Effects of Morphine,Fentanyl and Tramadol on Human Immune Response

Summary： Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF- K B and IL-2 from both laboratory and clinical perspective. Jurkat cells were incubated with ten times clinically relevant concentrations of morphine, fentanyl and tramadol before being stimulated with PMA. NF- κB binding activity and IL-2 levels were measured, In the clinical study, 150 consenting patients were randomized into 3 groups according to the analgesics used in them, namely, group morphine （M）, group fentanyl （F） and group tramadol （T）. IL-2 was measured preoperatively and 1, 3 and 24 h after operation. Consequently, NF-κB activation was suppressed by morphine and fentanyl but not by tramadol. IL-2 was significantly decreased by morphine and fentanyl but not by tramadol in vitro. In the PCA patients, IL-2 was decreased in group M and increased in group F postoperatively. Whereas in group T, IL-2 was unchanged 1 h after operation but was significantly elevated 3 and 24 h after operation. Our results showed that the inhibition of morphine on IL-2 was most probably related to its suppression on NF-κB, Fentanyl had different effects on human immune response in vitro and in vivo. Tramadol may have immune enhancing effect.

Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation

Premature ejaculation （PE） is the most common sexual disorder. It affects 20%-30% of adult men; the aetiology of this condition has not yet been elucidated. The aim of this study is to evaluate the efficacy, safety, tolerability, undesirable effects and improved satisfaction with sexual intercourse with tramadol hydrochloride at different dosages for the treatment of PE. A total of 300 patients who presented with lifelong （primary） PE were included in this study. The study was performed for 28 weeks, in which placebo （starch tablet） was given for 4 weeks, and active ingredient （tramadol hydrochloride） was administered at different therapeutic dosages for 24 weeks. Patients were divided into three equal groups, each consisting of 100 patients. The first group （A） was given tramadol hydrochloride capsule 25 mg. The second group （B） was given tramadol hydrochloride capsule 50 mg. The third group （C） was given tramadol hydrochloride capsule 100 mg. All of the 300 participants included completed the study voluntarily. The age of the patients varied from 25 to 50 years. After the treatment period, the recorded data were collected for each group and analysed. The results showed a highly significant increase in the mean intravaginal ejaculatory latency time （IELT） in all groups compared to baseline data （P〈0.0001）. We concluded that using tramadol hydrochloride at different doses on demand for the treatment of PE is effective, safe and tolerable, with minimal undesirable effects, and approval for this indication should be souRht.

Enhancement in antinociceptive and anti-inflammatory effects of tramadol by transdermal proniosome gel

Oral therapy of tramadol,an opiate analgesic,undergoes extensive hepatic metabolism and requires frequent administration.Transdermal therapy by virtue can overcome these issues and can improve the efficacy and reduce abuse liability of tramadol.The aim of this research was to investigate the possibility of transdermal delivery of tramadol by formulating proniosome gel and evaluate its therapeutic potential in vivo.The effect of formulation composition as well as amount of drug on physicochemical characteristics of prepared proniosomes were examined.Best proniosome gel(F4)was selected and evaluated for drug release,stability and transdermal efficacy by ex vivo and in vivo experiments.The vesicles demonstrated optimal properties including spherical shape,nanosize with good entrapment efficiency,adequate zeta potential,higher stability and greater transdermal flux.The amorphization and dispersion of tramadol in the aqueous core of proniosome vesicles was confirmed by differential scanning calorimeter.Release profile of F4 was distinct(P<0.001)from control and displayed steady and prolonged tramadol release by Fickian diffusion.Transdermal therapy of F4 showed prominent reduction of induced twitches(P<0.005)in mice and edema(P<0.05)in rats,as compared to oral tramadol.The improvement in clinical efficacy of tramadol in transdermal therapy is correlated with the pharmacokinetic data observed.In conclusion,the observed improvement in antinociceptive and anti-inflammatory effects from proniosome carriers signifies its potential to be a suitable alternative to oral therapy of tramadol with greater efficacy.

