Dose Of Tramadol Research Articles

Effects of Intravenous Lipid Emulsion on Tramadol-Induced Seizure; a Randomized Clinical Trial

Introduction:There are numerous studies on the efficacy of intralipid emulsion (ILE) in various xenobiotic toxicities. This study aimed to evaluate the potential role of ILE as an antidote in tramadol-induced seizure. Methods:A single-blind clinical trial was undertaken to establish the efficacy and safety of ILE in patients with acute tramadol intoxication, who referred to Booali Hospital in Qazvin. Patients were randomly assigned to 2 groups. The Control group received standard care while the intervention group received intralipid emulsion (ILE) 20% in addition to the standard care. The occurrence of in-hospital seizure was compared between the groups.Results:80 patients who abused tramadol and met the study criteria were randomly assigned to either the intervention (40 cases) or the control (40 cases) group. Seizure occurred in 44 (56%) patients before admission to the emergency department. There were not any statistical differences between the groups regarding sex distribution (p=0.513) and mean age (p=0.19), presenting vital signs (p < 0.05), laboratory findings (p < 0.05), and mean abused dose of tramadol (p = 0.472) as well as occurrence of prehospital seizure (p = 0.7). In-hospital seizure occurred in 15 (18.75%) cases (all in the control group; p < 0.001). The mean duration of admission was 2.01 ± 1.13 days in the control group and 2.15 ± 1.04 days in the intervention group (p = 0.6). The number needed to treat for ILE to prevent tramadol-induced seizure was 2.7 (37.5% absolute risk reduction).Conclusions:The findings of this study supported ILE administration, as an adjunct to standard antidote protocols, in tramadol intoxication to prevent tramadol-induced seizures.

Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats.

Tramadol and tapentadol, two structurally related synthetic opioid analgesics, are widely prescribed due to the enhanced therapeutic profiles resulting from the synergistic combination between μ-opioid receptor (MOR) activation and monoamine reuptake inhibition. However, the number of adverse reactions has been growing along with their increasing use and misuse. The potential toxicological mechanisms for these drugs are not completely understood, especially for tapentadol, owing to its shorter market history. Therefore, in the present study, we aimed to comparatively assess the putative lung, cardiac, and brain cortex toxicological damage elicited by the repeated exposure to therapeutic doses of both prescription opioids. To this purpose, male Wistar rats were intraperitoneally injected with single daily doses of 10, 25, and 50 mg/kg tramadol or tapentadol, corresponding to a standard analgesic dose, an intermediate dose, and the maximum recommended daily dose, respectively, for 14 consecutive days. Such treatment was found to lead mainly to lipid peroxidation and inflammation in lung and brain cortex tissues, as shown through augmented thiobarbituric acid reactive substances (TBARS), as well as to increased serum inflammation biomarkers, such as C reactive protein (CRP) and tumor necrosis factor-α (TNF-α). Cardiomyocyte integrity was also shown to be affected, since both opioids incremented serum lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) activities, while tapentadol was associated with increased serum creatine kinase muscle brain (CK-MB) isoform activity. In turn, the analysis of metabolic parameters in brain cortex tissue revealed increased lactate concentration upon exposure to both drugs, as well as augmented LDH and creatine kinase (CK) activities following tapentadol treatment. In addition, pneumo- and cardiotoxicity biomarkers were quantified at the gene level, while neurotoxicity biomarkers were quantified both at the gene and protein levels; changes in their expression correlate with the oxidative stress, inflammatory, metabolic, and histopathological changes that were detected. Hematoxylin and eosin (H & E) staining revealed several histopathological alterations, including alveolar collapse and destruction in lung sections, inflammatory infiltrates, altered cardiomyocytes and loss of striation in heart sections, degenerated neurons, and accumulation of glial and microglial cells in brain cortex sections. In turn, Masson’s trichrome staining confirmed fibrous tissue deposition in cardiac tissue. Taken as a whole, these results show that the repeated administration of both prescription opioids extends the dose range for which toxicological injury is observed to lower therapeutic doses. They also reinforce previous assumptions that tramadol and tapentadol are not devoid of toxicological risk even at clinical doses.

