Tramadol Research Articles

Rapid Quantitative Determination Control Male Sexual Dysfunction Drug Content of Sildenafil and Tramadol Mixture by Spectrophotometry Along With Smart Chemometrics Approaches Compared to the HPLC Reference Method.

There are reports for the simultaneous estimation of sildenafil (SIL) and tramadol (TM) using chromatographic techniques. Some limitations of these methods are high cost and time, more usage of pollutant solvents, and complicated instruments. Simultaneous determination of SIL and TM in the anti-sexual dysfunction pharmaceutical formulation using rapid and smart chemometrics approaches along with spectrophotometry. In this study, a spectrophotometric analysis method based on continuous wavelet transform (CWT), partial least-squares (PLS), and radial basis function neural network (RBF-NN) was presented. In the CWT method, the Symlet (Sym2) and Daubechies (db2) wavelet families with wavelengths of 268 and 221 nm were considered the best families for SIL and TM, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) values were found to be 0.0185, 0.0054 μg/mL and 0.0458, 0.3092 μg/mL for SIL and TM, respectively. The mean recovery values were 101.06 and 101.49% for SIL and TM, respectively. The results of PLS revealed that the root-mean-square error (RMSE) of SIL and TM was 0.0286 and 0.0635, respectively. Also, the mean recovery of both drugs was obtained over 99%. The mean square error (MSE) of RBF-NN was 5.88 × 10-29 and 4.61 × 10-27 for SIL and TM, respectively. A statistical comparative study conducted for the proposed methods with the high-performance liquid chromatography (HPLC) technique demonstrated no significant difference between these methods. The suggested approaches were simple, fast, accurate, and affordable. Three smart UV spectrophotometric methods based on chemometrics were presented to determine SIL and TM simultaneously. The efficient chemometrics methods, including CWT, PLS, and RBF-NN, were used. The mentioned methods are rapid, simple, inexpensive, and accurate. The comparison was performed between the proposed models and HPLC technique.

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™.

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.

Fabrication and Evaluation of Matrix Type Novel Transdermal Patch Loaded with Tramadol Hydrochloride

Transdermal drug delivery as a novel drug delivery system has become a major research interest to the scientists for its controlled drug release and improved patient compliance. This study was conducted to develop an optimized transdermal patch of tramadol hydrochloride using an appropriate amount of suitable polymers. It was also planned to control the drug permeation rate from the device to achieve a sustained release pattern. Several numbers of formulations were prepared by altering the amount of excipients. Physicochemical and biopharmaceutical parameters were checked to get the optimized formulation with desired characteristics. Fourier transform infrared spectroscopy results displayed no abnormal peaks and hence concluded that the drug and polymers were compatible with each other. The minimum standard deviation values of different physicochemical parameters assured that the method of preparation was skilled to develop patches with least intra-batch variability. A higher percentage of hydroxypropyl methylcellulose (HPMC) resulted in the greater tensile strength, moisture content and water vapor transmission rate of the patches. A high folding endurance value (>200) indicated the flexibility of the prepared patches and their integrity to the skin. The transdermal patches coded as F26 containing only HPMC polymer demonstrated the desired drug permeation rate (65.51%) within 12 hours through ex vivo permeation studies. The formulation coded as F26 was found to be the most optimized patch as it exhibited sustained drug permeation rate followed by higuchi diffusion kinetics, that also confirmed the capability of the formulation to exhibit matrix type drug delivery.