Determination of Tramadol in Human Serum by Capillary Electrophoresis with the End-Column Electrochemiluminescence Detection

A capillary electrophoresis (CE) coupled with end-column electrochemiluminescence (ECL) detection method for the analysis of tramadol (TMD) has been investigated. ECL detection was working electrode biased at 1.2 V in a 20mmol·L-1 sodium phosphate buffer (pH = 8.0) containing 5 mmol·L-1 Ru (where bpy = 2,2’-bipyridyl). Linear correlation (r ≥ 0.997) between ECL intensity and drug concentration was obtained in the range 3 × 10-4 - 6 × 10-6 mol·L-1. The limits of detection (LODs) for tramadol in water was 3.012 × 10-8 mol·L-1(S/N = 3). The relative standard deviation values on peak size (10-5 mol·L-1 level) and migration time for the tramadol were 4.58% and 1.39% (n = 10), respectively. Applicability of the CE-ECL method to the analysis of human serum spiked with tramadol was

A single subcutaneous dose of tramadol for mild to moderate musculoskeletal trauma in the emergency department

BACKGROUND: Mild to moderate musculoskeletal trauma is a common cause for an emergency room visit, and frequent pain is one of the cardinal symptoms of consultation. The objective of this study is to assess the perception of a single subcutaneous dose of 50 mg tramadol for pain management in patients with mild to moderate musculoskeletal trauma, likewise to appraise the perception of pain by subcutaneous injection.METHODS: A total of 77 patients, who met inclusion criteria, received a single subcutaneous dose of tramadol. Pain control was evaluated based on the verbal numerical pain scale(0–10) at baseline, 20 and 60 minutes; similarly, pain perception was evaluated secondary to subcutaneous injection of the analgesic.RESULTS: On admission, the average pain perceived by patients was 8; twenty minutes later, 89% of the patients reported fi ve or less, and after sixty minutes, 94% had three or less on the verbal numerical pain scale. Of the patients, 88% reported pain perception by verbal numeric scale of 3 or less by injection of the drug, and 6.5% required a second analgesic for pain control. Two events with drug administration(soft tissue infection and mild abdominal rectus injection) were reported.CONCLUSION: We conclude that a single subcutaneous dose of tramadol is a safe and effective option for the management of patients with mild to moderate pain and musculoskeletal disease in the emergency department.

Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats

Background:Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats.The alpha-2 agonist,dexmedetomidine,has gained popularity in laboratory animal anesthesia.Tramadol is a weak opioid mu agonist.The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine(ZD)combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol(ZDT)in a minor procedure in rats.Methods:Rats were induced with ZD or ZDT.After the loss of paw withdrawal,a small incision was made on the rats’left thighs as a surgical stimulus.Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes,then atipamezole was administered.Monitored anesthesia parameters included:(a)physiological parameters-pulse rate(PR),respiratory rate(RR),tissue oxygen saturation(%SpO 2),and body temperature;(b)duration parameters-induction time,onset and duration of surgical anesthesia plane,onset of recovery,and recovery time.Results:PR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups.No difference was observed for RR,%SpO 2,and body temperature.Likewise,there were no differences for duration parameters:induction time was less than 3 minutes;onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes,respectively;onset of recovery(time to move)was 51 minutes;and recovery time was 52 minutes,respectively.Conclusion:These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

Quality Control of Tramadol in Kisangani: Development, Validation, and Application of a UV-Vis Spectroscopic Method

Context: Substandard and falsified medicines are circulating in low-income countries mostly without any control. We availed a simple and not expensive UV-Vis spectroscopic method to evaluate the quality of tramadol in Kisangani before and during the Covid-19 period. Methods: For the analytical quantitative method, an experimental design was applied to set up the optimal levels of the selected factors, namely, pH of dissolution medium, type of cuvette, and wavelength. Taking into account the capsule pharmaceutical formulation within 80 - 120 μg·mL-1 concentration range, we analyzed 89 tramadol samples from pharmacies and hospitals of the six Kisangani municipalities. Results: pH showed a significant effect on absorbance, whereas quartz cuvette and wavelength did not. A typical 100 μg·mL-1 tramadol solution gave an absorbance of 0.64 at 272 nm. Validation highlighted a matrix effect observed with a 6% bias. A correction factor of 0.9372 allowed to improve the accuracy profile, which were then totally included within the 10% acceptance limits. Quality control revealed that 25 samples out of 89 were not compliant in terms of manufacturing license, registration status in DRC and content as well. Conclusion: This study showed that the strengthening of analytical strategy in Kisangani is a need.

