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Sample records for intravenosa con tramadol

  1. Tramadol

    PubMed Central

    2009-01-01

    This ongoing column is dedicated to the challenging clinical interface between psychiatry and primary care—two fields that are inexorably linked. Tramadol (Ultram®) is a commonly prescribed analgesic because of its relatively lower risk of addiction and better safety profile in comparison with other opiates. However, two significant adverse reactions are known to potentially occur with tramadol—seizures and serotonin syndrome. These two adverse reactions may develop during tramadol monotherapy, but appear much more likely to emerge during misuse/overdose as well as with the coadministration of other drugs, particularly antidepressants. In this article, we review the data relating to tramadol, seizures, and serotonin syndrome. This pharmacologic intersection is of clear relevance to both psychiatrists and primary care clinicians. PMID:19724727

  2. [Hyponatremia due to tramadol].

    PubMed

    Le Berre, J-P; Desramé, J; Lecoules, S; Coutant, G; Béchade, D; Algayres, J-P

    2007-12-01

    We reported a 92-year-old woman with hyponatremia (117 mmol/l) occurring three days after the introduction of tramadol. Diagnosis of inappropriate antidiuretic hormone secretion was based on blood and urinary analysis and dosage of antidiuretic hormone. Natremia became normal after tramadol cessation and fluid restriction. Natremia must be measured when neurological abnormality occurs with tramadol treatment.

  3. [Pharmacology of tramadol].

    PubMed

    Dayer, P; Desmeules, J; Collart, L

    1997-01-01

    (+/-)-Tramadol is a synthetic 4-phenyl-piperidine analogue of codeine. It is a central analgesic with a low affinity for opioid receptors. Its selectivity for mu receptors has recently been demonstrated, and the M1 metabolite of tramadol, produced by liver O-demethylation, shows a higher affinity for opioid receptors than the parent drug. The rate of production of this M1 derivative (O-demethyl tramadol), is influenced by a polymorphic isoenzyme of the debrisoquine-type, cytochrome P450 2D6 (CYP2D6). Nevertheless, this affinity for mu receptors of the CNS remains low, being 6000 times lower than that of morphine. Moreover, and in contrast to other opioids, the analgesic action of tramadol is only partially inhibited by the opioid antagonist naloxone, which suggests the existence of another mechanism of action. This was demonstrated by the discovery of a monoaminergic activity that inhibits noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake, making a significant contribution to the analgesic action by blocking nociceptive impulses at the spinal level. (+/-)-Tramadol is a racemic mixture of 2 enantiomers, each one displaying differing affinities for various receptors. (+/-)-Tramadol is a selective agonist of mu receptors and preferentially inhibits serotonin reuptake, whereas (-)-tramadol mainly inhibits noradrenaline reuptake. The action of these 2 enantiomers is both complementary and synergistic and results in the analgesic effect of (+/-)-tramadol. After oral administration, tramadol demonstrates 68% bioavailability, with peak serum concentrations reached within 2 hours. The elimination kinetics can be described as 2-compartmental, with a half-life of 5.1 hours for tramadol and 9 hours for the M1 derivative after a single oral dose of 100mg. This explains the approximately 2-fold accumulation of the parent drug and its M1 derivative that is observed during multiple dose treatment with tramadol. The recommended daily dose of tramadol

  4. The Pharmacogenetics of Tramadol.

    PubMed

    Lassen, Dorte; Damkier, Per; Brøsen, Kim

    2015-08-01

    Tramadol hydrochloride is used worldwide as an analgesic drug with a unique dual function. The metabolic enzymes cytochrome P450 (CYP) 3A4, CYP2B6, and CYP2D6 and the various transporters [adenosine triphosphate-binding cassette B1/multidrug resistance 1/P-glycoprotein, organic cation transporter 1, serotonin transporter (SERT), norepinephrine transporter (NET)] and receptor genes (opioid receptor μ 1 gene) give possible genetic differences that might affect the pharmacokinetics and/or pharmacodynamics of tramadol. Therefore, the aim of this review is to present a systematic walkthrough of all possible genetic factors involved in the pharmacology of tramadol. A systematic literature search was conducted in PubMed and EMBASE involving all metabolic enzymes, drug transporters and receptors, as well as SERT and NET that are involved in the pharmacokinetics and pharmacodynamics of tramadol. An additional search on population pharmacokinetics with genetic factors as covariates was performed separately. A total of 56 studies (45 cohort and case-control studies, three case reports, six in vitro studies, and two animal studies) were included. In this systematic review, the current knowledge on all possible genetic factors that might influence the metabolism or clinical efficacy of tramadol has been collected and summarized. Only the effect of CYP2D6 polymorphisms on the metabolism of tramadol and the consequent effect on pain relief has been thoroughly studied and sufficiently established as clinically relevant.

  5. Cognitive Impairment and Tramadol Dependence.

    PubMed

    Bassiony, Medhat M; Youssef, Usama M; Hassan, Mervat S; Salah El-Deen, Ghada M; El-Gohari, Hayam; Abdelghani, Mohamed; Abdalla, Ahmed; Ibrahim, Dalia H

    2017-02-01

    Cognitive impairment is one of the consequences of substance abuse. Tramadol abuse is a public health problem in Egypt. The objective of this study was to estimate the prevalence and correlates of cognitive impairment among tramadol-abuse patients and control subjects. This study included 100 patients with tramadol abuse and 100 control subjects (matched for age, sex, and education) who were recruited from Zagazig University Hospital, Egypt. Patients were divided into 2 groups: patients who used tramadol only (tramadol-alone group) and patients who used tramadol and other substances (polysubstance group). The participants were interviewed using Montreal Cognitive Assessment test and had urine screening for drugs. Twenty-four percent of the cases used tramadol alone, whereas the remaining used tramadol and other substances, mainly cannabis (66%) and benzodiazepines (27%). Tramadol-abuse patients were about 3 times more likely to have cognitive impairment than control subjects (81% vs 28%). Tramadol-alone patients were more than 2 times more likely to have cognitive impairment than control subjects (67% vs 28%). Cognitive impairment was significantly associated with polysubstance abuse. There was no association between cognitive impairment and sociodemographic or clinical factors. Cognitive impairment occurs commonly among tramadol-abuse patients. Memory impairment is the most common cognitive domain to be affected. There is a significant association between cognitive impairment and polysubstance abuse.

  6. Adolescent tramadol use and abuse in Egypt.

    PubMed

    Bassiony, Medhat M; Salah El-Deen, Ghada M; Yousef, Usama; Raya, Yasser; Abdel-Ghani, Mohamed M; El-Gohari, Hayam; Atwa, Samar A

    2015-05-01

    Tramadol abuse liability is underestimated and the evidence of abuse and dependence is emerging. It has many health and social consequences especially in adolescents. Tramadol abuse has not been well studied in Egypt. The aim of this study was to estimate the prevalence and associated correlates of tramadol use and abuse among school students in Egypt. A total of 204 students, aged 13-18 years, from six schools in Zagazig, Egypt, were screened for tramadol use using The Drug Use Disorders Identification Test and a urine screen for tramadol. The prevalence of tramadol use was 8.8% among school students and the average age at onset of tramadol use was 16.5 ± 1.1. Some 83% of the users were using tramadol alone while the rest (17%) were using a combination of tramadol, alcohol, and cannabis. Two-thirds of these students started with tramadol as the first drug after the onset of tobacco smoking. Over one third of tramadol users had drug-related problems and 6% had dependence. There was a significant association between tramadol use and older age, male gender, and smoking. Drug-related problems were negatively correlated with age at onset of tramadol use. Tramadol use was common among adolescents and over one third of tramadol users had drug-related problems. Population-based longitudinal studies are needed to investigate tramadol use and the possible role of tramadol as a gateway drug in the development of substance abuse in Egypt.

  7. New clinical experience with tramadol.

    PubMed

    Sunshine, A

    1994-01-01

    The analgesic efficacy of tramadol has been recently reassessed as part of a new clinical development programme to support an application for registration in the USA. This article reviews the results of single dose and short term studies of oral tramadol 50, 75, 100 and 150 mg in various acute pain conditions. In a double-blind single dose study conducted in 161 patients with severe pain following caesarean section, tramadol 75 and 150 mg and the combination of paracetamol 650 mg with dextropropoxyphene napsylate 100 mg were shown to be effective and statistically superior to placebo. The results from this and 17 other similar studies in patients with pain after surgery (n = 1594) or dental extraction (n = 1859) including other comparators were included in a pooled analysis. Tramadol 100 mg was the optimal single dose for acute pain and tramadol 50 mg showed similar analgesic efficacy to codeine 60 mg. Multiple dose short term studies (n = 520) with tramadol 50, 75 and 100 mg demonstrated a statistically significant and dose-dependent reduction in the consumption of either ibuprofen or morphine as escape medication. New pharmacokinetic data show that steady-state plasma tramadol concentrations reached after oral administration of 50 mg doses every 6 hours are similar to those obtained after administration of a 100 mg single oral dose (250 micrograms/L). This rationale is supported by the results of long term studies in which the average daily dose of tramadol was approximately 250 mg.

  8. What is the main mechanism of tramadol?

    PubMed

    Minami, Kouichiro; Ogata, Junichi; Uezono, Yasuhito

    2015-10-01

    Tramadol is an analgesic that is used worldwide for pain, but its mechanisms of action have not been fully elucidated. The majority of studies to date have focused on activation of the μ-opioid receptor (μOR) and inhibition of monoamine reuptake as mechanisms of tramadol. Although it has been speculated that tramadol acts primarily through activation of the μOR, no evidence has revealed whether tramadol directly activates the μOR. During the past decade, major advances have been made in our understanding of the physiology and pharmacology of ion channels and G protein-coupled receptor (GPCR) signaling. Several studies have shown that GPCRs and ion channels are targets for tramadol. In particular, tramadol has been shown to affect GPCRs. Here, the effects of tramadol on GPCRs, monoamine transporters, and ion channels are presented with a discussion of recent research on the mechanisms of tramadol.

  9. [Comparison of tramadol, tramadol-metamizol and tramadol-lornoxicam administered by intravenous PCA in management of postoperative pain].

    PubMed

    Kemal, Sibel Ozçakir; Sahin, Saziye; Apan, Alparslan

    2007-10-01

    Comparison of tramadol, tramadol-metamizol and tramadol-lornoxicam administered by intravenous PCA in management of postoperative pain. The aim of the present study was to compare of the postoperative analgesic effects of tramadol, combinations of tramadol-metamizol and tramadol-lornoxicam administered by intravenous Patient Control Analgesia (PCA) in lower abdominal surgery. Sixty adult, female patients who undergoing lower abdominal surgery, were included in this study. Patients were randomized to three groups. The solutions were prepared containing 500 mg tramadol in 50 ml saline (10 mg/ml tramadol) for Group I, 250 mg tramadol+3000 mg metamizol in 50 ml saline (5 mg/ml tramadol+60 mg/ml metamizol) for Group II and 250 mg tramadol+20 mg lornoxicam in 50 ml saline (5mg/ml tramadol + 0.4 mg/ml lornoxicam) for Group III. Loading dose 10 ml was administrated within 30 min 30 to 40 min before the end of the surgery. PCA was started at the first complaint of pain. Pain was evaluated by VAS in every 15 minute intervals at the first hour and later at 2nd, 4th, 8th, 12th, 18th and 24th hours postoperatively. Vital parameters, side-effects, sedation scores and total analgesic consumptions were also recorded concurrently. Total tramadol and anti-emetic consumption, the incidence of postoperative nausea and vomiting (PONV) were significantly higher in group I than the other groups (p<0.05). In conclusion; Tramadol-metamizol and tramadol-lornoxicam combinations administered by intravenous PCA provide efficient postoperative analgesia with less side effects.

  10. Tramadol: a new centrally acting analgesic.

    PubMed

    Lewis, K S; Han, N H

    1997-03-15

    The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol are reviewed. Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake. It is rapidly and extensively absorbed after oral doses and is metabolized in the liver. Analgesia begins within one hour and starts to peak in two hours. In patients with moderate postoperative pain, i.v. or i.m. tramadol is roughly equal in efficacy to meperidine or morphine; for severe acute pain, tramadol is less effective than morphine. Oral tramadol can also be effective after certain types of surgery. Tramadol and meperidine are equally effective in postoperative patient-controlled analgesia. In epidural administration for pain after abdominal surgery, tramadol is more effective than bupivacaine but less effective than morphine. In patients with ureteral calculi, both dipyrone and butylscopolamine are more effective than tramadol. For labor pain, i.m. tramadol works as well as meperidine and is less likely to cause neonatal respiratory depression. Oral tramadol is as effective as codeine for acute dental pain. In several types of severe or refractory cancer pain, tramadol is effective, but less so than morphine; for other types of chronic pain, such as low-back pain, oral tramadol works as well as acetaminophen-codeine. Common adverse effects of tramadol include dizziness, nausea, dry mouth, and sedation. The abuse potential seems low. The recommended oral dosage is 50-100 mg every four to six hours. Tramadol is an effective, if expensive, alternative to other analgesics in some clinical situations.

  11. Tramadol-associated mania: A case report.

    PubMed

    Nimah, Jamaluddin; Chen, Alexander; Gable, Kelly N; Felthous, Alan R

    A variety of medications, most notably tricyclic antidepressants, and other antidepressants including venlafaxine have been reported to have triggered manic episodes in patients with bipolar disorder. The synthetic opioid tramadol has also been associated with mania activation. This report describes an unusual case of tramadol-associated mania in a patient without a charted diagnosis of bipolar disorder. However, she had a history of two prior episodes of mania following administration of tramadol that were also believed to be related to medication-induced mood disorder rather than underlying bipolar disorder. We hypothesize that tramadol-associated mania may have an underlying mechanism involving monoamine neurotransmission and increased oxidative stress.

  12. Synthetic Origin of Tramadol in the Environment.

    PubMed

    Kusari, Souvik; Tatsimo, Simplice Joel N; Zühlke, Sebastian; Spiteller, Michael

    2016-01-04

    The presence of tramadol in roots of Sarcocephalus latifolius trees in Northern Cameroon was recently attributed to point contamination with the synthetic compound. The synthetic origin of tramadol in the environment has now been unambiguously confirmed. Tramadol samples isolated from tramadol pills bought at a street market in downtown Maroua and highly contaminated soil at Houdouvou were analyzed by high-precision (14)C measurements by accelerator mass spectrometry ((14)C AMS): Tramadol from the pills did not contain any radiocarbon, thus indicating that it had been synthesized from (14)C-free petroleum-derived precursors. Crucially, tramadol isolated from the soil was also radiocarbon-free. As all biosynthetic plant compounds must contain radiocarbon levels close to that of the contemporary environment, these results thus confirm that tramadol isolated from the soil cannot be plant-derived. Analyses of S. latifolius seeds, in vitro grown plants, plants from different origins, and stable-isotope labeling experiments further confirmed that synthetic tramadol contaminates the environment.

  13. Maintainence Treatment of Opioid Dependence with Tramadol

    PubMed Central

    Sarkar, Siddharth; Varshney, Mohit; Patil, Vaibhav; Lal, Rakesh

    2017-01-01

    Background: Although tramadol has been used in the management of acute withdrawal in patients with opioid dependence, its use for maintenance treatment as a harm reduction approach has not been assessed systematically. This case series describes patients with opioid dependence who were treated with tramadol for long-term maintenance. Methods: Patients with opioid dependence who received treatment at the National Drug Dependence Treatment Centre of All India Institute of Medical Sciences, New Delhi, were included in the study. Patients who received at least 6 months of tramadol and had follow-up adherence of more than 80% were included in the case series. Results: A total of 25 cases were included, all of whom were males. The types of opioids being taken at the time of initiation of tramadol were natural opiates (poppy husk and raw opium), followed by heroin. The median dose of tramadol at initiation and maintenance was 300 mg/day. Nineteen patients were able to achieve complete abstinence to other opiates on tramadol. Conclusion: Tramadol may be an effective option in the long-term management of patients with opioid dependence. Further studies are required for establishing the efficacy of tramadol for agonist management of patients with opioid dependence. PMID:28936080

  14. Maintainence Treatment of Opioid Dependence with Tramadol.

    PubMed

    Sarkar, Siddharth; Varshney, Mohit; Patil, Vaibhav; Lal, Rakesh

    2017-08-01

    Although tramadol has been used in the management of acute withdrawal in patients with opioid dependence, its use for maintenance treatment as a harm reduction approach has not been assessed systematically. This case series describes patients with opioid dependence who were treated with tramadol for long-term maintenance. Patients with opioid dependence who received treatment at the National Drug Dependence Treatment Centre of All India Institute of Medical Sciences, New Delhi, were included in the study. Patients who received at least 6 months of tramadol and had follow-up adherence of more than 80% were included in the case series. A total of 25 cases were included, all of whom were males. The types of opioids being taken at the time of initiation of tramadol were natural opiates (poppy husk and raw opium), followed by heroin. The median dose of tramadol at initiation and maintenance was 300 mg/day. Nineteen patients were able to achieve complete abstinence to other opiates on tramadol. Tramadol may be an effective option in the long-term management of patients with opioid dependence. Further studies are required for establishing the efficacy of tramadol for agonist management of patients with opioid dependence.

  15. Paracetamol + tramadol: new preparation. No advance.

    PubMed

    2003-12-01

    (1) First-line treatment for both acute and chronic pain is paracetamol or, if necessary, ibuprofen, a nonsteroidal antiinflammatory drug. If relief is inadequate, the best option is a combination of paracetamol with codeine (a weak opiate). (2) A fixed-dose combination of paracetamol (325 mg) and tramadol (37.5 mg), a weak opiate, arrived on the French market in May 2003. (3) In the acute setting, three trials in a total of 1197 patients showed that a single dose of the paracetamol 650 mg + tramadol 75 mg combination after dental surgery was no more effective than ibuprofen 400 mg. Compared with each drug used alone, the paracetamol + tramadol combination prolongs the analgesic effect but does not increase its intensity. (4) A trial after gynaecological surgery and another trial after orthopaedic surgery showed that a single dose of paracetamol 975 mg + tramadol 112.5 mg had similar efficacy to tramadol alone at 112.5 mg. (5) In the chronic setting, we found no trials comparing the paracetamol + tramadol combination with each drug used alone. A comparative double-blind trial in 462 patients with low back pain or osteoarthritic pain showed no difference in efficacy between paracetamol 325 mg + tramadol 37.5 mg and paracetamol 300 mg + codeine 30 mg. (6) The main adverse effects of the paracetamol + tramadol combination are the same as other weak opiates: nausea, vomiting, dizziness, headache, drowsiness and constipation. Tramadol carries a higher risk of drug interactions than codeine. (7) In practice, the paracetamol + tramadol combination offers patients no advantages relative to standard analgesics.

  16. Discriminative Stimulus Effects of Tramadol in Humans

    PubMed Central

    Duke, Angela N.; Bigelow, George E.; Lanier, Ryan K.

    2011-01-01

    Tramadol is an unscheduled atypical analgesic that acts as an agonist at μ-opioid receptors and inhibits monoamine reuptake. Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low. The present study further characterized tramadol in a three-choice discrimination procedure. Nondependent volunteers with active stimulant and opioid use (n = 8) participated in this residential laboratory study. Subjects were trained to discriminate between placebo, hydromorphone (8 mg), and methylphenidate (60 mg), and tests of acquisition confirmed that all volunteers could discriminate between the training drugs. The following drug conditions were then tested during discrimination test sessions: placebo, hydromorphone (4 and 8 mg), methylphenidate (30 and 60 mg), and tramadol (50, 100, 200, and 400 mg). In addition to discrimination measures, which included discrete choice, point distribution, and operant responding, subjective and physiological effects were measured for each test condition. Both doses of hydromorphone and methylphenidate were identified as hydromorphone- and methylphenidate-like, respectively. Lower doses of tramadol were generally identified as placebo, with higher doses (200 and 400 mg) identified as hydromorphone, or opioid-like. The highest dose of tramadol increased ratings on the stimulant scale, but was not significantly identified as methylphenidate-like. Tramadol did not significantly increase subjective ratings associated with reinforcement. Taken together, these results extend previous work with tramadol as a potential medication for the treatment of opioid dependence and withdrawal, showing acute doses of tramadol exhibit a profile of effects similar to opioid agonists and may have abuse liability in certain populations. PMID:21467190

  17. Tramadol induced seizure: A 3-year study

    PubMed Central

    Boostani, Reza; Derakhshan, Siavash

    2012-01-01

    Background: Tramadol is a synthetic analgesic. Seizures have been reported in patients receiving this drug. In this study we evaluated the correlation between tramadol consumption and seizure occurrence. Methods: Twenty-eight subjects with a history of tramadol consumption and seizure were studied. Electroencephalograms (EEG) were performed in the first 24 hours and again one week later. Subjects were followed up for a mean of 18 months after the initial attack. Results: In the 28 subjects, 26 (92.8%) were males and 2 (7.2%) were females. The mean age of the subjects was 28.4 years. Thirteen patients had abused more than 400 mg/day of tramadol. Sixteen subjects concomitantly used other drugs. The seizures occurred within the first 24 hours of tramadol intake in 25 of the subjects. The first EEG was abnormal in 12 cases, but the second EEG was abnormal in only one case. Neuroimaging of only one subject displayed patchy white matter lesions. Conclusion: In conclusion, the neurotoxicity of tramadol commonly manifests as generalized tonic clonic seizures most frequently within 24 hours after tramadol intake and was more common in subjects concomitantly consuming alcohol, illicit drugs, anti-psychotics, or anti-depressants. PMID:24009919

  18. Tramadol induced seizure: A 3-year study.

    PubMed

    Boostani, Reza; Derakhshan, Siavash

    2012-01-01

    Tramadol is a synthetic analgesic. Seizures have been reported in patients receiving this drug. In this study we evaluated the correlation between tramadol consumption and seizure occurrence. Twenty-eight subjects with a history of tramadol consumption and seizure were studied. Electroencephalograms (EEG) were performed in the first 24 hours and again one week later. Subjects were followed up for a mean of 18 months after the initial attack. In the 28 subjects, 26 (92.8%) were males and 2 (7.2%) were females. The mean age of the subjects was 28.4 years. Thirteen patients had abused more than 400 mg/day of tramadol. Sixteen subjects concomitantly used other drugs. The seizures occurred within the first 24 hours of tramadol intake in 25 of the subjects. The first EEG was abnormal in 12 cases, but the second EEG was abnormal in only one case. Neuroimaging of only one subject displayed patchy white matter lesions. In conclusion, the neurotoxicity of tramadol commonly manifests as generalized tonic clonic seizures most frequently within 24 hours after tramadol intake and was more common in subjects concomitantly consuming alcohol, illicit drugs, anti-psychotics, or anti-depressants.

  19. Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

    PubMed

    Miotto, Karen; Cho, Arthur K; Khalil, Mohamed A; Blanco, Kirsten; Sasaki, Jun D; Rawson, Richard

    2017-01-01

    Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects. The importance of the CYP metabolism has led to the adoption of computer clinical decision support with pharmacogenomics tools guiding tramadol treatment in major medical centers. Tramadol's simultaneous opioid agonist action and serotonin (5-HT) and norepinephrine reuptake inhibitory effects result in a unique side effect profile and important drug interactions that must be considered. Abrupt cessation of tramadol increases the risk for both opioid and serotonin-norepinephrine reuptake inhibitor withdrawal syndromes. This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.

  20. Tramadol--a true natural product?

    PubMed

    Kusari, Souvik; Tatsimo, Simplice Joel N; Zühlke, Sebastian; Talontsi, Ferdinand M; Kouam, Simeon Fogue; Spiteller, Michael

    2014-11-03

    We have independently investigated the source of tramadol, a synthetic analgesic largely used for treating moderate to severe pain in humans, recently found in the roots of the Cameroonian medicinal plant, Nauclea latifolia. We found tramadol and its three major mammalian metabolites (O-desmethyltramadol, N-desmethyltramadol, and 4-hydroxycyclohexyltramadol) in the roots of N. latifolia and five other plant species, and also in soil and local water bodies only in the Far North region of Cameroon. The off-label administration of tramadol to cattle in this region leads to cross-contamination of the soil and water through feces and urine containing parent tramadol as well as tramadol metabolites produced in the animals. These compounds can then be absorbed by the plant roots and also leached into the local water supplies. The presence of tramadol in roots is, thus, due to an anthropogenic contamination with the synthetic compound. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Tramadol wound infiltration is not different from intravenous tramadol in children: a randomized controlled trial.

    PubMed

    Giraldes, Ana Laura Albertoni; Sousa, Angela Maria; Slullitel, Alexandre; Guimarães, Gabriel Magalhães Nunes; Santos, Melina Geneviève Mary Egan; Pinto, Renata Evangelista; Ashmawi, Hazem Adel; Sakata, Rioko Kimiko

    2016-02-01

    The purpose of this trial was to assess if tramadol wound infiltration is superior to intravenous (IV) tramadol after minor surgical procedures in children because tramadol seems to have local anesthetic-like effect. Randomized double-blind controlled trial. Postanesthesia care unit. Forty children, American Society of Anesthesiologists physical status I or II, scheduled to elective inguinal hernia repair. Children were randomly distributed in 1 of 2 groups: IV tramadol (group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the surgery, group 1 received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline into the surgical wound; group 2 received 2 mg/kg tramadol (3 mL) into the surgical wound and 3-mL saline by IV route. In the postanesthesia care unit, patients were evaluated for pain intensity, nausea and vomiting, time to first rescue medication, and total rescue morphine and dipyrone consumption. Pain scores measured during the postanesthesia recovery time were similar between groups. Time to first rescue medication was shorter, but not statistically significant in the IV group. The total dose of rescue morphine and dipyrone was also similar between groups. We concluded that tramadol was effective in reducing postoperative pain in children, and there was no difference in pain intensity, nausea and vomiting, or somnolence regarding IV route or wound infiltration. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [Effects of Tramadol on Insulin Resistance during Cesarean Section Complicated with Gestational Diabetes Mellitus].

    PubMed

    Lin, Yuan-Gui; Huang, Wei

    2017-05-01

    To investigate the effects of tramadol on insulin resistance (IR) during cesarean section complicated with gestational diabetes mellitus (GDM). 120 patients of elective caesarean sectioncomplicated with GDM (level A1) were collected from Dec.2015 to Oct.2016, randomly divided into the tramadol injection treated groups (0.5 mg/kg-TRM1, 1 mg/kg-TRM2 and 1.5 mg/kg-TRM3) and the control group (CON) (n=30). The patients of TRM groups were injected with tramadol after delivery of fetus during caesarean delivery under combined spinal-epidural anaesthesia (CSEA) and the patients of CON group were treated with normal saline as control. The plasma were collected before CSEA (T0), after delivery of fetus (T1) and immediately after caesarean section (T2) for determination of the expression of blood glucose, insulin, HOMA-IR, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by hexokinase, chemiluminescence method and ELISA. The activation of PI3K/Akt signaling pathway of epiploon were detected by RT-PCR and Western blot. Compared with T0, the concentration of blood glucose, insulin, HOMA-IR, IL-6 and TNF-α increased significantly in T1 and T2 (P<0.05). The factors of above decreased in T2 of TRM2 group and TRM3 group comparing with CON group, but of no significant differences between TRM1 group and CON group. Compared with CON group in T2, PI3K/Akt signaling pathway activated significantly in TRM2 group and TRM3 group (P<0.05). The tramadol can attenuate IR during cesarean section complicated with GDM and may regulate the secretion of IL-6, TNF-α and PI3K/Akt signaling pathway in the treatment of IR of GDM.

  3. A comparative study on the analgesic effect of tramadol, tramadol plus magnesium, and tramadol plus ketamine for postoperative pain management after major abdominal surgery.

    PubMed

    Unlügenç, H; Gündüz, M; Ozalevli, M; Akman, H

    2002-09-01

    We tested whether, after major abdominal surgery, the addition of magnesium or ketamine to tramadol for intravenous (IV) patient-controlled analgesia (PCA) improved analgesia and lowered pain scores, compared to a PCA containing only tramadol. Sixty-six patients were allocated randomly to receive a PCA with tramadol alone (T), tramadol plus magnesium (TM) or tramadol plus ketamin (TK), in a double-blind randomized study. Postoperative analgesia was started when the verbal rating scale (VRS) score was 2 or more. Following a loading dose of the study solution (which contained 1 mg/kg tramadol), a background infusion of 0.4 mg/kg/h was started. Patients were allowed to use bolus doses of 0.2 mg/kg every 20 min without a time limit. Discomfort, sedation, pain scores, total and bolus PCA tramadol consumption, and side-effects, were recorded for up to 24 h after the start of PCA. Pain and discomfort scores were lower (P < 0.01) in groups TM and TK at 15, 30, 60 and 120 min than in group T. The addition of magnesium or ketamine significantly reduced the consumption of tramadol at 6, 12 and 24 h (P < 0.01). The incidence of nausea did not differ between the groups. Adding magnesium or ketamine to tramadol improved analgesia and patient comfort and decreased the amount of tramadol required for postoperative pain management after major abdominal surgery.

