medicine sales data (PBS-subsidised and private prescriptions), 28 May 2018 - 6 June 2021. MAIN OUTCOME MEASURES: Mean amount of PBS-subsidised opioid medicines dispensed per day and mean overall amount sold per day - each expressed as oral morphine equivalent milligrams (OME) - overall, by formulation type (IR, CR), and by specific formulation. RESULTS: During the twelve months following the PBS changes, daily PBS-subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, -106 146 to -56 984 OME) than the mean daily level for 2018-20, a decline of 3.8% after adjusting for the pre-intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS-subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half-pack sizes comprised 8.4% of PBS-subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. CONCLUSIONS: The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS-subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions.

Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol-induced nephrotoxicity.

Tramadol (TR), a commonly prescribed pain reliever for moderate to severe pain, has been associated with kidney damage. This study investigates TR-induced nephrotoxicity mechanisms, focusing on its effects on renal proximal tubular cells (PTCs). The study findings demonstrate that TR disrupts PTC bioenergetic processes, leading to oxidative stress and inflammation. Significant toxicity to PTCs was observed with estimated effective concentration 50 values of 9.8 and 11.5 µM based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. TR also interferes with the function of PTC transporters, including organic cation uptake transporter 1, organic cation transporter 2, P-glycoprotein, and multidrug resistance protein 2. Furthermore, bioenergetics assays showed that TR reduced the activities of mitochondrial complexes I and III, adenosine triphosphate production, mitochondrial membrane potential, and oxygen consumption rate while increasing lactate release. TR also increased the production of reactive oxygen species, lipid peroxidation thiobarbituric acid reactive substances end products, and the expression of the NRf2 gene while decreasing reduced glutathione (GSH-R) stores and catalase and superoxide dismutase antioxidant activities. Additionally, TR increased the production of inflammatory cytokines (TNF-α and IL-6) and their coding genes expression. Interestingly, the study found that antioxidants like GSH-R, inhibitors of IL-6 and TNF-α, and mitochondrial activating Co-Q10 could protect cells against TR-induced cytotoxicity. The study suggests that TR causes nephrotoxicity by disrupting bioenergetic processes, causing oxidative stress and inflammation, but antioxidants and agents targeting mitochondria may have protective and curative potential.

A case study on pharmaceutical residues and antimicrobial resistance genes in Costa Rican rivers: A possible route of contamination for feline and other species.

In this investigation, the presence of antibiotics and pharmaceuticals in Costa Rican surface waters, specifically in regions near feline habitats, was examined. The study revealed that 47% of the water samples contained detectable traces of at least one antibiotic. Ciprofloxacin and norfloxacin were the most frequently detected compounds, each with a detection rate of 27%. Other antibiotics, such as erythromycin, roxithromycin, and trimethoprim, were also found but at lower frequencies, around 14%. Notably, all antibiotic concentrations remained below 10 ng/L, with ciprofloxacin, norfloxacin, and erythromycin showing the highest concentrations. Furthermore, the investigation revealed the presence of non-antibiotic pharmaceutical residues in the water samples, typically at concentrations below 64 ng/L. Tramadol was the most frequently detected compound, present in 18% of the samples. The highest concentrations were observed for acetaminophen and tramadol, measuring 64 and 10 ng/L, respectively. Comparing these findings with studies conducted in treated wastewater and urban rivers, it became evident that the concentrations of antibiotics and pharmaceuticals were notably lower in this study. While previous research reported higher values, the limited number of studies conducted in protected areas raises concerns about the potential environmental impact on biodiversity. In summary, these results emphasize the importance of monitoring pharmaceutical residues and antimicrobial resistance genes ARGs in vulnerable ecosystems, especially those in close proximity to feline habitats in Costa Rica. Additionally, the study delved into the detection of (ARGs). All tested water samples were positive for at least one ARG, with the blaTEM gene being the most prevalent at 82%, followed by tetS at 64% and qnrB at 23%. Moreover, this research shed light on the complexity of evaluating ARGs in environmental samples, as their presence does not necessarily indicate their expression. It also highlighted the potential for co-selection and co-regulation of ARGs, showcasing the intricate behaviors of these genes in aquatic environments.

Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

Opioid analgesics prescribing trends 2010-2019 in Slovenia: National database study.