Effect of pretreatment with different concertrations of morphine, fentanyl and tramadol on the differentiation of human helper T cells in vitro

Objective： To investigate and compare the .effects of different concentrations of morphine, fentanyl and tramadol on the differentiation of human adult helper T cells in vitro. Methods： Twenty out-patients without immune disease were selected and their peripheral blood was collected. Then the Whole blood of peripheral blood mononuclear cells （PBMCs） were pretreated with different concentration of morphine, fentanyl and tramadol for 24 h. The level of CD4^＋ IFN-γ^＋ IL-2^＋/CD4^＋ IL-4^＋ IL-10^＋ was analyzed by three-color flow cytometry, and the CD4^＋ CCR5^＋ and CD4^＋ CCR3 ^＋ cells were counted to observe the imbalance of Th2/Th2. Results： The number of Th2 increased significantly and the ratio of Th2/Th2 decreased dramatically compared with the control group, and there was a dose-dependent fashion in all drugs. Conclusion： Morphine, fentanyl and tramadol can direct Th0 cells toward Th2 differentiation, especially morphine and fentanyl.

Continuous Intra-Articular Ropivacaine/Tramadol Combination Infusion Therapy Improves Postoperative Outcome of Total Knee Arthroplasty

Objectives: To evaluate the postoperative analgesic yield of continuous intra-articular (IA) ropivacaine/tramadol infusion as against infusion of ropivacaine alone after total knee arthroplasty. Patients and Methods: Sixty patients accompanied by arthrosis were randomly divided into three equal groups: The ropivacaine group, which obtained a continuous intraarticular (IA) infusion of ropivacaine alone;the combination group, which obtained a continuous (IA) infusion of a combination of ropivacaine and tramadol at a rate of 6 ml/h for 72 h postoperatively;and the control group, which did not receive IA medications. After release of the ischemic tourniquet and assurance of haemostasis, a vacuum drainage tube was applied. The (IA) infusion was delivered through a multipored catheter for 72 h. Postoperative pain was assessed using visual analogue pain scale (VAS), and intravenous meperidine was administered as rescue analgesia if the (VAS) pain score was greater than or equal to (4) or on patient’s request. The total rescue analgesia consumption, angle of flexion of the knee and hospital stay were recorded. Results: The ability to achieve better angle of flexion was significantly higher in the combination group compared with the other groups, with a significant difference in favour of the ropivacaine group compared with the control group. At 2 h postoperatively, the mean pain (VAS) scores were significantly lower in patients who received (IA) analgesia compared with the control group and in the ropivacaine/tramadol group versus the ropivacaine group. The number of requests and total dose of rescue analgesia consumed were significantly lower with (IA) analgesia, with a significant difference in favour of the combination group. There was significant correlation between pain (VAS) scores and angle of flexion of the knee joint. Conclusion: Continuous (IA) ropivacaine/tramadol infusion safely reduced postoperative pain and spared administration of rescue analgesics with a significantly improved range of joint movement.

Effects of Dexamethasone, Clonidine, Tramadol and Nalbuphine on Fentanyl-Induced Hyperalgesia in Rats

Opioids are drugs used to alleviate pain. However, studies have demonstrated that these drugs can cause an increase in pain sensitivity, which is called opioid-induced hyperalgesia. The objective of this study was to describe the effects of dexamethasone, clonidine, tramadol and nalbuphine on fentanyl-induced hyperalgesia in rats. After obtaining approval from the Committee for the Ethical Use of Animals (CEUA), 36 male Wistar rats were divided into 6 groups: Group 1 (GCSSL) wherein the rats received 1 ml 0.9% saline solution in two injections;Group 2 (GFTSL), received fentanyl at a dose of 100 ug·kg-1 followed by 1 ml 0.9% saline solution via intraperitoneal;the remaining groups (3, 4, 5, 6) received fentanyl at a dose of 100 ug·kg-1 following doses via intraperitoneal: Group 3 (GFTDX), dexamethasone at a dose of 1.0 mg·kg-1;Group 4 (GFTCL), clonidine at a dose of 20 mg·kg-1;Group 5 (GFTTR), tramadol at a dose of 50 mg·kg-1, and Group 6 (GFTNB), nalbuphine at a dose of 5 mg·kg-1. Under general anestesia using isoflurane, the animals were submitted to a surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments at 2 hours after the incision and on the 1st, 3rd and 5th days afterward. At 2 hours after the surgical procedure, there was lower intensity of pain in the fentanyl group (GFTSL) compared to the other groups, and on the fifth day there were no significant differences for pain intensity between groups. The results suggest the presence of fentanyl-induced hyperalgesia and efficacy in its reduction by dexamethasone, clonidine, tramadol and nalbuphine.

