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JPMA. the Journal of the Pakistan... Nov 2022To observe the effect of a single dose of tramadol 1mg/kg on haemodynamic changes related to extubation, and to assess the quality of emergence as judged by incidence of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To observe the effect of a single dose of tramadol 1mg/kg on haemodynamic changes related to extubation, and to assess the quality of emergence as judged by incidence of cough, laryngospasm and bronchospasm.
METHODS
The double-blind randomised controlled trial was conducted at the Department of Anaesthesiology, Aga Khan University Hospital, Karachi, from 2016 to 2017, and comprised patients of either gender aged 18-65 years scheduled for elective supratentorial craniotomy under general anaesthesia. The patients were randomised to two Tramadol and Saline groups. The drug was given 45 minutes before extubation at the time of dura closure. The patients were extubated after resumption of adequate spontaneous breathing. Invasive blood pressure and heart rate were recorded one minute before reversal, at 1 minute interval for five minutes and then every 10 minute for 30 minutes after extubation. Cough, laryngospasm and bronchospasm were noted. Pain, post-operative nausea, vomiting, convulsions and conscious levels were also noted till 6 hours post-operatively. Data was analysed using SPSS 19.
RESULTS
Of the 80 patients enrolled, 79(98.75%) completed the study. Of them, 38(48%) were in the Tramadol group; 27(71.1%) males and 11(28.9%) females with a mean age of 43.42±13.2 years. The remaining 41(52%) patients were in the Saline group; 28(68.3%) males and 13(31.7%) females with a mean age of 45.9±15.9 years. Intergroup comparison showed no significant difference in the extubation response (p>0.05), but the changes in blood pressure and heart rate were shorter in magnitude and duration in the Tramadol group compared to the baseline. Significant rise in blood pressure and heart rate were observed in the Saline group at 5 minutes after extubation (p=0.046). There was no difference in the quality of emergence as judged by cough or secondary complications (p>0.05).
CONCLUSIONS
Tramadol 1mg/kg was considered superior in attenuating the duration and magnitude of haemodynamic response in the shape of hypertension and tachycardia during extubation, but did not affect other parameters in patients undergoing craniotomy.
CLINICAL TRIAL NUMBER
Clinical Trials.gov PRS: NCT02964416, https://clinicaltrials.gov/ct2/show/NCT02964416.
Topics: Male; Female; Humans; Adult; Middle Aged; Tramadol; Airway Extubation; Cough; Bronchial Spasm; Laryngismus; Double-Blind Method
PubMed: 37013278
DOI: 10.47391/JPMA.4082 -
The Cochrane Database of Systematic... Jun 2017This review is an update of a review of tramadol for neuropathic pain, published in 2006; updating was to bring the review in line with current standards. Neuropathic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of a review of tramadol for neuropathic pain, published in 2006; updating was to bring the review in line with current standards. Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Peripheral neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the peripheral nervous system.
OBJECTIVES
To assess the analgesic efficacy of tramadol compared with placebo or other active interventions for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing tramadol (any route of administration) with placebo or another active treatment for neuropathic pain, with subjective pain assessment by the participant.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH), using standard methods. We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.