OBJECTIVE: Significant increases in global opioid use have been reported in recent decades. This study analyzed opioid utilization in outpatient care in Slovenia between 2010 and 2019. METHODS: This retrospective cross-sectional study performed a nationwide database analysis of all outpatient opioid analgesic prescriptions based on Slovenian health insurance claims data. Prevalence was defined as the number of recipients prescribed at least one opioid per 1000 inhabitants. Opioid consumption was presented as the total number of dispensed prescriptions per 1000 inhabitants and dispensed defined daily doses (DDD) per 1000 inhabitants for each year analyzed. RESULTS: The age-standardized prevalence of opioid recipients decreased by 21.5% during the study period. Total opioid consumption decreased both in the number of prescriptions (-9.2%) and DDD (-5.4%). Tramadol consumption decreased in terms of the number of prescriptions (-12.2%) and DDD (-2.7%), whereas prescriptions for strong opioids increased (10.2%) and DDDs decreased (-16.2%). The results suggest less intensive prescribing of strong opioids and more intensive prescribing for tramadol. The most frequently used strong opioids were fentanyl and oxycodone/naloxone. CONCLUSIONS: The prevalence of opioid recipients and opioid consumption is decreasing in Slovenia. Further research is needed to understand whether this finding reflects safe use or underuse of these important analgesics.

Nitric oxide and potassium channels but not opioid and cannabinoid receptors mediate tramadol-induced peripheral antinociception in rat model of paw pressure withdrawal.

Tramadol, an analgesic classified as an "atypical opioid", exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 µg/paw); AM251 (80 µg/paw) and AM630 (100 µg/paw) as the selective antagonists for types 1 and 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 µg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ, and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol's effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol's antinociception effect. Notably, glibenclamide blocked tramadol's antinociception in a dose-dependent manner. These findings suggest that tramadol's peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Risk Factors for Opioid Misuse, Abuse, and Dependence Among Pain Clinic Patients: A Cross-Sectional Study at King Khalid University Hospital during 2020.

BACKGROUND Physicians are faced with the risk of patients developing opioid use disorders (OUDs) when prescribing patients opioids for long periods of time. Therefore, it is highly recommended to continuously monitor and evaluate long-term non-cancer pain patients who are prescribed opioids. This study aims to estimate the prevalence of OUDs in 103 patients with active opioid prescriptions attending the Pain Clinic at King Khalid University Hospital. MATERIAL AND METHODS A cross-sectional study was conducted at King Khalid University Hospital's pain clinic from 2020 to 2022. A list of all patients attending the Pain Clinic with an opioid prescription was provided by the hospital. Through telephone interviews, consent was secured followed by the collection of demographic variables and prescription-related variables. Additionally, patients were asked to complete the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST 3.1) opioid questionnaire. RESULTS Most of the 103 patients were at moderate risk for abuse (91.3%), while a smaller percentage were at high risk (dependence) (5.8%) and low risk (misuse) (2.9%). Tramadol was the most-prescribed opioid (43.7%). Young age (<50) (Z=2.534; P=0.011), opioid use for more than 90 days (Z=2.788; P=0.005), and the prescription of tramadol (Z=4.124; P<0.001) were associated with higher risk of OCDs. CONCLUSIONS Younger patients, opioid use >90 days, and tramadol are associated with a higher risk of opioid misuse. However, further studies on a larger scale and in various settings are needed to provide evidence accurately reflecting the general population, as this study focused on the population of pain clinic attendees.

Relations Between Self-reported Prescription Hydrocodone, Oxycodone, and Tramadol Use and Unintentional Injuries Among Those With Spinal Cord Injury.

OBJECTIVE: To identify the relations of 3 frequently used prescription opioids (hydrocodone, oxycodone, tramadol) with unintentional injuries, including fall-related and non-fall-related injuries among adults with chronic, traumatic spinal cord injury (SCI). DESIGN: Cross-sectional cohort study. SETTING: Community setting; Southeastern United States. PARTICIPANTS: Adult participants (N=918) with chronic traumatic SCI were identified from a specialty hospital and state population-based registry and completed a self-report assessment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self-reported fall-related and non-fall-related unintentional injuries serious enough to receive medical care in a clinic, emergency room, or hospital within the previous 12 months. RESULTS: Just over 20% of participants reported ≥1 unintentional injury in the past year, with an average of 2.16 among those with ≥1. Overall, 9.6% reported fall-related injuries. Only hydrocodone was associated with any past-year unintentional injuries. Hydrocodone taken occasionally (no more than monthly) or regularly (weekly or daily) was related to 2.63 (95% confidence interval [CI], 1.52-4.56) or 2.03 (95% CI, 1.15-3.60) greater odds of having ≥1 unintentional injury in the past year, respectively. Hydrocodone taken occasionally was also associated with past-year non-fall-related injuries (OR, 2.20; 95% CI, 1.12-4.31). Each of the 3 opioids was significantly related to fall-related injuries. Taking hydrocodone occasionally was associated with 2.39 greater odds of fall-related injuries, and regular use was associated with 2.31 greater odds. Regular use of oxycodone was associated with 2.44 odds of a fall-related injury (95% CI, 1.20-4.98), and regular use of tramadol was associated with 2.59 greater odds of fall-related injury (95% CI, 1.13-5.90). CONCLUSIONS: Injury prevention efforts must consider the potential effect of opioid use, particularly hydrocodone. For preventing fall-related injuries, each of the 3 opioids must be considered.