Physiologically based pharmacokinetic modeling of tramadol to inform dose adjustment and drug-drug interactions according to CYP2D6 phenotypes.

The objective of this study was to establish physiologically based pharmacokinetic (PBPK) models of tramadol and its active metabolite O-desmethyltramadol (M1) and to explore the influence of CYP2D6 gene polymorphism on the pharmacokinetics of tramadol and M1. Furthermore, we used PBPK modeling to prospectively predict the extent of drug-drug interactions (DDIs) in the presence of genetic polymorphisms when tramadol was co-administered with the CYP2D6 inhibitors duloxetine and paroxetine. Plasma concentrations of tramadol and M1 were used to adjust the turnover frequency (Kcat ) of CYP2D6 for phenotype populations with different CYP2D6 genotypes. PBPK models were developed to capture the pharmacokinetics between CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), poor metabolizers (PMs), and ultra-rapid metabolizers (UMs). The validated models were then used to support dose adjustment in different CYP2D6 phenotypes and to predict the extent of CYP2D6-mediated DDIs when tramadol was co-administered with paroxetine or duloxetine. The PBPK models we built accurately describe tramadol and M1 exposure in the population with different CYP2D6 phenotypes. In our prediction, the area under the concentration-time curve (AUCinf-tDlast ) of M1 is 70% lower in PMs than in EMs, 27% lower in IMs, and 15% higher in UMs. Based on the models we built, we suggest that the oral dose of tramadol should be 50% higher for IMs and 25% lower for UMs to achieve an approximately equivalent plasma exposure of M1 as in EMs. When tramadol was co-administered with paroxetine or duloxetine, the magnitude of the inhibitor-substrate interaction was lowest in EMs (0.45), secondary in IMs (0.39), and highest in PMs (0.18) in terms of M1. The current example uses the PBPK model to guide dose adjustment of tramadol and to predict the effect of CYP2D6 genetic polymorphisms on DDIs for rational clinical use of tramadol in the future.

Tumescent local anesthesia as an alternative to general anesthesia in release of post-burn neck contracture and skin graft harvesting: A comparative study

Background: Anesthetic management of severe post burn neck contracture is difficult, demanding due to fixed flexion deformity of neck, incomplete oral occlusion and insufficient mouth opening leading to difficulty in intubation. Patients undergoing contracture release, skin graft harvest under general anesthesia (GA) were compared with patients undergoing the same surgery under tumescent local anesthesia (TLA) technique.&#x0D; Methodology: Twenty-one patients with post burn neck contracture undergoing contracture release with split skin grafting under GA were compared with twenty-one patients undergoing the same surgery under TLA. Post-operative pain and satisfaction were assessed using 10 cm VAS (Visual Analogue Scale).&#x0D; Results: Demographic profile was comparable in both groups. Changes in intra-operative vital parameters remained insignificant. The average volume of tumescent solution used was 254.76 + 49.05ml. Blood loss was significantly decreased, postoperative pain relief was more than sixteen hours in thirteen patients and extended beyond twenty-four hours in six patients in the TLA group. Time for the first rescue analgesia was significantly lesser in the GA group and the average dose of injection tramadol used in the GA group was significantly higher within the first 24 h. Overall satisfaction in the TLA group was significantly higher than in the GA group.&#x0D; Conclusion: TLA can be used as sole technique for release of post burn neck contracture and harvest of split skin grafts with less blood loss and significantly better postoperative pain relief avoiding complications of general anesthesia.&#x0D; Key words: Tumescent local anesthesia; Post burn neck contracture; Skin graft harvest; General anesthesia&#x0D; Citation: Prasad MK, Jain P, Varshney RK, Khare A, Jheetay GS. Tumescent local anesthesia as an alternative to general anesthesia in the release of post-burn neck contracture and skin graft harvesting: A comparative study. Anaesth. Pain intensive care 2021;25(1):34–39.&#x0D; DOI: 10.35975/apic.v25i1.1434&#x0D; Received: 18 February 2020, Reviewed: 16 March 2020, Accepted: 30 April 2020