The effects of nefopam hydrochloride and tramadol hydrochloride on postoperative pain in patients undergoing long bone fracture fixations: A randomised triple blinded study

Orthopaedic surgery has one of the most painful post-operative periods. Pain management is an important consideration in Orthopaedic department. The purpose of this study was to assess the effect of Nefopam hydrochloride and Tramadol hydrochloride in postoperative analgesia in patients undergoing long bone fracture fixations.Triple blindedRandomization and allocation to study groups were carried out by odd and even number method. The study was conducted in tertiary care center from May 2019 till March 2020.184 patients who underwent Orthopaedic surgery were included in this randomized study. 92 patients were placed each in group-A and B. Patients in group-A received Tramadol hydrochloride and in group-B received Nefopam hydrochloride. The primary outcome measures were pain intensity assessed by using a Visual Analogue Scale (VAS) Score, Verbal Rating Scale (VRS) score whereas the secondary outcome measures included side effects related to the drugs and number of patients who required rescue analgesia. Unpaired t-test and Chi-square test was used to carry out all the data analysis. The pain intensity assessed on VAS score was significantly better for Tramadol group compared to Nefopam group at all time periods except at 15 minutes and a significant difference was present in verbal rating scale score between the groups only at 24 hours. Side effect profile and requirement of rescue analgesia were more in Nefopam hydrochloride group.Tramadol hydrochloride was more effective in providing post-operative pain relief in patients compared to Nefopam hydrochloride.

Effect of the analgesics dipyrone, tramadol, and meloxicam on the behavior of laboratory rats

Awareness about the ethical use of laboratory animals has increased over recent decades alongside the development of strict guidelines and legislation concerning the welfare of animals in scientific research. Although minimization of animal suffering during experimentation is of paramount importance, it is sometimes neglected because of the presumed interference of analgesics on behavioral patterns. For this reason, comprehensive research with multiple pharmacological agents is vital if analgesics are to be included in experimental procedures. In this context, we aimed to evaluate the effects of the analgesics dipyrone (DIP), tramadol (TRA), meloxicam (MEL), and combinations thereof on the behavioral parameters of naïve laboratory rats. Forty-eight SPF male Wistar-Han rats were divided randomly into 6 equal groups (n = 8 per group) and treated by intraperitoneal injection with DI (178 mg/kg), TRA (17.8 mg/kg), MEL (1.5 mg/kg), DIP+TRA (178 + 17.8 mg/kg), MEL+TRA (1.5 + 17.8 mg/kg) or saline (SAL; control). The behavior of the treated animals was assessed 30 minutes after injection of analgesic by sequential submission to Open Field, Elevated Plus Maze, and Grooming Transfer tests. Treatment with DIP+TRA provoked the most significant alterations in rat behavior by reducing locomotion, rearing, and grooming. Although treatment with DI alone diminished exploratory behavior, the effect on grooming was not remarkable, thereby suggesting that DI has a suppressive motor effect, possibly caused by its action on the endocannabinoid system, which is potentiated by TRA. In the Open Field tests, the grooming behavior of all TRA-treated animals was reduced while treatment with MEL increased locomotion. Given that analgesia is an ethical duty, the experimental design should always consider the behavioral effects of the drugs themselves.

Quantitative and histological evaluations for the potentiality of pilocarpine on tramadol induced xerostomia and structural alterations in Rats parotid gland

Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. Tramadol is generally well tolerated and the most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. The effect of intraperitoneal injection of tramadol and pilocarpine were studied in rats on the flow of saliva, histological and histochemical change in the parotid salivary gland. The rats were divided into three groups, first group, rats received saline and used as control. The second group treated with 10 mg tramadol hydrochloride for three days. The third group treated with tramadol hydrochloride for three days followed with 1 mg pilocarpine. The rats were sacrificed at the fourth day after the end of experimental procedure. The administration of tramadol caused decreased in salivary flow rate by approximately 60 %. The parotid histopathological changes include vacuolation and atrophy of acini and excessive widening of the interstitial tissue area which are replaced by extensive fibrosis fibrosis mostly associated with the degenerated ducts and acini and their replaced by inflammatory cells.