Comparative safety of tramadol and other opioids following total hip and knee arthroplasty.

BACKGROUND: Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models. RESULTS: The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons. CONCLUSIONS: Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.

Adverse childhood experiences, individual-level risk and protective factors, and recent drug use in a community sample of Nigerian women.

Adverse childhood experiences (ACEs) are associated with a wide range of health problems and health-compromising behaviors, including drug use, but are understudied in sub-Saharan Africa. Further, some data suggest that some types of ACEs are more strongly associated with outcomes than others. We investigated associations between different types of ACEs and recent drug use among 2,011 women living in Katsina State, Nigeria. This community-based survey included questions on ACE exposure, modifiable individual-level risk and promotive factors, and past-year drug use. Tobacco, cannabis, and the nonmedical use of cough syrup with codeine and tramadol were the most frequently used drugs. Logistic regressions revealed that across most drugs, ACEs reflecting abuse, neglect, and household dysfunction, but not community violence, increased the likelihood of drug use, odds ratios (ORs) = 1.30-3.10. Ease of access to drugs, ORs = 1.33-2.98, and personal religiosity, ORs = 1.19-2.27, also enhanced the risk of drug use, and higher depressive affect was associated with codeine, OR = 1.27, and tramadol use, ORs = 2.42. Practicing religious rites, ORs = 0.38-0.70; disapproval of drug use, ORs = 0.36-0.57; and perceived harm from drug use, ORs = 0.54-0.71, reduced the likelihood of drug use. Efforts to prevent abuse, neglect, and household dysfunction; reduce access to drugs; treat depression; and increase disapproval and harm associated with drug use may reduce drug use in the context of ACE exposure.

Comparison of diclofenac with tramadol, tizanidine or placebo in the treatment of acute low back pain and sciatica: multi-center randomized controlled trial.

BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

Comparative Evaluation of the Local Anesthetic Action of Tramadol Hydrochloride With Adrenaline Versus Lidocaine Hydrochloride With Adrenaline for Maxillary Exodontia: A Randomized Control Trial.

BACKGROUND: Tramadol hydrochloride (T-HCl) has demonstrated to have a local anesthetic effect similar to lidocaine hydrochloride (L-HCl) when administered locally for minor oral surgical procedures. PURPOSE: Our study aimed to compare the anesthetic effect of T-HCl versus L-HCl in maxillary premolar extraction. STUDY DESIGN, SETTING AND SAMPLE: The study is a split-mouth, double-blind randomized clinical trial at the Faculty of Dental Sciences, Ramaiah University of Applied Sciences, Bengaluru, India. The study sample was composed of patients referred for maxillary bicuspid extraction. Patients were excluded from the sample if, allergic to the study drugs, pregnant or lactating females, and smokers. EXPOSURE VARIABLE: The variable is an anesthetic drug administered for local anesthesia and it is grouped into 2 categories, T-HCl and L-HCl. A supraperiosteal infiltration of T-HCl with adrenaline on one side and L-HCl with adrenaline on the contralateral side was injected. MAIN OUTCOME VARIABLE: The primary outcome variable was profound anesthesia of T-HCl, where the patient sensed the loss of sensation of touch, temperature, and pain. Secondary outcomes were onset and duration of anesthesia, intraoperative pain, postoperative analgesia, and adverse reactions, were recorded. ANALYSES: Inferential statistics, the χ2 Test, the Mann-Whitney Test, and the Wilcoxon signed-rank test were used to compare the parameters. The level of significance was set at ≤ 0.05. RESULTS: A total of 40 patients were included, and 80 teeth were extracted. Profound anesthesia was achieved in all the cases. The mean subjective duration of anesthesia in the T-HCl and L-HCl groups was 130.80 ± 20.01 minutes and 111.40 ± 14.87 minutes, respectively, with a P value of .001. The mean Visual Analogue Scale (VAS) score for pain during the procedure in the T-HCl and L-HCl groups was 0.60 ± 0.67 and 1.10 ± 0.71, respectively, with a P value of .002. The mean Visual Analogue Scale score for pain postoperatively in the T-HCl and L-HCl groups was 0.70 ± 0.72 and 1.40 ± 0.67, respectively, with a P value of .001. Six patients in T-HCl required postoperative analgesia when compared to 18 patients in L-HCl (P value < .003). CONCLUSIONS AND RELEVANCE: T-HCl provides similar anesthetic outcomes in the extraction of maxillary bicuspids as L-HCl.