  4. Tramadol

    MedlinePlus

    ... in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain ... promethazine; quinidine; rifampin (Rifadin, Rimactane, others); 5-HT3 receptor antagonists such as alosetron (Lotronex), dolasetron (Anzemet), granisetron ( ...

  5. Possible serotonin syndrome associated with tramadol and sertraline coadministration.

    PubMed

    Mason, B J; Blackburn, K H

    1997-02-01

    To report a possible case of serotonin syndrome associated with coadministration of tramadol hydrochloride and sertraline hydrochloride. A 42-year-old woman developed atypical chest pain, sinus tachycardia, confusion, psychosis, sundowning, agitation, diaphoresis, and tremor. She was taking multiple medications, including tramadol and sertraline. The tramadol dosage had recently been increased, resulting in what was believed to be serotonergic syndrome. Serotonin syndrome is a toxic hyperserotonergic state that develops soon after initiation or dosage increments of the offending agent. Patients may differ in their susceptibility to the development of serotonin syndrome. The (+) enantiomer of tramadol inhibits serotonin uptake. Tramadol is metabolized to an active metabolite, M1, by the CYP2D6 enzyme. If this metabolite has less serotonergic activity than tramadol, inhibition of CYP2D6 by sertraline could have been a factor in the interaction. Clinicians should be aware of the potential for serotonin syndrome with concomitant administration of sertraline and tramadol.

  6. Effect of tramadol on depth of anaesthesia.

    PubMed

    Coetzee, J F; Maritz, J S; du Toit, J C

    1996-03-01

    We have studied 51 patients who were anaesthetized with propofol and suxamethonium followed by 0.7% isoflurane and 66% nitrous oxide in oxygen to see if tramadol caused lightening of anaesthesia. A two-channel EEG was recorded and music was played via headphones. Two groups received tramadol 200 and 100 mg i.v. and the third group received saline. Tramadol caused significant, dose-dependent activation of the EEG, evidenced by increased frequencies and decreased amplitudes, but these changes were small and probably unimportant. Derived EEG variables did not approach values known to be associated with near-awakening during isoflurane anaesthesia. No patient moved on skin incision and there were no incidences of free recall.

  7. A 15-year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom.

    PubMed

    Chen, Teng-Chou; Chen, Li-Chia; Knaggs, Roger David

    2017-09-24

    This study aimed to develop hypotheses to explain the increasing tramadol utilisation, evaluate the impact of tramadol classification, and explore the trend between tramadol utilisation and related deaths in the United Kingdom. This cross-sectional study used individual patient data, the Clinical Practice Research Datalink from 1993 to 2015, to calculate monthly defined daily dose (DDD)/1000 registrants, monthly prevalence and incidence of tramadol users, annual supply days, and mean daily dose of tramadol. Aggregated-level national statistics and reimbursement data from 2004 to 2015 were also used to quantify annual and monthly tramadol DDD/1000 inhabitants and rate of tramadol-related deaths in England and Wales. Interrupted time-series analysis was used to evaluate the impact of tramadol classification in June 2014. Prevalence of tramadol users increased from 23 to 97.6/10 000 registrants from 2000 to 2015. Both annual dose and annual supply days of existing tramadol users were higher than new users. Level and trend of monthly utilisation (β2 : -12.9, β3 : -1.6) and prevalence of tramadol users (β2 : -6.4, β3 : -0.37) significantly reduced after classification. Both annual tramadol utilisation and rate of tramadol-related deaths increased before tramadol classification and decreased thereafter. Increasing tramadol utilisation was influenced by the increase in prevalence and incidence of tramadol users, mean daily dose, and day of supply. Prevalence of tramadol users, tramadol utilisation, and reported deaths declined after tramadol classification. Future studies need to evaluate the influencing factors to ensure the safety of long-term tramadol use. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

    PubMed

    Lagard, Camille; Chevillard, Lucie; Malissin, Isabelle; Risède, Patricia; Callebert, Jacques; Labat, Laurence; Launay, Jean-Marie; Laplanche, Jean-Louis; Mégarbane, Bruno

    2016-11-01

    Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon-Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P=0.04). Tramadol induced dose-dependent sedation (P<0.05), early-onset seizures (P<0.001) and increase in inspiratory (P<0.01) and expiratory times (P<0.05). The diazepam/tramadol combination abolished seizures but significantly enhanced sedation (P<0.01) and respiratory depression (P<0.05) by reducing tidal volume (P<0.05) in addition to tramadol-related increase in respiratory times, suggesting a pharmacodynamic mechanism of interaction. Plasma M1 and M5 metabolites were mildly increased, contributing additionally to tramadol-related respiratory depression. Tramadol-induced early-onset increase in brain concentrations of serotonin and norepinephrine was not significantly altered by the diazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern with enhanced

  9. Worldwide research productivity on tramadol: a bibliometric analysis.

    PubMed

    Sweileh, Waleed M; Shraim, Naser Y; Zyoud, Sa'ed H; Al-Jabi, Samah W

    2016-01-01

    Pain management and safe use of analgesics is an important medical issue. Tramadol is an old analgesic with controversial properties. Evaluation of worldwide scientific output on tramadol has not been explored. Therefore, the main objective of this study was to give a bibliometric overview of global research productivity on tramadol. SciVerse Scopus was used to retrieve and quantitatively and qualitatively analyze worldwide publications on tramadol. A total of 2059 original and review research articles on tramadol were retrieved from Scopus. Forty-six documents (2.23 %) were published in Anesthesia and Analgesia Journal whereas 30 (1.46 %) were published in Arzneimittel Forschung Drug Research Journal. Retrieved tramadol documents were published from 71 countries and appeared in 160 peer reviewed journals. Although the United States of America (259; 12.86 %) had the largest contribution to tramadol publications; the contribution by other countries like Turkey (232; 11.27) India (189; 8.09 %) and Germany (176; 8.56 % was not far away from that of USA. The most productive institution was Grunenthal, Germany (47; 2.28 %) followed by Tehran University of Medical Sciences, Iran (29; 1.41 %), and, Ortho-McNeil Pharmaceutical Incorporated, USA (25; 1.21 %). Of the 2059 documents, there were 370 documents about dependence. The leading institution in documents pertaining to tramadol dependence was Grunenthal GmbH (18; 4.86 %) followed by Ortho-McNeil Pharmaceutical Incorporated (17; 4.59 %). The current study showed that there is an obvious interest in tramadol research. More efforts are needed to clarify the abuse potential and safety profile of tramadol to help in determining the legal status of tramadol. Collaboration among pharmaceutical industry, clinical researchers and academic institutions can improve research quantity and quality on tramadol.

  10. Discovery and development of tramadol for the treatment of pain.

    PubMed

    Bravo, Lidia; Mico, Juan Antonio; Berrocoso, Esther

    2017-09-17

    Tramadol is an opioid drug that, unlike classic opioids, also modulates the monoaminergic system by inhibiting noradrenergic and serotoninergic reuptake. For this reason, tramadol is considered an atypical opioid. These special pharmacological characteristics have made tramadol one of the most commonly prescribed analgesic drugs to treat moderate to severe pain. Areas covered: The aim of this review is to provide a historical description of the biochemistry, pharmacokinetics and particularly, the mechanisms of action of tramadol. In addition, a summary is offered of the analgesic effects of tramadol in a variety of animal models of acute and chronic pain. Finally, clinical studies that demonstrate the efficacy and safety of tramadol in the treatment of pain are also assessed. Expert opinion: The discovery that tramadol combines opioid and monoaminergic effects represented a milestone in the evolution of pain treatment. Given its 'mild effect' on opioid receptors, tramadol induces fewer side effects than classic opioids. Tramadol produces satisfactory analgesia against various types of pain and it is currently approved for the treatment of moderate to severe pain. Thus, the combination of monoamine and opioid mechanisms opens new avenues for the design of innovative analgesics.

  11. Tramadol, but not its major metabolite (mono-O-demethyl tramadol) depresses compound action potentials in frog sciatic nerves

    PubMed Central

    Katsuki, R; Fujita, T; Koga, A; Liu, T; Nakatsuka, T; Nakashima, M; Kumamoto, E

    2006-01-01

    Background and purpose: Although tramadol is known to exhibit a local anaesthetic effect, how tramadol exerts this effect is not understood fully. Experimental approach: The effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) were examined by applying the air-gap method to frog sciatic nerves, and the results were compared with those of other local anaesthetics, lidocaine and ropivacaine. Key results: Tramadol reduced the peak amplitude of the CAP in a dose-dependent manner (IC50=2.3 mM). On the other hand, M1 (1–2 mM), which exhibits a higher affinity for μ-opioid receptors than tramadol, did not affect CAPs. These effects of tramadol were resistant to the non-selective opioid receptor antagonist naloxone and the μ-opioid receptor agonist, DAMGO, did not affect CAPs. This tramadol action was not affected by a combination of the noradrenaline uptake inhibitor, desipramine, and the 5-hydroxytryptamine uptake inhibitor, fluoxetine. Lidocaine and ropivacaine also concentration-dependently reduced CAP peak amplitudes with IC50 values of 0.74 and 0.34 mM, respectively. Conclusions and implications: These results indicate that tramadol reduces the peak amplitude of CAP in peripheral nerve fibres with a potency which is less than those of lidocaine and ropivacaine, whereas M1 has much less effect on CAPs. This action of tramadol was not produced by activation of μ-opioid receptors nor by inhibition of noradrenaline and 5-hydroxytryptamine uptake. It is suggested that the methyl group present in tramadol but not in M1 may play an important role in producing nerve conduction block. PMID:16921387

  12. Study of interaction of tramadol with amlodipine in mice

    PubMed Central

    Modi, Hiral; Mazumdar, Bipa; Bhatt, Jagatkumar

    2013-01-01

    Objective: To study a possible interaction between tramadol, an opioid analgesic and amlodipine, a dihydropyridine calcium channel blocker with proposed antinociceptive property. Materials and Methods: Albino mice of Haffkine strain were used for the study. The experiment was carried out using tail-flick method. Different doses of tramadol (50 mg/kg, 22.8 mg/kg and 10 mg/kg) were administered intraperitoneally to select the nonanalgesic dose. The animals were treated with different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg, 3.5 mg/kg) to study its antinociceptive action. Combination of different doses of both the drugs were administered to study antinociceptive effect of the combination. Results: Tramadol, showed dose dependent antinociception which persisted for entire two hours of the study period. Antinociceptive action was seen with amlodipine at a dose of 3.5 mg/kg. Different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg) in combination with the nonanalgesic dose of tramadol (10 mg/kg) produced a significant enhancement of antinociceptive effect of tramadol. Combination of 3.5 mg/kg dose of amlodipine with nonanalgesic dose of tramadol (10 mg/kg) further enhances antinociceptive activity. Conclusion: It is concluded that combination of amlodipine, a N - type calcium channel blocker, with tramadol produce significant enhancement of antinociceptive activity of tramadol. PMID:23543914

  13. Tramadol versus clonidine in management of heroin withdrawl.

    PubMed

    Chattopadhyay, Somsubhra; Singh, O P; Bhattacharyya, Amit; Sen, Subrata; Roy, Paromita; Debnath, Sharmistha

    2010-12-01

    Opiod dependence is one of the leading psychiatric morbidities in India. The deaddiction centres are meager in number; stigma attached to admission in deaddiction centre is high and most addicts want outpatient treatment so that they do not miss daily wages. Several recent reports stated effectiveness of tramadol in treating opioid withdrawal. This study attempts to compare effectiveness of tramadol with clonidine in opioid withdrawal. A total of 60 patients having heroin dependence were selected and out of them 30 got clonidine treatment and the other 30 got tramadol treatment. The clinical opioid withdrawal scale was used. "t"-Test was used using SPSS (version-16) for comparison. Tramadol was more effective in preventing sweating, restlessness, aches, runny nose, GI upset, yawning, anxiety and goose skin. i.e., Tramadol can be used effectively in opioid withdrawal in outpatient based treatment programme. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

    PubMed

    Belin, Nicolas; Clairet, Anne-Laure; Chocron, Sidney; Capellier, Gilles; Piton, Gaël

    2017-04-01

    Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

  15. Regulation of cerebral CYP2D alters tramadol metabolism in the brain: interactions of tramadol with propranolol and nicotine.

    PubMed

    Wang, Qiaoli; Han, Xiaotong; Li, Jian; Gao, Xinghui; Wang, Yan; Liu, Mingzhou; Dong, Guicheng; Yue, Jiang

    2015-04-01

    1. Cytochrome P450 2D (CYP2D) protein is widely expressed across brain regions in human and rodents. We investigated the interactions between tramadol, a clinically used analgesic, and brain CYP2D regulators, by establishing concentration-time curves of tramadol and O-desmethyltramadol (M1) in rat cerebrospinal fluid (CSF) and plasma, as well as by analyzing the analgesia-time course of tramadol. 2. Propranolol (20 μg, intracerebroventricular injection), CYP2D inhibitor, prolonged the elimination t1/2 of tramadol (40 mg/kg, intraperitoneal injection) in the CSF; meanwhile, lower Cmax and AUC0-∞ values of M1 were observed. Nicotine (1 mg base/kg, subcutaneous injection, seven days), brain CYP2D inducer, induced a shorter Tmax and elevated Cmax of M1 in CSF. No differences in the peripheral metabolism of tramadol were observed following propranolol and nicotine pretreatment. Nicotine increased areas under the analgesia-time curve (AUC) for 0-45 min and 0-90 min of tramadol, which was attenuated by propranolol administration. The analgesic actions of tramadol positively correlated with cerebral M1 concentration. 3. The results suggest that the regulation of brain CYP2D by xenobiotics may cause drug-drug interactions (DDIs) of tramadol. Brain CYPs may play an important role in DDIs of centrally active substances.

  16. Acute and chronic tramadol administration impair spatial memory in rat

    PubMed Central

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  17. Tramadol for neuropathic pain in adults.

    PubMed

    Duehmke, Rudolf Martin; Derry, Sheena; Wiffen, Philip J; Bell, Rae F; Aldington, Dominic; Moore, R Andrew

    2017-06-15

    This review is an update of a review of tramadol for neuropathic pain, published in 2006; updating was to bring the review in line with current standards. Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Peripheral neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the peripheral nervous system. To assess the analgesic efficacy of tramadol compared with placebo or other active interventions for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing tramadol (any route of administration) with placebo or another active treatment for neuropathic pain, with subjective pain assessment by the participant. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH), using standard methods. We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables. We identified six randomised, double-blind studies involving 438 participants

  18. Preemptive intraarticular tramadol for pain control after arthroscopic knee surgery.

    PubMed

    Tuncer, Bilge; Babacan, Avni; Arslan, Mustafa

    2007-01-01

    The purpose of this study was to determine the effectiveness of intraarticular (ia) bupivacaine and tramadol injection and preemptive intraarticular tramadol in providing pain control after arthroscopic knee surgery. Following local research ethics committee approval, 60 patients were assigned in a randomized manner into three groups: Group I received ia 20 ml of 0.25 % bupivacaine at the end of the operation, Group II received ia 20 ml of 0.25 % bupivacaine and 100 mg of tramadol at the end of the operation and Group III received ia 100 mg of tramadol diluted in 20 ml of saline solution 30 minutes before skin inscision and 20 ml of 0.25% bupivacaine at the end of the operation as well. Analgesic duration, total analgesic consumption and postoperative VAS pain scores recorded at rest and with movement were significantly lower and patient satisfaction was significantly higher in Group II and III, compared to Group I. Total analgesic consumption and the number of patients requiring supplementary analgesics were significantly lower in the preemptive tramadol group compared to the postoperative tramadol group. In conclusion, preemptive ia tramadol provided effective and reliable pain control after artroscopic knee surgeries and may be preferred to postoperative administration.

  19. Transport characteristics of tramadol in the blood-brain barrier.

    PubMed

    Kitamura, Atsushi; Higuchi, Kei; Okura, Takashi; Deguchi, Yoshiharu

    2014-10-01

    Tramadol is a centrally acting analgesic whose action is mediated by both agonistic activity at opioid receptors and inhibitory activity on neuronal reuptake of monoamines. The purpose of this study was to characterize the blood-brain barrier (BBB) transport of tramadol by means of microdialysis studies in rat brain and in vitro studies with human immortalized brain capillary endothelial cells (hCMEC/D3). The Kp,uu,brain value of tramadol determined by rat brain microdialysis was greater than unity, indicating that tramadol is actively taken up into the brain across the BBB. Tramadol was transported into hCMEC/D3 cells in a concentration-dependent manner. The uptake was inhibited by type II cations (pyrilamine, verapamil, etc.), but not by substrates of organic cation transporter OCTs or OCTN2. It was also inhibited by a metabolic inhibitor but was independent of extracellular sodium or membrane potential. The uptake was altered by changes of extracellular pH, and by ammonium chloride-induced intracellular acidification, suggesting that transport of tramadol is driven by an oppositely directed proton gradient. Thus, our in vitro and in vivo results suggest that tramadol is actively transported, at least in part, from blood to the brain across the BBB by proton-coupled organic cation antiporter.

  20. Pharmacodynamic Profile of Tramadol in Humans: Influence of Naltrexone Pretreatment

    PubMed Central

    Stoops, William W.; Lofwall, Michelle R.; Nuzzo, Paul A.; Craig, Lori B.; Siegel, Anthony J.; Walsh, Sharon L.

    2012-01-01

    Rationale Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects. Objectives This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans. Methods This inpatient, double-blind, randomized, within-subject study examined the effects of oral placebo, tramadol (87.5, 175 and 350 mg) and hydromorphone (4 and 16 mg; positive control) after 1 hr pretreatment with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the study. Pharmacodynamic effects were measured before and for 7 hr after initial drug administration. Results Lower doses of tramadol and hydromorphone were generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced miosis and increased ratings of “Good Effects” and “Liking ,” but also increased ratings of “Bad Effects.” Naltrexone reversed tramadol-induced physiological effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone only partially attenuated tramadol’s positive subjective effects and actually enhanced several unpleasant subjective ratings. Conclusions Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol. High dose tramadol produces a mixed profile of effects. These data suggest that both mu and non-mu opioid actions play a role in tramadol’s subjective profile of action. PMID:22623016

  1. A thought for tramadol hydrochloride as labor analgesic

    PubMed Central

    Kushtagi, Pralhad; Surpaneni, Nandini

    2012-01-01

    Aims: To evaluate and compare the analgesic efficacy and adverse effects of tramadol and meperidine in labor. Subjects and Methods: One hundred sixty-three of the 213 parturients at term in active labor were randomly assigned to one of three groups to receive intramuscularly either tramadol 50 mg (N = 54), tramadol 100 mg (N = 55) or meperidine 75 mg (N = 54). Single person who was not aware of the given drug (NS) assessed analgesic effect using visual analogue scale (VAS). Maternal side effects, effect on labor, and perinatal outcome were also studied. Statistical Analysis: Effect of the drugs used on maternal and fetal wellbeing was compared within study groups in reference to the control group. The quantitative analysis was done using unpaired t-test and for qualitative analysis chi-square test was applied. Results: Proportion of cases with satisfactory to good pain relief (VAS difference >5) after 2 h of administration was 35.2 (19 of 54), 61.8 (34 of 55) and 70.3% (38 of 54) in tramadol 50 mg, tramadol 100 mg and meperidine 75 mg groups, respectively. Nausea and/or vomiting (11% vs. 7%), drowsiness (20.4% vs. 5.5%) and fatigue (16.7% vs. 6%) were significantly high in meperidine than in tramadol groups (P<0.05). Proportion of cases with nonreassuring fetal heart rate and neonates with <7 Apgar were high in the meperidine group. Meconium stained liquor was seen equally in tramadol 100 mg and meperidine groups, and was lower in tramadol 50 mg group. All the intervention groups had relatively shorter observed active phase of labor than controls. Conclusions: Tramadol 100 mg is an equally effective labor analgesic as meperidine with less maternal and perinatal side effects. PMID:25885607

  2. Influence of pre- or intraoperational use of tramadol (preemptive or preventive analgesia) on tramadol requirement in the early postoperative period.

    PubMed

    Wordliczek, Jerzy; Banach, Marcin; Garlicki, Jarosław; Jakowicka-Wordliczek, Joanna; Dobrogowski, Jan

    2002-01-01

    The aim of this study was to assess the influence of iv tramadol on opioid requirement in the early postoperative period. The subjects were 90 patients scheduled for colon surgery (hemicolectomy) who received general anesthesia using the (N2O/O2) isoflurane technique. Thirty patients (group I) were administered 100 mg of tramadol iv before induction of general anesthesia (preemptive analgesia). Group II (30 patients) was administered 100 mg of tramadol iv immediately after peritoneal closure (preventive analgesia) and control group (30 patients) received 100 mg of tramadol iv immediately after operation. Following the operation, all patients were administered tramadol in the PCA-iv mode in order to treat postoperative pain. In the postoperative period, the following parameters were measured: pain intensity (using VAS), total consumption of tramadol, time until the first PCA activation, and frequency of side effects (drowsiness, nausea, vomiting). In patients of groups I and II who had received preemptive or preventive analgesia, a significantly lower total consumption of tramadol, as compared with control group, was observed in the early postoperative period. However, the time until the first PCA activation was significantly shorter in group I as compared to the other two groups. No significant differences between the groups were found regarding pain intensity and frequency of side effects.

  3. A physiologically based model for tramadol pharmacokinetics in horses.

    PubMed

    Abbiati, Roberto Andrea; Cagnardi, Petra; Ravasio, Giuliano; Villa, Roberto; Manca, Davide

    2017-09-21

    This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species. The proposed model is based on physiology but adopts the minimal compartmental architecture necessary to describe the experimental data. The model features a system of ordinary differential equations, where most of the model parameters are either assigned or individualized for a given horse, using literature data and correlations. Conversely, residual parameters, whose value is unknown, are regressed exploiting experimental data. The model proved capable of simulating pharmacokinetic profiles with accuracy. In addition, it provides further insights on un-observable tramadol data, as for instance tramadol concentration in the liver or hepatic metabolism and renal excretion extent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. [Neonatal abstinence syndrome after maternal use of tramadol].

    PubMed

    de Wit, Djoeke; Koomen-Botman, Irene

    2013-01-01

    Tramadol is an opioid with lipophilic characteristics that freely crosses the placenta. Due to the placental transfer, there is a risk of neonatal withdrawal symptoms. Therefore, chronic use during pregnancy is not advised. A 25-year-old pregnant woman, gravida 3, para 1, used tramadol 100 mg 3 times a day for chronic headache and migraine during this pregnancy. Because of the risk for neonatal abstinence syndrome, delivery took place in the hospital and the neonate had to stay at least 3 days for observation. The newborn developed neonatal withdrawal symptoms 36 hours after delivery. Treatment with phenobarbital was effective; 9 days after delivery the newborn was discharged without further treatment. When tramadol is used during pregnancy, there is a serious risk for neonatal abstinence syndrome. Phenobarbital proved to be effective for the treatment of neonatal tramadol withdrawal.

  5. Use of tramadol in early pregnancy and congenital malformation risk.

    PubMed

    Källén, Bengt; Reis, Margareta

    2015-12-01

    Only few studies exist regarding the risk of a teratogenic effect of tramadol when used in early pregnancy. Using the Swedish Medical Birth Register, women (deliveries in 1997-2013) who had reported the use of tramadol in early pregnancy were identified. Maternal characteristics and concomitant drug use were analyzed. Among 1,682,846 women (1,797,678 infants), 1751 (1776 infants) had used tramadol, 96 of the infants had a congenital malformation and 70 of them were relatively severe. The adjusted odds ratio for a relatively severe malformation was 1.33 (95% CI 1.05-1.70). The odds ratios for cardiovascular defects (1.56, 95% CI 1.04-2.29) and for pes equinovarus (3.63, 95% CI 1.61-6.89) were significantly increased. The study suggests a teratogenic effect of tramadol but the risk increase is moderate. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Tramadol-induced hyponatraemia following unicompartmental knee replacement surgery.

    PubMed

    Udy, A; Deacy, N; Barnes, D; Sigston, P

    2005-08-01

    We report a case of postoperative hyponatraemia following routine knee surgery, followed by a subsequent, less severe, episode after identical surgery on the contralateral knee. On each occasion the patient had been given the weak opioid tramadol for postoperative pain relief. Through its effects on serotonergic neurotransmission in the central nervous system, we hypothesise that tramadol may have been directly involved in this patient's biochemical disorder.

  7. Pre-Emptive Tramadol Could Reduce Pain after Ureteroscopic Lithotripsy

    PubMed Central

    Denčić, Nataša; Jovičić, Jelena; Mirković, Jelena; Durutović, Otaš; Milenković-Petronić, Dragica; Lađević, Nebojša

    2014-01-01

    Purpose Optimal analgesia in ambulatory urology patients still remains a challenge. The aim of this study was to examine if the pre-emptive use of intravenous tramadol can reduce pain after ureteroscopic lithotripsy in patients diagnosed with unilateral ureteral stones. Materials and Methods This prospective pilot cohort study included 74 patients diagnosed with unilateral ureteral stones who underwent ureteroscopic lithotripsy under general anesthesia in the Urology Clinic at the Clinical Center of Serbia from March to June 2012. All patients were randomly allocated to two groups: one group (38 patients) received intravenous infusion of tramadol 100 mg in 500 mL 0.9%NaCl one hour before the procedure, while the other group (36 patients) received 500 mL 0.9%NaCl at the same time. Visual analogue scale (VAS) scores were recorded once prior to surgery and two times after the surgery (1 h and 6 h, respectively). The patients were prescribed additional postoperative analgesia (diclofenac 75 mg i.m.) when required. Pre-emptive effects of tramadol were assessed measuring pain scores, VAS1 and VAS2, intraoperative fentanyl consumption, and postoperative analgesic requirement. Results The average VAS1 score in the tramadol group was significantly lower than that in the non-tramadol group. The difference in average VAS2 score values between the two groups was not statistically significant; however, there were more patients who experienced severe pain in the non-tramadol group (p<0.01). The number of patients that required postoperative analgesia was not statistically different between the groups. Conclusion Pre-emptive tramadol did reduce early postoperative pain. The patients who received pre-emptive tramadol were less likely to experience severe post-operative pain. PMID:25048508

  8. Physical dependence potential of daily tramadol dosing in humans

    PubMed Central

    Lofwall, Michelle R.; Mintzer, Miriam Z.; Bigelow, George E.; Strain, Eric C.

    2011-01-01

    Rationale Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence. Objectives The current study assessed the level of physical dependence and opioid blockade efficacy produced by daily maintenance on oral tramadol. Methods Nine residential opioid-dependent adults were maintained on two doses of daily oral tramadol (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. The acute effects of intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were tested under double-blind, randomized conditions. Outcomes included observer- and subject-rated measures and physiologic indices. Results Challenge doses of naloxone resulted in significantly higher mean peak withdrawal scores compared to placebo. Withdrawal intensity from naloxone was generally greater during 800 versus 200 mg/day tramadol maintenance. Mean peak ratings of agonist effects were elevated at higher hydromorphone challenge doses, but did not differ significantly between tramadol doses. Physiologic measures were generally affected by challenge conditions in a dose-dependent manner, with few differences between tramadol maintenance dose conditions. Conclusions Chronic tramadol administration produces dose-related opioid physical dependence, without producing dose-related attenuation of agonist challenge effects. Tramadol may be a useful treatment for patients with low levels of opioid dependence or as a treatment for withdrawal during opioid detoxification, but does not appear to be effective as a maintenance medication due to a lack of opioid cross-tolerance. PMID:20589494

  9. Tramadol for noncancer pain and the risk of hyponatremia.

    PubMed

    Fournier, Jean-Pascal; Yin, Hui; Nessim, Sharon J; Montastruc, Jean-Louis; Azoulay, Laurent

    2015-04-01

    Case reports have signaled a possible association between tramadol, a weak opioid analgesic, and hyponatremia. The objective of this study was to determine whether the use of tramadol is associated with an increased risk of hyponatremia, when compared with codeine. Using the UK Clinical Practice Research Datalink and Hospital Episodes Statistics database, a population-based cohort of 332,880 patients initiating tramadol or codeine was assembled from 1998 through 2012. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of hospitalization for hyponatremia associated with the use of tramadol, compared with codeine, in the first 30 days after initiation. A similar analysis was conducted within a highly restricted sub-cohort, which additionally excluded patients with any serum sodium level abnormality in the year before cohort entry. All models were adjusted for propensity score quintiles. The incidence rates of hospitalization for hyponatremia were 4.6 (95% CI, 2.4-8.0) and 1.9 (95% CI, 1.4-2.5) per 10,000 person-months for tramadol and codeine users, respectively. In the adjusted model, the use of tramadol was associated with a 2-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 2.05; 95% CI, 1.08-3.86). In the highly restricted sub-cohort, the use of tramadol was associated with an over 3-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 3.54; 95% CI, 1.32-9.54). In this first population-based study, the use of tramadol was associated with an increased risk of hyponatremia requiring hospitalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Does tramadol affect coagulation status of patients with malignancy?