Chronic and Acute Effect of Tramadol Intoxication on Some Immunological Parameters

Tramadol intoxication is rapidly on the increase in Nigeria with unestablished short-term and long-term effects. The study was aimed at elucidating the dose-dependent effect of acute or chronic tramadol intoxication on some immunological parameters using male rats (Rattus norvegicus). A total of fifty adult rats were used for the study as indicated by Mead's Resource Equation. The study consisted of acute and chronic categories of fifty adult rats randomly pair-divided into groups of six rats each. The acute phase consisted of a control group of 6 rats administered with normal saline solution and a treatment group of 6 rats administered with lethal dose of tramadol. The chronic phase comprised of control group of 6 rats and 3 tramadol-dependent groups of 6 rats each administered orally with 50, 100 and 200 mg/kg of tramadol for a period of 90 days respectively. Student t-test, one-way Anova and Pearson correlations were the statistical tools used for the data analysis employing JMP statistical discovery™ software version 14.1. Blood samples were collected by cardiac puncture for immunological examination using World Health Organization (WHO) approved methods. The study revealed that concentrations IgG, IgM and CD4 were significantly elevated (p>0.05) in the acute treatment group compared with the controls. However, the chronic phase of the study showed a progressive significant increase (p>0.05) in CD4 count. Conclusively, the study has demonstrated that tramadol intoxication has the preponderances of altering the immune apparatuses of the body.

Comparative effects of dexmedetomidine and fentanyl as adjuvants to hyperbaric bupivacaine in elective caesarean sections: an observational study at tertiary care centre

Aim: The aim of the present study to compare the effects of Dexmedetomidine and fentanyl as adjuvants to hyperbaric bupivacaine in elective ceasearen sections. Methods: This prospective study was done in the Department of anaesthesiology, LD hospital an associated hospital of GMC, Srinagar, India from December 2019 to November 2020. The participants included 130 parturient with gestational age ≥37 weeks and ASA I and II candidates for elective caesarean section under spinal anesthesia were included in this study. All 130 patients were randomly and equally divided into the following two groups: Group B-D received 10 mg hyperbaric bupivacaine 0.5%+10 μg dexmedetomidine. Group B-F received 10 mg hyperbaric bupivacaine 0.5%+25 μg fentanyl. Hemodynamic monitoring including SBP and DBP, mean arterial pressure (MAP), heart rate (HR) and peripheral oxygen saturation level (SpO2) were recorded. Patient’s pain score was assessed using visual analogue scale (VAS); scored from 0–10 (where 0=no pain and 10=the worst pain imaginable) during the recovery room (T0) and at one, three, and six hours (T1, T3, and T6) in the postoperative period. If the VAS score was more than 3, a rescue dose of tramadol (100 mg) was administered intravenously. Results: The mean dose of mephentermine in the B-D and B-F groups were 5.45±6.74 and 6.79±5.69mg, respectively. The Mann–Whitney test showed that there was no significant difference between the two groups (P=0.78). With respect to the bradycardia, the mean dose of atropine in the B-D and B-F groups were 0.12±0.28 and 0.06±0.15 mg, respectively. According to the Mann–Whitney test, in this regard, no significant difference was seen between the two groups. (P=0.32). The results of the Mann–Whitney U-test indicated that the onset of block in the B-D group (97.88±32.78 seconds) was significantly faster than in the B-F group (112.03±36.68 seconds) (P=0.041). Considering the level of sensory block, T4 level was shown in 81 (62.31%) patients, from whom 47 (58.02%) and 34 (41.98%) patients were in the B-D and B-F groups, respectively. Moreover, T6 level was observed in 49 (37.69%) patients, from whom 19 (38.78%) and 30 (61.22%) patients were in the B-D and B-F groups, respectively. Chi-squared test revealed that there was no statistically significant difference between the two groups (P=0.13). Conclusion: Compared with fentanyl, it seems that adding 10μg dexmedetomidine to bupivacaine has a better effect on postoperative pain management in cesarean section under spinal anesthesia.