Lethal intoxications of medical staff with substances used in the profession – Presentation of a group of cases

The access medical staff has to special drugs through the nature of the job can lead to undesirable situations (illicit consumption, abuse and addiction, accidental overdoses, suicide, homicide). We focus on identifying situations of lethal intoxication of the medical staff with substances used within the profession and we propose a forensic approach to these types of cases. We made a review of the literature using MEDLINE, EMBASE, Scopus, Cochrane and internet search data of deaths among nurses and doctors due to intoxication with special regime drugs used in the profession. Five cases of autopsies performed at INML “Mina Minovici” Bucharest and Ilfov Medical-Legal Service, Romania, are presented (a veterinarian, a nurse and three anesthesiologist doctors). A 27-year-old female, a veterinarian, was found dead in bed, in her apartment, next to a 10-mL syringe with an attached branch, containing 4 ml of transparent liquid. It's a case of intravenous self-administration of T61, with a suicidal intention. T61 is a solution used for animal euthanasia, a mixture of 3 substances: embutramide (opioid analgesic), mebezonium iodide (curare-compound) and tetracaine hydrochloride (local anesthetic). A 38-year-old man, a male nurse, was found dead in his home, surrounded by several empty containers of Fentanyl and Mialgin. A bag with partially empty containers of medicines was found in his car: Enalapril, Telmisartan, Mialgin, Diazepam, Fentanyl, Acupan (nefopan chloridate), Dormicum (Midazolam), syringes and needles, used, but also sealed. The cause of death was an acute intoxication with a cocktail medication (opioid analgesics and benzodiazepines), stolen from the workplace. A 37-year-old man, an anesthesiologist doctor, was found by a colleague, at 7.00 a.m, in the on call room of the hospital, at the end of his shift. The cause of death was the acute intoxication with morphine (0.448 μg/mL). A 34-year-old woman, anesthesiologist doctor, was found dead by her father, on the bathroom floor of her apartment. Next to the body were found: a 5 mL syringe with 3 mL liquid content and 2 ampoules of tramadol hydrochloride (Mabron). In the trash, there was an empty bottle of ketamine hydrochloride (Ketamidor, for veterinary use) and fragments of ampoules of Midazolam and Calypsol. More than 150 ampoules labeled with various substances used in anesthesia were found in the house. In the last period, the woman doctor was exhausted as she had been working both in the public and private system. Female, 51 years old, anesthesiologist doctor, known as a consumer of analgesic substances for about 3 years, was found dead at home by her husband, on the bedroom floor. Cause of death was acute pulmonary edema, the consequence of an acute intoxication with drugs (pethidine > 2/mL μg/mL and nordazepam 0.03 μg/mL). The paper analyzes all the findings: the on-site investigations (extremely important to gather information), the necropsy data and the results of the histopathological, toxicological, tanatochemical and serological examinations. The analytical methods currently used for highlighting and dosing the identified substances are also presented. Autopsy findings were nonspecific, except for the stigma of chronic injectable drug use. That is why an algorithm for step by step approaching these types of cases could be very useful in order not to go beyond the possibility of an acute drug intoxication of medical staff. Nurses and doctors are vulnerable to chemical dependence due to the high work-related stress associated with easy access to medicines. This must always be suspected by the forensic doctors when they perform an autopsy of a medical staff person and they must follow a special algorithm in such cases.

Removal of nonsteroidal anti-inflammatory drugs and analgesics from wastewater by adsorption on cross-linked β-cyclodextrin

We present a method using the material in the form of cross-linked β-cyclodextrin (CD) showing high efficiency in the simultaneous removal of hazardous pollutants from sewage, such as diclofenac (DIC), ibuprofen (IBU), ketoprofen (KETO), naproxen (NAPR), salicylic acid (SALI) and tramadol (TRAM). The material is stable and particularly easy to regenerate. The sorbent probably remembers the shape of the contaminants, which increases its sorption capacity after the second use. The kinetics of the KETO adsorption process from one-, two- and three-component solutions are well described by the pseudo-second-order model. The maximum polymer capacity was 162.60 mg g−1. The interactions of KETO with CD were investigated, indicating that the main sorption mechanism is based on supramolecular interaction and uptake by a polymer network. The material is not sensitive to low pH and high salinity, so it can be used for the treatment of DIC, IBU, and KETO post-production wastewaters.