    PubMed Central

    Bilir, Ayten; Akay, Meltem Olga; Ceyhan, Dilek; Andıc, Neslihan

    2014-01-01

    Aim: The study investigated the direct effects of tramadol on the coagulation status of women with gynecologic malignancies in vitro. Materials and Methods: Citrated whole-blood samples from 21 patients with gynecologic tumors were spiked ex vivo with 2 or 6 μl/ml tramadol. Thrombelastography (TEG) analysis was performed using ROTEM® to assess clotting time (CT), clot formation time (CFT) and maximum clot formation (MCF). Results: In the INTEM assay, CT (P < 0.05) and CFT (P < 0.01) were significantly prolonged with tramadol at a 6 μl/ml concentration compared with baseline. There were no significant differences in MCF values between the baseline and the tramadol-treated samples (P > 0.05). Blood medicated with tramadol (6 μl/ml) clotted slowly (increased CT and CFT). Conclusion: The changes observed by TEG demonstrated that tramadol impairs hemostasis in a concentration-dependent manner in the whole blood of women with gynecologic malignancies in vitro. PMID:25097280

  11. Comparative metabolism of tramadol and tapentadol: a toxicological perspective.

    PubMed

    Barbosa, Joana; Faria, Juliana; Queirós, Odília; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2016-11-01

    Tramadol and tapentadol are centrally acting, synthetic opioid analgesics used in the treatment of moderate to severe pain. Main metabolic patterns for these drugs in humans are well characterized. Tramadol is mainly metabolized by cytochrome P450 CYP2D6 to O-desmethyltramadol (M1), its main active metabolite. M1 and tapentadol undergo mainly glucuronidation reactions. On the other hand, the pharmacokinetics of tramadol and tapentadol are dependent on multiple factors, such as the route of administration, genetic variability in pharmacokinetic components and concurrent consumption of other drugs. This review aims to comparatively discuss the metabolomics of tramadol and tapentadol, namely by presenting all their known metabolites. An exhaustive literature search was performed using textual and structural queries for tramadol and tapentadol, and associated known metabolizing enzymes and metabolites. A thorough knowledge about tramadol and tapentadol metabolomics is expected to provide additional insights to better understand the interindividual variability in their pharmacokinetics and dose-responsiveness, and contribute to the establishment of personalized therapeutic approaches, minimizing side effects and optimizing analgesic efficacy.

  12. Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain.

    PubMed

    Miranda, Hugo F; Noriega, Viviana; Prieto, Juan Carlos; Zanetta, Pilar; Castillo, Rodrigo; Aranda, Nicolás; Sierralta, Fernando

    2016-08-01

    Neuropathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive interaction between both drugs using the isobolographic analysis and changes of the IL-1β concentration in a mouse model of neuropathic pain (partial sciatic nerve ligation or PSNL). The i.p. administration of gabapentin (5-100 mg/kg) or tramadol (12.5-100 mg/kg) displayed a dose-dependent antinociception in the hot plate assay of PSNL mice, and effects induced by gabapentin with tramadol were synergistic. Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1β induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1β. The synergism obtained by the co-administration of gabapentin and tramadol is proposed to result from action on different mechanisms in pain pathways. Gabapentin or tramadol or their combination modulates the expression of pro-inflammatory cytokine, IL-1β, in a model of mice PSNL which could be due to an inhibition of glial function. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  13. Successful treatment of mixed (mainly cancer) pain by tramadol preparations.

    PubMed

    Kawahito, Shinji; Soga, Tomohiro; Mita, Naoji; Satomi, Shiho; Kinoshita, Hiroyuki; Arase, Tomoko; Kondo, Akira; Miki, Hitoshi; Takaishi, Kazumi; Kitahata, Hiroshi

    2017-01-01

    The patient, a 70-year-old Japanese woman diagnosed with parotid gland cancer, underwent wide excision and reconstruction (facial nerve ablation, nerve transposition). At 1 month after the surgery, she was brought to our hospital's pain medicine department because her postoperative pain and cancer-related pain were poorly controlled. She had already been prescribed a tramadol (37.5 mg)/acetaminophen (325 mg) combination tablet (5 tablets/day). However, in addition to the continuous pain in her face and lower limbs, she was troubled by a trigeminal neuralgia-like prominence ache. Because this pain could not be controlled by an increase to eight combination tablets per day, we switched her medication to a tramadol capsule. At 11 months post-surgery, we then switched her medication to an orally disintegrating tramadol tablet to improve medication adherence of the drug. From 14 months post-surgery, the patient also used a sustained-release tramadol preparation, and she was then able to sleep well. Her current regimen is an orally disintegrating sustained-release tablet combination (total 300 mg tramadol) per day, and she achieved sufficient pain relief. Because tramadol is not classified as a medical narcotic drug, it widely available and was shown here to be extremely useful for the treatment of our patient's mixed (mainly cancer) pain. J. Med. Invest. 64: 311-312, August, 2017.

  14. Tramadol combined with fentanyl in awake endotracheal intubation

    PubMed Central

    Wang, Sai-Ying; Mei, Yang; Sheng, Hui; Li, Yang; Han, Rui; Quan, Cheng-Xuan; Hu, Zhong-Hua; Ouyang, Wen; Liu, Zhao-Qian

    2013-01-01

    Objective To explore the feasibility and dosage of tramadol combined with fentanyl in awake endotracheal intubation. Methods Using Dixon’s up-and-down sequential design, the study enrolled patients from each of the 20-49, 50-60 and 70-and-above age groups scheduled for elective surgery under general anesthesia. The feasibility and dosage of tramadol combined with fentanyl in awake endotracheal intubation, guided by fiberoptic bronchoscopy, were verified. Results After intravenous injection with fentanyl 2.2 μg/kg and tramadol 2.0 mg/kg in the 20-49 age group, fentanyl 1.6 μg/kg and tramadol 1.9 mg/kg in the 50-69 age group and fentanyl 1 μg/kg and tramadol 1.8 mg/kg in those at the age of 70 or above, the patients achieved conscious sedation without obvious respiratory depression. Meanwhile, under these dosages, the patients could easily tolerate the thyrocricocentesis airway surface anesthesia and fiberoptic bronchoscope guided tracheal intubation. Postoperative follow-up showed that most patients had memory of the intubation process but without significant discomfort. No awake endotracheal intubation-related side effect was noted. Conclusions Fiberoptic bronchoscope guided nasotracheal intubation can be successfully completed with background administration of fentanyl and tramadol. However, the specific dosages need to be tailored in different age of patients. PMID:23825758

  15. The effect of single-dose tramadol on oxycodone clearance.

    PubMed

    Curry, Steven C; Watts, David J; Katz, Kenneth D; Bikin, Dale; Bukaveckas, Bonny L

    2007-11-01

    We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (C(max)) and time until peak oxycodone concentrations (T(max)) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, C(max), and T(max) were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance.

  16. The effects of ketoconazole and cimetidine on the pharmacokinetics of oral tramadol in greyhound dogs.

    PubMed

    KuKanich, B; KuKanich, K; Black, J

    2017-06-11

    Tramadol is administered to dogs for analgesia but has variability in its extent of absorption, which may hinder its efficacy. Additionally, the active opioid metabolite (M1) occurs in low concentrations. The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1. Six healthy Greyhounds were included. They were administered tramadol orally and intravenously, M1 intravenously, oral tramadol with oral ketoconazole and oral tramadol with oral cimetidine. Oral tramadol bioavailability was low (2.6%). Ketoconazole and cimetidine significantly increased tramadol bioavailability to 18.2% and 20.3%, respectively. The mean maximum plasma concentration of tramadol alone was 22.9 ng/ml, and increased to 109.9 and 143.2 μg/ml with ketoconazole and cimetidine, respectively. However, measured tramadol plasma concentrations were below the minimum concentration considered effective in humans (228 μg/ml). In all treatment groups, measured M1 concentrations (<7 μg/ml) were below concentrations associated with efficacy in humans. To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined. © 2017 John Wiley & Sons Ltd.

  17. Quantification in postmortem blood and identification in urine of tramadol and its two main metabolites in two cases of lethal tramadol intoxication.

    PubMed

    De Backer, B; Renardy, F; Denooz, R; Charlier, C

    2010-11-01

    Tramadol is an opioid analgesic considered to induce fewer side effects than other compounds of this class. It has been extensively prescribed for two decades. However, serious complications may occur in case of intoxication. We report here two cases of fatal intoxication due to tramadol ingestion. Tramadol, O-desmethyltramadol (ODT), and N-desmethyltramadol (NDT) were quantitatively and qualitatively determined in postmortem blood and urine, respectively. An HPLC method coupled with fluorescence detection was validated using total error approach for the analysis of tramadol, ODT, and NDT in blood. In case 1, concentrations of tramadol and its metabolites were 7.7 mg/L (tramadol), 1.33 mg/L (ODT), and 0.6 mg/L (NDT). In case 2, concentrations found were 48.34 mg/L (tramadol), 2.43 mg/L (ODT), and 10.09 mg/L (NDT). The tramadol concentration found in case 2 is one of the highest ever described in the literature. Opposite ratios of ODT/NDT concentrations observed in different cases were suggested to be useful for the evaluation of the delay between ingestion and death. However, the changes in metabolites levels may also be explained by pharmacokinetic interactions and quantitative differences in the activity of the cytochrome-P450 2D6. Interestingly, norfluoxetine was detected in subtherapeutic levels in case 2. Most of these aspects in tramadol-related fatalities are reviewed in this paper, and an overview of fatal intoxications due to tramadol is presented.

  18. Post-operative pain control after tonsillectomy: dexametasone vs tramadol.

    PubMed

    Topal, Kubra; Aktan, Bulent; Sakat, Muhammed Sedat; Kilic, Korhan; Gozeler, Mustafa Sitki

    2017-06-01

    Tramadol was found to be more effective than dexamethasone in post-operative pain control, with long-lasting relief of pain. This study aimed to compare the effects of pre-operative local injections of tramadol and dexamethasone on post-operative pain, nausea and vomiting in patients who underwent tonsillectomy. Sixty patients between 3-13 years of age who were planned for tonsillectomy were included in the study. Patients were divided into three groups. Group 1 was the control group. Patients in Group 2 received 0.3 mg/kg Dexamethasone and Group 3 received 0.1 mg/kg Tramadol injection to the peritonsillary space just before the operation. Patients were evaluated for nausea, vomiting, and pain. When the control and the dexamethasone groups were compared; there were statistically significant differences in pain scores at post-operative 15 and 30 min, whereas there was no statistically significant difference in pain scores at other hours. When the control and tramadol groups were compared, there was a statistically significant difference in pain scores at all intervals. When tramadol and dexamethasone groups were compared, there was no statistically significant difference in pain scores at post-operative 15 and 30 min, 1 and 2 h, whereas there was a statistically significant difference in pain scores at post-operative 6 and 24 h.

  19. The effects of tramadol on postoperative shivering after sevoflurane and remifentanil anesthesia.

    PubMed

    Nakagawa, Taku; Hashimoto, Miki; Hashimoto, Yasunori; Shirozu, Kazuhiro; Hoka, Sumio

    2017-01-03

    Remifentanil has been reported to cause post-anesthetic shivering (PAS). Higher doses of remifentanil reportedly induce more intense PAS. Tramadol, a synthetic opioid that acts at multiple sites, is considered to be an effective treatment for PAS, but the evidence for its therapeutic benefit after remifentanil anesthesia is limited. We investigated the effect of tramadol on the incidence of PAS after remifentanil anesthesia. Sixty-three patients who had undergone upper abdominal surgery under general anesthesia were studied retrospectively. Tramadol was administered at induction of anesthesia. The patients were divided into four groups: HT(+), high dose remifentanil (1-1.5 μg/kg/min) with tramadol; HT(-), high dose remifentanil without tramadol; LT(+), low dose remifentanil (0.15-0.25 μg/kg/min) with tramadol; and LT(-), low dose remifentanil without tramadol. We recorded perioperative changes in nasopharyngeal temperature and episodes of PAS on emergence from anesthesia. The incidences of PAS in both tramadol treatment groups were significantly lower than the groups that did not receive tramadol. Nasopharyngeal temperature after surgery fell significantly more from baseline in the tramadol treatment groups compared with the non-treatment groups. Tramadol administered at induction of anesthesia appears to suppress PAS following remifentanil anesthesia.

  20. Acute-withdrawal restless legs syndrome following abrupt cessation of short-term tramadol.

    PubMed

    Park, Young-Min; Park, Hye Kyeong; Kim, Leen; Lee, Heon-Jeong; Kang, Seung-Gul

    2014-04-01

    We report a young man who had received tramadol for pain control and experienced an uncomfortable sensation in both legs immediately after tramadol withdrawal that worsened at rest and at night, and which could be relieved only by moving the legs. He suffered from insomnia and paced up and down in his house every night. Readministration of tramadol dramatically resolved his symptoms of restless legs syndrome (RLS), but they reappeared after tramadol withdrawal. Tramadol was therefore replaced with ropinirole, which was discontinued after several weeks, and there was no recurrence of his RLS symptoms. This patient appeared to have developed tramadol-withdrawal-induced RLS, and this case report emphasizes the importance of monitoring for withdrawal-type symptoms like RLS when tramadol intake is being stopped.

  1. Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms.

    PubMed

    Carrillo-Munguía, Norma; González-Trujano, Ma Eva; Huerta, Miguel; Trujillo, Xochitl; Díaz-Reval, M Irene

    2015-01-01

    Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception.

  2. Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

    PubMed Central

    Carrillo-Munguía, Norma; González-Trujano, Ma. Eva; Huerta, Miguel; Trujillo, Xochitl; Díaz-Reval, M. Irene

    2015-01-01

    Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception. PMID:26146627

  3. Cardiovascular effects of tramadol in dogs anesthetized with sevoflurane.

    PubMed

    Itami, Takaharu; Tamaru, Naomichi; Kawase, Kodai; Ishizuka, Tomohito; Tamura, Jun; Miyoshi, Kenjirou; Umar, Mohammed A; Inoue, Hiroki; Yamashita, Kazuto

    2011-12-01

    Cardiovascular effects of tramadol were evaluated in dogs anesthetized with sevoflurane. Six beagle dogs were anesthetized twice at 7 days interval. The minimum alveolar concentration (MAC) of sevoflurane was earlier determined in each dog. The dogs were then anesthetized with sevoflurane at 1.3 times of predetermined individual MAC and cardiovascular parameters were evaluated before (baseline) and after an intravenous injection of tramadol (4 mg/kg). The administration of tramadol produced a transient and mild increase in arterial blood pressure (ABP) (P=0.004) with prolonged increase in systemic vascular resistance (SVR) (P<0.0001). Compared with baseline value, mean ABP increased significantly at 5 min (119% of baseline value, P=0.003), 10 min (113%, P=0.027), and 15 min (111%, P=0.022). SVR also increased significantly at 5 min (128%, P<0.0001), 10 min (121%, P=0.026), 30 min (114%, P=0.025), 45 min (113%, P=0.025) and 60 min (112%, P=0.048). Plasma concentrations of tramadol were weakly correlated with the percentage changes in mean ABP (r=0.642, P<0.0001) and SVR (r=0.646, P<0.0001). There was no significant change in heart rate, cardiac output, cardiac index, stroke volume, pulmonary arterial pressure, right atrial pressure and pulmonary capillary wedge pressure. In conclusion, the administration of tramadol produces a prolonged peripheral vascular constriction in dogs anesthetized with sevoflurane, which is accompanied with a transient and mild increase in arterial blood pressure. It also indicated that the degree of vasoconstriction might depend on the plasma concentration of tramadol.

  4. Tramadol does not enhance sedation induced by acepromazine in dogs

    PubMed Central

    Monteiro, Eduardo R.; Lobo, Renan B.; Nunes, Juarez S.; Rangel, Julia P.P.; Bitti, Flavia S.

    2016-01-01

    The sedative effect of acepromazine combined with 2 doses of tramadol [3 and 5 mg/kg body weight (BW)] was compared with the sedative effect of acepromazine alone in dogs and the effects of each sedative protocol on cardiorespiratory variables were examined. This was a prospective, randomized, blinded, crossover study. Each of 6 dogs received 3 treatments at 1-week intervals. During all anesthetic episodes, dogs received 0.05 mg/kg BW acepromazine. Approximately 25 min later, dogs were given physiological saline (control) or tramadol [3 mg/kg BW (TR3) or 5 mg/kg BW (TR5)]. All drugs were administered intravenously. Variables evaluated included heart rate (HR), respiratory rate (RR), systolic, mean, and diastolic blood pressures (SAP, MAP, and DAP), and sedation [by use of a simple descriptive scale (SDS, range: 0 to 3) and a numeric rating scale (NRS, range: 0 to 10)]. Variables were recorded 25 min after acepromazine and for 80 min after saline or tramadol. Acepromazine administration resulted in mild sedation in most dogs and decreased RR, SAP, MAP, and DAP in all treatments. Tramadol administration did not significantly increase SDS or NRS scores compared to acepromazine alone. The only exception to this rule was observed at 20 min after TR3, when NRS was higher in this group than in the control treatment. Administration of tramadol (TR3 and TR5) decreased HR. Under the conditions of this study, sedation induced by acepromazine with tramadol was similar to that of acepromazine alone. The main adverse effects of the combination were a decrease in blood pressure and HR, without clinical significance. PMID:27733788

  5. Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish.

    PubMed

    Zhuo, Huiqin; Jin, Hongwei; Peng, Huifang; Huang, Heqing

    2016-12-01

    The current study aimed to develop a rapid, robust and adequately sensitive method for simultaneous determination of the concentration of tramadol and its active metabolites in zebrafish. The pharmacokinetic and elimination pattern of tramadol and its major phase I metabolites following oral or intramuscular administration in zebrafish tissues was achieved using electrospray ionization‑quadrupole‑time of flight/mass spectrometry (ESI‑Q‑TOF/MS) and gas chromatography/mass spectrometry (GC‑MS). Following administration, the metabolisms were detected in the brain, eyes, muscle and gill tissues within 1 h. Two tramadol metabolites, O‑ and N‑desmethyltramadol, were detected in brain tissue, with N‑desmethyltramadol detected at a higher level. Following GC‑MS detection the curve indicated an initial rapid phase, corresponding to the detection of the tramadol within 1 min, and reached peak value in the brain at 5 min. Faster drug clearance was detected in low‑dose groups, and concentration had dropped around the to initial level (1.11 µg) at 20 min, but was detectable for up to 3 h. However, it took 80 min to fall back to the initial value (1.73 µg) in the high‑dose groups, and tramadol was detectable for up to 4 h. This study developed and validated a simple and high throughput analytical procedure to determine the distribution and pharmacokinetic profiles of tramadol, and its primary metabolites in tissues of zebrafish.

  6. Tramadol does not enhance sedation induced by acepromazine in dogs.

    PubMed

    Monteiro, Eduardo R; Lobo, Renan B; Nunes, Juarez S; Rangel, Julia P P; Bitti, Flavia S

    2016-10-01

    The sedative effect of acepromazine combined with 2 doses of tramadol [3 and 5 mg/kg body weight (BW)] was compared with the sedative effect of acepromazine alone in dogs and the effects of each sedative protocol on cardiorespiratory variables were examined. This was a prospective, randomized, blinded, crossover study. Each of 6 dogs received 3 treatments at 1-week intervals. During all anesthetic episodes, dogs received 0.05 mg/kg BW acepromazine. Approximately 25 min later, dogs were given physiological saline (control) or tramadol [3 mg/kg BW (TR3) or 5 mg/kg BW (TR5)]. All drugs were administered intravenously. Variables evaluated included heart rate (HR), respiratory rate (RR), systolic, mean, and diastolic blood pressures (SAP, MAP, and DAP), and sedation [by use of a simple descriptive scale (SDS, range: 0 to 3) and a numeric rating scale (NRS, range: 0 to 10)]. Variables were recorded 25 min after acepromazine and for 80 min after saline or tramadol. Acepromazine administration resulted in mild sedation in most dogs and decreased RR, SAP, MAP, and DAP in all treatments. Tramadol administration did not significantly increase SDS or NRS scores compared to acepromazine alone. The only exception to this rule was observed at 20 min after TR3, when NRS was higher in this group than in the control treatment. Administration of tramadol (TR3 and TR5) decreased HR. Under the conditions of this study, sedation induced by acepromazine with tramadol was similar to that of acepromazine alone. The main adverse effects of the combination were a decrease in blood pressure and HR, without clinical significance.

  7. In vitro and in vivo vasodilator activity of racemic tramadol and its enantiomers in Wistar rats.

    PubMed

    Raimundo, Juliana Montani; Sudo, Roberto Takashi; Pontes, Luana Braga; Antunes, Fernanda; Trachez, Margarete Manhães; Zapata-Sudo, Gisele

    2006-01-13

    Tramadol ((+/-)-tramadol) is an analgesic agent formulated as a racemic mixture (1:1) of (-)- and (+)-tramadol, which differ in their potency to bind to mu-opioid receptors and to inhibit monoamine-reuptake. We investigated the stereoselectivity of in vitro tramadol-induced vasodilatation of aortic rings and its effect on the arterial blood pressure measured in conscious Wistar rats. (+)-Tramadol, but not (-)-tramadol, produced a concentration-dependent relaxation of aorta precontracted with phenylephrine. The concentration-response curve was significantly altered by the removal of endothelium. Vascular relaxation was also inhibited by pre-incubation of endothelium-intact aorta with naloxone, suggesting the involvement of opioid receptors. The vasodilatation produced by tramadol was stereoselective, and the (+)-tramadol-induced vasodilatation was mediated by mu-opioid receptors and partially dependent on endothelium integrity. The hypotensive response induced by (+)-tramadol was also observed after bolus injection of 5.0 and 10.0 mg/kg. The results indicate that only high doses of tramadol cause cardiac depression and hypotension, indicating that it can be used safely.

  8. [Clinical anesthetic effects of epidural ropivacaine with tramadol].

    PubMed

    Cai, Jin; Guo, Qu-Lian; Zou, Wang-Yuan

    2004-04-01

    To observe the anesthesic effects of epidural ropivacaine with tramadol during lower limbs surgery. Thirty patients (ASA I - II) scheduled for the lower limbs surgery were randomly divided into 2 groups with 15 patients in each group: group ropivacaine (R) and group ropivacaine with tramadol (T). The puncture was performed at the interspace of L2-3. Each patient was given 2% lidocaine 3 ml with 0.75% ropivacaine 10 ml which included NS 1 ml in Group R or tramadol 50 mg in Group T. The potency of analgesia, the time of sensation block to T12 and T10, the time to the highest plane of analgesia, the lasting time of analgesia, the degree of sedation, the degree of motor block, and the side effects were recorded and analyzed during anesthesia after the first dose. The time of sensation block which reached T12 and T10 and the time to the highest plane of analgesia decreased significantly in Group T than that in Group R (P < 0.05). The lasting time of analgesia in Group T was longer than that in Group R (P < 0.05). There was no significant difference in the potency of analgesia, the degree of sedation and motor block, and the side effects (P > 0.05). The epidural ropivacaine with tramadol enhanced the anesthetic effects of ropivacaine.

  9. [Mucoadhesive buccal films of tramadol for effective pain management].

    PubMed

    Li, Xiao-Qin; Ye, Zhao-Ming; Wang, Jian-Bing; Fan, Cai-Rong; Pan, Ai-Wu; Li, Cong; Zhang, Ren-Bing

    Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Synergism between tramadol and parecoxib in the orofacial formalin test.

    PubMed

    Isiordia-Espinoza, Mario Alberto; Zapata-Morales, Juan Ramón; Castañeda-Santana, Demian Ismael; de la Rosa-Coronado, Maximiliano; Aragon-Martinez, Othoniel Hugo

    2015-05-01

    The aim of this study was to evaluate the interaction between tramadol and parecoxib in the orofacial formalin test. Tramadol (10, 31.6, 56, and 100 mg/kg ip) or parecoxib (31.6, 56, 100, and 178 mg/kg ip) were administered 10 min before formalin (2.5%) injection into the upper lip to characterize the dose-response curve of each individual drug in the orofacial pain test in mice. Once the dose-response curve of each drug was obtained, an experimental effective dose 50 (ED50 ) value was determined for each drug. The tramadol-parecoxib combination was evaluated in four different groups of animals. The isobolographic analysis and the interaction index were used to evaluate the nature of interaction between both drugs. The isobologram and the interaction index showed increased in the antinociceptive effect of the combination. The tramadol-parecoxib combination produces a synergism in the second phase of the orofacial formalin test. © 2015 Wiley Periodicals, Inc.

  11. Abuse Liability and Reinforcing Efficacy of Oral Tramadol in Humans

    PubMed Central

    Babalonis, Shanna; Lofwall, Michelle R.; Nuzzo, Paul A.; Siegel, Anthony J.; Walsh, Sharon L.

    2012-01-01

    BACKGROUND Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally. The purpose of this study was to examine the relative abuse liability and reinforcing efficacy of tramadol in comparison to a high (oxycodone) and low efficacy (codeine) opioid agonist. METHODS Nine healthy, non-dependent prescription opioid abusers (6 male, 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample, 7 self-administration). During each sample session, an oral dose of tramadol (200, 400 mg), oxycodone (20, 40 mg), codeine (100, 200 mg) or placebo was administered, and a full array of abuse liability measures was collected. During self-administration sessions, volunteers were given the opportunity to work (via progressive ratio) for the sample dose or money. RESULTS All active doses were self-administered; placebo engendered no responding. The high doses of tramadol and oxycodone were readily self-administered (70%, 59% of available drug, respectively); lower doses and both codeine doses maintained intermediate levels of drug taking. All three drugs dose-dependently increased measures indicative of abuse liability, relative to placebo; however, the magnitude and time course of these and other pharmacodynamic effects varied qualitatively across drugs. CONCLUSIONS This study demonstrates that, like other mu opioids, higher doses of tramadol function as reinforcers in opioid abusers, providing new empirical data for regulatory evaluation. PMID:23098678

  12. Cutaneous silent period in hand muscles is lengthened by tramadol: Evidence for monoaminergic modulation?

    PubMed

    Pujia, Francesco; Coppola, Gianluca; Anastasio, Maria G; Brienza, Marianna; Vestrini, Elisa; Valente, Gabriele O; Parisi, Leoluca; Serrao, Mariano; Pierelli, Francesco

    2012-10-18

    The purpose of this study was to shed light on the neurochemical modulatory mechanisms of the noxious spinal inhibitory cutaneous silent period (CSP). We study the effects of 100mg of oral tramadol in 11 healthy volunteers. Tramadol has low affinity for opioid receptors and has the ability to inhibit serotonin and noradrenaline reuptake. We elicited CSPs in the first dorsal interosseus muscle and noxious withdrawal flexor reflexes (NWR) in the right biceps femoris muscle before, 30 min and each hour up to the 6th after tramadol. Subjective pain sensation was checked on an 11-point numerical scale. Tramadol increased duration of CSP, and reduced the NWR area under the curve maximally 2h after tramadol and paralleled the reduction of subjective pain perception. We suggest that the monoaminergic action of tramadol reinforces the activity of spinal inhibitory interneurons on α-motoneurons for the hand muscles. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Spectral characteristics of tramadol in different solvents and β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Anton Smith, A.; Manavalan, R.; Kannan, K.; Rajendiran, N.