Abuse and misuse of tramadol among the youth in hodan district mogadishu somalia

Objectives: Tramadol is a synthetic (man-made) pain reliever (analgesic). Researchers and doctors do not know the exact mechanism of action of tramadol, but it is similar to morphine. The objective of the study was is to assess the knowledge and contact traces of tramadol in Hodan district Mogadishu Somalia. A descriptive cross-sectional survey was adopted using structured questionnaire as the major instrument for the collection of data- this was both closed and open-ended. Methodology: A sample size of 130 respondents was used through the use of simple random sampling technique. Quantitative data analysis methods were used with the aid of Statistical Package for Social Sciences (SPSS) version 21.0 in the analysis of the data. Results: The study found that majority (70%) of respondents knew about tramadol of which more happened to be males. The study found that participants take higher doses of tramadol. The study found that preponderance (58.5%) of respondents knew people who use tramadol of which majority were their friends and co-workers. It also turned out that (83.1%) of the respondents knew where tramadol is readily available. Conclusions: In determining the main purpose of tramadol as energy booster, (30%) attested sexual ecstasy and performance. In conclusion, the availability of tramadol in our Somali community should be highly regulated since its abuse among the youth is on the ascendency. It is a real issue that should be tackled with concerted effort to curtail this menace most especially in the Hodan district.

Effect of Opioids on All-cause Mortality and Opioid Addiction in Total Hip Arthroplasty: a Korea Nationwide Cohort Study.

BackgroundThe purpose of this study was to investigate the use of opioids before and after total hip arthroplasty (THA), to find out the effect of opioid use on mortality in patients with THA, and to analyze whether preoperative opioid use is a risk factor for sustained opioid use after surgery using Korean nationwide cohort data.MethodsThis retrospective nationwide study identified subjects from the Korean National Health Insurance Service-Sample cohort (NHIS-Sample) compiled by the Korean NHIS. The index date (time zero) was defined as 90 days after an admission to a hospital to fulfill the eligibility criteria of the THA.ResultsIn the comparison of death risk according to current use and the defined daily dose of tramadol and strong opioids in each patient group according to past opioid use, there were no statistically significant differences in the adjusted hazard ratio for death compared to the current non-users in all groups (P > 0.05). Past tramadol and strong opioid use in current users increased the risk of the sustained use of tramadol and strong opioids 1.45-fold (adjusted rate ratio [aRR]; 95% confidence interval [CI], 1.12–1.87; P = 0.004) and 1.65-fold (aRR; 95% CI, 1.43–1.91; P < 0.001), respectively, compared to past non-users.ConclusionIn THA patients, the use of opioids within 6 months before surgery and within 3 months after surgery does not affect postoperative mortality, but a past-use history of opioid is a risk factor for sustained opioid use. Even after THA, the use of strong opioids is observed to increase compared to before surgery.

Effectiveness of tramadol compared to lignocaine as local anesthesia in the extraction of firm teeth: a randomized controlled trial.