Bilateral coronoidectomy associated with the use of acrylic resin for fixation of fractures in the mandible of a dog - Case Report

Mandibular fractures are relatively common in dogs, and damage to the temporomandibular joint (TMJ) can cause jaw immobility. A mixed breed dog with a history of escape and trauma of unknown origin and time of occurrence was treated at Animal Care Barueri Veterinary Clinic, in Barueri, São Paulo, due to which he returned home with lesions distributed throughout the body, mainly located in the face. The animal was sent for radiographs that showed a fracture in the mandibular symphysis, left mandibular ramus and bilateral mandibular coronoid processes. We then opted for bilateral coronoidectomy followed by fixation of the symphysis and mandibular ramus fractures. A curvilinear incision was made over each temporomandibular joint followed by exposure of the fragment of the coronoid processes which were then excised. The correction of symphysis and mandibular ramus fractures was performed by applying acrylic resin throughout the lower dental arch. Finally, an esophageal tube was passed for food and medication and external coaptation of the mouth and muzzle was made with Vetrap elastic bandage. The postoperative period was performed with enrofloxacin, tramadol hydrochloride, meloxicam dipyrone and tube fededing. After 60 days of post-surgical evaluation, no complications were observed and good outcome was reached with treatment.

RP-HPLC-METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF DEXKETOPROFEN TROMETAMOL AND TRAMADOL HYDROCHLORIDE IN PHARMACEUTICAL DOSAGE FORM

Objective: For the measurement and quantification of Dexketoprofen Trometamol and Tramadol Hydrochloride, a rapid, sensitive, and reliable RP-HPLC technique using the Waters HPLC System with PDA detection was designed and validated.
 Methods: Chromatography was carried out on an Inertsil-ODS C18 (250 x 4.6 mm, 5) column with a flow rate of 1.0 ml/min and effluent of 240 nm using filtered and mixed Degassed Methanol: Buffer (75:25) v/v as a mobile phase.
 Results: Dexketoprofen Trometamol and Tramadol hydrochloride has a retention time of 3.617 min and 5.013 min, respectively. % recovery for Dexketoprofen trometamol and tramadol hydrochloride was found to be 100.21% and 100.20%, respectively. LOD and LOQ values obtained for Dexketoprofen trometamol and tramadol hydrochloride are 0.074µg/ml, 0.225µg/ml and 0.175µg/ml, 0.531µg/ml respectively. Regression equation of Dexketoprofen trometamol is y = 7446.1273x-284.0702 and y = 39535.8782x-1580.4211 of Tramadol hydrochloride.
 Conclusion: Dexketoprofen trometamol and tramadol hydrochloride has developed and validated in pharmaceutical dosage form using RP-HPLC method.

DANTE Study: The First Randomized, Double-Blind, Placebo and Active-Controlled, Parallel Arm Group Study Evaluating the Analgesic Efficacy and Safety of Dexketoprofen TrometAmol aNd Tramadol Hydrochloride Oral FixEd Dose Combination on Moderate to Severe Acute Pain in Patients with Acute Low Back Pain-Rationale and Design.