    2009-10-01

    Effect of solvents and β-cyclodextrin on the absorption and fluorescence spectra of tramadol drug has been investigated and compared with anisole. The solid inclusion complex of tramadol with β-CD is investigated by FT-IR, 1H NMR, scanning electron microscope (SEM), DSC and semiempirical methods. The thermodynamic parameter (Δ G) of inclusion process is determined. A solvent study shows (i) the spectral behaviour of both tramadol and anisole molecules is similar to each other and (ii) the cyclohexanol group in tramadol is not effectively conjugated with anisole group. However, in β-CD, due to space restriction of the CD cavity, a weak interaction is present between the above groups in tramadol. β-Cyclodextrin studies show that tramadol forms 1:2 inclusion complex with β-CD. A mechanism is proposed for the inclusion process.

  14. Nalbuphine could decrease the rewarding effect induced by tramadol in mice while enhancing its antinociceptive activity.

    PubMed

    Abdel-Ghany, Rasha; Nabil, Mahmoud; Abdel-Aal, Mohamed; Barakat, Waleed

    2015-07-05

    Nalbuphine, a kappa-opioid agonist and mu-opioid partial agonist, has been used as an analgesic or an adjuvant with morphine to attenuate the development of morphine dependence and rewarding effect. In this study, we investigated the effect of nalbuphine on tramadol rewarding effect and antinociception. Using the conditioned place preference (CPP) paradigm in mice, we demonstrated that co-administration of nalbuphine (7mg/kg, s.c.) with tramadol (70mg/kg, s.c.) during conditioning completely blocked the CPP induced by tramadol. Co-administration of nalbuphine blocked the increase in dopamine level in the nucleus accumbens induced by tramadol. These actions were accompanied by an increase rather than attenuation of the antinociceptive effect of tramadol. These results suggest that nalbuphine could have a great potential as a pharmacotherapy for tramadol abuse. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Tramadol with or without paracetamol (acetaminophen) for cancer pain.

    PubMed

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2017-05-16

    Tramadol is an opioid analgesic licensed for use in moderate to severe pain. It is considered as a low risk for abuse, so control regulations are not as stringent as for 'strong' opioids such as morphine. It has a potential role as a step 2 option of the World Health Organization (WHO) analgesic ladder. To assess the benefits and adverse effects of tramadol with or without paracetamol (acetaminophen) for cancer-related pain. We searched the following databases using a wide range of search terms: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched three clinical trials registry databases. The date of the last search was 2 November 2016. We selected studies that were randomised, with placebo or active controls, or both, and included a minimum of 10 participants per treatment arm. We were interested particularly in blinded studies, but also included open studies.We excluded non-randomised studies, studies of experimental pain, case reports, and clinical observations. Two review authors independently extracted data using a standard form and checked for agreement before entry into Review Manager 5. We included information about the number of participants treated and demographic details, type of cancer, drug and dosing regimen, study design (placebo or active control) and methods, study duration and follow-up, analgesic outcome measures and results, withdrawals, and adverse events. We collated multiple reports of the same study, so that each study, rather than each report, was the unit of interest in the review. We assessed the evidence using GRADE and created a 'Summary of findings' table.The main outcomes of interest for benefit were pain reduction of 30% or greater and 50% or greater from baseline, participants with pain no worse than mild, and participants feeling much improved or very much improved. We included 10 studies (12 reports) with 958 adult participants. All the studies enrolled participants with

  16. A Comparative Study of the Efficacy of IV Dexketoprofen, Lornoxicam, and Diclophenac Sodium on Postoperative Analgesia and Tramadol Consumption in Patients Receiving Patient-Controlled Tramadol

    PubMed Central

    Kılıçkaya, Refika; Güleç, Ersel; Ünlügenç, Hakkı; Gündüz, Murat; Işık, Geylan

    2015-01-01

    Objective This study was designed to compare the effects of dexketoprofen, lornoxicam, and diclophenac sodium on postoperative analgesia and tramadol consumption in patients receiving postoperative patient-controlled tramadol after a major abdominal surgery. Methods Eighty patients were randomized to receive one of the four study drugs. Patients in group dexketoprofen (DT) received IV 50 mg dexketoprofen, group lornoxicam (LR) received IV 8 mg lornoxicam, group diclophenac sodium (DS) received 75 mg IV diclophenac sodium and group saline (S) received 0.9% saline in 2 mL syringes, 20 min before the end of anaesthesia. A standardized (1 mg kg−1) dose of tramadol was routinely administered to all patients as the loading dose at the end of surgery. Postoperatively, whenever patients requested, they were allowed to use a tramadol patient-controlled analgesia device giving a bolus dose (0.2 mg kg−1) of tramadol. Pain, discomfort, and sedation scores, cumulative tramadol consumption, supplemental meperidine requirement, and side effects were recorded. Results Visual rating scale and patient discomfort scores were significantly lower in DT, LR and DS groups compared to those in in group S (p<0.001). Cumulative tramadol consumption was significantly lower in non-steroidal anti-inflammatory drug (NSAID)-treated groups at each study period after the second postoperative hour than in group S (p<0.001). Supplemental meperidine requirement was significantly higher in group S at each study period after postoperative 30 min than in NSAID-treated groups (p<0.01). Conclusion After major abdominal surgery, adding IV diclophenac, lornoxicam or dexketoprofen to patient-controlled tramadol resulted in lower pain scores, smaller tramadol consumption, less rescue supplemental analgesic requirement, and fewer side effects compared with the tramadol alone group. PMID:27366491

  17. Postmortem Concentrations of Tramadol and O-Desmethyltramadol in 11 Aviation Accident Fatalities

    DTIC Science & Technology

    2010-12-01

    Crump University of Central Oklahoma Edmond, OK 73034 December 2010 Final Report Postmortem Concentrations of Tramadol and O-Desmethyltramadol in...Subtitle 5. Report Date Postmortem Concentrations of Tramadol and O-Desmethyltramadol in 11 Aviation Accident Fatalities December 2010 6. Performing...This work was accomplished under the approved task AM-B-10-TOX-204. 16. Abstract Tramadol is a centrally acting analgesic used to treat moderate

  18. Bioavailability of tramadol hydrochloride after administration via different routes in rats.

    PubMed

    Zhang, Hua; Zhao, Youyou; Wang, Xueqing; Zhang, Qiang

    2014-12-01

    Tramadol is a synthetic non-opiate analgesic drug and effective for many kinds of chronic and acute pain. This study compared the bioavailability of tramadol after different administration routes in rats (oral, buccal and nasal). A simple HPLC analytical approach was used to determine the concentration of tramadol in plasma. The pharmacokinetic behavior and bioavailability of tramadol after administration via different routes in rats were investigated. Nasal and buccal administration of tramadol resulted in a fast increase followed by a rapid decrease in the plasma tramadol concentration. The Cmax values following buccal and nasal administration were 6 times and 20 times higher than that of oral administration, respectively, (6827.85 ± 7970.87 ng/ml, 22191.84 ± 5364.86 ng/ml, vs 1127.03 ± 778.34 ng/ml). The relative bioavailabilities of the nasal- and buccal-administered drug when compared with the oral route were 504.8% and 183.4%, respectively, which is much higher than that of oral administration. Nasal and buccal administration increased the bioavailability of tramadol, which may allow for a reduction in the dose of tramadol and a subsequent decrease in both side effects and toxicity. Therefore, this approach provides an effective choice for the delivery of tramadol, an analgesic drug.

  19. Does Tramadol Increase the Severity of Nicotine Dependence? A Study in an Egyptian Sample.

    PubMed

    Shalaby, Amr Said; El-Hady Sweilum, Ola Abd; Ads, Mahmoud Khalid

    2015-01-01

    In Egypt, tramadol abuse is increasing, especially among youths and the middle- aged. Tobacco smoking is a worldwide health problem responsible for more deaths and disease than any other noninfectious cause. To investigate if there is a relationship between tramadol and nicotine dependence. 48 tramadol addicts completed a demographic sheet, drug use questionnaire, and the Fagerstrom Test for Nicotine Dependence (FTND). Numbers of cigarettes smoked were recorded every week or two weeks at follow-up or by phone calls, and the FTND was completed again five weeks after abstinence. All participants underwent full psychiatric assessment, plus a urine toxicology screening at first visit, and once again during follow-ups. All subjects of the study were cigarette smokers. The mean numbers of cigarettes smoked per day were 13, 31.8, 20.2, and 14.3 during the phase before tramadol taking, addiction phase, two weeks and five weeks after stopping tramadol. The mean FTND score dropped from 6.67 during the tramadol addiction phase to 4.31 only five weeks after stopping tramadol. Tramadol increases the severity of nicotine dependence. The relation seems to be bi-directional, so increased cigarette smoking also increases tramadol intake.

  20. Tramadol inhibits proliferation, migration and invasion via α2-adrenoceptor signaling in breast cancer cells.

    PubMed

    Xia, M; Tong, J-H; Zhou, Z-Q; Duan, M-L; Xu, J-G; Zeng, H-J; Wang, S-H

    2016-01-01

    The aim of this study was to examine the function of tramadol on cell proliferation, migration and invasion in breast cancer cells in vitro, and to evaluate the effect of tramadol in vivo. Further, we explore the mechanism accounting for the role of tramadol on breast cancer cells. Cell proliferation was detected by the methyl thiazolyl tetrazolium (MTT) assay. Wound healing assay and transwell assay was applied to quantify the migration and invasion ability of MDA-MB-231 cells. The expression of endogenous α2-adrenoceptor and ERK was measured by Western blotting. Tramadol at a clinical dose of up to 2 μM significantly inhibited the proliferation, migration and invasion in a time-dependent manner from day 0 to 28 in vitro. Moreover, tramadol suppressed the growth of xenotransplant tumor in vivo markedly. Furthermore, the protein levels of α2-adrenoceptor and phosphorylated ERK were decreased by tramadol, whereas the expression of total ERK remained unchanged. In addition, downregulation of α2-adrenoceptor by yohimbine could mimic the effect of tramadol treatment. Collectively, we demonstrated that tramadol could inhibit proliferation, migration and invasion of breast cancers via inactivating α2-adrenoceptor signaling pathway. Our data provide the experimental fundamental for further investigation of the anti-cancer effect of tramadol in breast cancer cells.

  1. Evaluation of the Ecstasy influence on tramadol and its main metabolite plasma concentration in rats.

    PubMed

    Jamali, Bardia; Sheikholeslami, Behjat; Hosseinzadeh Ardakani, Yalda; Lavasani, Hoda; Rouini, Mohammad-Reza

    2017-09-26

    Tramadol is prone to be abused alone, or in combination with 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). It was reported that 95% of people with a history of substance abuse in the United States used tramadol in 2004. According to the WHO report in 2016, there was a growing number of tramadol abusers alone or in combination with psychoactive substances such as MDMA in particular in some Middle East countries. Higher concentrations of tramadol in plasma may lead to adverse drug reactions or lethal intoxication. In this study, the effect of MDMA on the pharmacokinetics of tramadol was examined in male rats. The effect of MDMA on Tmax, Cmax, area under the curve, elimination rate, and half-life of tramadol and its metabolites was examined. Two control and two treatment groups were designed. The treatment groups received MDMA 18 h before the administration of tramadol. Jugular vein blood samples were analyzed by high-performance liquid chromatography with fluorescent detector to determine the concentrations of tramadol and its metabolites. Independent-sample t-test was used to define the differences between pharmacokinetic parameters of control and treatment groups. When tramadol administered intraperitoneally, the absorption rate of this drug was reduced, and a lower Cmax (40%) with longer Tmax (eight-fold) was achieved. MDMA exerted greater inhibitory effects on cytochrome P450 3A4 (CYP3A4) than on cytochrome P450 2D6 (CYP2D6). The M2 metabolite ratio was reduced by half, and because of the inhibition of M2 production, the M1 plasma concentration slightly increased. According to the obtained data, MDMA treatment affected the absorption, distribution and metabolism phases of tramadol. This treatment increased the concentration of tramadol if administered intravenously and can latent the absorption of tramadol in oral route. However, MDMA was introduced as CYP2D6 inhibitor; in this study, MDMA inhibited CYP3A4 isoenzymes as well. This finding is important for

  2. Panicolytic-like effect of tramadol is mediated by opioid receptors in the dorsal periaqueductal grey.

    PubMed

    Fiaes, Gislaine Cardoso de Souza; Roncon, Camila Marroni; Sestile, Caio Cesar; Maraschin, Jhonatan Christian; Souza, Rodolfo Luis Silva; Porcu, Mauro; Audi, Elisabeth Aparecida

    2017-05-30

    Tramadol is a synthetic opioid prescribed for the treatment of moderate to severe pain, acting as agonist of μ-opioid receptors and serotonin (5-HT) and noradrenaline (NE) reuptake inhibitor. This study evaluated the effects of tramadol in rats submitted to the elevated T-maze (ETM), an animal model that evaluates behavioural parameters such as anxiety and panic. Male Wistar rats were intraperitoneally (i.p.) treated acutely with tramadol (16 and 32mg/kg) and were submitted to the ETM. Tramadol (32mg/kg) promoted a panicolytic-like effect. Considering that dorsal periaqueductal grey (dPAG) is the main brain structure related to the pathophysiology of panic disorder (PD), this study also evaluated the participation of 5-HT and opioid receptors located in the dPAG in the panicolytic-like effect of tramadol. Seven days after stereotaxic surgery for implantation of a cannula in the dPAG, the animals were submitted to the test. To assess the involvement of 5-HT1A receptors on the effect of tramadol, we combined the 5-HT1A receptor antagonist, WAY100635 (0.37nmol), microinjected intra-dPAG, 10min prior to the administration of tramadol (32mg/kg, i.p.). WAY100635 did not block the panicolytic-like effect of tramadol. We also associated the non-selective opioid receptor antagonist, naloxone, systemically (1mg/kg, i.p.) or intra-dPAG (0.5nmol) administered 10min prior to tramadol (32mg/kg, i.p.). Naloxone blocked the panicolytic-like effect of tramadol in both routes of administrations, showing that tramadol modulates acute panic defensive behaviours through its interaction with opioid receptors located in the dPAG. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment.

    PubMed

    Awadalla, Eatemad A; Salah-Eldin, Alaa-Eldin

    2016-08-01

    Tramadol abuse is one of the most frequent health problems in Egypt and worldwide. In most cases, tramadol abused by men face a problem with premature ejaculation. Tramadol like other opioids induces a decrease in plasma antioxidant levels, which may reflect a failure of the antioxidant defense mechanism against oxidative damage. The present work aimed to study the possible deleterious effects of oral administration of tramadol on brain and lung tissues in rats. Twenty adult male albino rats were divided into two groups; a control administered with normal saline and tramadol-treated (40mg/kg b.w.) group for 20 successive days. At the end of experimental period, blood was collected and specimens from brains and lungs were taken for histopathological and molecular studies. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities were measured in serum of control and tramadol-treated groups. Brain and lung specimens were histopathological evaluated using light microscopy. The expression levels of apoptotic related genes; Bcl-2, Bax and Caspase-3 were study in brain and lung tissues using RT-PCR analysis. We recorded a significant increase MDA level, while antioxidant enzymes; GSH, SOD and CAT were significantly decreased after tramadol-treatment. The obtained results revealed that tramadol induced a remarkable histomorphological changes in rats' brains (cerebral cortex and hippocampus) and severe histopathological changes in rats' lung when compared to that of control. On molecular level, the expression of the pro-apoptotic Bax and Caspase-3 showed a significant increase whereas the anti-apoptotic Bcl-2 decreased markedly indicating that tramadol is harmful at cellular level and can induce apoptotic changes in brain tissues. Our data confirmed the risk of increased oxidative stress, neuronal and pulmonary damage due to tramadol abuse. Although tramadol is reported to be effective in pain management, its toxicity should

  4. Stability-Indicating UPLC Method for Tramadol HCl Impurities in the Tramadol Injection after Dilution by Infusion Fluids (5% Dextrose and 0.9% Sodium Chloride).

    PubMed

    Binnor, Anil K; Mukkanti, Khagga; Suryanarayana, Mulukutla V; Roy, Sunilendu B

    2013-01-01

    A novel, rapid, and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated as per ICH guidelines for the determination of tramadol HCl impurities in the tramadol HCl injection after reconstitution by infusion fluids (5% dextrose and 0.9% sodium chloride). The tramadol HCl injection is for the treatment of patients with moderate-to-severe pain. The stability of the reconstituted solution is critical before intravenous injection. The literature search resulted in few published articles on assays of tramadol in infusion fluids by conventional HPLC. No attempts have yet been made to determine the impurities in infusion fluids, as the concentration of tramadol after reconstitution is extremely low (0.4 mg/mL) and that of impurities is even lower. The proposed method is novel as it allows the quantitation of the impurities of tramadol HCl and is based on modern chromatographic techniques like UPLC. The method was developed using the Waters Acquity BEH C18 column with a mobile phase consisting of a gradient mixture of solvent A (trifluroacetic acid buffer) and solvent B (methanol: acetonitrile). The model stability study was designed by diluting the tramadol HCl injection in the 5% dextrose injection and 0.9% sodium chloride injection. Each mixture was kept under storage at room temperature (25 ± 2°C) for testing at initial, 2, 4, 8, 12, 18 & 24 hours. The validation study illustrates that the proposed method is suitable for the determination of tramadol and its impurities. The proposed method makes use of the LC-MS-compatible mobile phase. It can be useful for the determination of tramadol HCl and its impurities in plasma samples and other pharmaceutical dosage forms.

  5. Treatment of Neurogenic Cough with Tramadol: A Pilot Study.

    PubMed

    Dion, Gregory R; Teng, Stephanie E; Achlatis, Efstratios; Fang, Yixin; Amin, Milan R

    2017-07-01

    This study employs validated cough assessment tools to prospectively determine the impact of tramadol on cough severity and quality of life in subjects with neurogenic cough. The study was a prospective case series with planned data collection at a tertiary care academic medical center laryngology practice. Sixteen consecutive collected subjects with neurogenic cough prospectively completed pre- and posttreatment validated cough assessment tools, the cough severity index (CSI) and Leicester Cough Questionnaire (LCQ). All subjects in the study reported at least some improvement in their cough symptoms. In a Wilcoxon signed rank test that compared paired results, CSI scores improved from 23 to 14 and LCQ scores improved from 74 to 103 ( P = .003 and P = .005, respectively). This small preliminary assessment suggests that tramadol warrants additional evaluation as a treatment for neurogenic cough.

  6. Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis.

    PubMed

    Monteiro, Beatriz P; Klinck, Mary P; Moreau, Maxim; Guillot, Martin; Steagall, Paulo V M; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Gauvin, Dominique; Del Castillo, Jérôme R E; Troncy, Eric

    2017-01-01

    This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.

  7. Tramadol Metabolism to O-Desmethyl Tramadol (M1) and N-Desmethyl Tramadol (M2) by Dog Liver Microsomes: Species Comparison and Identification of Responsible Canine Cytochrome P450s

    PubMed Central

    Mealey, Katrina L.; Grubb, Tamara L.; Greene, Stephen A.; Court, Michael H.

    2016-01-01

    Tramadol is widely used to manage mild to moderately painful conditions in dogs. However, this use is controversial, since clinical efficacy studies in dogs showed conflicting results, whereas pharmacokinetic studies demonstrated relatively low circulating concentrations of O-desmethyltramadol (M1). Analgesia has been attributed to the opioid effects of M1, whereas tramadol and the other major metabolite (N-desmethyltramadol, M2) are considered inactive at opioid receptors. This study aimed to determine whether cytochrome P450 (P450)–dependent M1 formation by dog liver microsomes is slower compared with cat and human liver microsomes and to identify the P450s responsible for M1 and M2 formation in canine liver. Since tramadol is used as a racemic mixture of (+)- and (−)-stereoisomers, both (+)-tramadol and (−)-tramadol were evaluated as substrates. M1 formation from tramadol by liver microsomes from dogs was slower than from cats (3.9-fold) but faster than humans (7-fold). However, M2 formation by liver microsomes from dogs was faster than those from cats (4.8-fold) and humans (19-fold). Recombinant canine P450 activities indicated that M1 was formed by CYP2D15, whereas M2 was largely formed by CYP2B11 and CYP3A12. This was confirmed by dog liver microsome studies that showed selective inhibition of M1 formation by quinidine and M2 formation by chloramphenicol and CYP2B11 antiserum, as well as induction of M2 formation by phenobarbital. Findings were similar for both (+)-tramadol and (−)-tramadol. In conclusion, low circulating M1 concentrations in dogs are explained in part by low M1 formation and high M2 formation, which is mediated by CYP2D15 and CYP2B11/CYP3A12, respectively. PMID:27758804

  8. Tramadol or fentanyl analgesia for ambulatory knee arthroscopy.

    PubMed

    Cagney, B; Williams, O; Jennings, L; Buggy, D

    1999-03-01

    In a double-blind, randomized, controlled study, 61 patients who received a standardized anaesthetic for day case arthroscopic knee surgery were studied. Group T (n = 31) received tramadol 1.5 mg kg-1, and group F (n = 30) received fentanyl 1.5 micrograms kg-1 at the induction of anaesthesia. All patients also received 20 mL of intra-articular bupivacaine 0.5% at the end of surgery. Assessments were made of pain at rest and on movement, analgesic requirements and side-effects at hourly intervals up to 6 h and by means of a postal questionnaire at 24 h and 48 h post-operatively. Group F had higher pain scores than group T at 4 h only [VAS 3.3 (1.6-5.5) vs. 2.4 (1-4), P = 0.039, respectively; median (interquartile range)]. There were no other significant differences between the groups in terms of pain scores, supplemental analgesic requirements or incidence of side-effects. We conclude that tramadol offers little benefit clinically compared with fentanyl when used at induction of anaesthesia for day case arthroscopic knee surgery. Further studies are indicated in patients with more severe pain to determine the role of tramadol in post-operative analgesia.

  9. Efficacy of tramadol vs meperidine in vasoocclusive sickle cell crisis.

    PubMed

    Uzun, Belkan; Kekec, Zeynep; Gurkan, Emel

    2010-05-01

    Despite progress in management, patients with sickle cell disease who are experiencing acute painful episode are often incompletely treated. We compared meperidine and tramadol with respect to their effects on the hemodynamics and pain relief in patients with sickle cell disease who were admitted to the emergency department with painful crisis. A total of 68 patients with sickle cell disease were randomly assigned to receive either tramadol 1.5 mg/kg (n = 34) or meperidine 1 mg/kg (n = 34). Hemodynamic parameters were recorded at regular intervals after analgesic infusions. Pain intensity and relief were documented by visual analog and pain relief scale, respectively. Sedation level was defined according to Ramsay sedation scale. Both meperidine and tramadol administration resulted in a significant reduction in systolic and diastolic blood pressure after 2 hours (P < .05). Efficacy in pain relief between the analgesics was more rapid and better in the meperidine group, although the degree of relief were significantly improved compared to baseline levels in both groups (P < .05). Sedation was more commonly seen in the meperidine arm. None of the patients had experienced neurotoxicity. In summary, both agents had proven safe and effective for emergent use in patients with sickle cell disease. Avoiding meperidine injections as recommended with previous guidelines needs to be carefully reconsidered especially when low doses are mentioned.

  10. Formulation Development and Optimization of Matrix Tablet of Tramadol Hydrochloride.

    PubMed

    Deb, Pulak; Singha, Jubaraj; Chanda, Indranil; Chakraborty, Prithviraj

    2017-01-01

    The aim of the present investigation is to formulate and optimize oral sustained release matrix tablet of highly water soluble drug Tramadol HCl and to evaluate the effect of varying concentration of hydrophilic and hydrophobic polymer on drug release, based on a survey done on the recent patents of Tramadol HCl (US7374781, CA 2479252) and sustained release matrix tablets. The tablets were prepared by double granulation process, by melt granulation and wet granulation technique using Carnauba wax (CW) and HPMC K100 as release retardant. Pre and post compression factors were evaluated and all the parameters were found within the limit. The drug release data were subjected to different models in order to evaluate release kinetics and mechanism of drug release. The prepared formulations showed drug release in the range 100±2% in 6hrs, 7hrs, 8hrs and 9hrs and upto 12 hrs respectively. The optimized tablet having 25% CW and 20% HPMC showed sustained drug release pattern. Hydrophilic matrix of HPMC alone could not control the Tramadol release effectively for 12 h whereas when combined with CW could slow down the release of drug and can be successfully employed for formulating sustained-release matrix tablets. Similarity factor, f2 shows the test and reference profile are identical. Double granulation technique with CW and HPMC K100 proved as a better technique for sustaining the drug release from the matrix tablet. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Tramadol and caffeine produce synergistic interactions on antinociception measured in a formalin model.

    PubMed

    Díaz-Reval, M Irene; Carrillo-Munguía, Norma; Martínez-Casas, Maribel; González-Trujano, Ma Eva

    2010-12-01

    Drug combinations have been used in clinical practice for the main purpose of increasing therapeutic effect efficacy. The aim of this study was to determine the antinociceptive effect of tramadol and caffeine administered separately or in combination, as well as their synergistic interaction. The formalin test was used. Nociceptive behavior was evaluated by flinching response of the formalin-treated paw. Rats were divided into five groups and received tramadol alone (4.9-49.6mg/kg, s.c.), caffeine alone (1-17.8mg/kg, p.o.), or combinations of tramadol (4.9, 8.8, 15.6 and 20.8mg/kg, s.c.) and caffeine (1, 3.16 and 10mg/kg, p.o.). Tramadol showed dose-dependent antinociceptive effect in both phases of the formalin test. Caffeine only presented antinociceptive effect in the second phase and this effect was also dose-dependent. In Phase 1, combinations of tramadol and caffeine showed antinociceptive effect similar to that of tramadol alone. In Phase 2, the dose-response curve shifted to the left with the combination of tramadol and each dose of caffeine. Synergism analysis resulted in synergistic effect in ten combinations and antagonism in two combinations. In conclusion, the synergism observed in the majority of tramadol and caffeine combinations used in this study suggests that this drug combination is useful in the treatment of pain. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  13. Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

    PubMed

    Mohamed, Tarek Mostafa; Ghaffar, Hamdy M Abdel; El Husseiny, Rabee M R

    2015-12-01

    The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively. © The Author(s) 2012.

  14. A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

    PubMed

    Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud

    2017-07-01

    Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (P<0.05). The decrease in the hepatic metabolism of tramadol and increase in the half-life of the elimination of tramadol in rats with BDL suggests that personalized treatment and the therapeutic drug monitoring (TDM) data examination are necessary for patients with bile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta).

    PubMed

    Kelly, K R; Pypendop, B H; Christe, K L

    2015-08-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration.

  16. Tramadol-related psychosis in a patient with bipolar I disorder.

    PubMed

    Chen, Kuan-Jen; Lu, Mong-Liang; Shen, Winston W

    2015-04-01

    Tramadol hydrochloride (HCl) is a centrally acting synthetic opioid analgesic. Psychotic symptoms are relatively rare in reported adverse events. Here, we report a patient who presented with tramadol-related psychotic symptoms. A 59-year-old female had underlying bipolar I disorder and received lithium treatment with stable affective status. 1 month before hospitalisation, she had been taking tramadol HCl/acetaminophen for joint pain. She then developed obvious persecutory delusion. However, her clinical picture did not meet the criteria of any mood episode. After treatment of risperidone in addition to lithium, she was discharged without any psychotic symptom. She remained euthymic without any psychotic symptom on monotherapy of lithium (300 mg) three tablets once daily. Tramadol HCl is commonly prescribed in clinical practice and psychotic symptoms related to it are uncommon. We should be careful about the rare but important adverse events while prescribing tramadol HCl.

  17. Comparison of caudal tramadol vs bupivacaine for post-operative analgesia in children undergoing hypospadias surgery.

    PubMed

    Batra, Y K; Prasad, M K; Arya, V K; Chari, P; Yaddanapudi, L N

    1999-05-01

    In a prospective double-blind study, 40 children scheduled for hypospadias repair were allocated randomly to receive either caudal tramadol (1 mg/kg) or 0.25% plain bupivacaine (0.5 ml/kg). Postoperative pain score, side-effects and oxygen saturation (SaO2) were recorded during 24-hour observation period. The results point toward a significantly lower pain scores with caudal bupivacaine in the immediate postoperative period, whereas caudal tramadol caused a significantly lower pain score in the late postoperative period. Total consumption of rescue analgesics was significantly higher in bupivacaine group as compared to tramadol group during the study period (p < 0.001). The incidence of side-effects such as vomiting was more frequent with caudal tramadol, but there was no detectable difference in SaO2. We conclude that caudal tramadol can safely be used for postoperative analgesia with a longer duration as compared to caudal bupivacaine.