Acetylcholinesterase,butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis,tramadol or both

Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.Methods:rats were treated with cannabis resin(5,10 or 20 mg/kg)(equivalent to the active constituent A'-tetrahydrocannabinol),tramadol(5,10 and 20 mg/kg) or tramadol(10 mg/kg)combined with cannabis resin(5,10 and 20 mg/kg) subcutaneously daily for 6 weeks.Acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) activities were measured in brain and serum.We also measured the activity of paraoxonase-1(PONl) in serum of rats treated with these agents.Results:(i) AChE activity in brain increased after 10-20 mg/kg cannabis resin(by 16.3%-36.5%).AChE activity in brain did not change after treatment with 5-20 mg/kg tramadol.The administration of both cannabis resin(5,10 or 20 mg/kg) and tramadol(10 mg/kg) resulted in decreased brain AChE activity by 14.1%,12.9%and 13.6%,respectively;(ii) BChE activity in serum was markedly and dose-dependenlly inhibited by cannabis resin(by 60.9%-76.9%).BChE activity also decreased by 17.6%-36.5%by 10-20mg/kg tramadol and by 57.2%-63.9%by the cannabis resin/tramadol combined treatment;(iii)Cannabis resin at dose of 20 mg/kg increased serum PONl activity by 25.7%.In contrast,tramadol given at 5,10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%,36.7%,and 46.1%,respectively.Meanwhile,treatment with cannabis resin plus tramadol resulted in 40.2%,35.8%,30.7%inhibition of PONl activity compared to the saline group.Conclusions:these data suggest that cannabis resin exerts different effects on AChE and BChE activities which could contribute to the memory problems and the decline in cognitive function in chronic users.

The Effect of Tramadol Hydrochloride In-traarticular Injection on IL-6 Level in Patients with Tempromandibular Joint Internal Derangement

Purpose: This study was conducted to detect IL-6 in synovial fluid in cases with TMJ internal derangement. Patients & Methods: This study was conducted on forty patients ASA class I with TMJ Internal derangement. All patients had been subjected to arthrocentesis. The synovial fluid was collected before wash and lavage was done for the affected joint. Then, the selected patients were divided randomly into two equal groups, group I: consisted of 20 patients where arthrocentesis was performed for the affected joint followed by intraarticular injection of one ml, tramadol hydrochloride. Group II: consisted of 20 patients where arthrocentesis was performed for the affected joint followed by intraarticular injection of one ml. sodium hyaluronate. Another synovial fluid sample was aspirated after one month. The interlieukin-6 receptors in the aspirated synovial fluid were measured using humans IL-6 enzyme-linked immunosorbent assay. Results: IL-6 was detected in the synovial fluid of joints with internal derangement. During follow up assessment of IL-6, the maximum decrease in IL-6 level was in the patients of group I who subjected to arthrocentesis with tramadol injection, as the mean IL-6 was (4.93 ± 1.36) followed by the patients of group II who subjected to arthrocentesis with sodium hyaluronate injection where the mean IL-6 level was (6.88 ± 1.76). There were significant p-value = (P = 0.000). Conclusions: It had been concluded that the detection of IL-6 in the synovial fluid of joints with internal derangement considered an indicator for inflammatory reaction in the joint and also the efficacy of arthrocentesis with tramadol suggested its anti-inflammatory effect.

Therapeutic levels of short-term tramadol administration negatively affect testis function in rats

Objective:To investigate the effects of 30-day treatment with therapeutic dose equivalent levels of tramadol on serum testosterone level,sperm parameters,and testicular histology in rats.Methods:Thirty-five Wistar rats were equally divided into seven groups.Group 1(the control group)received distilled water(0.5 mL)daily for 30 days.Groups 2-4 were gavaged with therapeutic dose equivalent levels of tramadol(1.25,2.50 and 5.00 mg/kg/day body weight,respectively)in two equal divided doses for 30 consecutive days,and sacrificed on day 31.Groups 5-7 received similar tramadol treatments as above but they were allowed for another 30 days to recover after receiving the last dose and sacrificed on day 61 for reversibility study.Serum testosterone level and epididymal sperm were analyzed,and histopathological examination of the testis was carried out.Results:Tramadol treatment significantly decreased serum testosterone levels compared with the control group.Furthermore,tramadol treatment inhibited sperm motility and significantly and dose-dependently decreased sperm count and viability compared with the control group.In addition,tramadol significantly increased morphological abnormalities in sperm(P<0.05).The above effects of tramadol were reduced in the reversible groups.Testis histopathological examination revealed disintegrated cell architecture,eroded and atrophied seminiferous tubules,and a marked decrease in the number of spermatogenic cells in the tramadol treated groups.The histopathological changes were restored in the reversible groups,but improvement was not complete in the 5.00 mg/kg tramadol treated reversible group.Conclusions:Long term treatment with tramadol at clinical dose levels may adversely affect testosterone level,sperm parameters,and testicular histology,but they are reversible at lower doses.