IntroductionDespite a wide range of treatment approaches and the availability of treatment recommendations or guidelines, no consensus on the most effective pharmacological therapy of low back pain (LBP) has been reached yet. Therefore, additional clinical evidence, particularly if built upon a rigorous clinical trial design, an evidence-based medication choice, and broader inclusion criteria better acknowledging the heterogeneity and intrinsic variability of LBP is needed. The DANTE study has been designed to comprehensively assess the analgesic efficacy and tolerability of dexketoprofen/tramadol (DKP/TRAM) 75/25 mg in a large cohort of patients with moderate to severe acute LBP.MethodsThe DANTE study is a phase IV, multicenter, randomized, double-blind, double-dummy parallel group, placebo, and active controlled study. The DANTE study encompasses a single-dose phase (day 1, t0–t8h) and a multiple-dose phase (from t8h to 8 h after intake of last dose at day 5). The DANTE study population includes patients naïve to LBP or patients with previous history of LBP experiencing a new episode of moderate to severe intensity with or without radiculopathy. The clinical phase of the DANTE study started in September 2020 and the anticipated completion date is April 2022.Planned OutcomesThe primary endpoint is the time to first achieve a numeric rating scale-pain intensity (NRS-PI) score of < 4 or a pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose (t8h). Secondary objectives aim are: (1) to evaluate the analgesic efficacy of TRAM/DKP 75/25 mg versus TRAM 100 mg after the first dose; (2) to evaluate the analgesic efficacy of TRAM/DKP 75/25 mg versus TRAM 100 mg after the multiple doses (from t8h until day 5, multiple dose); and (3) to assess the safety and tolerability of the TRAM/DKP 75/25 mg fixed combination after single and multiple doses.DANTE Study RegistrationEudraCT number: 2019-003656-37.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-022-00407-8.

Persulfate contribution to photolytic and pulsed corona discharge oxidation of metformin and tramadol in water

Degradation and mineralization of antidiabetic metformin (MTF) and opioid tramadol (TMD) in water were studied in UV photolytic oxidation and pulsed corona discharge (PCD) combined with extrinsic persulfate (PS) as UV/PS and PCD/PS systems. The effect of PS dose variation on the oxidation rate and efficiency was assessed. The UV/PS combination showed considerable effect in MTF and TMD removal, enhancing the removal of TOC up to 60–65% at maximum applied PS dose, thus providing the highest cost efficiency. As for the PCD/PS oxidation, the synergy was noticed for MTF, moderately increasing the oxidation rate and mineralization at somewhat increased expense. The PS addition to PCD treatment, however, demonstrated no effect on TMD oxidation. The highest energy efficiency in MTF and TMD degradation was thus showed by non-assisted PCD treatment with an energy yield at 90% conversion of the target compound of 5.6 and 13 g kW-1 h-1, respectively, confirming its practical applicability. The effective mineralization of the target compounds in persulfate photolysis makes it promising for use in advanced water purification. To assess the environmental safety of the studied oxidation processes, the acute toxicity of the treated MTF and TMD solutions to luminous bacteria (Vibrio fischeri) was examined.

Cross-talk between down-regulation of steroidogenic genes expression and oxidative and apoptotic biomarkers in testes induced by administration of tramadol and boldenone and their combination in male albino rats.

Objective(s):The testis is the male reproductive gland or gonad having two vital functions: to produce both sperm and androgens, primarily testosterone. The study aimed to investigate the effect of tramadol and boldenone injected alone or in combination for 2 months in rats on testicular function.Materials and Methods:Group 1, normal control; Group 2, tramadol HCl (TRAM) (20 mg/kg bwt.) (IP); Group 3, boldenone undecylenate (BOLD) (5 mg/kg bwt) (i.m); Group 4, combination of TRAM (20 mg/kg bwt.) and BOLD (5 mg/kg); respectively for 2 months. Results:TRAM and BOLD alone and in combination showed deteriorated testicular functions, lowered serum steroid levels (FSH, LH, and testosterone), elevation in oxidative biomarkers (MDA & NO) and reduction in GSH and SOD, down-regulation of StaR and HSD17B3 as well as histopathological testicular assessment using H&E staining revealing massive degenerative changes in the seminiferous epithelium and vacuolar changes of most of the spermatogenic stages in both TRAM and BOLD groups. PAS stain showed an intensive reaction in the interstitial tissue between the tubules in the TRAM group. Masson trichrome stain showed abundant collagen fiber deposits in the tunica albuginea with congested BV in the TRAM group. Conclusion:The study illuminated the hazard of administration of these drugs for a long period as well as the prominent deleterious effects reported on concurrent use of both drugs.