MAIN RESULTS
We identified six randomised, double-blind studies involving 438 participants with suitably characterised neuropathic pain. In each, tramadol was started at a dose of about 100 mg daily and increased over one to two weeks to a maximum of 400 mg daily or the maximum tolerated dose, and then maintained for the remainder of the study. Participants had experienced moderate or severe neuropathic pain for at least three months due to cancer, cancer treatment, postherpetic neuralgia, peripheral diabetic neuropathy, spinal cord injury, or polyneuropathy. The mean age was 50 to 67 years with approximately equal numbers of men and women. Exclusions were typically people with other significant comorbidity or pain from other causes. Study duration for treatments was four to six weeks, and two studies had a cross-over design.Not all studies reported all the outcomes of interest, and there were limited data for pain outcomes. At least 50% pain intensity reduction was reported in three studies (265 participants, 110 events). Using a random-effects analysis, 70/132 (53%) had at least 50% pain relief with tramadol, and 40/133 (30%) with placebo; the risk ratio (RR) was 2.2 (95% confidence interval (CI) 1.02 to 4.6). The NNT calculated from these data was 4.4 (95% CI 2.9 to 8.8). We downgraded the evidence for this outcome by two levels to low quality because of the small size of studies and of the pooled data set, because there were only 110 actual events, the analysis included different types of neuropathic pain, the studies all had at least one high risk of potential bias, and because of the limited duration of the studies.Participants experienced more adverse events with tramadol than placebo. Report of any adverse event was higher with tramadol (58%) than placebo (34%) (4 studies, 266 participants, 123 events; RR 1.6 (95% CI 1.2 to 2.1); NNH 4.2 (95% CI 2.8 to 8.3)). Adverse event withdrawal was higher with tramadol (16%) than placebo (3%) (6 studies, 485 participants, 45 events; RR 4.1 (95% CI 2.0 to 8.4); NNH 8.2 (95% CI 5.8 to 14)). Only four serious adverse events were reported, without obvious attribution to treatment, and no deaths were reported. We downgraded the evidence for this outcome by two or three levels to low or very low quality because of small study size, because there were few actual events, and because of the limited duration of the studies.
AUTHORS' CONCLUSIONS
There is only modest information about the use of tramadol in neuropathic pain, coming from small, largely inadequate studies with potential risk of bias. That bias would normally increase the apparent benefits of tramadol. The evidence of benefit from tramadol was of low or very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood is very high that the effect will be substantially different from the estimate in this systematic review.
Topics: Adult; Aged; Analgesics, Opioid; Humans; Middle Aged; Neuralgia; Randomized Controlled Trials as Topic; Tramadol
PubMed: 28616956
DOI: 10.1002/14651858.CD003726.pub4 -
Journal of Clinical Pharmacology Jan 2022Tramadol is an opioid medication used to treat moderately severe pain. Cytochrome P450 (CYP) 2D6 inhibition could be important for tramadol, as it decreases the...
Physiologically Based Pharmacokinetic Modeling to Assess the Impact of CYP2D6-Mediated Drug-Drug Interactions on Tramadol and O-Desmethyltramadol Exposures via Allosteric and Competitive Inhibition.
Tramadol is an opioid medication used to treat moderately severe pain. Cytochrome P450 (CYP) 2D6 inhibition could be important for tramadol, as it decreases the formation of its pharmacologically active metabolite, O-desmethyltramadol, potentially resulting in increased opioid use and misuse. The objective of this study was to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol pharmacokinetics using quinidine and metoprolol as prototypical perpetrator drugs. A physiologically based pharmacokinetic model for tramadol and O-desmethyltramadol was developed and verified in PK-Sim version 8 and linked to respective models of quinidine and metoprolol to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol exposure. Our results show that there is a differentiated impact of CYP2D6 inhibitors on tramadol and O-desmethyltramadol based on their mechanisms of inhibition. Following allosteric inhibition by a single dose of quinidine, the exposure of both tramadol (51% increase) and O-desmethyltramadol (52% decrease) was predicted to be significantly altered after concomitant administration of a single dose of tramadol. Following multiple-dose administration of tramadol and a single-dose or multiple-dose administration of quinidine, the inhibitory effect of quinidine was predicted to be long (≈42 hours) and to alter exposure of tramadol and O-desmethyltramadol by up to 60%, suggesting that coadministration of quinidine and tramadol should be avoided clinically. In comparison, there is no predicted significant impact of metoprolol on tramadol and O-desmethyltramadol exposure. In fact, tramadol is predicted to act as a CYP2D6 perpetrator and increase metoprolol exposure, which may necessitate the need for dose separation.
Topics: Analgesics, Opioid; Area Under Curve; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Drug Interactions; Half-Life; Humans; Metabolic Clearance Rate; Metoprolol; Models, Biological; Quinidine; Tramadol
PubMed: 34383318
DOI: 10.1002/jcph.1951 -
Neuroscience Letters Feb 2023Tramadol is one of the most commonly prescribed analgesic opioids in various pharmacopeias. Tramadol has been linked to abuse in recent clinical investigations. However,...