BackgroundThe aim of this study was to compare the local anesthetic effect of tramadol with that of lignocaine in the extraction of immobile (grade 0) maxillary first molars.MethodsThis was a randomized, double-blind, equally balanced, controlled trial conducted on a sample population of 116 patients. The patients were randomly divided into two groups: group A (control) and group B (study). Group A and group B participants received 1.8 ml of 2% lignocaine without adrenaline and 1.8 ml of 5% tramadol, respectively through the supra-periosteal infiltration technique before extraction. Intraoperative pain was recorded on the Visual Analog Scale (VAS) and was evaluated using two unpaired t-tests.ResultsIntraoperative pain was evaluated in both the control and study groups. In the control group, the mean VAS score was 0.71 ± 0.81, while in the study group, the mean intraoperative VAS score was 1.21 ± 0.86, with the difference between the two mean values being statistically significant (P = 0.001).ConclusionTramadol has a less potent local anesthetic effect than lignocaine. As a higher dose of tramadol is required to obtain the desired anesthetic effect, it should be used as a supplement to lignocaine in extensive surgical procedures. It can also be used in patients allergic to lignocaine.

Comparison of Tramadol with Combination of Tramadol and Ketorolac for Post Cesarean Section Analgesia

Introduction: Effective post-operative analgesia is mandatory following cesarean section (CS), as parturients need to recover quickly to breast feed and provide care for their newborns. Till date no single drug has been able to achieve this goal. Multimodal analgesia with opioids and non-steroidal anti-inflammatory drugs (NSAID) combination has shown promising results. Aims: To compare the analgesic efficacy, patient satisfaction and maternal adverse effects, between intravenous (IV) tramadol and multimodal analgesia with IV tramadol and IV ketorolac combination for post cesarean section analgesia. Methods: This is a prospective, randomized and single-blinded comparative study, conducted in 60 parturients who underwent Lower Segment Cesarian Section. They were divided into two groups: Group 1 (IV Tramadol 50 mg given 8 hourly) and Group 2 (IV Tramadol 50 mg + IV Ketorolac 30 mg given 8 hourly). IV Promethazine was given with each dose of tramadol in both groups. Results: The (Visual analogue scale) VAS scores were significantly low in IV tramadol + IV ketrolac group than with IV tramadol alone group at 2 hours and 12 hours with p value of 0.003 and 0.08 respectively. Rescue analgesia was significantly reduced in group 2 (p value 0.005). Patient satisfaction was good in group 2 and fair in group 1(p value 0.002). No maternal side effects were found. Conclusion: IV tramadol and IV ketorolac combination used for post cesarean section analgesia significantly decreases post-operative pain, need of rescue analgesia and significantly increases patient satisfaction in comparison to IV tramadol alone.

Pre-emptive analgesia VS Prophylactic analgesia and its influence on postoperative pain in postoperative laparoscopic cholecystectomy patients

Introduction: There are no studies on the use of dexketoprofen for postoperative pain control in patients undergoing laparoscopic cholecystectomy. Purpose: To assess if the timing of dexketoprofen administration influences the intensity of postoperative pain in patients undergoing laparoscopic cholecystectomy. Materials and methods used: Experimental, longitudinal, double-blind, randomized study. 50 mg of dexketoprofen diluted in 50 ml of 0.9% saline was administered to 50 patients divided into two groups: Pre-operative group: the substance was administered one hour before the beginning of surgery. Trans-operative group: the substance was administered at the moment when the gallbladder was separated from the liver base. The Numerical Pain Scale was evaluated and the number of doses and the total dose of tramadol that the patients received as analgesic rescue was quantified. Results: Administration of dexketoprofen before starting laparoscopic cholecystectomy tends to reduce the intensity of postoperative pain without being statistically significant. Conclusion: The timing of dexketoprofen administration has no impact on postoperative pain in patients operated for laparoscopic cholecystectomy.