The effect of two doses of tramadol hydrochloride on fentanyl induced Cough: A double-blinded, randomized, controlled study

The effect of two doses of tramadol hydrochloride on fentanyl induced Cough: A double-blinded, randomized, controlled study

SELECTION AND OPTIMIZATION OF MOST EFFICIENT SUPERDISINTEGRANT FOR THE FORMULATION OF DISPERSIBLE TABLETS OF TRAMADOL HYDROCHLORIDE

Objective: The intent and objective of this research work were to find out the most effective superdisintegrants on the basis of disintegration time dissolution rate and other secondary tablet properties among the three mostly used superdisintegrants (Crospovidone, sodium starch glycolate and croscarmellose). This endeavour was initiated to mitigate dysphagia and for better bioavailability of drugs. Methods: Nine formulations of Tramadol HCl (50 mg) dispersible tablets were fabricated by direct compression process using different concentrations (3%, 5% and 8%) of mentioned superdisintegrants. Dispersible tablets were formulated and evaluated for various parameters such as thickness, hardness, friability, weight variation, disintegration time, drug content and dissolution rate. Then the stability study was carried out on the selected formulation batch to get a conclusion. Results: Results were interpreted in mean±SD where the value of n is equal to 3. The formulated dispersible tablets were evaluated for their post-compression parameters after achieving the desired pre-compression attributes. In pre-compression evaluation, the flow property and compressibility of powder were checked and the results found to be acceptable of all the nine formulations having an angle of repose less than 19 °, compressibility index in the range of 14.45 to 15.27 and Hausner’s ratio (≤ 1.29). The thickness of the tablets was found to be 4.19 to 4.28 mm. The tablets have optimum hardness just above 4 kg/sq. cm for better sustainability against mechanical stress and the percentage loss on friability found to be less than 1%. The drug content in the tablets of all nine formulations was found to be in the range of 97.48±0.9% to 99.46±0.4%. The wetting time and disintegration time were found to be within 20 sec and 40 sec, respectively, for all nine batches. The dissolution profile showed that more than 97% of the drug were released within 14 min, which is a great achievement in comparison to marketed dispersible tablets. The formulation batch (B2) with crospovidone as superdisintegrant has shown supremacy in tableting properties with better disintegration and dissolution profile. The bioavailability of the drug would be enhanced due to the increment in these parameters. The results of the stability studies of formulation batch (B2) were satisfactory. This batch with crospovidone as a super disintegrant was selected as the best formulation and recommended for scale-up. Conclusion: The outcome of the research work suggests that the disintegration efficiency of crospovidone is the most among the three super disintegrants and is recommended for the formulation of most effective dispersible tablets of Tramadol Hydrochloride.

A Comparative Study on the Efficacy of Tramadol and Fentanyl Added To Low Dose Bupivacaine in Subarachnoid Block for Caesarean Section