  18. Effects of tramadol and o-desmethyltramadol on canine innate immune system function.

    PubMed

    Axiak-Bechtel, Sandra M; Tsuruta, Kaoru; Amorim, Juliana; Donaldson, Rebecca; Lino, Giulia; Honaker, Allyson; Monibi, Farrah; Dodam, John; DeClue, Amy

    2015-05-01

    Tramadol is a commonly used opioid analgesic in dogs, particularly in dogs with a compromised immune system. An opioid may be selected for its immunomodulatory effects. Consequently, the objective of this study was to investigate the effects of tramadol on immune system function by evaluating the effect of tramadol and o-desmethyltramadol (M1) on the function of canine leukocytes in vitro. The hypothesis was that tramadol and M1 would not alter polymorphonuclear leukocyte (PMN) phagocytosis, PMN oxidative burst, or stimulated leukocyte cytokine production capacity of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. In vitro pharmacodynamic study. Six healthy dogs. Blood from six dogs was obtained and incubated with various concentrations of tramadol and M1. Phagocytosis and oxidative burst were assessed using flow cytometry, and lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay. No differences were detected in phagocytosis or oxidative burst with any drug concentration. Tramadol did not alter leukocyte cytokine production, however, M1 significantly blunted IL-10 production. Tramadol and its metabolite M1 were sparing to PMN phagocytosis and oxidative burst in dogs in vitro. Tramadol did not alter leukocyte cytokine production, however, M1 blunted IL-10 production at clinically achievable concentrations suggesting that M1 may promote a proinflammatory shift. These data suggest that tramadol has minimal effect on phagocytosis and oxidative burst, and may promote a proinflammatory shift. Therefore, tramadol may be an ideal opioid analgesic in dogs at high risk of infection. Further investigation in vivo is warranted. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  19. Hypoglycemic effects of tramadol analgesia in hospitalized patients: a case-control study.

    PubMed

    Golightly, Larry K; Simendinger, Bonita A; Barber, Gerard R; Stolpman, Nancy M; Kick, Steven D; McDermott, Michael T

    2017-01-01

    In outpatient populations, hypoglycemia has been associated with tramadol. We sought to determine the magnitude of risk for hypoglycemia associated with tramadol use in hospitalized patients. During a 2-year period of observation, adult inpatients who received ≥1 dose of tramadol were identified and their medical records were reviewed. Patients were included if they had blood or plasma glucose (BG) concentrations measured on at least two occasions within five days after the initial administration of tramadol. A contemporary comparator group of hospitalized oxycodone recipients was similarly reviewed. Tramadol was administered to 2927 patients who met inclusion criteria. Among these, hypoglycemia (BG ≤70 mg/dL) was documented in 22 (46.8%) of 47 patients with type 1 diabetes, 113 (16.8%) of 673 patients with type 2 diabetes, and 103 (4.7%) of 2207 patients who did not have a diabetes mellitus diagnosis. In those without a diabetes diagnosis, the causality association between hypoglycemia and tramadol use was probable in 77 patients (3.5%). By comparison, hypoglycemia was documented in 8 (1.1%) of 716 matched oxycodone recipients without diabetes (p = 0.002). As compared with tramadol recipients who did not develop low BG concentrations, those who experienced tramadol-related hypoglycemia were relatively young (mean age 52.0 versus 59.8 years; p = 0.027) and predominantly female (74.0% versus 59.8%; p = 0.012). Tramadol use was causally associated with hypoglycemia in hospitalized patients. The proportion of patients without diabetes who developed hypoglycemia was higher among those who received tramadol than among those who received oxycodone. Colorado Multiple Institutional Review Board Protocol № 15-2215. Registered/approved 8 December 2015.

  20. Effects of a single bolus intravenous dose of tramadol on minimum alveolar concentration (MAC) of sevoflurane in dogs.

    PubMed

    Itami, Takaharu; Kawase, Kodai; Tamaru, Naomichi; Ishizuka, Tomohito; Tamura, Jun; Miyoshi, Kenjirou; Umar, Mohammed A; Inoue, Hiroki; Yamashita, Kazuto

    2013-01-01

    Tramadol is an atypical opioid analgesic widely used in small animal practice. This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Six beagle dogs were anesthetized twice to determine the sevoflurane MAC with or without an administration of tramadol (4 mg/kg, IV) at 7 days interval. The sevoflurane MAC was determined using a tail clamp method in each dog ventilated with positive pressure ventilation. The tramadol administration produced a significant reduction in the sevoflurane MAC by 22.3 ± 12.2% (1.44 ± 0.28% with tramadol versus 1.86 ± 0.30% without tramadol, P=0.010). This MAC reduction had been determined from 122 ± 19 to 180 ± 41 min following the tramadol administration. During this period, the plasma concentrations of tramadol and its metabolite, O-desmethyltramadol (M1), decreased from 429 ± 64 to 332 ± 55 ng/ml and from 136 ± 24 to 114 ± 68 ng/ml, respectively, but these changes were not statistically significant. There was no significant difference in heart rate, mean arterial blood pressure and SpO2 between the control and tramadol treatment. The dogs that received tramadol treatment sometimes breathed spontaneously. Therefore, their respiratory rates significantly increased, and PETCO2 decreased during the MAC determination. In conclusion, the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dogs.

  1. Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

    PubMed

    Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P < 0.01), while intracerebroventricular methysergide lowered the seizure threshold (P < 0.05 vs. saline). The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

  2. Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats.

    PubMed

    Sousa, Angela Maria; Ashmawi, Hazem Adel

    2015-01-01

    Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5mg, naloxone 200 μg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  3. Effects of Addition of Systemic Tramadol or Adjunct Tramadol to Lidocaine Used for Intravenous Regional Anesthesia in Patients Undergoing Hand Surgery

    PubMed Central

    Yektaş, Abdulkadir; Gümüş, Funda; Karayel, Abdulhalim; Alagöl, Ayşin

    2016-01-01

    Intravenous regional anesthesia (IVRA) is used in outpatient hand surgery as an easily applicable and cost-effective technique with clinical advantages. The present study aimed to investigate the effects of addition of systemic tramadol or adjunct tramadol to lidocaine for IVRA in patients undergoing hand surgery. American Society of Anesthesiologists (ASA) I-II patients (n = 60) who underwent hand surgery were included. For this purpose, only lidocaine (LDC), lidocaine+adjunct tramadol (LDC+TRA group), or lidocaine+systemic tramadol (LDC+SysTRA group) was administered to the patients for IVRA and the groups were compared in terms of onset and recovery time of sensory and motor blocks, quality of anesthesia, and the degree of intraoperative and postoperative pain. The onset time of sensorial block was significantly shorter in the LDC+TRA group than that in the LDC+SysTRA group. The motor block recovery time was significantly shorter in the LDC+SysTRA group than that in the LDC+TRA and LDC groups. Administration of tramadol as an adjunct showed some clinical benefits by providing a shorter onset time of sensory and motor block, decreasing pain and analgesic requirement, and improving intraoperative conditions during IVRA. It was determined that systemic tramadol administration had no superiority. PMID:27313608

  4. Pharmacokinetics of intravenous and oral tramadol in the bald eagle (Haliaeetus leucocephalus).

    PubMed

    Souza, Marcy J; Martin-Jimenez, Tomas; Jones, Michael P; Cox, Sherry K

    2009-12-01

    Analgesia is becoming increasingly important in veterinary medicine, and little research has been performed that examined pain control in avian species. Tramadol is a relatively new drug that provides analgesia by opioid (mu), serotonin, and norepinephrine pathways, with minimal adverse effects. To determine the pharmacokinetics of tramadol and its major metabolite O-desmethyltramadol (M1) in eagles, 6 bald eagles (Haliaeetus leucocephalus) were each dosed with tramadol administered intravenously (4 mg/kg) and orally (11 mg/kg) in a crossover study. Blood was collected at various time points between 0 and 600 minutes and then analyzed with high-performance liquid chromatography to determine levels of tramadol and M1, the predominate active metabolite. The terminal half-life of tramadol after intravenous dosing was 2.46 hours. The maximum plasma concentration, time of maximum plasma concentration, and terminal half life for tramadol after oral dosing were 2156.7 ng/ml, 3.75 hours, and 3.14 hours, respec vely. In addition, the oral bioavailability was 97.9%. Although plasma concentrations of ramadol and M1 associated with analgesia in any avian species is unknown, based on the obtained data and known therapeutic levels in humans, a dosage of 5 mg/kg PO q12h is recommended for bald eagles. Pharmacodynamic studies are needed to better determine plasma levels of tramadol and M1 associated with analgesia in birds.

  5. The fear of using tramadol for pain control (tramadolophobia) among Egyptian patients with cancer.

    PubMed

    Alsirafy, Samy A; Saleh, Radfan N; Fawzy, Radwa; Alnagar, Ahmed A; Hammad, Ahmed M; El-Sherief, Wessam; Farag, Dina E; Radwan, Riham H

    2015-01-01

    The fear of using tramadol for pain control (tramadolophobia) by Egyptian patients with cancer is a frequent problem in our practice. This study was conducted to explore the prevalence of and the reasons behind tramadolophobia among Egyptian patients with cancer. A structured interview including open-ended and closed questions. The study included 178 adult patients with cancer from two cancer centers in Cairo and Sharkia, Egypt. The source of information about tramadol was a non-healthcare-related source in 168 (94 percent) patients, mainly the media (50 percent). The believed uses of tramadol were abuse related in 94 (53 percent) patients, stimulant (physical, sexual, and to boost alertness) in 59 (33 percent), and analgesic in 55 (31 percent). Twenty-six (15 percent) patients gave history of tramadol use, largely (69 percent) as a stimulant. In case tramadol was prescribed for pain control, 90 (51 percent) patients refused to take it, 59 (33 percent) patients agreed to take it with concern about addiction, and only 29 (16 percent) patients agreed without concerns. Among those who refused taking tramadol for pain, the mentioned reason of refusal was addiction-related fears in 57 percent. The stigmatization and misconceptions about tramadol may have resulted in tramadolophobia among the majority of Egyptian patients with cancer. This further complicates the barriers to cancer pain control in Egypt. Being the only available World Health Organization step-II analgesic in Egypt, interventions to overcome tramadolophobia should be taken.

  6. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

    PubMed

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

  7. Pharmacokinetics of tramadol and its primary metabolite O-desmethyltramadol in African penguins (Spheniscus demersus).

    PubMed

    Kilburn, Jennifer J; Cox, Sherry K; Kottyan, Jen; Wack, Allison N; Bronson, Ellen

    2014-03-01

    Analgesia is an important part of veterinary medicine, but until recently there have been limited studies on analgesic drugs in avian species. Tramadol represents an orally administered opioid drug that has shown analgesic potential in numerous species, including mammals, birds, and reptiles. The objective of this study was to determine the pharmacokinetic parameters of tramadol and its primary metabolite, O-desmethyltramadol (M1), after oral administration of tramadol hydrochloride (HCl) in African penguins (Spheniscus demersus). A dose of 10 mg/kg of tramadol HCl was administered orally to 15 birds, and blood was collected at various time points from 0 to 36 hr. Tramadol and M1 concentrations were determined and were consistent with therapeutic concentrations in humans through 12 hr in 9/15 birds for tramadol and 36 hr in 14/15 birds for M1. Based on these findings and a comparison with other avian studies, an oral dose of 10 mg/kg of tramadol once daily appears to be a promising analgesic option for African penguins.

  8. Pharmacokinetics of tramadol hydrochloride and its metabolite O-desmethyltramadol in peafowl (Pavo cristatus).

    PubMed

    Black, Peter A; Cox, Sherry K; Macek, Michael; Tieber, Anne; Junge, Randall E

    2010-12-01

    Tramadol is a centrally acting opiate analgesic that has not been well studied in avian species. Tramadol and its metabolites exert their effects at multiple sites, including opiate (mu, kappa, and delta), adrenergic (alpha-2), and serotonin (5HT) receptors. This multi-receptor mode of action is advantageous for avian patients because the mechanisms for analgesia have not been fully elucidated in all species. The objective of this study was to document the pharmacokinetics of tramadol and its active metabolite O-desmethyltramadol (M1) in common peafowl (Pavo cristatus). Based on results from a pilot animal, six adult peafowl (three male, three female) judged to be clinically healthy based on physical exam and routine bloodwork were selected for this study. Each bird was anesthetized for placement of a jugular catheter, and 7.5 mg/kg tramadol was administered orally via gavage tube. Blood samples were collected just prior to drug administration; at 30 min; and at 1, 2, 3, 4, 6, 8, 10, 12, 24, and 34 hr. Plasma levels of tramadol and M1 were measured and the pharmacokinetics for each drug was calculated. Although tramadol was quickly metabolized, plasma levels of M1 remained at or near human analgesic levels for 12-24 hr. Based on these data, tramadol may be a practical option as an orally administered analgesic agent in avian patients. Further studies, including antinociceptive studies, are needed.

  9. Antinociceptive effects of tramadol hydrochloride after intravenous administration to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Geelen, Saskia; Sanchez-Migallon Guzman, David; Souza, Marcy J; Cox, Sherry; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2013-02-01

    To determine the antinociceptive and sedative effects of tramadol in Hispaniolan Amazon parrots (Amazona ventralis) following IV administration. 11 healthy Hispaniolan Amazon parrots of unknown sex. Tramadol hydrochloride (5 mg/kg, IV) and an equivalent volume (≤ 0.34 mL) of saline (0.9% NaCl) solution were administered to parrots in a complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 15, 30, 60, 120, and 240 minutes after treatment administration; agitation-sedation scores were determined for parrots at each of those times. The estimated mean changes in temperature from the baseline value that elicited a foot withdrawal response were 1.65° and -1.08°C after administration of tramadol and saline solution, respectively. Temperatures at which a foot withdrawal response was elicited were significantly higher than baseline values at all 5 evaluation times after administration of tramadol and were significantly lower than baseline values at 30, 120, and 240 minutes after administration of saline solution. No sedation, agitation, or other adverse effects were observed in any of the parrots after administration of tramadol. Tramadol hydrochloride (5 mg/kg, IV) significantly increased the thermal nociception threshold for Hispaniolan Amazon parrots in the present study. Sedation and adverse effects were not observed. These results are consistent with results of other studies in which the antinociceptive effects of tramadol after oral administration to parrots were determined.

  10. PHARMACOKINETICS OF TRAMADOL AND O-DESMETHYLTRAMADOL IN LOGGERHEAD SEA TURTLES (CARETTA CARETTA).

    PubMed

    Norton, Terry M; Cox, Sherry; Nelson, Steven E; Kaylor, Michelle; Thomas, Rachel; Hupp, Amy; Sladky, Kurt K

    2015-06-01

    The objective of this study was to determine the pharmacokinetics of two orally administered doses of tramadol (5 and 10 mg/kg) and its major metabolite (O-desmethyltramadol) (M1) in loggerhead sea turtles (Caretta caretta). After oral administration, the half-life of tramadol administered at 5 and 10 mg/kg was 20.35 and 22.67 hr, whereas the half-life of M1 was 10.23 and 11.26 hr, respectively. The maximum concentration (Cmax) for tramadol after oral administration at 5 mg/kg and 10 mg/kg was 373 and 719 ng/ml, whereas that of M1 was 655 and 1,376 ng/ml, respectively. Tramadol administered orally to loggerhead sea turtles at both dosages provided measurable plasma concentrations of tramadol and O-desmethyltramadol for several days with no adverse effects. Plasma concentrations of tramadol and O-desmethyltramadol remained ≥100 ng/ml for at least 48 and 72 hr when tramadol was administered at 10 mg/kg.

  11. Biochemical and Neurotransmitters Changes Associated with Tramadol in Streptozotocin-Induced Diabetes in Rats

    PubMed Central

    Ezzeldin, Essam; Souror, Wafaa A. H.; El-Nahhas, Toqa; Soudi, Abdel Nasser M. M.; Shahat, Abdelaaty A.

    2014-01-01

    The incidence of diabetes is increasing worldwide. Chronic neuropathic pain occurs in approximately 25% of diabetic patients. Tramadol, an atypical analgesic with a unique dual mechanism of action, is used in the management of painful diabetic neuropathy. It acts on monoamine transporters to inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA). The purpose of this study was to evaluate the effects of diabetes on the brain neurotransmitter alterations induced by tramadol in rats, and to study the hepatic and renal toxicities of the drug. Eighty Sprague-Dawley rats were divided randomly into two sets: the normal set and the diabetic set. Diabetes was induced in rats. Tramadol was administered orally once daily for 28 days. The levels of DA, NE, and 5-HT in cerebral cortex, thalamus/hypothalamus, midbrain, and brainstem were evaluated in rats. In addition, the renal toxicity and histopathological effects of the drug were assessed. The induction of diabetes altered neurotransmitter levels. Oral administration of tramadol significantly decreased the neurotransmitter levels. Diabetes significantly altered the effects of tramadol in all brain regions. Tramadol affected function and histology of the liver and kidney. The clinical effects of tramadol in diabetic patients should be stressed. PMID:24971322

  12. The non-medical use of tramadol in the UK: findings from a large community sample.

    PubMed

    Winstock, A R; Borschmann, R; Bell, J

    2014-09-01

    Prescription drug misuse has become a public health problem in several developed countries. In the UK, there has been no increase in people seeking treatment for prescription drug dependence, but there has been a progressive rise in fatal overdoses involving tramadol. To explore the source, motivations for use and patterns of use of tramadol in the UK. We conducted anonymous online survey of drug use and related behaviours as part of an ongoing drug trend monitoring initiative. We included questions assessing the patterns of use, source and function of tramadol. UK Survey respondents (n = 7360) were predominantly young (mean age 29), and 90% reported being employed or studying. Less than 1% reported past-year use of heroin or methadone, but about 1/3 reported past-year use of cocaine. 326 (5% of respondents) reported having used tramadol in the preceding year, usually obtained by prescription but in 1/3 of cases from a friend; rarely from a dealer or from the internet. Most used the drug for pain relief, but 163 respondents (44%) reported using tramadol for reasons other than pain relief - particularly, using it to relax, to sleep, to get high or to relieve boredom. Nineteen per cent took doses higher than prescribed, and 10% reported difficulty discontinuing. Twenty-eight per cent combined tramadol with alcohol or other drugs to enhance its effect. Misuse and sharing of tramadol, supplied by prescription, was common. © 2014 John Wiley & Sons Ltd.

  13. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    PubMed Central

    Sousa, A.M.; Ashmawi, H.A.; Costa, L.S.; Posso, I.P.; Slullitel, A.

    2011-01-01

    Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics. PMID:22183244

  14. A comparative study on the efficacy of dexmedetomidine and tramadol on post-spinal anesthesia shivering.

    PubMed

    Kundra, Tanveer Singh; Kuthiala, Gaurav; Shrivastava, Anupam; Kaur, Parminder

    2017-01-01

    Shivering is a common postanesthesia adverse event with multiple etiologies. At present tramadol is a widely used drug for the control of shivering. However, tramadol may cause a lot of nausea and vomiting. Hence, the need to find a better drug with less of side effects. The aim of this study was to compare the efficacy of dexmedetomidine and tramadol in the treatment of post-spinal anesthesia (SA) shivering as well as to compare their side-effect profile. This prospective, double-blind, randomized controlled trial was conducted in a tertiary care hospital. A total of 100 patients having shivering after SA were enrolled, out of which fifty received dexmedetomidine (Group A) and 50 received tramadol (Group B). The response rate, time to cessation of shivering and side effects (if any) was noted. All the results were analyzed using Student's t-test and Chi-square test. All patients who received dexmedetomidine as well as tramadol had cessation of shivering. The time to cessation of shivering was significantly less with dexmedetomidine (174.12 ± 14.366 s) than with tramadol (277.06 ± 23.374 s) (P < 0.001). The recurrence rate of shivering with dexmedetomidine was less (6%) as compared to tramadol (16%). Nausea and vomiting was found to be higher in the case of tramadol. On the other hand, dexmedetomidine caused moderate sedation (modified Ramsay sedation score = 3-4) from which the patient could be easily awoken up. Dexmedetomidine offers better results than tramadol with fewer side effects.

  15. µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1).

    PubMed

    Minami, Kouichiro; Sudo, Yuka; Miyano, Kanako; Murphy, Robert S; Uezono, Yasuhito

    2015-06-01

    Tramadol has been used as an analgesic for several decades. µ-Opioid receptors (µORs) are the major receptors that mediate the analgesic effects of opioids. Although µORs have been thought to be one of the sites of action of tramadol, there has been no report that directly proves whether tramadol is an agonist of μOR or not. In this study, we examined the effects of tramadol and its main active metabolite O-desmethyltramadol (M1), on the function of µORs using Xenopus oocytes expressing cloned human µORs. The effects of tramadol and M1 were evaluated using the Ca(2+)-activated Cl(-) current assay method for G(i/o)-protein-coupled receptors by using a µOR fused to G(qi5) (µOR-G(qi5)) in Xenopus oocytes. DAMGO [(D-Ala(2), N-MePhe(4), Gly(5)-ol)-enkephalin] evoked Cl(-) currents in oocytes expressing µOR-G(qi5) in a concentration-dependent manner. Tramadol and M1 also evoked Cl(-) currents in the oocytes expressing µOR-G(qi5); however, relatively higher concentrations (compared to DMAGO) were necessary to induce such currents. Tramadol and M1 had a direct effect on µORs expressed in Xenopus oocytes. Although the monoamine uptake system and several types of ligand-gated ion channels are thought to be one of the targets for tramadol, tramadol-induced antinociception may be mediated at least in part, by the direct activation of µORs.

  16. A comparative study on the efficacy of dexmedetomidine and tramadol on post-spinal anesthesia shivering

    PubMed Central

    Kundra, Tanveer Singh; Kuthiala, Gaurav; Shrivastava, Anupam; Kaur, Parminder

    2017-01-01

    Background: Shivering is a common postanesthesia adverse event with multiple etiologies. At present tramadol is a widely used drug for the control of shivering. However, tramadol may cause a lot of nausea and vomiting. Hence, the need to find a better drug with less of side effects. The aim of this study was to compare the efficacy of dexmedetomidine and tramadol in the treatment of post-spinal anesthesia (SA) shivering as well as to compare their side-effect profile. Materials and Methods: This prospective, double-blind, randomized controlled trial was conducted in a tertiary care hospital. A total of 100 patients having shivering after SA were enrolled, out of which fifty received dexmedetomidine (Group A) and 50 received tramadol (Group B). The response rate, time to cessation of shivering and side effects (if any) was noted. All the results were analyzed using Student's t-test and Chi-square test. Results: All patients who received dexmedetomidine as well as tramadol had cessation of shivering. The time to cessation of shivering was significantly less with dexmedetomidine (174.12 ± 14.366 s) than with tramadol (277.06 ± 23.374 s) (P < 0.001). The recurrence rate of shivering with dexmedetomidine was less (6%) as compared to tramadol (16%). Nausea and vomiting was found to be higher in the case of tramadol. On the other hand, dexmedetomidine caused moderate sedation (modified Ramsay sedation score = 3–4) from which the patient could be easily awoken up. Conclusion: Dexmedetomidine offers better results than tramadol with fewer side effects. PMID:28217045

  17. Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants?

    PubMed

    Park, Susie H; Wackernah, Robin C; Stimmel, Glen L

    2014-02-01

    There is a warning associated with all serotonergic antidepressants and its concomitant use with tramadol due to the concern for a drug-drug interaction resulting in serotonin syndrome (SS). The prescribing of antidepressants with tramadol may be unnecessarily restricted due to fear of causing this syndrome. There are 3 objectives of this review. To (1) review case reports of SS associated with the combination of tramadol and antidepressant drugs in recommended doses, (2) describe the mechanisms of the drug interaction, and (3) identify the potential risk factors for SS. Case reports of SS associated with tramadol and antidepressants were identified via Cochrane Library, PubMed, and Ovid (through October 2012) using search terms SS, tramadol, antidepressants, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, venlafaxine, desvenlafaxine, duloxetine, mirtazapine, milnacipran, trazodone, vilazodone, and bupropion. Cases involving monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants were excluded. Nine articles were identified describing 10 cases of suspected SS associated with therapeutic doses of tramadol combined with an antidepressant. Mechanisms of the drug-drug interactions involve pharmacodynamic, pharmacokinetic, and possible pharmacogenetic factors. Review of the available case reports of tramadol combined with antidepressant drugs in therapeutic doses indicates caution in regard to the potential for SS but does not constitute a contraindication to their use. Tramadol is only contraindicated in combination with MAOIs but not other antidepressants in common use today. These case reports do suggest several factors associated with a greater risk of SS, including increased age, higher dosages, and use of concomitant potent cytochrome P450 2D6 inhibitors. Tramadol can be safely combined with antidepressants; however, monitoring and counseling patients are prudent when starting a new serotonergic agent or when doses are

  18. Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors.

    PubMed

    Shiraishi, Munehiro; Minami, Kouichiro; Uezono, Yasuhito; Yanagihara, Nobuyuki; Shigematsu, Akio; Shibuya, Izumi

    2002-05-01

    1. Tramadol has been used clinically as an analgesic; however, the mechanism of its analgesic effects is still unknown. 2. We used bovine adrenal chromaffin cells to investigate effects of tramadol on catecholamine secretion, nicotine-induced cytosolic Ca(2+) concentration ([Ca(2+)](i)) increases and membrane current changes. We also investigated effects of tramadol on alpha7 nicotinic acetylcholine receptors (AChRs) expressed in Xenopus oocytes. 3. Tramadol concentration-dependently suppressed carbachol-induced catecholamine secretion to 60% and 27% of the control at the concentration of 10 and 100 microM, respectively, whereas it had little effect on veratridine- or high K(+)-induced catecholamine secretion. 4. Tramadol also suppressed nicotine-induced ([Ca(2+)](i)) increases in a concentration-dependent manner. Tramadol inhibited nicotine-induced inward currents, and the inhibition was unaffected by the opioid receptor antagonist naloxone. 5. Tramadol inhibited nicotinic currents carried by alpha7 receptors expressed in Xenopus oocytes. 6. Tramadol inhibited both alpha-bungarotoxin-sensitive and -insensitive nicotinic currents in bovine adrenal chromaffin cells. 7. In conclusion, tramadol inhibits catecholamine secretion partly by inhibiting nicotinic AChR functions in a naloxone-insensitive manner and alpha7 receptors are one of those inhibited by tramadol.

  19. Tramadol regulates proliferation, migration and invasion via PTEN/PI3K/AKT signaling in lung adenocarcinoma cells.

    PubMed

    Xia, M; Tong, J-H; Ji, N-N; Duan, M-L; Tan, Y-H; Xu, J-G

    2016-06-01

    Tramadol is used mainly for the treatment of moderate to severe chronic cancer pain. However, the effect of tramadol on lung cancer remains unclear. Therefore, it is important to explore the mechanism accounting for the function of tramadol on lung cancer. We investigated the effects of tramadol on the proliferation, migration and invasion in human lung adenocarcinoma cells in vitro by CCK-8 assay, wound healing assay and Transwell assay, respectively. We also explored the potential mechanism of tramadol on lung cancer cells by Western blotting. A549 and PC-9 cells were incubated with 2 µM tramadol for different time (0, 7, 14 and 28 d). The in vitro experiments showed that tramadol treatment significantly inhibited cell proliferation, migration and invasion in a time-dependent manner. Moreover, administration of tramadol suppressed tumor growth in vivo. The data also revealed that tramadol could up-regulate the protein expression level of PTEN and consistently inhibit the phosphorylation level of PI3K and Akt, whereas the total level of PI3K and Akt remain unchanged. These findings indicated that tramadol inhibited proliferation, migration and invasion of human lung adenocarcinoma cells through elevation of PTEN and inactivation of PI3K/Akt signaling.

  20. Metabolite to parent drug concentration ratios in hair for the differentiation of tramadol intake from external contamination and passive exposure.