Comparative effect of intrathecal meperidine,tramadol,magnesium sulfate,and dexmedetomidine on preventing post-spinal anesthesia shivering and adverse events in hip fracture repair patients:A randomized clinical trial

Objective:To compare effect of intrathecal meperidine,tramadol,magnesium sulfate,and dexmedetomidine on the prevention of post-spinal anesthesia shivering and adverse events in hip fracture repair patients.Methods:In a randomized,double-blind trial,132 patients with American Society of Anesthesiology(ASA)ⅠandⅡspinal anesthesia who needed hip fracture surgery were enrolled.Patients were stratified into 4 intervention groups based on a randomized block pattern:meperidine,tramadol,magnesium sulfate,and dexmedetomidine.Hemodynamic parameters including blood pressure,heart rate,and oxygen saturation,as well as the severity of shivering,core body temperature,Ramsay sedation score,adverse events,meperidine consumption were recorded and compared.Results:There was no statistically significant difference in the normal hemodynamic parameters,temperature,duration of surgery,meperidine consumption,and adverse events such as dizziness,hypotension,nausea,and bradycardia among groups(P>0.05).Compared to other groups,severity of shivering was the lower in the dexmedetomidine group 6 and 8 h after surgery.The Ramsay sedation scores were higher in the dexmedetomidine and meperidine groups 4 h after surgery(P=0.020).Conclusion:Dexmedetomidine acts better than the other three adjuvants in reducing complications such as shivering.Overall,these four adjuvants are helpful to prevent postoperative shivering and could be put forward as promising local anesthetics in spinal anesthesia,based on anesthesiologists’discretion and patients’general conditions.Clinical registration:The study was approved by the Research and Ethics Committee at the Valiasr Hospital(Arak,Iran)with the clinical trial code of IRCT20141209020258N153.

Flow Injection Determination of Tramadol Based on Its Sensitizing Effect on the Chemiluminescent Reaction of Permanganate-Sulfite

In this paper, a novel chemiluminescence (CL) method for the determination of tramadol has been developed by combining the flow injection technique and its sensitizing effect on the weak CL reaction between sulfite and acidic KMnO4. A mechanism for the CL reaction has been proposed on the basis of fluorescent and CL spectra. Under the optimized conditions, the proposed method allows the measurement of tramadol hydrochloride over the range of 0.04 - 4 ?g/mLwith a correlation coefficient of 0.9995 (n = 8) and a detection limit of 0.01 ?g/mL (3σ), and the relative standard deviation for 2.0 ?g/mL tramadol (n = 11) is 2.1%. The utility of this method was demonstrated by determining tramadol hydrochloride in tablets and injections.

Tramadol use in pediatric sickle cell disease patients with vaso-occlusive crisis

AIM: To evaluate whether the addition of scheduled oral tramadol to intravenous morphine and intravenous ketorolac reduces morphine requirements.METHODS: This single-centered, Institutional Review Board-approved, retrospective study at Moses Cone Memorial Hospital included pediatric patients who were ≥ 2 years old with vaso-occlusive crisis(VOC) caused by sickle cell disease(SCD), were on morphine patientcontrolled analgesia(PCA), and had scheduled oral tramadol added to their standard pain regimen. The study population was admitted between March 2008 and March 2011. The data was collected from electronic records and included age, weight, morphine use, tramadol use, hemoglobin, pain scores, number of days on PCA, length of hospital stay, respiratory rate, and polyethylene glycol use. Thirty patients were analyzed as independent admissions and seven patients as paired admissions. RESULTS: Eighteen pediatric SCD patients with VOC received morphine PCA and intravenous ketorolac and twelve patients received morphine PCA and intravenous ketorolac and scheduled oral tramadol. Baseline characteristics were similar between both groups with the exception of the average weight, which was greater in the tramadol group than in the morphine group. The average morphine requirements in patients with and without the use of tramadol were similar, both for the independent admissions [0.58 mg/kg per day vs 0.65 mg/kg per day(P = 0.31)] and the paired admissions [0.71 mg/kg per day vs 0.77 mg/kg per day(P = 0.5)]. The daily polyethylene glycol requirement was less in the tramadol group for both the independent [0.5 g/kg per day vs 0.6 g/kg per day(P = 0.64)] and paired admissions analyses [and 0.41 g/kg per day vs 0.55 g/kg per day(P = 0.67)].CONCLUSION: The addition of scheduled tramadol in patients receiving concomitant morphine and ketorolac demonstrates a trend toward decreased morphine and polyethylene glycol use.