Background: A caesarean section is the utmost communal surgical procedure. An adjuvant with a low dose of bupivacaine added to a cesarean section is a better option. Aim of the study: It is planned to study the effect of fentanyl and tramadol added to a low dose of bupivacaine on subarachnoid blockade in caesarean section. Place and duration: In the Anesthesia and Obstetrics and Gynecology department of Khyber Teaching Hospital, Peshawar and Arif Memorial Teaching Hospital, Lahore for six-moths duration from July 2021 to December 2021. Methods: 90 patients were randomized into three groups, 30 pregnant females in each group. Group A received 0.5% bupivacaine 7.5 mg (one and a half ml), 5% dextrose in 0.5 ml water and total of 2 ml, group B 0.5% bupivacaine 5 mg, fentanyl 50 µg, total 2 ml. In group C, 0.5% bupivacaine was used together with 50 mg of tramadol, and a total of 2 ml was used for spinal anesthesia. The height of the sensory block was evaluated by the method of pinprick and the quality of the motor block by the Bromage scale. The effective duration of analgesia was recorded when patients requested the 1st dose of analgesia. The APGAR score was documented at one and five minutes after the baby was born. Results: In group A; mean duration of blockade was 118.50 ± 23.60; It was 168.00 ± 30.21 mints in Group B and 215.00 ± 26.51 mints in C Group, which was significant between the three groups (P = 0.01). The systolic blood pressure has mean change among the three groups after 3, 4, 5, 6, 8, 9, 10, 20 and 30 min was significant after SAB, and the diastolic blood pressure mean change after SAB was significant at 2, 3, 8, 9, 10, 20 minutes and the p-value were 0.021, 0.037, 0.059, 0.032, 0.042, 0.065, respectively. Hypotension developed in 9 cases of A group; 10 patients of B Group and 6 in the C group. There was one case pruritus in group A; group B has 7 patients with itching and no group C has no case of itching. The measurement of VAS after SAB was significant between groups. There was also a significant variance in VLAS among the groups in the first hour (P = 0.00049), the 2nd hr. (P - 0.007), and the 3rd hr. (P = 0.001) after SAB, and the interaction between the groups was significant (P = 0.001). Conclusion: The combination of bupivacaine and tramadol may be a better option as an intrathecal anesthetic compared to 0.5% bupivacaine in 0.5 ml of 5% dextrose or 0.5% bupivacaine in combination with fentanyl. Keywords: SAB, Bupivacaine, Fentanyl and Tramadol

Exercise training amplifies SIRT1/Nrf2/antioxidant/testosterone pathway after long-time tramadol toxicity in rat testicles; insights into miR-126-3p and miR-181a induced roles

A long-time consumption of the tramadol (TRA) is shown to negatively affect spermatogenesis development through inducing oxidative stress and suppressing testicular endocrine status. Therefore, by focusing on miRNAs-related roles in the SIRT1/Nrf2/antioxidant/Testosterone-related pathway, the effects of exercise training protocols (ETPs) with different intensities on the TRA-reduced antioxidant and endocrine capacities were investigated. Thus, 36 mature Wistar rats were divided into control and TRA-received groups. Following 60 days, 6 rats from TRA group euthanized (TRA), and the others subdivided into TRA (C.TRA), TRA+low-intensity (TRA+LICT), TRA+moderate-intensity (TA+MICT), and TRA+high-intensity continuous (TRA+HICT) ETP-induced groups (N = 6/group, ETPs were induced for 60 days after stopping TRA consumption). Next, the SIRT1, Nrf2, SOD1, HO-1, miR-126-3p, and miR-181a expression levels were evaluated. The sperm count, testosterone levels, testicular total antioxidant status (TAC), total oxidant status (TOS), superoxide dismutase (SOD) levels, protein carbonyl groups (PCGs), Thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPX) and glutathione reductase (GR), oxidative DNA damage were investigated. The TRA group exhibited a significant (p < 0.05) disruption in testicular antioxidant (TAC↓, TOS↑, SOD1↓, SOD enzyme↓, GPX↓, GR↑, TBARS↓, PCGs↑, and HO-1↓) and endocrine (testosterone↓) capacities, a reduction in SIRT1, Nrf2, miR-126-3p, and increment in miR-181a expression levels, a reduction in sperm count and increment in the sperm and testicular oxidative DNA damage. However, The ETPs (mainly LICT) could significantly decrease the TRA-induced molecular and histological alterations 60 days after stopping TRA consumption. In conclusion, ETPs (mainly LICT) through upregulating miR-126-3p and suppressing miR-181a expression levels could promote the SIRT1/Nrf2/antioxidant/Testosterone-related pathway in the testicular tissue.