Tramadol is one of the most commonly prescribed analgesic opioids in various pharmacopeias. Tramadol has been linked to abuse in recent clinical investigations. However, the behavioral effects and neural substrates of the drug have not been well characterized in preclinical studies. As a result, the present study investigated the effects of tramadol on behavioral sensitizations in rats. Its impacts on cellular and molecular alterations in the brain were also investigated. In conditioned place preference (CPP) paradigm, tramadol induced behavioral as well as motor sensitizations. These effects were dramatically reduced by intraperitoneal administration of naltrexone, an opioid receptor antagonist. Tramadol caused changes in several molecular markers (pERK1/2, Δ-FosB, PKCγ, PKMζ GAD67) in the anterior cingulate cortex, which could indicate an increase in excitation within this structure. Tramadol is demonstrated in the present study to be a reinforcing drug in rats, as it increased both behavioral and motor sensitizations. Tramadol's effects are most likely due to the high levels of excitation it causes in the brain, which is mostly caused by the activation of opioid receptors.
Topics: Rats; Animals; Tramadol; Analgesics, Opioid; Narcotic Antagonists; Naltrexone; Conditioning, Classical
PubMed: 36621588
DOI: 10.1016/j.neulet.2023.137053 -
European Review For Medical and... May 2019Chronic pancreatitis (CP) is a disease leading to irreversible pancreas dysfunction. One of the main symptoms is pain. Many patients require pharmacological therapy...
OBJECTIVE
Chronic pancreatitis (CP) is a disease leading to irreversible pancreas dysfunction. One of the main symptoms is pain. Many patients require pharmacological therapy which should be started with paracetamol or, in selected groups of patients, ketoprofen. If the effect of ketoprofen is irrelevant, patients receive tramadol. The aim of this study is the evaluation of ketoprofen and tramadol pharmacokinetics (PK) in CP patients.
PATIENTS AND METHODS
36 patients were divided into two groups: I - receiving ketoprofen (n=18; mean [SD] age, 48.61 [13.32] years; weight, 73.28 [20.48] kg), II - receiving tramadol (n=18; mean [SD] age, 46.78 [10.28] years; weight, 74.22 [14.04] kg, and BMI (Body Mass Index), 24.61 [4.51] kg/m2). The plasma concentrations of ketoprofen and tramadol with its active metabolite M1 (0-desmethyltramadol) were measured with the validated high-performance liquid chromatography method.
RESULTS
The main PK parameters for ketoprofen were as follows: Cmax (maximum plasma concentration), 3.41 [2.32] mg/L; AUC0-inf (area under the plasma concentration-time curve from time zero to infinity), 10.45 [5.57] mg⋅h/L; tmax (time to first occurrence of Cmax), 1.94 [1.25] h; Cl (clearance), 0.199 [0.165] L/kg·h, and Vd/kg (volume of distribution per kilogram of body weight), 0.71 [0.58] L/kg. The main PK parameters for TRM and M1 were as follows: Cmax, 226.4 [80.5] and 55.6 [23] ng/mL; AUC0-inf, 1903.3 [874.8] and 790.4 [512.4] ng⋅h/mL; tmax, 1.78 [0.73] and 2.67 [1.19] h, respectively.
CONCLUSIONS
Chronic pancreatitis led to a decrease in the total amount of absorbed ketoprofen. Consequently, the analgesic effect of the drug may be weaker. Cmax of tramadol for most CP patients was within the therapeutic range associated with its analgesic activity. M1/TRM ratios for Cmax and AUC were unchanged.
Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Ketoprofen; Male; Middle Aged; Pancreatitis, Chronic; ROC Curve; Tramadol
PubMed: 31115034
DOI: 10.26355/eurrev_201905_17835 -
The Cochrane Database of Systematic... May 2017Tramadol is an opioid analgesic licensed for use in moderate to severe pain. It is considered as a low risk for abuse, so control regulations are not as stringent as for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tramadol is an opioid analgesic licensed for use in moderate to severe pain. It is considered as a low risk for abuse, so control regulations are not as stringent as for 'strong' opioids such as morphine. It has a potential role as a step 2 option of the World Health Organization (WHO) analgesic ladder.
OBJECTIVES
To assess the benefits and adverse effects of tramadol with or without paracetamol (acetaminophen) for cancer-related pain.
SEARCH METHODS
We searched the following databases using a wide range of search terms: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched three clinical trials registry databases. The date of the last search was 2 November 2016.
SELECTION CRITERIA
We selected studies that were randomised, with placebo or active controls, or both, and included a minimum of 10 participants per treatment arm. We were interested particularly in blinded studies, but also included open studies.We excluded non-randomised studies, studies of experimental pain, case reports, and clinical observations.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standard form and checked for agreement before entry into Review Manager 5. We included information about the number of participants treated and demographic details, type of cancer, drug and dosing regimen, study design (placebo or active control) and methods, study duration and follow-up, analgesic outcome measures and results, withdrawals, and adverse events. We collated multiple reports of the same study, so that each study, rather than each report, was the unit of interest in the review. We assessed the evidence using GRADE and created a 'Summary of findings' table.The main outcomes of interest for benefit were pain reduction of 30% or greater and 50% or greater from baseline, participants with pain no worse than mild, and participants feeling much improved or very much improved.
MAIN RESULTS
We included 10 studies (12 reports) with 958 adult participants. All the studies enrolled participants with chronic malignant tumour-related pain who were experiencing pain intensities described as moderate to severe, with most experiencing at least 4/10 with current treatment. The mean ages were 59 to 70 years, with participants aged between 24 and 87 years. Study length ranged from one day to six months. Five studies used a cross-over design. Tramadol doses ranged from 50 mg as single dose to 600 mg per day; doses of 300 mg per day to 400 mg per day were most common.Nine studies were at high risk of bias for one to four criteria (only one high risk of bias for size). We judged all the results to be very low quality evidence because of widespread lack of blinding of outcome assessment, inadequately described sequence generation, allocation concealment, and small numbers of participants and events. Important outcomes were poorly reported. There were eight different active comparators and one comparison with placebo. There was little information available for any comparison and no firm conclusions could be drawn for any outcome.Single comparisons of oral tramadol with codeine plus paracetamol, of dihydrocodeine, and of rectal versus oral tramadol provided no data for key outcomes. One study used tramadol combined with paracetamol; four participants received this intervention. One study compared tramadol with flupirtine - a drug that is no longer available. One study compared tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen, but the dosing schedule poorly explained.Two studies (191 participants) compared tramadol with buprenorphine. One study (131 participants) reported a similar proportion of no or mild pain at 14 days.Three studies (300 participants) compared tramadol with morphine. Only one study, combining tramadol, tramadol plus paracetamol, and paracetamol plus codeine as a single weak-opioid group reported results. Weak opioid produced reduction in pain of at least 30% from baseline in 55/117 (47%) participants, compared with 91/110 (82%) participants with morphine. Weak opioid produced reduction in pain of at least 50% in 49/117 (42%) participants, compared with 83/110 (75%) participants with morphine.There was no useful information for any other outcome of benefit or harm.
AUTHORS' CONCLUSIONS
There is limited, very low quality, evidence from randomised controlled trials that tramadol produced pain relief in some adults with pain due to cancer and no evidence at all for children. There is very low quality evidence that it is not as effective as morphine. This review does not provide a reliable indication of the likely effect. The likelihood that the effect will be substantially different is very high. The place of tramadol in managing cancer pain and its role as step 2 of the WHO analgesic ladder is unclear.