A rational approach to opioid dose reduction in the treatment of bone pain. Clinical discussion

Narcotic drugs have become more available for use, but it is obvious that monotherapy of pain syndrome with narcotic drugs is not always effective. Patients sometimes change prescribed opiates to NSAIDs on their own, because it is more effective despite the high risk of complications. In this case patient has a grade 2 pain syndrome associated with bone metastases despite taking the maximum daily dose of tramadol complicated by nausea. Treatment was successfully changed with medium doses of tramadol and dexketoprophen. We consider the combination of narcotic drugs and NSAIDs as opiate-sparing and suggest that dexketoprophen is effective for treatment of pain associated with bone metastases because of the effect on neuropathiс and central components of pain syndrome. We have analyzed the main mechanisms and options for systemic pharmacotherapy of pain syndrome in bone metastases. Some NSAIDs are known to have central analgesic effects. For example, the analgesic effect of ketorolac after an injury of sciatic nerve is explained by its ability to inhibit the synthesis of algogenic peptides in the posterior horns of the spinal cord and the decrease in astrocyte activation. However, it is the dexketoprofen/tramadol combination that is recognized as the most effective in the world.

Haematological Presentations in Acute and Chronic Tramadol Intoxication

Introduction Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, but now abused as a euphoria generating substance. The short- and long-term implications of tramadol intoxication on blood cells and its components are still hazy and controversial. Aim Our primary aim was to evaluate the alterative pattern of haematological parameters resulting from acute or chronic tramadol intoxication. Method The study was made of acute and chronic phases of sixty male rats (Rattusnorvegicus) randomly pair-divided into established groups of six male rats each. The acute stage consisted of a control group of 6 rats administered with normal saline solution, and a treatment group of 6 rats administered with lethal dose of tramadol. The control group for the chronic stage consisted of 6 rats that were administered normal saline solution. Whereas, the tramadol-dependent groups comprised of 3 groups of 6 rats each administered orally with 50 mg/kg, 100 mg/kg, and 200 mg/kg of tramadol for 90 days respectively. Statistical analyses consisted of the one-way analysis of variance (ANOVA), Student’s t-test, and Pearson’s Correlation using the JMP statistical discovery™ software version 14.1. Blood samples were collected after anesthetic sacrifice by cardiac puncture for the analysis of full blood count and red cell indices using SYSMEX Automated Blood Count machine (SYSMEX KX-21N ANALYZER) and microscopy for blood film reading. Results Results of the acute phase of the study showed that the packed cell volume (PCV) in the treatment group (51.00±2.96%) was significantly higher (t=3.99, p=0.002) than control (37.83±1.43%). Similarly, the haemoglobin concentration (Hb) in the treatment group (14.70±0.46 g/dL) was significantly higher (t=5.10, p=0.005) than control (11.55±0.41 g/dL). The mean cell haemoglobin concentration (MCHC) was significantly lower (t=2.67, p=0.02) in the control group (28.30±0.52 g/dL) than treatment (30.43±0.61 g/dL). However, that of the chronic phase exhibited a progressive increase in platelet count which was proportional to increasing dosage of treatment (t=8.59, p=0.007). Conclusion This study has demonstrated that tramadol administration could cause haematological alterations which could be beneficial if administrated optimally and deleterious, if abused. Therefore, indiscriminate and prolonged use of tramadol should be monitored to avert haemotoxicity.

Efficacy of Magnesium Sulphate as an Adjunct to Ropivacaine in Local Subcutaneous Infiltration for Postoperative Analgesia Following Lower Segmental Ceasfrean Section in Parturents under Spinal Anesthesia

Introduction: Magnesium is an antagonist of NMDA receptors and associated ion channels. It is found in very small concentrations in the plasma and is chiefly an intracellular ion. It is suggested that magnesium has many important roles to play in nociception. An inverse relationship has been documented between the severity of pain with different painful medical and surgical conditions and the serum magnesium levels. Methodology: Patients were monitored for postoperative pain and any analgesic requirement for a period of 24 hours. Any patient complaining of pain or reporting VAS ≥ at any time was administered In tramadol 100 mg IV slowly over 2-3 minutes. If pain was not relieved after 30 minutes and patients still complained of pain, additional doses of Inj tramadol 50mg IV was given and this dose could be repeated every 30 minutes upto a total dose of 250 mg in 6 hourly and maximum of 400mg of Inj tramadol over 24 hours. Results: The number of patients who were administered 2nd, 3rd and 4th doses of rescue analgesics was significantly greater in group A as compared to group B. None of the patients in group B needed more than 4 doses of rescue analgesia while in group A, 5 patients were administered a rescue analgesic for 5th time. The study suggests that local infiltration of local anaesthetic agent alone or in conjunction with magnesium is safe. Conclusion: The addition of magnesium to local anaesthetics potentiates the effect of local anaesthetics and reduces the postoperative opioid requirement.