Analgesic efficacy of ultrasound-guided transversus abdominis plane block and lateral approach quadratus lumborum block after laparoscopic appendectomy: A randomized controlled trial

BackgroundLaparoscopic appendectomy is the most performed emergency surgical technique worldwide. Transversus abdominis plane (TAP) blocks, which are easier to achieve with ultrasound, are frequently used in multimodal analgesia techniques for this surgery. Quadratus lumborum (QL) block has become a standard block, first used in gynecological and other abdominal surgeries. This study was planned to compare the analgesic efficacy of ultrasound-guided QL and TAP blocks for postoperative analgesia after laparoscopic appendectomy. Materials and methodsA total of 136 patients aged 18–65 years who underwent laparoscopic appendectomy were randomized and divided into two groups. A volume of 40 ml of local anesthetic containing 0.375% bupivacaine was administered for block applications in group TAP (n = 68) and group QL (n = 68). In addition, a patient-controlled analgesia device was used to administer bolus tramadol hydrochloride at a dose of 10 mg to relieve pain in the postoperative period. Postoperative opioid consumption of patients was recorded as the primary outcome and pain scores (1, 6, 12, 18, 24 h) as the secondary outcome. ResultsBoth groups were statistically similar in demographic and surgical data. There were no statistically significant differences between the groups over 24 h in terms of intraoperative remifentanil consumption (p = 0.584), postoperative cumulative opioid consumption (p = 0.807), and pain scores. No complications were observed in either group related to the block. ConclusionUltrasound-guided lateral approach QL block may provide adequate analgesia efficacy in patients undergoing laparoscopic appendectomy, like TAP block, and may be included in multimodal analgesia in pain control.

Comparison of lidocaine and ropivacaine stellate ganglion blockade in treating upper limb postherpetic neuralgia.

To provide a basis for treating postherpetic neuralgia (PHN), we compared the efficacy of lidocaine and ropivacaine stellate ganglion block (SGB) in PHN treatment in the upper limbs.Data from 252 patients with upper-limb PHN were retrospectively analyzed. The lidocaine group (n = 118) was treated with oral pregabalin capsules 75 mg twice a day, tramadol hydrochloride sustained release tablets 100 mg twice a day, and amitriptyline 25 mg once at night combined with ultrasound-guided lidocaine SGB; the ropivacaine group (n = 134) was orally administered the same medicines combined with ultrasound-guided ropivacaine SGB. The visual analog scale (VAS), self-rating anxiety scale (SAS), and adverse reactions were compared between the groups before treatment and at 1 week, 1 month, and 3 months after treatment.There were no significant differences between the lidocaine and ropivacaine groups in terms of sex, age, height, weight, and pain duration (P > .05). There was no significant difference between the groups in VAS and SAS scores before treatment (P > .05). At 1 week, 1 month, and 3 months after ultrasound-guided SGB treatment, the VAS and SAS scores were significantly lower in the ropivacaine group than in the lidocaine group (P < .05). There were no significant differences between the groups in terms of adverse reactions (P > .05).For ultrasound-guided SGB treatment of upper limb PHN, ropivacaine is superior to lidocaine. Ultrasound-guided ropivacaine SGB is safe and effective for the treatment of upper limb PHN.

COMBINED MIXTURE DESIGN IN OPTIMIZATION OF EXTRACTION SOLVENT FOR ASSAY TEST OF ETHYL CELLULOSE COATED TRAMADOL TABLETS

The aim of the present study was to apply combined mixture design to optimize extraction solvent composition to enhance filtration volume and recovery of assay test sample with ethyl cellulose coated tablets. Solvent composition, centrifugation time and additional filtration step were evaluated as variables. Filtrate volume through Whatman™ No: 1 filter paper followed by 0.45 micron PVDF membrane filter were selected as responses. Results indicated that higher organic phase in solvent composition, extended centrifugation time and inclusion of additional filtration step enhanced filtrate volume and assay recovery. Conclusively, design of experiments as an effective tool for optimization of extraction solvent in assay method was established and validated. The proposed method has adequate reproducibility and proved to be accurate for estimation of tramadol HCl in ethyl cellulose coated extended release tablets.