Topics: Acetaminophen; Adult; Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Cancer Pain; Drug Therapy, Combination; Humans; Middle Aged; Randomized Controlled Trials as Topic; Tramadol; Young Adult
PubMed: 28510996
DOI: 10.1002/14651858.CD012508.pub2 -
Clinical Drug Investigation May 2022Knee osteoarthritis pain is a chronic form of pain for which conventional non-steroidal anti-inflammatory drugs may provide insufficient analgesia. Twice-daily tramadol... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Tramadol Hydrochloride Twice-Daily Sustained-Release Bilayer Tablets with an Immediate-Release Component for Chronic Pain Associated with Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled, Treatment-Withdrawal Study.
BACKGROUND AND OBJECTIVES
Knee osteoarthritis pain is a chronic form of pain for which conventional non-steroidal anti-inflammatory drugs may provide insufficient analgesia. Twice-daily tramadol hydrochloride (65% sustained-release/35% immediate-release) bilayer tablets are a novel formulation of tramadol developed for managing chronic pain. The objectives of this study were to examine the effectiveness and safety of this formulation in patients with chronic knee osteoarthritis pain.
METHODS
This was a multicenter, randomized, placebo-controlled, double-blind, parallel-group, treatment-withdrawal study. Patients with a reduction in Numeric Rating Scale (NRS) for pain of ≥2 points during a 1-3-week, open-label, tramadol dose-escalation period (100-300 mg/day) were randomized to continue tramadol or switched to placebo for 4 weeks (double-blind period). Patients with inadequate efficacy (increase in NRS ≥2 points/patient request) were withdrawn. Outcomes included the time to inadequate analgesic efficacy from randomization (primary endpoint), the cumulative retention rate, and safety.
RESULTS
Overall, 249 and 160 patients entered the dose-escalation and double-blind periods, respectively (tramadol 79; placebo 81). Kaplan-Meier analysis revealed superiority of tramadol (log-rank p = 0.042), and a hazard ratio of 0.50 (95% confidence interval [CI] 0.25-0.99). Documentation of an inadequate analgesic effect was less frequent in the tramadol group (15.4%, 95% CI 8.2-25.3% vs. 30.9%, 95% CI 21.1-42.1%). The cumulative retention rate was greater in the tramadol group (83.7% vs. 69.0%). Adverse events occurred in 80.6% (200/248) of patients in the open-label period, and in 38.5% (30/78) and 13.6% (11/81) of patients in the tramadol and placebo groups, respectively, in the double-blind period. Opioid-associated adverse events, such as nausea, vomiting, constipation, somnolence, and dizziness, were the most frequent events.
CONCLUSION
This study demonstrated the analgesic efficacy and safety of sustained-release tramadol tablets with an immediate-release component for chronic knee osteoarthritis pain.
TRIAL REGISTRATION
JapicCTI-132103 (Japan Pharmaceutical Information Center; registration date February 25, 2015).
Topics: Analgesics; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Double-Blind Method; Humans; Osteoarthritis, Knee; Tablets; Tramadol
PubMed: 35435639
DOI: 10.1007/s40261-022-01139-5 -
Basic & Clinical Pharmacology &... Mar 2021This study aimed to evaluate the influence of CYP2D6 activity and cachexia progression on the enantiomeric alteration of plasma tramadol and its demethylated metabolites...
Impact of CYP2D6 activity and cachexia progression on enantiomeric alteration of plasma tramadol and its demethylated metabolites and their relationships with central nervous system symptoms in head and neck cancer patients.
This study aimed to evaluate the influence of CYP2D6 activity and cachexia progression on the enantiomeric alteration of plasma tramadol and its demethylated metabolites in head and neck cancer patients. Fifty-three head and neck cancer patients receiving oral tramadol were enrolled. The plasma concentrations of tramadol, O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) enantiomers were determined. The CYP2D6 activity score (AS) and degree of cachexia progression were assessed according to genotype and the Glasgow Prognostic Score (GPS), respectively. The enantiomeric ratio of NDT was (+)-form dominant in all patients. CYP2D6 AS had negative correlations with the plasma concentrations of (+)-NDT and (-)-NDT. The plasma concentrations of (+)-tramadol and (+)-ODT were higher in patients with GPS 1 or 2 than in those with GPS 0. Lower metabolic ratios to NDT enantiomers were observed in patients with GPS 1 or 2. In patients with GPS 1 or 2, the plasma (-)-tramadol was associated with the incidence of central nervous system symptoms. In conclusion, CYP2D6 AS partially explained the contribution of CYP2D6 activity to plasma tramadol and its demethylated metabolite enantiomers. Additionally, cachexia progression elevated the plasma (+)-tramadol and (+)-ODT levels through the reduction of N-demethylation of (+)-tramadol.