Factors Affecting Tramadol-Associated Seizure

Background: Tramadol is a widely prescribed analgesic and due to its opioid-like effects, the potential for abuse of tramadol is noticeable. Besides, the complications of tramadol abuse have become a public health concern. This study aimed to investigate the affecting factors on the seizure, as one of the most common complications of tramadol consumption. Methods: A total number of 64 patients from 315 patients who were referred to Sina Hospital, Tabriz, Iran because of tramadol toxicity were included in this 9 months cross-sectional retrospective study. Results: There were 52 males and 12 females in the study. The seizure happened in 53.1% of the subjects and the Mean±SD time between tramadol consumption and seizure was 5.9±7.36 hours. There was no significant association between seizure and sex, age, the dose of tramadol, and previous tramadol consumption history. A significant association was seen between the dose of tramadol and the time of seizure. Conclusion: Seizure that happens due to tramadol overdose is not dependent on sex, age, and previous history of tramadol consumption. As the dose of tramadol is higher, the seizure happens later. More research is needed to understand why the seizure occurs later in higher doses.

Evaluation of vitamin C protective effect on the cerebrocortical antioxidant defense, histopathological, pro-apoptotic p53 and anti-apoptotic Bcl2 expressions against tramadol neurotoxicity in rats

BackgroundReported tramadol toxicity emphasizes the necessity to recognize its mechanism of toxicity, particularly to the brain tissue. Aim: This study aimed to evaluate the protective effect of vitamin C (Vit C) in cerebrocortical toxicity mediated by tramadol in rats using biochemical and histological parameters. Material and methodsForty-eight albino rats were randomly divided into eight groups, (n = 6/group) as follow: the control group received normal saline and vitamin C group received vitamin C (200 mg/kg per oral). Tramadol 50, 100, 150 groups received tramadol in doses of (50, 100 and 150 mg/kg per oral, respectively); Tramadol 50+ Vit C, 100+ Vit C, 150+ Vit C groups received vitamin C (200 mg/kg per oral) plus tramadol in doses of (50, 100 and 150 mg/kg per oral, respectively). Rats had received vitamin C and tramadol daily for 30 days. Blood and brain tissues samples were harvested for biochemical, histopathological, immunohistochemical and electron microscopic examinations. ResultsTramadol administration leads to a significant elevation of MDA, NO levels and a significant decrease in antioxidants parameters (CAT, SOD and GSH) in the tissues of cerebral cortices in rats which were directly proportional to the dose of tramadol. In histological investigations, tramadol-treated groups showed pyknotic pyramidal cells, multiple red neurons and shrinking red neurons with hallows around it and apoptotic cells were detected. These biochemical abnormalities and histological impairment were ameliorated in groups with tramadol low doses by the co-treatment with vitamin C. Conclusionvitamin C has antioxidant and anti-apoptotic potentials against tramadol neurotoxicity via suppression of oxidative stress, lipid peroxidation, structural abnormalities, and down-regulation of p53 and overexpression of Bcl2 in the nervous tissues.

Preconditioning by ultra-low dose of tramadol reduces the severity of tramadol-induced seizure: Contribution of glutamate receptors

Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.