Some Marker Enzymes and Histological Alteration on the Administration of Tramadol Hydrochloride on Rat Liver

The ease of availability and potential tendency to abuse tramadol hydrochloride prompted this research. Making use of biochemical and histological techniques, concentrations of marker enzymes were monitored along with alterations in the liver architecture of wistar albino rats in graded doses of tramadol hydrochloride for 28 days. Specifically, levels of gammaglutamyltransferase (-GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Statistical evaluation of the results at a p < 0.05 elucidated significantly elevated values of these enzymes when compared with controls that were not on tramadol hydrochloride. The variations were time and dose dependent. Histological evaluation presented various degrees of inflammatory cells of the liver, cytolysis in hepatocytes and some portal tract hypertrophy. These findings support the need for caution in administration of tramadol particularly for long term administration.

Tramadol in Japanese Population: the Relative Contribution of M1 Metabolite as Assessed by <i>CYP</i>2<i>D</i>6</i>*10 Genotype

Several preclinical and clinical studies suggested that tramadol has a multi-mechanistic analgesic action. Upon in vitro evaluation, tramadol parent drug was determined to have only very weak affinity for opioid receptors. Metabolism via CYP2D6, though, yields the O-desmethyl metabolite (M1), which has much greater opioid receptor affinity. In tests in animals and human volunteers, tramadol’s analgesic effect is only partially blocked by the opioid antagonist naloxone. Yet the contribution of parent drug to analgesia is still debated. Observance of good analgesic response to tramadol in Japanese and other Asian populations that express the CYP2D6*10 genotype suggests that parent drug accounts for the majority of tramadol’s analgesic effect in most clinical settings. Understanding of tramadol’s multi-mechanistic action continues to form the basis for understanding its clinical attributes.

Cardiopulmonary,Biochemical and Haematological Effects of the Tiletamine/Zolazepam-Xylazine-Tramadol Combination to Provide Anaesthesia in Miniature Pigs

The objective of this study was to investigate the suitability of tiletamine/zolazepam-xylazine-tramadol combination for miniature pigs. Fourteen Chinese experimental miniature pigs subjected to this study received 3.5 mg tiletamine/zolazepam kg-1 bw, 1.32 mg xylazine kg-1 bw and 1.8 mg tramadol kg-1 bw intramuscularly, as a mixture of the drugs. Cardiopulmonary, biochemical and haematological parameters were recorded before drug administration and after anaesthesia. The combination of the compounds resulted in anaesthesia lasting about 87 min and a satisfactory immobilization for handling. Cardiopulmonary parameters were changed after administration, but there were within biologically acceptable limits. Biochemical and haematological values decreased after drug administration, however, they returned to the baseline at 24 h. At the doses described, tiletamine/zolazepam-xylazine-tramadol combination produced good immobilization in miniature pigs with minimal changes over time in cardiopulmonary, biochemical and haematological parameters.

Prophylactic Effect of Oral Clonidine and Tramadol in Postoperative Shivering in Lower Abdominal Surgery

Background and Objectives: Several drugs and methods are used to reduce postoperative shivering, the most common complications occurring after surgery. This study aimed to evaluate the effects of the oral Clonidine and Tramadol premedication in reducing postoperative shivering after spinal anesthesia. Materials and Methods: In this study, patients aged 20 - 60 years, based on the American Society of Anesthesia functional class I (Anesthesiologists grade-1), were included in controlled double-blind clinical trials. Each was a candidate of a hydrocele, varicocele, and inguinal hernia under spinal anesthesia. The patients were assigned to three groups and 1 h prior to surgery, group A received 0.2 mg of Clonidine, group B received 50 mg of a Tramadol tablet, and group C received a placebo. We collected information on the severity of shivering, pain intensity levels (VAS score), duration of analgesia, and the patients’ hemodynamic condition at base time of 5, 15, and 30 min and 1, 2, 4, and 6 h postoperatively. Results: The incidence of shivering was significantly lower in the Clonidine group than that in the other groups. Analgesia duration was significantly longer in the Clonidine group than that in the control group. In this study, side effects in different groups were not significantly different from each other. Conclusion: Results of this study showed that the oral administration of Clonidine can be effective in preventing the side effects and shivering after spinal anesthesia.