    PubMed

    Madry, Milena M; Rust, Kristina Y; Guglielmello, Rosetta; Baumgartner, Markus R; Kraemer, Thomas

    2012-11-30

    Tramadol was found in a man's hair sample during an abstinence test necessary to regain his driving license. The suspect denied having taken tramadol claiming external contamination as the reason for the positive result, as he was working in a tramadol production company. Nevertheless, low concentrations of both major metabolites, N-desmethyltramadol (NDMT) and O-desmethyltramadol (ODMT), were found in hair (180 and 6 pg/mg hair, respectively). To assess this case, tramadol concentrations and metabolite to parent drug concentration ratios were determined in hair samples of 75 patients taking tramadol and of eight employees working in the production and laboratory site of the same company. Additionally, wash water used for decontaminating hair was analyzed for both groups, patients and employees. Analysis of hair sample extracts was performed by LC-MS/MS using multiple reaction monitoring (MRM), information dependent acquisition (IDA) and enhanced product ion scan (EPI). High variations of metabolite to parent drug concentration ratios in hair samples of patients were observed. Differences in NDMT and ODMT to tramadol concentration ratios were found when comparing the cohort of patients to employees. The suspect could be included in the cohort of employees considering the ODMT to tramadol concentration ratio in hair and tramadol concentration ratio in wash water versus hair. Metabolite to parent drug concentration ratios of hair samples may represent a helpful tool for the differentiation of tramadol intake versus external contamination. Ratios of tramadol concentrations in wash water versus the subjects' hair may provide additional information for case assessments.

  1. Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review.

    PubMed

    Vadivelu, Nalini; Chang, Daniel; Helander, Erik M; Bordelon, Gregory J; Kai, Alice; Kaye, Alan D; Hsu, Dora; Bang, Daniel; Julka, Inderjeet

    2017-06-01

    Pain remains a tremendous burden on patients and for the health care system, with uncontrolled pain being the leading cause of disability in this country. There are a variety of medications that can be used in the treatment of pain, including ketorolac, oxymorphone, tapentadol, and tramadol. Depending on the clinical situation, these drugs can be used as monotherapy or in conjunction with other types of medications in a multimodal approach. A strong appreciation of pharmacologic properties of these agents and potential side effects is warranted for clinicians. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis

    PubMed Central

    Guillot, Martin; Steagall, Paulo V. M.; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Gauvin, Dominique; del Castillo, Jérôme R. E.

    2017-01-01

    Objectives This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Methods Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Results Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5–30)] than in OA cats [14 (8.5–28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Conclusion Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment. PMID:28403198

  3. Seizures associated with low-dose tramadol for chronic pain treatment

    PubMed Central

    Beyaz, Serbülent Gökhan; Sonbahar, Tuğba; Bayar, Fikret; Erdem, Ali Fuat

    2016-01-01

    The management of cancer pain still poses a major challenge for clinicians. Tramadol is a centrally acting synthetic opioid analgesic. Its well-known side effects include nausea, vomiting, and dizziness; seizures are a rare side effect. Some reports have found that tramadol triggers seizure activity at high doses, whereas a few preclinical studies have found that this seizure activity is not dose-related. We herein present a case involving a patient with laryngeal cancer who developed seizures while on low-dose oral tramadol. PMID:27212778

  4. Effect of Tramadol on Rabbit Uterine Contractile Activity Induced in Late Pregnancy.

    PubMed

    Yakovleva, A A; Nazarova, L A; Prokopenko, V M; Pavlova, N G

    2017-01-01

    Effect of Tramadol infusion (5 mg/ml) on oxytocin-induced uterine contractile activity was studied in chronic experiment on female rabbits with different degrees of biological readiness for parturition. In case of sufficient biological readiness for parturition, Tramadol did not change the number of uterine contractions, but increased the amplitude and duration of each contraction against the background of increased creatine phosphate consumption by the myometrium. At the same time, Tramadol infusion to females without biological readiness for partirition suppressed induced uterine contractile activity by reducing the amplitude of each uterine contraction.

  5. Comparative analgesic and sedative effects of tramadol, tramadol-lidocaine and lidocaine for caudal epidural analgesia in donkeys (Equus asinus).

    PubMed

    Marzok, Mohamed A; El-khodery, Sabry A

    2015-03-01

    To compare anti-nociceptive and sedative effects of tramadol, a combination of tramadol-lidocaine, and lidocaine alone for perineal analgesia in donkeys. Experimental 'blinded' randomized cross-over study. Six healthy adult donkeys. Treatments were tramadol (TR) (1.0 mg kg(-1) ), tramadol-lidocaine (TRLD) (0.5 and 0.2 mg kg(-1) respectively) and lidocaine (LD) (0.4 mg kg(-1) ) given into the epidural space. The volume of all treatments was 0.02 mL kg(-1) . Nociception was tested at the perineal region by pin prick, followed, if no reaction, by pressure from a haemostat clamp. Times to onset, degree and duration of anti-nociception of the perineal region were recorded. Response was tested immediately after drug administration and at: 2, 5, 10, 15, 30, 45, and 60 minutes post-administration and then at 30 minute intervals thereafter until a response re-occurred. Physiologic data and degree of sedation and ataxia were recorded pre-administration and at intervals for 240 minutes post-administration. Results were analyzed using anova, Kruskal-Wallis tests, and Wilks' Lambda test as relevant. Significance was taken as p < 0.05. Times (minutes, mean ± SD) to onset and duration of anti-nociception, respectively were; TR 13 ± 1.6 and 220 ± 4.6; TRLD 6 ± 0.8 and 180 ± 8.5; LD 4 ± 1.4 and 75 ± 4. Onset and duration times were significantly longer with TR than the other two treatments. TR never produced complete anti-nociception, whereas the TRLD and LD induced complete anti-nociceptive effects. Duration was significantly longer with TRLD than with LD alone. Epidural injections of TR and TRLD induced mild sedation. Epidural combination of TRLD produced an anti-nociceptive effect in the perineum, which was rapid in onset and had a longer duration of action than LD alone. An epidural single dose of TRLD combination would appear to provide an acceptable analgesic effect in the perineal region of donkeys. © 2014 Association of Veterinary

  6. Pharmacokinetics and Pharmacodynamics Evaluation of Tramadol in Thermoreversible Gels

    PubMed Central

    Papini, Juliana Zampoli Boava; Pedrazzoli Júnior, José; Calafatti, Silvana Aparecida; de Araújo, Daniele Ribeiro

    2017-01-01

    We evaluated pharmacokinetics (PK) and pharmacodynamics (PD) induced by new formulations of tramadol (TR) in thermoreversible gels. The poloxamer- (PL-) tramadol systems were prepared by direct dispersion of the drug in solutions with PL 407 and PL 188. The evaluated formulations were as follows: F1: TR 2% in aqueous solution and F2: PL 407 (20%) + PL 188 (10%) + TR 2%; F3: PL 407 (25%) + PL 188 (5%) + TR 2%; F4: PL 407 (20%) + TR 2%. New Zealand White rabbits were divided into four groups (n = 6) and treated by subcutaneous route with F1, F2, F3, or F4 (10 μg·kg−1). PK evaluation used TR and M1 plasma levels. PD evaluation was performed with the measurement of both pupils' diameters. F2 showed higher TR plasma concentration after 180 minutes and presented lower M1 concentrations at almost all evaluated periods. Areas under the curve (ASC0–480 and ASC0–∞) and clearance of F2 presented differences compared to F1. F2 presented significant correlation (Pearson correlation) between the enhancement of TR and M1 concentrations and the decrease of pupil size (miosis). Thus, F2 was effective in altering pharmacokinetics and pharmacodynamics effects of TR. PMID:28819627

  7. Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative stress in kidney ischemia/reperfusion injury in rats.

    PubMed

    Oliveira, Rita de Cássia Silva de; Brito, Marcus Vinicius Henriques; Ribeiro, Rubens Fernando Gonçalves; Oliveira, Leonam Oliver Durval; Monteiro, Andrew Moraes; Brandão, Fernando Mateus Viegas; Cavalcante, Lainy Carollyne da Costa; Gouveia, Eduardo Henrique Herbster; Henriques, Higor Yuri Bezerra

    2017-03-01

    To evaluate the effects of tramadol hydrochloride associated to remote ischemic perconditioning on oxidative stress. Twenty five male rats (Wistar) underwent right nephrectomy and were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during kidney ischemia; Tramadol group (T) treated with tramadol hydrochloride (40mg/kg); remote ischemic perconditioning + Tramadol group (Per+T) with both treatments. Oxidative stress was assessed after 24 hours of reperfusion. Statistical differences were observed in MDA levels between I/R group with all groups (p<0.01), in addition there was difference between Tramadol with Sham, Per and Per+T groups (p<0.05), both in plasma and renal tissue. Remote ischemic perconditioning was more effective reducing renal ischemia-reperfusion injury than administration of tramadol or association of both treatments.

  8. Does Tramadol Have a Role in Pain Control in Palliative Care?

    PubMed

    Gonçalves, José António Ferraz; Silva, Paula; Araújo, Patrícia

    2015-09-01

    The effectiveness of the step II of the World Health Organization analgesic ladder including tramadol has been questioned recently. Retrospective study of patients treated with tramadol admitted as inpatients to one palliative care unit between November 1, 2009, and October 30, 2012. In the study period, 730 patients were admitted and 66 (9%) of them met the criteria for inclusion; 45 (68%) continued medication with tramadol until discharge from the unit, while 21 (32%) had to switch to an opioid for moderate to severe pain. The reason for switching was uncontrolled pain in 16 (76%) patients, and for 5 (24%) patients, the switch was made for other reasons. The data suggest that tramadol may have a role to play in the treatment of pain in palliative care. © The Author(s) 2014.

  9. Tramadol: Effects on sexual behavior in male rats are mainly caused by its 5-HT reuptake blocking effects.

    PubMed

    Olivier, Jocelien D A; Esquivel Franco, Diana C; Oosting, Ronald; Waldinger, Marcel; Sarnyai, Zoltan; Olivier, Berend

    2016-11-24

    Tramadol is a well-known and effective analgesic. Recently it was shown that tramadol is also effective in human premature ejaculation. The inhibitory effect of tramadol on the ejaculation latency is probably due to its mechanism of action as a μ-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake inhibitor. In order to test this speculation, we tested several doses of tramadol in a rat model of male sexual behavior and investigated two types of drugs interfering with the μ-opioid and the 5-HT system. First the μ-opioid receptor agonist properties of tramadol were tested with naloxone, a μ-opioid receptor antagonist. Second, the effects of WAY100,635, a 5-HT1A receptor antagonist, were tested on the behavioral effects of tramadol. Finally the effects of paroxetine, a selective serotonin reuptake inhibitor, combined with naloxone or WAY100,635 treatment, were compared to the effects of tramadol combined with these drugs. Results showed that naloxone, at a sexually inactive dose, could only partially antagonize the inhibitory effect of tramadol. Moreover, low and behaviorally inactive doses of WAY100,635, strongly decreased sexual behavior when combined with a behaviorally inactive dose of tramadol. Finally we showed that the effects of paroxetine on sexual behavior resembled the effects of tramadol, indicating that tramadol's inhibitory effects on sexual behavior are primarily and mainly caused by its SSRI properties and that its μ-opioid receptor agonistic activity only contributes marginally. These findings support the hypothesis that tramadol exerts inhibition of premature ejaculations in men by its 5-HT reuptake inhibiting properties.

  10. Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction.

    PubMed

    Moore, P A; Crout, R J; Jackson, D L; Schneider, L G; Graves, R W; Bakos, L

    1998-06-01

    Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects. A two-center randomized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg, aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug. Of the 200 patients enrolled, seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up. Using standard measures of analgesia, including total pain relief score (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference scores (SPID), peak pain intensity difference (Peak PID), remedication, and global evaluations, all active treatments were found to be numerically superior to placebo. ASA/codeine was found to be statistically superior to placebo for all measures of efficacy. Tramadol 100 mg was statistically superior to placebo for TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time. Codeine was not found to be statistically superior to placebo for any efficacy measure. A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different. Gastrointestinal side effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol 100 mg, ASA/ codeine, and codeine 60 mg than with placebo.

  11. Tramadol Induced QTc-Interval Prolongation: Prevalence, Clinical Factors and Correlation to Plasma Concentrations.

    PubMed

    Keller, Guillermo A; Etchegoyen, María C V; Fernandez, Nicolás; Olivera, Nancy M; Quiroga, Patricia N; Belloso, Waldo H; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. To evaluate the effect of tramadol on QT-interval in the clinical setting. Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean ± SD (range), showed QTcB 372±32 (305 to 433), QTcFri 356±37 (281 to 429), QTcFra 363±33 (299 to 429), QTcH 362±30 (304 to 427), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and .QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for .QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.

  12. Psychiatric Comorbidity Among Egyptian Patients With Opioid Use Disorders Attributed to Tramadol.

    PubMed

    Bassiony, Medhat M; Youssif, Usama M; Hussein, Ramadan A; Saeed, Mervat

    2016-01-01

    Opioid use disorders attributed to tramadol (OUD-T) is a public health problem in Egypt. The objective of this study was to assess the psychiatric comorbidity among patients with opioid use disorder attributed to tramadol. This study included 100 patients with opioid use disorders attributed to tramadol (according to DSM-IV-TR) and 100 control persons (matched for age, sex, and education), who were recruited from Zagazig University Hospital, Egypt. The participants were interviewed using Structured Clinical Interview for DSM disorders (SCID-I and SCID-II), Addiction Severity Index scale (patients), and urine screening for drugs. Twenty-four percent of the patients used tramadol only (pure tramadol group), whereas 76% of the patients used other substances in addition to tramadol (polysubstance group). Most (91%) of the patients had tramadol dependence. Forty-nine percent of the patients had psychiatric comorbidity, especially mood disorders (59.2%), whereas only 24% of the control persons had psychiatric comorbidity, especially anxiety disorders (83.3%). The most common personality disorders among patients were borderline (24%) and antisocial (22%), whereas in control persons, the most common personality disorders were obsessive compulsive personality disorder (8%) and the avoidant personality disorder (7%). Cluster B (76.6%) was the most common category among patients (compared with 25.8% in control persons), whereas cluster C (51.6%) was the most common category among control persons (compared with 15.6% in patients). Most of the patients were dependent on tramadol, and approximately 3 out of 4 used many substances. Almost half of the patients had psychiatric comorbidity, and approximately 3 out of 4 had cluster B personality disorders.

  13. Effect of topical administration of tramadol on corneal wound healing in rats.

    PubMed

    Cuvas Apan, Ozgun; Ozer, Murat Atabey; Takir, Selcuk; Apan, Alparslan; Sengul, Demet

    2016-10-01

    In this study, we aimed to investigate the effects of topical tramadol administration on corneal wound healing, and examine ophthalmic structures and intraocular pressure 7 days after tramadol administration. The experiments were conducted on eight male Wistar rats (250-300 g). After ophthalmic examination, epithelial cell layers in the central cornea were wounded. Rats received 30 μL of tramadol hydrochloride in one eye (Group Tramadol) and the same volume of vehicle in the other (Group Control) every 12 h for 7 days. Both eyes were stained with fluorescein dye, photographed, and wound area was calculated every 8 h until complete healing was observed. Eye blink frequency and corneal reflex tests were measured before and after drug administrations. After 7 days, slit lamp biomicroscopy, fundoscopy, Goldmann applanation tonometry, and histological evaluation were performed. There was no difference in the corneal wound healing rates between the tramadol and control groups. Reduction in wound area over time was also similar; group-time interaction was insignificant (F = 738.911; p = 0.225). Tramadol application resulted in blinking and blepharospasm for 30 s, but vehicle did not. Corneal reflex was intact and eye blink frequency test results were similar in all measurement times in both groups. Slit lamp biomicroscopy, fundoscopy, and intraocular pressures were within normal range. Corneal cells appeared unaffected by the repeated doses of tramadol for 7 days. Topical tramadol application on the cornea did not cause any side effect, except for initial temporary blinking and blepharospasm. Corneal wound healing was not affected, either.

  14. Enhanced analgesic effects of tramadol and common trace element coadministration in mice.

    PubMed

    Alexa, Teodora; Marza, Aurelia; Voloseniuc, Tudor; Tamba, Bogdan

    2015-10-01

    Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadol's analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail-flick (TF) and hot-plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadol's analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol-alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drug's analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia. © 2015 Wiley Periodicals, Inc.

  15. Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test.

    PubMed

    Déciga-Campos, Myrna; Ramírez-Marín, Pamela Moncerrat; López-Muñoz, Francisco Javier

    2015-10-15

    Pharmacological synergism has been used to obtain a higher efficacy using drug concentrations at which side effects are minimal. In this study, the pharmacological antinociceptive interaction between N-palmitoylethanolamide (PEA) and tramadol was investigated. The individual concentration-response curves for PEA (0.1-56.2 μg/paw) and tramadol (1-56.2 μg/paw) were evaluated in mice in which nociception was induced by an intraplantar injection of 2% formalin. Isobolographic analysis was used to evaluate the pharmacological interaction between PEA (EC50=23.7±1.6 μg/paw) and tramadol (EC50=26.02±2.96 μg/paw) using the EC50 and a fixed 1:1 ratio combination. The isobologram demonstrated that the combinations investigated in this study produced a synergistic interaction; the experimental values (Zexp=9.5±0.2 μg/paw) were significantly smaller than those calculated theoretically (Zadd=24.8±0.2 μg/paw). The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-α). The sedative effect of the combination of PEA and tramadol was less than that generated by individual treatments. These findings suggest that the PEA and tramadol combination produced enhanced antinociceptive efficacy at concentrations at which side effects are minimal.

  16. Effect of intraarticular tramadol administration in the rat model of knee joint inflammation.

    PubMed

    Garlicki, Jarosław; Dorazil-Dudzik, Magdalena; Wordliczek, Jerzy; Przewłocka, Barbara

    2006-01-01

    Local administration of exogenous opioids may cause effective analgesia without adverse symptoms from the central nervous system. Experiments show that peripheral antinociceptive effect of opioids is observed especially in inflammatory pain. The aim of the research was to estimate the effect of tramadol on nociceptive process at the level of peripheral nervous system, after its local administration in the model of knee joint inflammation. Tramadol was administered intraarticulary into the rat knee joint, before the inflammation as a preemptive analgesia and, for comparison, after the intraarticular injection of carrageenan. The research determined the influence of tramadol injection on pain threshold for thermal stimuli, development of inflammatory processes using the measurement of joint edema and motor function following the induction of knee joint inflammation in the rat. Functional assessment of knee joint with inflammation, in terms of rats' mobility and body position as well as joint loading and mobility were studied. The results of the experiments show that local administration of tramadol induces antinociceptive effect. The effect of tramadol, which elicits also a decrease in inflammatory edema, appears not only after its administration after carrageenan when inflammation was already present, but also in the case of its injection prior to carrageenan in the scheme of preemptive analgesia. The results of the described research show that not only morphine but also another opioid, tramadol, widely used in clinical practice, inhibits nociception, edema and functional impairment of the paw after its local application directly to the inflamed knee joint.

  17. Randomised double-blind comparative study of dexmedetomidine and tramadol for post-spinal anaesthesia shivering

    PubMed Central

    Mittal, Geeta; Gupta, Kanchan; Katyal, Sunil; Kaushal, Sandeep

    2014-01-01

    Background and Aims: Dexmedetomidine (α2 adrenergic agonist) has been used for prevention of post anaesthesia shivering. Its use for the treatment of post-spinal anaesthesia shivering has not been evaluated. The aim of this study was to evaluate and compare the efficacy, haemodynamic and adverse effects of dexmedetomidine with those of tramadol, when used for control of post-spinal anaesthesia shivering. Methods: A prospective, randomised, and double-blind study was conducted in 50 American Society of Anaesthesiologists Grade I and II patients of either gender, aged between 18 and 65 years, scheduled for various surgical procedures under spinal anaesthesia. The patients were randomised in two groups of 25 patients each to receive either dexmedetomidine 0.5 μg/kg or tramadol 0.5 mg/kg as a slow intravenous bolus. Grade of shivering, onset of shivering, time for cessation of shivering, recurrence, response rate, and adverse effects were observed at scheduled intervals. Unpaired t-test was used for analysing the data. Results: Time taken for cessation of shivering was significantly less with dexmedetomidine when compared to tramadol. Nausea and vomiting was observed only in tramadol group (28% and; 20% respectively). There was not much difference in the sedation profile of both the drugs. Conclusion: We conclude that although both drugs are effective, the time taken for cessation of shivering is less with dexmedetomidine when compared to tramadol. Moreover, dexmedetomidine has negligible adverse effects, whereas tramadol is associated with significant nausea and vomiting. PMID:25024466

  18. Mu Opioid Mediated Discriminative-Stimulus Effects of Tramadol: An Individual Subjects Analysis

    PubMed Central

    Strickland, Justin C.; Rush, Craig R.; Stoops, William W.

    2015-01-01

    Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human subjects. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human subjects first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to subjects after acquiring the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all subjects. These effects were attenuated by naltrexone. Individual subject records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure. PMID:25664525

  19. Synergic antinociceptive interaction between tramadol and gabapentin after local, spinal and systemic administration.

    PubMed

    Granados-Soto, Vinicio; Argüelles, Carlos F

    2005-07-01

    The possible interaction between tramadol and gabapentin on formalin-induced nociception in the rat was assessed. Tramadol, gabapentin or a fixed-dose ratio combination of gabapentin and tramadol were administered peripherally, spinally and orally to rats, and the antinociceptive effect was determined in the 1% formalin test. Isobolographic analyses were used to define the nature of the interactions between drugs. Tramadol, gabapentin and tramadol-gabapentin combinations produced a dose-dependent antinociceptive effect when administered locally, spinally or orally. ED30 values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED30 values for the combination estimated from the isobolograms were 126.8 +/- 11.1 microg/paw, 23.1 +/- 2.6 microg/rat, and 2.23 +/- 0.32 mg/kg for the local, intrathecal and oral routes, respectively. These values were significantly higher than the actually observed ED30 values which were 13.3 +/- 2.1 microg/paw, 8.1 +/- 0.6 microg/rat and 0.71 +/- 0.10 mg/kg, indicating a synergistic interaction. Although efficacy was not improved, local peripheral administration resulted in the highest increase in potency, being about tenfold. Spinal and systemic administration increased potency threefold. Data indicate that low doses of the tramadol-gabapentin combination can interact synergistically to reverse formalin-induced nociception and may represent a therapeutic advantage for clinical treatment of inflammatory pain.

  20. The effects of tramadol on hepatic ischemia/reperfusion injury in rats

    PubMed Central

    Mahmoud, Mona F.; Gamal, Samar; Shaheen, Mohamed A.; El-Fayoumi, Hassan M.

    2016-01-01

    Objectives: Tramadol is a centrally acting synthetic analgesic. It has a cardioprotective effect against myocardial ischemia-reperfusion (I/R) injury in isolated rat heart. We hypothesized that tramadol may exert a similar protective effect on hepatic I/R injury. Hence, the current investigation was designed to study the possible protective effects of tramadol on experimentally-induced hepatic I/R injury in rats. Materials and Methods: Tramadol was administered 30 min before ischemia following which the rats were subjected to 45 min of ischemia followed by 1 h of reperfusion. Results: Tramadol attenuated hepatic injury induced by I/R as evidenced by the reduction of transaminases, structural changes, and apoptotic cell death. It decreased the level of inflammatory markers such as tumor necrosis factor-alpha (TNF-α), TNF-α/interleukin-10 (IL-10) ratio, and nuclear factor-κB gene expression. It also increased the anti-inflammatory cytokine, IL-10 levels in hepatic tissues. Furthermore, it reduced oxidative stress parameters except manganese superoxide dismutase activity. Conclusion: The results suggest that tramadol has hepatoprotective effects against hepatic I/R injury via anti-inflammatory, antiapoptotic, and antioxidant effects. PMID:27298497

  1. Altered Antinociceptive Efficacy of Tramadol Over Time in Rats with Painful Peripheral Neuropathy

    PubMed Central

    Hama, Aldric; Sagen, Jacqueline

    2007-01-01

    Pain due to peripheral nerve injury or disease is a dynamic process, such that the mechanism that underlies it alters over time. Tramadol has been reported to be analgesic in clinical neuropathic pain, with varying levels of efficacy due to a patient population that has had neuropathic pain for a wide range of time. In order to address examine issue, the antinociceptive efficacy of tramadol over time was tested in rats with a chronic constriction injury (CCI) of the left sciatic nerve. Rats developed a robust hind paw hypersensitivity to innocuous mechanical stimulation ipsilateral to CCI surgery. Subcutaneous injection of tramadol in rats two weeks after CCI surgery dose-dependently attenuated mechanical hypersensitivity, which was abolished with the μ-opioid receptor antagonist naloxone but not the α2-adrenoceptor antagonist yohimbine. Systemic tramadol also attenuated mechanical hypersensitivity four weeks after CCI surgery, but the efficacy significantly diminished at this time point. In addition, the effect of tramadol at this later time point could be reduced with yohimbine as well as naloxone. These data demonstrate that the efficacy of tramadol depends in part on the duration of nerve injury-evoked nociception, and that its antinociceptive mechanism changes over time. Alteration in antinociceptive mechanism over time may explain the inconsistency in efficacy of this and other analgesic drugs in chronic pain patients. PMID:17207479

  2. Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in Wistar rats.

    PubMed

    Faria, Juliana; Barbosa, Joana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Moreira, Roxana; Queirós, Odília; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2017-06-15

    Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively). 24h after intraperitoneal administration, biochemical and oxidative stress analyses were performed in blood, and specimens from brain, lung and heart were taken for histopathological and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio, in LDH, CK and CK-MB activities in serum samples, and an increase in lactate levels in serum and brain samples. Oxidative damage, namely protein oxidation, was found in heart and lung tissues. In histological analyses, tramadol and tapentadol were found to cause alterations in cell morphology, inflammatory cell infiltrates and cell death in all tissues under study, although tapentadol caused more damage than tramadol. Our results confirmed the risks of tramadol exposure, and demonstrated the higher risk of tapentadol, especially at high doses. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The effects of tramadol on hepatic ischemia/reperfusion injury in rats.

    PubMed

    Mahmoud, Mona F; Gamal, Samar; Shaheen, Mohamed A; El-Fayoumi, Hassan M

    2016-01-01

    Tramadol is a centrally acting synthetic analgesic. It has a cardioprotective effect against myocardial ischemia-reperfusion (I/R) injury in isolated rat heart. We hypothesized that tramadol may exert a similar protective effect on hepatic I/R injury. Hence, the current investigation was designed to study the possible protective effects of tramadol on experimentally-induced hepatic I/R injury in rats. Tramadol was administered 30 min before ischemia following which the rats were subjected to 45 min of ischemia followed by 1 h of reperfusion. Tramadol attenuated hepatic injury induced by I/R as evidenced by the reduction of transaminases, structural changes, and apoptotic cell death. It decreased the level of inflammatory markers such as tumor necrosis factor-alpha (TNF-α), TNF-α/interleukin-10 (IL-10) ratio, and nuclear factor-κB gene expression. It also increased the anti-inflammatory cytokine, IL-10 levels in hepatic tissues. Furthermore, it reduced oxidative stress parameters except manganese superoxide dismutase activity. The results suggest that tramadol has hepatoprotective effects against hepatic I/R injury via anti-inflammatory, antiapoptotic, and antioxidant effects.

  4. Effect of Tramadol/Acetaminophen on Motivation in Patients with Chronic Low Back Pain.

    PubMed

    Tetsunaga, Tomoko; Tetsunaga, Tomonori; Tanaka, Masato; Nishida, Keiichiro; Takei, Yoshitaka; Ozaki, Toshifumi

    2016-01-01

    Background. The contribution of apathy, frequently recognized in individuals with neurodegenerative diseases, to chronic low back pain (LBP) remains unclear. Objectives. To investigate levels of apathy and clinical outcomes in patients with chronic LBP treated with tramadol-acetaminophen. Methods. A retrospective case-control study involving 73 patients with chronic LBP (23 male, 50 female; mean age 71 years) treated with tramadol-acetaminophen (n = 36) and celecoxib (n = 37) was performed. All patients were assessed using the self-reported questionnaires. A mediation model was constructed using a bootstrapping method to evaluate the mediating effects of pain relief after treatment. Results. A total of 35 (55.6%) patients met the criteria for apathy. A four-week treatment regimen in the tramadol group conferred significant improvements in the Apathy scale and numerical rating scale but not in the Rolland-Morris Disability Questionnaire, Pain Disability Assessment Scale, or Pain Catastrophizing Scale. The depression component of the Hospital Anxiety and Depression Scale was lower in the tramadol group than in the celecoxib group. The mediation analysis found that the impact of tramadol-acetaminophen on the change in apathy was not mediated by the pain relief. Conclusions. Tramadol-acetaminophen was effective at reducing chronic LBP and conferred a prophylactic motivational effect in patients with chronic LBP.