Comparison between periarticular injection and intraarticular infusion for pain control following total knee arthroplasty

Objectives: To compare periarticular infiltration and intraarticular continuous infusion methods in pain management following total knee arthroplasty (TKA). Methods: Patients who underwent TKA from May 2015 through September 2015 according to their postoperative pain protocol were compared. The patients who received bupivacaine by periarticular infiltration (PAI group) and intraarticular infusion (IAI group) were included in the study. Patients also received a treatment through intravenous patient-controlled analgesia (PCA) device. The frequency of patients’ bolus need and the tramadol dose used via PCA device, Visual Analogue Scale (VAS) scores and clinical evaluation as active knee flexion at the postoperative 3th day were obtained from the patient follow - up forms and records. Side effects related to narcotic analgesic medications were also obtained. Results: The study included 90 patients, of whom 46 were in the PAI group (median age, 65.5 years; females, 82.6%) and 44 were in the IAI group (median age: 65.5 years; females, 81.8%). The VAS pain scores assessed at various postoperative time points and tramadol consumption were usually lower in the IAI group than in the PAI group. No difference was determined between the groups regarding the 3th-day VAS scores in flexion and in terms of analgesia-associated side effects. Conclusions: Bupivacaine administration by IAI for postoperative pain management following TKA is associated with lower pain and lower tramadol consumption as compared with bupivacaine administration by PAI. The groups were comparable in terms of side effects. Accordingly, IAI seems to be an effective and safe analgesic technique for patients undergoing TKA.

Acute pain and side effects after tramadol in breast cancer patients: results of a prospective double-blind randomized study

The objective of this study was to evaluate the severity of acute pain and side effects in breast cancer patients postoperatively treated with two regimens of tramadol with paracetamol in a prospective double-blind study. Altogether 117 breast cancer patients who had axillary lymphadenectomy were randomized into two analgesic study groups and the analgesic treatment lasted 4 weeks. Stronger analgesia group received every 8 h 75/650 mg of tramadol with paracetamol, while weaker analgesia group received every 8 h 37.5/325 mg of tramadol with paracetamol. Patients with the higher dose of tramadol had less pain during the 1st and 4th week than patients with the lower dose. Frequency of nausea, vomiting, lymphedema or range of shoulder movement was not significantly different between the two groups of patients. Constipation was significantly more common in the group with stronger analgesia during the 2nd week in comparison to patients with weaker analgesia. The patients who were on 75/650 mg of tramadol with paracetamol had less pain in comparison to patients who were on 37.5/325 mg. Side effects were mild, but common in both groups of patients.

Enhancement motivations for using prescription drugs among young adults in Nigeria

BackgroundThe desire for enhancement is a common motive for non-medical use of prescription drugs in Western countries. Little is known about the factors that motivate use in non-Western contexts. MethodsThe study explores access to prescription drugs and the motivations for using them among educated young adults in a city located in Anambra State, South-Eastern Nigeria. Semi-structured interviews were conducted with 23 participants aged 23–29 years. Data were thematically analysed using NVivo 12 Software. ResultsThe data indicate that prescription drugs are widely available and easy to access without a prescription in the unregistered ‘pharmacies’ and medicine shops that form part of Nigeria's informal healthcare system. Social networks are also a source of drugs. Participants shared detailed perspectives on their use of prescription drugs, revealing that codeine, Rohypnol, and high doses of tramadol are used to enhance performance in several social life domains. These drugs were described as enhancing performance and productivity in the workplace, and were taken by participants working as labourers and sales representatives. Male participants also shared accounts of using high doses of tramadol to improve stamina and skill in sports. Some participants took Rohypnol to enhance their creative and academic performance. Participants stated that drug use enabled them to meet the pressures associated with work, academia, and parental expectations. ConclusionThe findings suggest that prescription drugs are being strategically and instrumentally deployed by users to enhance different domains of social life. This is driven by users’ experiences of the drugs’ bodily effects, and it is supported by a context in which self-medication and informal healthcare are common. Participants’ reasons for seeking drug-induced enhancement reflect sociocultural factors within Nigeria and some West African countries, such as employment scarcity and the championing of sporting prowess. The findings can be used to inform the design of tailored approaches to reduce the harms presented by the non-medical use of pharmaceuticals among young adults.