Topics: Aged; Cachexia; Cancer Pain; Cytochrome P-450 CYP2D6; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Stereoisomerism; Tramadol
PubMed: 33131142
DOI: 10.1111/bcpt.13528 -
Journal of Analytical Toxicology Sep 2021Tramadol is an opioid used in the treatment of moderate to moderately severe pain. Tramadol's use during pregnancy is generally avoided and may cause some reversible...
Tramadol is an opioid used in the treatment of moderate to moderately severe pain. Tramadol's use during pregnancy is generally avoided and may cause some reversible withdrawal effects in neonates, and its use during lactation is not licensed by the manufacturer. A small clinical trial reported infants were exposed to <3% of a mother's tramadol dose through breast milk with no evidence of harmful effects. Presented is a case study of breast milk, neonatal urine, and neonatal oral fluid for the analysis of tramadol and its metabolites, along with the validation of a method for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol in breast milk. Tramadol and its metabolites were extracted by solid-phase extraction after saponification of breast milk to remove lipids. Samples were analyzed by ultra-pressure liquid chromatography-tandem mass spectrometry. To the author's knowledge, this is the first report of tramadol and its metabolites in neonatal oral fluid. The breast milk concentrations were 63, 22, and 76 ng/mL for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol, respectively, on day of life 12. On day of life 20, the breast milk concentrations were 1,254, 388, and 937 ng/mL for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol, respectively. Oral fluid concentrations were 1,011, 1,499, and 406 ng/mL for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol, respectively, on day of life 20. Oral fluid concentrations were similar to breast milk for tramadol, almost four times higher for O-desmethyltramadol, and less than half for N-desmethyltramadol. The absolute infant dose was calculated to be 10 μg/kg/day and 294 μg/kg/day for tramadol on day of life 12 and 20, respectively.
Topics: Analgesics, Opioid; Chromatography, Liquid; Female; Humans; Infant, Newborn; Milk, Human; Mothers; Pregnancy; Tramadol
PubMed: 34037761
DOI: 10.1093/jat/bkab055 -
Scientific Reports Sep 2021Tramadol is an opioid extensively used to treat moderate to severe pain; however, prolonged therapy is associated with several tissues damage. Chronic use of tramadol...
Tramadol is an opioid extensively used to treat moderate to severe pain; however, prolonged therapy is associated with several tissues damage. Chronic use of tramadol was linked to increased hospitalizations due to cardiovascular complications. Limited literature has described the effects of tramadol on the cardiovascular system, so we sought to investigate these actions and elucidate the underlying mechanisms. Mice received tramadol hydrochloride (40 mg/kg body weight) orally for 4 successive weeks. Oxidative stress, inflammation, and cardiac toxicity were assessed. In addition, eNOS expression was evaluated. Our results demonstrated marked histopathological alteration in heart and aortic tissues after exposure to tramadol. Tramadol upregulated the expression of oxidative stress and inflammatory markers in mice heart and aorta, whereas downregulated eNOS expression. Tramadol caused cardiac damage shown by the increase in LDH, Troponin I, and CK-MB activities in serum samples. Overall, these results highlight the risks of tramadol on the cardiovascular system.
Topics: Analgesics, Opioid; Animals; Cytokines; Down-Regulation; Endothelium, Vascular; Heart; Inflammation Mediators; Mice; Mice, Inbred C57BL; Myocarditis; Nitric Oxide Synthase Type III; Oxidative Stress; Tramadol; Up-Regulation
PubMed: 34548593
DOI: 10.1038/s41598-021-98206-2