  5. [Severe hypoglycemia following tramadol intake in a 79 year old non-diabetic patient].

    PubMed

    Kürten, Cornelius; Tzvetkov, Mladen; Ellenrieder, Volker; Schwörer, Harald

    2016-09-01

    History and clinical findings | We report about a 79 year old non-diabetic patient who was admitted to the emergency room with severe hypoglycemia (blood glucose level: 36 mg / dl and Glasgow Coma Scale Score: 3). After the infusion of G40 % her blood glucose level stabilised. The patient reported to have taken 50 mg of Tramadol during the night to treat her headache. Investigations and diagnosis | No other differential diagnosis for hypoglycemia (i.e. diabetes, insulinoma, severe liver or kidney disease) could be established. Therefore, we suspected a tramadol induced hypoglycemia. The mechanisms and the risk factors for this potential side effect remain unclear. The patient showed no abnormality in metabolism (CYP2D6) or membrane transport (OCT1) of tramadol. Treatment and course | No further treatment for hypoglycemic episodes was needed. The patient was discharged after the differential diagnosis and pharmacogenetic testing was completed. Conclusions | Hypoglycemia is a little known adverse effect after tramadol intake, which has only been published in few cases. Tramadol, a weak opioid analgesic classified as step 2 of the WHO cancer pain ladder, is used in moderate pain. Given the continuous rise in tramadol prescription due to better management of chronic pain, further investigation of this issue seems needed as well as an increased awareness amongst physicians. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Mu opioid mediated discriminative-stimulus effects of tramadol: an individual subjects analysis.

    PubMed

    Strickland, Justin C; Rush, Craig R; Stoops, William W

    2015-03-01

    Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human participants. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human participants first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to participants after they acquired the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all participants. These effects were attenuated by naltrexone. Individual participant records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure. © Society for the Experimental Analysis of Behavior.

  7. The anti-inflammatory effect of tramadol in the temporomandibular joint of rats.

    PubMed

    Lamana, Simone Monaliza S; Napimoga, Marcelo H; Nascimento, Ana Paula Camatta; Freitas, Fabiana F; de Araujo, Daniele R; Quinteiro, Mariana S; Macedo, Cristina G; Fogaça, Carlos L; Clemente-Napimoga, Juliana T

    2017-07-15

    Tramadol is a centrally acting analgesic drug able to prevent nociceptor sensitization when administered into the temporomandibular joint (TMJ) of rats. The mechanism underlying the peripheral anti-inflammatory effect of tramadol remains unknown. This study demonstrated that intra-TMJ injection of tramadol (500µg/TMJ) was able to inhibit the nociceptive response induced by 1.5% formalin or 1.5% capsaicin, suggesting that tramadol has an antinociceptive effect, acting directly on the primary nociceptive neurons activating the nitric oxide/cyclic guanosine monophosphate signaling pathway. Tramadol also inhibited the nociceptive response induced by carrageenan (100µg/TMJ) or 5-hydroxytryptamine (225µg/TMJ) along with inhibition of inflammatory cytokines levels, leukocytes migration and plasma extravasation. In conclusion, the results demonstrate that peripheral administration of tramadol has a potential antinociceptive and anti-inflammatory effect. The antinociceptive effect is mediated by activation of the intracellular nitric oxide/cyclic guanosine monophosphate pathway, at least in part, independently from the opioid system. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation.

    PubMed

    Eassa, Bayoumy I; El-Shazly, Mohamed A

    2013-01-01

    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 sought.

  9. Analgesic efficacy of tramadol, pregabalin and ibuprofen in menthol-evoked cold hyperalgesia.

    PubMed

    Altis, Kosta; Schmidtko, Achim; Angioni, Carlo; Kuczka, Karina; Schmidt, Helmut; Geisslinger, Gerd; Lötsch, Jörn; Tegeder, Irmgard

    2009-12-15

    We investigated the analgesic efficacy of single doses of ibuprofen, tramadol and pregabalin in menthol-evoked cold pain in a randomized, placebo-controlled four-way cross-over study in 20 healthy volunteers. Tramadol 100mg significantly reduced menthol-evoked cold hyperalgesia. Effects of ibuprofen 600mg and pregabalin 100mg were not significant. Analgesic effects of tramadol were associated with minor side effects, particularly fatigue and nausea. Minor side effects also accompanied analgesic effects of pregabalin and ibuprofen in subjects responding to these drugs, mostly fatigue, dizziness and difficulties to concentrate for pregabalin and gastric upset for ibuprofen. Five out of 18 subjects had a 50% reduction of cold hyperalgesia with tramadol, three of these additionally responded to pregabalin, and two with all three drugs. The numbers needed to treat (NNT >or= 50% for tramadol 4.5, for pregabalin 9) largely agree with the reported efficacy of tramadol and of moderate dosages of pregabalin in patients with peripheral or central neuropathic pain suggesting that menthol-evoked cold pain hypersensitivity may represent a valid model for neuropathic pain, particularly cold allodynia.

  10. Tramadol antinociception is potentiated by clonidine through α₂-adrenergic and I₂-imidazoline but not by endothelin ET(A) receptors in mice.

    PubMed

    Andurkar, Shridhar V; Gendler, Liya; Gulati, Anil

    2012-05-15

    Tramadol is a centrally acting analgesic that acts via μ-opioid agonism and by blocking the neuronal uptake of norepinephrine and serotonin. Clonidine potentiates the antinociceptive effects of tramadol; however the receptors involved in this potentiation have not been studied. Endothelin ET(A) receptor antagonists potentiate antinociceptive effects of morphine and oxycodone; however the effects of endothelin ET(A) receptor antagonists on tramadol antinociception have not been evaluated. This study was conducted to determine the effect of clonidine on tramadol antinociception; the role of opioid, α₂-adrenergic and I₂-imidazoline receptors in clonidine potentiation of tramadol antinociception; and the effect of endothelin ET(A) receptor antagonists in modulating tramadol antinociception. Antinociceptive (tail-flick and hot-plate) latencies were measured in male Swiss Webster mice treated with tramadol; clonidine plus tramadol; or antagonists plus tramadol. Mice were pretreated with naloxone (opioid antagonist), yohimbine (α₂-adrenoceptor antagonist), idazoxan (α₂-adrenoceptor/I₂-imidazoline antagonist), BMS182874 or BQ123 (endothelin ET(A) receptor antagonists) to study the involvement of these receptors. Tramadol produced a dose dependent increase in antinociceptive latencies. Tramadol antinociception was partially blocked by naloxone but not by yohimbine or idazoxan. Clonidine potentiated tramadol antinociception; potentiation was blocked by naloxone, yohimbine and idazoxan. Idazoxan produced a more pronounced blockade of potentiation than yohimbine. BMS182874 or BQ123 had no effect on tramadol antinociception, indicating that endothelin ET(A) receptors are not involved in tramadol antinociception in mice. Results demonstrate the involvement of opioid but not α₂-adrenergic/I₂-imidazoline receptors in tramadol antinociception and that opioid, α₂-adrenergic and I₂-imidazoline receptors are involved in clonidine potentiation of tramadol

  11. Pharmacokinetics of tramadol and metabolites O-desmethyltramadol and N-desmethyltramadol in adult horses.

    PubMed

    Stewart, Allison J; Boothe, Dawn M; Cruz-Espindola, Crisanta; Mitchum, Emily J; Springfield, Jenny

    2011-07-01

    To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses. 12 mixed-breed horses. Horses received tramadol IV (5 mg/kg, over 3 minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized crossover design. Serum samples were collected over 48 hours. Serum tramadol, ODT, and NDT concentrations were measured via high-performance liquid chromatography and analyzed via noncompartmental analysis. Maximum mean ± SEM serum concentrations after IV administration for tramadol, ODT, and NDT were 5,027 ± 638 ng/mL, 0 ng/mL, and 73.7 ± 12.9 ng/mL, respectively. For tramadol, half-life, volume of distribution, area under the curve, and total body clearance after IV administration were 2.55 ± 0.88 hours, 4.02 ± 1.35 L/kg, 2,701 ± 275 h x ng/mL, and 30.1 ± 2.56 mL/min/kg, respectively. Maximal serum concentrations after oral administration for tramadol, ODT, and NDT were 238 ± 41.3 ng/mL, 86.8 ± 17.8 ng/mL, and 159 ± 20.4 ng/mL, respectively. After oral administration, half-life for tramadol, ODT, and NDT was 2.14 ± 0.50 hours, 1.01 ± 0.15 hours, and 2.62 ± 0.49 hours, respectively. Bioavailability of tramadol was 9.50 ± 1.28%. After oral administration, concentrations achieved minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10 ng/mL) for 2.2 ± 0.46 hours and 2.04 ± 0.30 hours, respectively. Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally.

  12. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    PubMed Central

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200 mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  13. Evaluation of the analgesic effects of oral and subcutaneous tramadol administration in red-eared slider turtles

    PubMed Central

    Baker, Bridget B.; Sladky, Kurt K.; Johnson, Stephen M.

    2011-01-01

    Objective To determine the dose- and time-dependent changes in analgesia and respiration caused by tramadol administration in red-eared slider turtles (Trachemys scripta). Design Crossover study. Animals 30 adult male and female red-eared slider turtles. Procedures 11 turtles received tramadol at various doses (1, 5, 10, or 25 mg/kg [0.45, 2.27, 4.54, or 11.36 mg/lb], PO; 10 or 25 mg/kg, SC) or a control treatment administered similarly. Degree of analgesia was assessed through measurement of hind limb thermal withdrawal latencies (TWDLs) at 0, 3, 6, 12, 24, 48, 72, and 96 hours after tramadol administration. Nineteen other freely swimming turtles received tramadol PO (5, 10, or 25 mg/kg), and ventilation (VE), breath frequency, tidal volume (VT and expiratory breath duration were measured. Results The highest tramadol doses (10 and 25 mg/kg, PO) yielded greater mean TWDLs 6 to 96 hours after administration than the control treatment did, whereas tramadol administered at 5 mg/kg, PO, yielded greater mean TWDLs at 12 and 24 hours. The lowest tramadol dose (1 mg/kg, PO) failed to result in analgesia. Tramadol administered SC resulted in lower TWDLs, slower onset, and shorter duration of action, compared with PO administration. Tramadol at 10 and 25 mg/kg, PO, reduced the VE at 12 hours by 51% and 67%, respectively, and at 24 through 72 hours by 55% to 62% and 61% to 70%, respectively. However, tramadol at 5 mg/kg, PO, had no effect on the VE. Conclusions and Clinical Relevance Tramadol administered PO at 5 to 10 mg/kg provided thermal analgesia with less respiratory depression than that reported for morphine in red-eared slider turtles. PMID:21235376

  14. Effects of Tramadol on Substantia Gelatinosa Neurons in the Rat Spinal Cord: An In Vivo Patch-Clamp Analysis

    PubMed Central

    Yamasaki, Hiroyuki; Funai, Yusuke; Funao, Tomoharu; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol is thought to modulate synaptic transmissions in the spinal dorsal horn mainly by activating µ-opioid receptors and by inhibiting the reuptake of monoamines in the CNS. However, the precise mode of modulation remains unclear. We used an in vivo patch clamp technique in urethane-anesthetized rats to determine the antinociceptive mechanism of tramadol. In vivo whole-cell recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) were made from substantia gelatinosa (SG) neurons (lamina II) at holding potentials of 0 mV and -70 mV, respectively. The effects of intravenous administration (0.5, 5, 15 mg/kg) of tramadol were evaluated. The effects of superfusion of tramadol on the surface of the spinal cord and of a tramadol metabolite (M1) were further analyzed. Intravenous administration of tramadol at doses >5 mg/kg decreased the sEPSCs and increased the sIPSCs in SG neurons. These effects were not observed following naloxone pretreatment. Tramadol superfusion at a clinically relevant concentration (10 µM) had no effect, but when administered at a very high concentration (100 µM), tramadol decreased sEPSCs, produced outward currents, and enhanced sIPSCs. The effects of M1 (1, 5 mg/kg intravenously) on sEPSCs and sIPSCs were similar to those of tramadol at a corresponding dose (5, 15 mg/kg). The present study demonstrated that systemically administered tramadol indirectly inhibited glutamatergic transmission, and enhanced GABAergic and glycinergic transmissions in SG neurons. These effects were mediated primarily by the activation of μ-opioid receptors. M1 may play a key role in the antinociceptive mechanisms of tramadol. PMID:25933213

  15. The influence of a single and chronic administration of venlafaxine on tramadol pharmacokinetics in a rabbit model.

    PubMed

    Szkutnik-Fiedler, Danuta; Grabowski, Tomasz; Balcerkiewicz, Monika; Michalak, Michał; Pilipczuk, Irina; Wyrowski, Łukasz; Urjasz, Hanna; Grześkowiak, Edmund

    2017-06-01

    The combined use of tramadol with selective serotonin and norepinephrine reuptake inhibitors e.g. venlafaxine may be associated with serotonin syndrome. No previous studies exist examining the influence of a weak CYP2D6 inhibitor venlafaxine on the pharmacokinetics of tramadol. Therefore, the aim of this study was to determine the effect of a single and chronic administration of venlafaxine on the pharmacokinetics of tramadol using a rabbit model. Adult New Zealand white rabbits of both sexes (n=21) were used. Animals received 100mg of tramadol per os (one slow release tablet) and 75mg of venlafaxine (one prolonged release capsule), and were divided into four groups: control group - a single dose of tramadol alone, 1day group - a single dose of tramadol and venlafaxine, 7 and 14days groups - seven and fourteen days administration of venlafaxine once daily plus a single dose of tramadol on the last day of the study. Venlafaxine administration over a period of 7 and 14days resulted in faster elimination of tramadol compared to the control group: significantly higher values of k el, and lower values of t1/2kel and MRT for the 7 and 14days group were observed. Although no differences in bioavailability of tramadol were obtained. Using a rabbit model, there is no evidence that the combined administration of tramadol and venlafaxine may increase the plasma exposure of tramadol and therefore increase the risk of serotonin syndrome. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Effects of tramadol on substantia gelatinosa neurons in the rat spinal cord: an in vivo patch-clamp analysis.

    PubMed

    Yamasaki, Hiroyuki; Funai, Yusuke; Funao, Tomoharu; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol is thought to modulate synaptic transmissions in the spinal dorsal horn mainly by activating µ-opioid receptors and by inhibiting the reuptake of monoamines in the CNS. However, the precise mode of modulation remains unclear. We used an in vivo patch clamp technique in urethane-anesthetized rats to determine the antinociceptive mechanism of tramadol. In vivo whole-cell recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) were made from substantia gelatinosa (SG) neurons (lamina II) at holding potentials of 0 mV and -70 mV, respectively. The effects of intravenous administration (0.5, 5, 15 mg/kg) of tramadol were evaluated. The effects of superfusion of tramadol on the surface of the spinal cord and of a tramadol metabolite (M1) were further analyzed. Intravenous administration of tramadol at doses >5 mg/kg decreased the sEPSCs and increased the sIPSCs in SG neurons. These effects were not observed following naloxone pretreatment. Tramadol superfusion at a clinically relevant concentration (10 µM) had no effect, but when administered at a very high concentration (100 µM), tramadol decreased sEPSCs, produced outward currents, and enhanced sIPSCs. The effects of M1 (1, 5 mg/kg intravenously) on sEPSCs and sIPSCs were similar to those of tramadol at a corresponding dose (5, 15 mg/kg). The present study demonstrated that systemically administered tramadol indirectly inhibited glutamatergic transmission, and enhanced GABAergic and glycinergic transmissions in SG neurons. These effects were mediated primarily by the activation of μ-opioid receptors. M1 may play a key role in the antinociceptive mechanisms of tramadol.

  17. What's Tramadol Got to Do with It? A Case Report of Rebound Hypoglycemia, a Reappraisal and Review of Potential Mechanisms.

    PubMed

    Odonkor, Charles A; Chhatre, Akhil

    2016-01-01

    Tramadol has gained traction as an analgesic of choice among pain practicing physicians. However some concerns regarding a previously unlabeled adverse reaction - hypoglycemia - have cast it in a dim light. Prior reports have noted an associated risk of hospitalization for hypoglycemia after tramadol use, but whether tramadol is the main causal agent is poorly understood and the underlying mechanisms are not well delineated. We present a unique case of rebound hypoglycemia as a variation of the theme of tramadol's adverse effect profile in a patient with type 1 diabetes mellitus, and reappraise potential mechanisms underlying this underappreciated phenomenon. A 71-year-old woman presented with right buttock pain and right lateral leg discomfort of 9-month duration. Her physical exam suggested sacroiliac joint (SIJ) etiology, confirmed by magnetic resonance imaging (MRI). She was scheduled for an SIJ-diagnostic and therapeutic block and started on tramadol 50 mg 3 times daily on as needed basis. The patient subsequently developed severe hypoglycemia initially resistant to euglycemia restorative interventions with a rebound episode. Hypoglycemia resolved with oral ingestion of high levels of glucose and the patient was taken off tramadol. Fortunately, she did not require hospitalization. The clinical scenario described is a case of rebound hypoglycemia after tramadol use in a patient with type-1 diabetes naïve to opioid analgesics. The episodes of hypoglycemia aligned perfectly with the anticipated pharmacodynamic and pharmacokinetic properties of tramadol. The specificity and temporality of events after tramadol use in this patient fulfilled causality criteria. Tramadol may cause rebound hypoglycemia in patients via interference of the intrinsic euglycemia-restoration pathways and a blunted autonomic counter-regulatory response to antecedent hypoglycemia. Its use must be tempered by this underappreciated adverse effect profile.Key words: Tramadol, hypoglycemia

  18. Design and Evaluation of Chronomodulated Drug Delivery of Tramadol Hydrochloride.

    PubMed

    Alekya, Thota; Narendar, Dudhipala; Mahipal, Donthi; Arjun, Narala; Nagaraj, Banala

    2017-09-26

    Rheumatoid arthritis is an auto immune disease which requires chronotherapy as it occurs during early morning. Tramadol hydrochloride (TH) is an analgesic drug, used to treat rheumatoid arthritis. The aim of the present investigation was to develop chronomodulated drug delivery system of tramadol hydrochloride such that it releases the drug early in the morning, during which the symptoms of rheumatoid arthritis worsen. To develop chronomodulated drug delivery system of TH, initially core tablets of TH were prepared using three different supradisintegrants followed by coating with pH dependent polymer of Eudragit S100. The prepared core tablets are evaluated for physical parameters and an optimal system was identified. Further, coating composition of Eudragit S100 was optimized and coating tablets of TH was prepared. The prepared coated tablets were evaluated for weight variation, hardness, drug content and in vitro release studies in 0.1N HCl, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer. Formulation with 7.5% of coating solution (ES2) had shown a significant drug release after a lag time of 3 h (in pH 6.8 medium), 6 h (in pH 6.8 medium) and 8 h (in pH 7.4 medium), respectively. DSC studies revealed that no interaction between core and coated materials with drug was observed. Thus, chronomodulated drug delivery system of TH was formulated and assuming that if a tablet is administered around 9 pm to 10 pm, the drug release starts after a lag time of 6 h i. e., around 3am to 4 am. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Analgesic effect of intra-articular tramadol compared with morphine after arthroscopic knee surgery.

    PubMed

    Akinci, Seda B; Saricaoğlu, Fatma; Atay, Ozgur Ahmet; Doral, Mahmut Nedim; Kanbak, Meral

    2005-09-01

    The aim of the study was to compare the analgesic effect of 5 mg intra-articular (IA) morphine with 50 mg IA tramadol. Prospective double-blind randomized trial. Seventy-five patients having elective arthroscopic surgery of the knee were randomized to receive IA tramadol 50 mg (tramadol group), IA morphine 5 mg (morphine group), or IA normal saline (control group), in equivalent volumes (20 mL). The tourniquet was released 10 minutes after analgesic administration. Verbal pain rating score between 0 and 10 (VRS), supplemental analgesic requirements, and incidence of side effects were recorded postoperatively. Results are given as (median [5-95 percentiles]). The control group had a significantly shorter time to first analgesic request (25 min [15-55]) than morphine group, (34 min [15-158], P < .008) and the tramadol group, (33 min [17-728], P < .008). The patients in the control group complained of more severe pain (VRS 7 [4-10]) when they arrived at the postanesthesia care unit compared with the morphine group (VRS 1 [0-9], P = .002) and with the tramadol group (VRS 0 [0-9], P = .002). These treatment benefits were especially prominent in the patients who had meniscectomy or in the subgroup of patients with more than 6 months of preoperative pain. There was no statistical difference between the tramadol and morphine groups in the time to first analgesia, postoperative pain scores after arrival at the postanesthesia care unit, consumption of rescue analgesic, or side effects. We conclude that 50 mg IA tramadol provides analgesia equivalent to 5 mg IA morphine. Level II, randomized controlled trial that shows no significant difference and lacks narrow confidence intervals.

  20. Combination of Foot Stimulation and Tramadol Treatment Reverses Irritation Induced Bladder Overactivity in Cats

    PubMed Central

    Mally, Abhijith D.; Zhang, Fan; Matsuta, Yosuke; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.; Tai, Changfeng

    2013-01-01

    Purpose We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. Materials and Methods Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. Results Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. Conclusions This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects. PMID:23088991

  1. Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

    PubMed Central

    Zhang, Fan; Mally, Abhijith D.; Ogagan, P. Dafe; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.

    2012-01-01

    Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3–7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50–60% of the saline control capacity. Tramadol administered alone in low doses (0.3–1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3–7 mg/kg) increased bladder capacity (50–60%). TNS in combination with tramadol (3–7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects. PMID:22496406

  2. Long-Term Stability of Tramadol and Ketamine Solutions for Patient-Controlled Analgesia Delivery

    PubMed Central

    Gu, Junfeng; Qin, Wengang; Chen, Fuchao; Xia, Zhongyuan

    2015-01-01

    Background Subanesthetic doses of ketamine as an adjuvant to tramadol in patient-controlled analgesia (PCA) for postoperative pain have been shown to improve the quality of analgesia. However, there are no such commercially available drug mixtures, and the stability of the combination has rarely been assessed. Material/Methods Admixtures were assessed for periods of up to 14 days at 4°C and 25°C. Three different mixtures of tramadol and ketamine (tramadol 5.0 mg/mL + ketamine 0.5 mg/mL, tramadol 5.0 mg/mL + ketamine 1.0 mg/mL, and tramadol 5.0 mg/mL + ketamine 2.0 mg/mL) were prepared in polyolefin bags by combining these 2 drugs with 0.9% sodium chloride (normal saline [NS]). The chemical stability of the admixtures was evaluated by a validated high-performance liquid chromatography (HPLC) method and by measurement of pH values. Solution appearance and color were assessed by observing the samples against black and white backgrounds. Solutions were considered stable if they maintained 90% of the initial concentration of each drug. Results The percentages of initial concentration of tramadol and ketamine in the various solutions remained above 98% when stored at 4°C or 25°C over the testing period. No changes in color or turbidity were observed in any of the prepared solutions. Throughout this period, pH values remained stable. Conclusions The results indicate that the drug mixtures of tramadol with ketamine in NS for PCA delivery systems were stable for 14 days when stored in polyolefin bags at 4°C or 25°C. PMID:26306476

  3. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice

    PubMed Central

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-01-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain. PMID:26224442

  4. Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.

    PubMed

    Hosono, Tomomi; Kondo, Aiko; Kambayashi, Yasuyuki; Homma, Masato

    2017-01-01

     Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or dose reduction of warfarin after coadministration of tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.

  5. Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2012-08-01

    To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

  6. Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Souza, Marcy J; Gerhardt, Lillian; Cox, Sherry

    2013-07-01

    To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots. Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. No changes in the parrots' behavior were observed. Twelve hours after the first dose was administered, mean ± SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 ± 57 ng/mL and 6 ± 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 ± 0.78 hours and 2.14 ± 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

  7. Long-Term Stability of Tramadol and Ketamine Solutions for Patient-Controlled Analgesia Delivery.

    PubMed

    Gu, Junfeng; Qin, Wengang; Chen, Fuchao; Xia, Zhongyuan

    2015-08-26

    Subanesthetic doses of ketamine as an adjuvant to tramadol in patient-controlled analgesia (PCA) for postoperative pain have been shown to improve the quality of analgesia. However, there are no such commercially available drug mixtures, and the stability of the combination has rarely been assessed. Admixtures were assessed for periods of up to 14 days at 4°C and 25°C. Three different mixtures of tramadol and ketamine (tramadol 5.0 mg/mL + ketamine 0.5 mg/mL, tramadol 5.0 mg/mL + ketamine 1.0 mg/mL, and tramadol 5.0 mg/mL + ketamine 2.0 mg/mL) were prepared in polyolefin bags by combining these 2 drugs with 0.9% sodium chloride (normal saline [NS]). The chemical stability of the admixtures was evaluated by a validated high-performance liquid chromatography (HPLC) method and by measurement of pH values. Solution appearance and color were assessed by observing the samples against black and white backgrounds. Solutions were considered stable if they maintained 90% of the initial concentration of each drug. The percentages of initial concentration of tramadol and ketamine in the various solutions remained above 98% when stored at 4°C or 25°C over the testing period. No changes in color or turbidity were observed in any of the prepared solutions. Throughout this period, pH values remained stable. The results indicate that the drug mixtures of tramadol with ketamine in NS for PCA delivery systems were stable for 14 days when stored in polyolefin bags at 4°C or 25°C.

  8. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice.

    PubMed

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-07-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain.

  9. Intraoperative end-tidal concentration of isoflurane in cats undergoing ovariectomy that received tramadol, buprenorphine or a combination of both.

    PubMed

    Bellini, Luca; Mollo, Antonio; Contiero, Barbara; Busetto, Roberto

    2017-02-01

    Objectives The aim of the study was to evaluate the end-tidal concentration of isoflurane required to maintain heart and respiratory rate within ± 20% of basal measurement in cats undergoing ovariectomy that received buprenorphine, tramadol or a combination of both. Methods Thirty cats, divided into three groups, were enrolled in a simple operator-blinded, randomised study. Cats received acepromazine (0.03 mg/kg) and one of the following treatments: buprenorphine (0.02 mg/kg), tramadol (2 mg/kg) or a combination of both. Anaesthesia was induced with propofol and maintained with isoflurane titrated in order to maintain heart and respiratory rate within the target values recorded before premedication. Results Groups were similar for age, weight, dose of propofol administered, sedation and recovery scores. Cats receiving tramadol with buprenorphine were extubated earlier after isoflurane discontinuation. No statistical differences were detected in end-tidal fraction of isoflurane between buprenorphine alone or with tramadol. In cats that received tramadol or buprenorphine alone, ovarian pedicle traction caused a statistical increase in end-tidal isoflurane concentration compared with that measured during incision and suture of the skin. In cats that received the combination of tramadol plus buprenorphine no differences among surgical time points were observed. Conclusions and relevance Tramadol added to buprenorphine did not provide any advantage in decreasing the end-tidal fraction of isoflurane compared with buprenorphine alone, although it is speculated there may be an infra-additive interaction between tramadol and buprenorphine in cats.

  10. Analgesic Effects of Tramadol, Tramadol–Gabapentin, and Buprenorphine in an Incisional Model of Pain in Rats (Rattus norvegicus)

    PubMed Central

    McKeon, Gabriel P; Pacharinsak, Cholawat; Long, Charles T; Howard, Antwain M; Jampachaisri, Katechan; Yeomans, David C; Felt, Stephen A

    2011-01-01

    Postoperative pain management in laboratory animals relies heavily on a limited number of drug classes, such as opioids and nonsteroidal antiinflammatory drugs. Here we evaluated the effects of saline, tramadol, tramadol with gabapentin, and buprenorphine (n = 6 per group) in a rat model of incisional pain by examining thermal hyperalgesia and weight-bearing daily for 6 d after surgery. All drugs were administered preemptively and continued for 2 consecutive days after surgery. Rats treated with saline or with tramadol only showed thermal hyperalgesia on days 1 through 4 and 1 through 3 after surgery, respectively. In contrast, buprenorphine-treated rats showed no thermal hyperalgesia on days 1 and 2 after surgery, and rats given tramadol with gabapentin showed reduced thermal hyperalgesia on days 2 and 4. For tests of weight-bearing, rats treated with saline or with tramadol only showed significantly less ipsilateral weight-bearing on day 1 after surgery, whereas rats given either buprenorphine or tramadol with gabapentin showed no significant change in ipsilateral weight-bearing after surgery. These data suggest that tramadol alone provides insufficient analgesia in this model of incisional pain; buprenorphine and, to a lesser extent, tramadol with gabapentin provide relief of thermal hyperalgesia and normalize weight-bearing. PMID:21439212

  11. Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats

    PubMed Central

    Chavez, Julio R.; Ibancovichi, José A.; Sanchez-Aparicio, Pedro; Acevedo-Arcique, Carlos M.; Moran-Muñoz, Rafael; Recillas-Morales, Sergio

    2015-01-01

    Background It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC. Methods Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MACISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg). Results The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MACISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively. Conclusions The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MACISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane. PMID:26605541

  12. Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats.

    PubMed

    Chavez, Julio R; Ibancovichi, José A; Sanchez-Aparicio, Pedro; Acevedo-Arcique, Carlos M; Moran-Muñoz, Rafael; Recillas-Morales, Sergio

    2015-01-01

    It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC. Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MACISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg). The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MACISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively. The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MACISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane.

  13. Simultaneous Determination of Tramadol and Its Metabolite in Human Urine by the Gas Chromatography-Mass Spectrometry Method.

    PubMed

    Yilmaz, Bilal; Erdem, Ali Fuat

    2015-08-01

    A sensitive and efficient method was developed for determination of tramadol and its metabolite (O-desmethyltramadol) in human urine by gas chromatography-mass spectrometry. Tramadol, O-desmethyltramadol and medazepam (internal standard) were extracted from human urine with a mixture of ethylacetate and diethylether mixture (1 : 1, v/v) at basic pH with liquid-liquid extraction. The calibration curves were linear (r = 0.99) over tramadol and O-desmethyltramadol concentrations ranging from 10 to 200 ng/mL and 7.5 to 300 ng/mL, respectively. The method had an accuracy of >95% and intra- and interday precision (relative standard deviation %) of ≤4.93 and ≤4.62% for tramadol and O-desmethyltramadol, respectively. The extraction recoveries were found to be 94.1 ± 2.91 and 96.3 ± 3.46% for tramadol and O-desmethyltramadol, respectively. The limit of quantification using 0.5 mL human urine was 10 ng/mL for tramadol and 7.5 ng/mL for O-desmethyltramadol. After oral administration of 100 mg of tramadol hydrochloride to a patient, the urinary excretion was monitored during 24 h. About 15% of the dose was excreted as unchanged tramadol. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Involvement of NMDA receptors in the antidepressant-like effect of tramadol in the mouse forced swimming test.

    PubMed

    Ostadhadi, Sattar; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Akbarian, Reyhaneh; Imran-Khan, Muhammad; Ghasemi, Mehdi; Dehpour, Ahmad-Reza

    2017-09-01

    Tramadol is an analgesic agent that is mainly used to treat moderate to severe pain. There is evidence that tramadol may have antidepressant property. However, the mechanisms underlying the antidepressant effects of tramadol have not been elucidated yet. Considering that fact that N-methyl-d-aspartate (NMDA) receptor signaling may play an important role in the pathophysiology of depression, the aim of the present study was to investigate the role of NMDA receptor signaling in the possible antidepressant-like effects of tramadol in the mouse forced swimming test (mFST). We found that tramadol exerted antidepressant-like effects at high dose (40mg/kg, intraperitoneally [i.p.]) in the mFST. Co-administration of non-effective doses of NMDA receptor antagonists (ketamine [1mg/kg, i.p.], MK-801 [0.05mg/kg, i.p.], or magnesium sulfate [10mg/kg, i.p.]) with sub-effective dose of tramadol (20mg/kg, i.p.) exerted significant antidepressant-like effects in the mFST. The antidepressant-like effects of tramadol (40mg/kg) was also inhibited by pre-treatment with non-effective dose of the NMDA receptor agonist NMDA (75mg/kg, i.p.). Our data suggest a role for NMDA receptor signaling in the antidepressant-like effects of tramadol in the mFST. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Efficacy of the prophylactic administration of tramadol against postoperative shivering: a meta-analysis of randomized controlled trials.

    PubMed

    Li, Shuying; Li, Ping; Lin, Xuemei

    2017-01-01

    Postoperative shivering (POS) is a common complication that occurs after regional and general anesthesia. Thus far, numerous studies have reported on the effectiveness of tramadol in preventing or treating POS. Here, we performed a meta-analysis to assess the efficacy of tramadol in the prevention of POS. We systematically searched PubMed, Embase and the Cochrane Library to identify studies of the efficacy of tramadol in the prevention of POS. The results are expressed as relative ratios (RRs) and the corresponding 95% confidence intervals (CIs). Seventeen studies with a total of 1438 patients were included. Seven hundred seventy-seven of these patients received tramadol, and 661 received placebo. Compared with placebo, the patients who received tramadol exhibited a significant reduction in the incidence of POS based on subgroup analyses according to anesthesia (RR: 0.27; 95% CI: 0.19-0.37; P<0.00001), different doses of tramadol (RR: 0.26; 95% CI: 0.19-0.35; P<0.00001), the rescue drug used (RR: 0.19; 95% CI: 0.10-0.35; P<0.00001) and the number of patients who experienced severe POS (RR: 0.17; 95% CI: 0.12-0.23; P<0.00001). Moreover, the administration of tramadol did not increase the risks of postoperative nausea and vomiting (PONV), hemodynamic turbulence, respiratory depression or deep sedation. This meta-analysis revealed that prophylactic tramadol effectively prevents POS and reduces rescue medication use without significant adverse effects.

  16. Comparison of local anesthetic efficacy of tramadol hydrochloride (with adrenaline) versus plain tramadol hydrochloride in the extraction of upper molar teeth.

    PubMed

    Al-Haideri, Yahya A A

    2013-12-01

    To evaluate the efficacy of local anesthesia using tramadol hydrochloride (HCl) with versus without adrenaline in the extraction of upper molar teeth. This was a double-blinded study that included 100 patients who required extraction of 1 upper molar by the conventional method and were allocated randomly into 1 of 2 groups: in group A (n = 50), each patient received an initial dose of drug A (tramadol HCl 50 mg and adrenalin 0.0225 mg diluted to 1.8 mL by distilled water); in group B (n = 50), each patient received an initial dose of drug B (tramadol HCl 50 mg diluted to 1.8 mL by distilled water). Degree of pain during tooth extraction, duration of surgery, and total number of cartridges used were recorded intraoperatively. Postoperatively, patients were instructed to record any adverse effects, such as nausea or vomiting, on the first day of the operation. There were significant differences in the number of cartridges used and the degree of intraoperative pain. However, there was no significant difference in duration of surgery or side effects. The results of this study suggest that tramadol HCl in combination with adrenaline can be used as an alternative local anesthetic in oral and maxillofacial surgery when, for some unusual reason, a patient cannot receive a conventional local anesthetic. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Topical review on the abuse and misuse potential of tramadol and tilidine in Germany.

    PubMed

    Radbruch, Lukas; Glaeske, Gerd; Grond, Stefan; Münchberg, Frank; Scherbaum, Norbert; Storz, Elisabeth; Tholen, Kathrin; Zagermann-Muncke, Petra; Zieglgänsberger, Walter; Hoffmann-Menzel, Helmut; Greve, Hendrik; Cremer-Schaeffer, Peter

    2013-01-01

    Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices. A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation. Analgesic efficiency in the treatment of acute and chronic pain has been proven for both tramadol and tilidine/naloxone. For tramadol, high evidence has been confirmed in systematic reviews, and tramadol is listed in national and international guidelines on acute and chronic pain management. Animal and human studies found a low potential for misuse, abuse, and dependency for both substances. Information from 2 tramadol safety databases allowed calculation of the incidence of abuse or dependency as 0.21 and 0.12 cases per million defined daily dosages (DDDs), with lower incidences in recent years. For tilidine/naloxone, the incidence was calculated as 0.43 cases per million DDDs for oral solution and 0.18 for slow-release tablets. In an online survey among German pharmacies as well as in the reports from state pharmacy boards, fraud attempts were repeated more frequently with tilidine/naloxone than with tramadol in the last 2 years. The Federal Bureau of Criminal Investigations reported prescription fraud only with tilidine

  18. Comparison of Intravenous Infusion of Tramadol Alone with Combination of Tramadol and Paracetamol for Postoperative Pain after Major Abdominal Surgery in Children

    PubMed Central

    Ali, Shayesta; Sofi, Khalid; Dar, Abdul Qayoom

    2017-01-01

    Background: Pain is a common complaint after surgery and seems to be difficult to manage in children because of fear of complications of pain treatment or misconception that infants and small children do not feel pain at all or feel less pain. A survey reported that 40% of pediatric surgical patients experienced moderate or severe postoperative pain and that more than 75% had insufficient analgesia. Our study was carried to provide continuous infusion of intravenous (i.v.) tramadol alone using a dedicated infusion device Graseby 2100 syringe pump and compared it to a combination of i.v. tramadol infusion and per rectal paracetamol. Subjects and Methods: A total of 124 children aged 1–8 years selected for the study were randomized into two groups using a table of random numbers. Power calculation had suggested a sample size of 62 in each group with a power of 80% and significance level of 5%. Group A comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively. Group B comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively in addition to per rectal suppository of paracetamol in a dose of 90 mg/kg in 24 h (30 mg/kg as first dose followed by 20 mg/kg every 6 hourly for the next 18 h). Postoperatively, patients were observed for 24 h. Results: A statistically significant difference (P ≤ 0.001) in Face, Legs, Activity, Cry, Consolability pain scores was seen between two groups at 4, 6, and 8 h. Pain scores being less in Group B patients who had received infusion of tramadol and per rectal suppositories of paracetamol compared to Group A patients who received only infusion of tramadol. A statistically significant difference (P < 0.05) was found in mean analgesic consumption during the first 24 h between the groups. Consumption was more in Group A as compared to Group B. In Group A, 13 patients (21%) required rescue analgesia as compared to only 4 patients (6.5%) in

  19. Comparison of Intravenous Infusion of Tramadol Alone with Combination of Tramadol and Paracetamol for Postoperative Pain after Major Abdominal Surgery in Children.

    PubMed

    Ali, Shayesta; Sofi, Khalid; Dar, Abdul Qayoom

    2017-01-01

    Pain is a common complaint after surgery and seems to be difficult to manage in children because of fear of complications of pain treatment or misconception that infants and small children do not feel pain at all or feel less pain. A survey reported that 40% of pediatric surgical patients experienced moderate or severe postoperative pain and that more than 75% had insufficient analgesia. Our study was carried to provide continuous infusion of intravenous (i.v.) tramadol alone using a dedicated infusion device Graseby 2100 syringe pump and compared it to a combination of i.v. tramadol infusion and per rectal paracetamol. A total of 124 children aged 1-8 years selected for the study were randomized into two groups using a table of random numbers. Power calculation had suggested a sample size of 62 in each group with a power of 80% and significance level of 5%. Group A comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively. Group B comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively in addition to per rectal suppository of paracetamol in a dose of 90 mg/kg in 24 h (30 mg/kg as first dose followed by 20 mg/kg every 6 hourly for the next 18 h). Postoperatively, patients were observed for 24 h. A statistically significant difference (P ≤ 0.001) in Face, Legs, Activity, Cry, Consolability pain scores was seen between two groups at 4, 6, and 8 h. Pain scores being less in Group B patients who had received infusion of tramadol and per rectal suppositories of paracetamol compared to Group A patients who received only infusion of tramadol. A statistically significant difference (P < 0.05) was found in mean analgesic consumption during the first 24 h between the groups. Consumption was more in Group A as compared to Group B. In Group A, 13 patients (21%) required rescue analgesia as compared to only 4 patients (6.5%) in Group B. We recommend use of an infusion of

  20. Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex.

    PubMed

    Freye, E; Latasch, L

    2000-01-01

    As has been demonstrated in binding studies the two opioids tilidine (CAS 27107-79-7)/naloxone (CAS 357-08-4) and tramadol (CAS 36282-47-0) differ in regard to their affinities to the opioid receptor site. Therefore it is of interest to evaluate whether such a difference in opioid affinity is also seen in the pharmacological effects of clinically relevant doses in man. Following institutional approval by the local ethical committee and informed consent, 12 volunteers received oral doses of tramadol (100 mg), tilidine/naloxone (100 mg) and placebo, respectively, in a randomized, double-blind cross-over design. In order to determine the degree of constipation, oral-caecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripheral and central mediated effects were compared to placebo. Tramadol as well as tilidine/naloxone induced a significant (p < 0.05) prolongation of oral-caecal transit when compared to placebo. However, prolongation of oral-caecal transit was significantly longer in the tilidine/naloxone (p < 0.05) than in the tramadol group. Compared to tramadol, the pronounced constipating effect of tilidine/naloxone is likely to be due to the 10 fold higher affinity of that drug to the peripheral opioid receptor sites in the intestinal tract, which are responsible for normal propulsion. Such difference in binding is underlined by a central effect, the pupillary light reflex response. The amount of constriction of the iris to light was reduced after both opioids. Again, tilidine/naloxone significantly reduced (p < 0.001) the pupillary light reflex when compared to tramadol. Other side effects such as tiredness, nausea, emesis and dry mouth were more often reported after tilidine/naloxone than after tramadol (40% versus 15%; p < 0.05). Vertigo and perspiration were more often reported after

  1. Differential Consequences of Tramadol in Overdosing: Dilemma of a Polymorphic Cytochrome P450 2D6-Mediated Substrate.

    PubMed

    Srinivas, Nuggehally R

    2015-09-01

    Tramadol is a centrally acting opioid analgesic that is prone to polymorphic metabolism via cytochrome P450 (CYP) 2D6. The generation of the active metabolite, O-desmethyltramadol, which occurs through the CYP 2D6 pathway, significantly contributes to the drug's activity. However, dosage adjustments of tramadol are typically not practiced in the clinic when treating patients who are homozygous extensive metabolizers, heterozygous extensive metabolizers, or poor metabolizers. In the event of a tramadol overdose, the consequences may be influenced importantly by the genotype or phenotype status of the subject. Depending on the individual subject's CYP 2D6 status, one may see excessive miotic-related toxicity driven by the excessive availability of O-desmethyltramadol or one may manifest mydriatic-related toxicity driven by the excessive availability of tramadol. This report provides pharmacokinetic perspectives in situations of tramadol overdosing.

  2. Determination of tramadol by dispersive liquid-liquid microextraction combined with GC-MS.

    PubMed

    Habibollahi, Saeed; Tavakkoli, Nahid; Nasirian, Vahid; Khani, Hossein

    2015-01-01

    Dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry (GC-MS) has been developed for preconcentration and determination of tramadol, ((±)-cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol-HCl), in aqueous and biological samples (urine, blood). DLLME is a simple, rapid and efficient method for determination of drugs in aqueous samples. Efficient factors on the DLLME process has defined and optimized for extraction of tramadol including type of extraction and disperser solvents and their volumes, pH of donor phase, time of extraction and ionic strength of donor phase. Based on the results of this study, under optimal conditions and by using 2-nitro phenol as internal standard, tramadol was determined by GC-MS, and the figures of merit of this work were evaluated. The enrichment factor, relative recovery and limit of detection were obtained 420, 99.2% and 0.08 µg L(-1), respectively. The linear range was between 0.26 and 220.00 µg L(-1) (R(2) = 0.9970). The relative standard deviation for 50.00 µg L(-1) of tramadol in aqueous samples by using 2-nitro phenol as IS was 3.6% (n = 7). Finally, the performance of DLLME was evaluated for analysis of tramadol in urine and blood.

  3. Analgesic effects of tramadol, carprofen or multimodal analgesia in rats undergoing ventral laparotomy.

    PubMed

    Zegre Cannon, Coralie; Kissling, Grace E; Goulding, David R; King-Herbert, Angela P; Blankenship-Paris, Terry

    2011-03-01

    In this study, the authors evaluated the analgesic efficacy of tramadol (an opioid-like analgesic), carprofen (a nonsteroidal anti-inflammatory drug) and a combination of both drugs (multimodal therapy) in a rat laparotomy model. The authors randomly assigned rats to undergo either surgery (abdominal laparotomy with visceral manipulation and anesthesia) or anesthesia only. Rats in each group were treated with tramadol (12.5 mg per kg body weight), carprofen (5 mg per kg body weight), a combination of tramadol and carprofen (12.5 mg per kg body weight and 5 mg per kg body weight, respectively) or saline (anesthesia control group only; 5 mg per kg body weight). The authors administered analgesia 10 min before anesthesia, 4 h after surgery or (for the rats that received anesthesia only) anesthesia and 24 h after surgery or anesthesia. They measured locomotor activity, running wheel activity, feed and water consumption, body weight and fecal corticosterone concentration of each animal before and after surgery. Clinical observations were made after surgery or anesthesia to evaluate signs of pain and distress. The authors found that carprofen, tramadol and a combination of carprofen and tramadol were all acceptable analgesia regimens for a rat laparotomy model.

  4. Tramadol premedication in operative extraction of the mandibular third molar: a placebo-controlled crossover study.

    PubMed

    Kanto, Dunja; Salo, Matti; Happonen, Risto-Pekka; Vahlberg, Tero; Kanto, Jussi

    2005-02-01

    Anxiolytic drugs are widely used for premedication in oral surgery. Since anxiety is usually associated with the fear of pain, we tested the effects of the analgesic tramadol in premedication before operative extraction of the mandibular third molar under local anesthesia. In a double-blind crossover study, 20 patients were randomized to receive 100 mg oral tramadol or placebo 1 h before operation. Anxiety, nausea, dryness of the mouth, pain and discomfort were recorded before administration of the drug, immediately before and after operation, and 0.5, 1, and 2 h postoperatively using ungraded 0-100 mm VAS scales. Blood pressure and heart rate were measured at the same times; vigilance was tested using the Maddox Wing Test and sensorimotor performance using the Trieger Dot Test; hemoglobin oxygen saturation (SpO2) was measured using a pulse oximeter. In addition, SpO2 and heart rate were recorded continuously in nine patients using a pulse oximeter connected to a computer. The surgeon assessed the quality of operating conditions on the VAS scale. Tramadol delayed and decreased the need of analgesics on the day of operation (p < 0.05). The operating conditions were better in patients on tramadol premedication than in those on placebo during the first operation (p < 0.05), but no differences were seen in patient well-being between treatments. The second operation was less stressful than the first. Tramadol is recommended only with special indications for premedication of patients undergoing third molar extraction under local anesthesia.

  5. Effects of chronic tramadol administration on testicular tissue in rats: an experimental study.

    PubMed

    Abdellatief, R B; Elgamal, D A; Mohamed, E E M

    2015-08-01

    In a prospective experimental study, the effects of chronic tramadol administration on gonadotrophic and sex hormones, histopathological and morphometrical alterations in rat testicular tissue were investigated in a laboratory setting. Tramadol was given alone to adult male albino rats. Gonadotrophic and serum sex hormone levels were measured and testicular pathological and morphometric changes were observed in treated vs. After 30 days of treatment, tramadol induced a decrease in LH, FSH and testosterone serum levels. Histologically, degenerative changes in the seminiferous tubules were observed. They showed shrinkage, separation of tubular basement membrane, disorganisation and vacuolisation of spermatogenic layers. Morphometric analysis revealed significant decrease in the mean values of the tubular diameter and epithelial height. Ultrastructural abnormalities were detected in all cells of spermatogenic lineage in addition to the appearance of apoptotic cells. Sertoli cell vacuolation, huge lipid droplets and disrupted Sertoli cell junctions were observed. Leydig cells showed euchromatic nuclei and dilated smooth endoplasmic reticulum. In view of these findings, it is concluded that tramadol induces alterations in sex hormonal levels in conjunction with disruption of the normal histological structure of rat testis. This might lead to the risk of male infertility. Therefore, tramadol should be used with caution with appropriate dose monitoring. © 2014 Blackwell Verlag GmbH.

  6. Prophylactic Use of Intravenous Clonidine Compared to Tramadol in Prevention of Intraoperative Shivering under Regional Anesthesia

    PubMed Central

    Guha (Banerjee), Sarmila; Nath, Pallab Kumar; Halder, Rita; Bandyopadhyay, Ujjwal

    2017-01-01

    Objectives: This study aimed to evaluate the relative efficacy of prophylactic intravenous (IV) clonidine and tramadol for control of intraoperative shivering following spinal anesthesia. Materials and Methods: After institutional ethical clearance, 142 patients were chosen from either gender, aged 20–60 years, physical status American Society of Anesthesiology Class I and II scheduled for elective infraumbilical surgery under spinal anesthesia. Patients were randomized into two groups: Group C (n = 71) received injection clonidine 50 μg) IV in 100 ml normal saline (NS) over 10 min and Group T (n = 71) received injection tramadol 50 mg IV. In 100 ml NS over 10 min after spinal anesthesia. Results: Incidence of shivering was not significant when compared between the two groups (P > 0.05). The axillary temperatures fell significantly in Group C from the baseline and remained at a significantly lower level up to 60 min after rescue drug was administered in patients who shivered. There was a similar fall in axillary temperature in Group T in patients having shivering, but the difference was not significant. When compared between the two groups among patients who shivered, the difference in fall of temperature was not significant. Side effects such as hypotension, bradycardia, and sedation were significantly more common in clonidine group, whereas nausea was significantly more common patients of tramadol group. Conclusion: Prophylactic administration of both tramadol and clonidine is effective for controlling shivering under spinal anesthesia. However, tramadol is better because of higher response rate, less sedation, and lesser hemodynamic alterations. PMID:28663645

  7. Two Fatal Intoxications Due to Tramadol Alone: Autopsy Case Reports and Review of the Literature.

    PubMed

    Gioia, Sara; Lancia, Massimo; Bacci, Mauro; Suadoni, Fabio

    2017-08-01

    Since tramadol was marketed, it has been widely prescribed as a pain killer because of its relatively safe profile among opioids.Nevertheless, intoxication can occur: overdose can lead to fatal outcomes mostly in association with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased central nervous system (CNS) depression.Fatal outcomes only attributable to tramadol are a rare entity. In this case report, 2 fatal cases are described due to tramadol stand-alone intoxication with peculiar characteristics.In case 1, gas chromatography - mass spectrometry analysis detected tramadol in all specimens (32 μg/mL in the heart blood, 23.9 μg/mL in the femoral blood, 3.3 μg/mL in the bile, and 1.4 μg/mL in the urine). No other CNS depressants were detected by toxicological analysis.In case 2, gas chromatography - mass spectrometry analysis detected tramadol in all specimens (7.5 μg/mL in the heart blood, 5.8 μg/mL in the femoral blood, and 18 μg/mL in the urine). No other CNS depressants were detected by toxicological analysis.Review of the literature was performed to clarify the actual knowledge on this topic.

  8. Prophylactic Use of Intravenous Clonidine Compared to Tramadol in Prevention of Intraoperative Shivering under Regional Anesthesia.

    PubMed

    Guha Banerjee, Sarmila; Nath, Pallab Kumar; Halder, Rita; Bandyopadhyay, Ujjwal

    2017-01-01

    This study aimed to evaluate the relative efficacy of prophylactic intravenous (IV) clonidine and tramadol for control of intraoperative shivering following spinal anesthesia. After institutional ethical clearance, 142 patients were chosen from either gender, aged 20-60 years, physical status American Society of Anesthesiology Class I and II scheduled for elective infraumbilical surgery under spinal anesthesia. Patients were randomized into two groups: Group C (n = 71) received injection clonidine 50 μg) IV in 100 ml normal saline (NS) over 10 min and Group T (n = 71) received injection tramadol 50 mg IV. In 100 ml NS over 10 min after spinal anesthesia. Incidence of shivering was not significant when compared between the two groups (P > 0.05). The axillary temperatures fell significantly in Group C from the baseline and remained at a significantly lower level up to 60 min after rescue drug was administered in patients who shivered. There was a similar fall in axillary temperature in Group T in patients having shivering, but the difference was not significant. When compared between the two groups among patients who shivered, the difference in fall of temperature was not significant. Side effects such as hypotension, bradycardia, and sedation were significantly more common in clonidine group, whereas nausea was significantly more common patients of tramadol group. Prophylactic administration of both tramadol and clonidine is effective for controlling shivering under spinal anesthesia. However, tramadol is better because of higher response rate, less sedation, and lesser hemodynamic alterations.

  9. Tramadol alleviates myocardial injury induced by acute hindlimb ischemia reperfusion in rats.

    PubMed

    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian; Shahzamani, Mehran; Takhtfooladi, Mohammad Ashrafzadeh; Allahverdi, Amin; Khansari, Mohammadreza

    2015-08-01

    Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  10. Tramadol for the management of premature ejaculation: a timely systematic review.

    PubMed

    Kirby, E W; Carson, C C; Coward, R M

    2015-07-01

    Premature ejaculation (PE) represents a common sexual dysfunction and is associated with a negative impact on quality of life and relationships. Recent evidence suggests that on-demand dosing of tramadol is effective at increasing intra-vaginal ejaculatory latency time (IELT) and improving subjective measures of satisfaction. A literature review was performed of journal articles published between January 2000 and July 2014 that matched the keywords 'tramadol' and 'premature ejaculation'. We identified eight relevant articles with the criteria that each article be published in a peer-reviewed journal, represent original work and be written in English. IELT was used as the primary outcome in each of the papers reviewed for efficacy. Additional subjective outcome measures were reviewed where available. Safety was assessed using adverse event data from the individual studies. We found that tramadol in on-demand dosing is effective at lengthening IELT in men with varying degrees of PE and improves patient satisfaction. Tramadol was generally well tolerated, particularly among those taking 25 and 50 mg doses. Although there is a risk of abuse and dependence, these events are rare, particularly at low doses taken intermittently. In conclusion, tramadol is an effective oral therapy for PE that is overall safe and well tolerated.

  11. Synthesis, antimicrobial and antifungal possessions of tramadol esters: In vitro studies.

    PubMed

    Qadir, Muhammad Abdul; Ahmed, Mahmood; Ikram, Rabia

    2015-07-01

    Tramadol esters were prepared by refluxing equimolar concentration of tramadol with leucine and asparagine separately with methanol, sulphuric acid and phthalic anhydride for 10 hours and temperature was maintained at 75°C. After refluxing, the colour of sample solutions were changed from colorless to yellow, blank solution was prepared in the same way as the sample solution except the Tramadol. Both the products and blank were neutralized with sodium carbonate and excess of sodium bicarbonate was precipitated as sodium sulphate, which was washed with acetone. The structures of both the products were confirmed with spectral data (FT-IR, 1HNMR and 13CNMR). Antimicrobial and anti-fungal property of derivative of analgesic tramadol drug was tested with one fungus and three sensitive bacteria belonging to both gram positive and gram-negative types. Esterified product of tramadol with leucine and asparagine showed moderate activity against Escherichia coli and Tricophyton rubrum. Both the products showed marked activity against Staphylococcus aureus and found no activity against Salmonella spp.

  12. The antinociceptive effects of systemic administration of tramadol, gabapentin and their combination on mice model of acute pain.

    PubMed

    Aydin, Osman Nuri; Ek, Rauf Onur; Temoçin, Sadun; Uğur, Bakiye; Alaçam, Bilge; Şen, Selda

    2012-01-01

    The aim of the present study was to investigate the possible antinociceptive effects of systemic administration of tramadol and gabapentin either alone or in combination on acute pain models in mice. After obtaining the approval of Animal Ethics Committee; 96 BALB/c albino male mice were divided into 12 groups: (I) control without injection, (II) control treated with saline, (III)-(IV) mice treated with tramadol 10 mg/kg or 30 mg/kg, (V)-(VIII) mice treated with gabapentin; 30, 100, 200, 300 mg/kg respectively. In order to determine possible interactions between tramadol gabapentin and; mice received four different combinations of tramadol + gabapentin (30+30, 30+100, 30+200 and 30+300 mg/kg) (Groups IX-XII respectively). Mice received 0.1 ml solution for every 10 g of their weight. The drug was injected into peritonea. Thirty minutes after the drug injection, tail-flick and hot-plate tests were conducted. Ten and 30 mg/kg tramadol produced dose dependent antinociceptive effect in tail-flick and hot plate tests. Gabapentin had no antinociceptive effect in the tail flick test except 300 mg/kg dose, and had dose dependent antinociceptive effect in hot-plate test. In both tests, various combinations of tramadol and gabapentin produced an antinociceptive effect that is greater than that produced by tramadol and gabapentin alone. But, just 30 mg/kg tramadol + 300 mg/kg gabapentin combination caused statistically significant increase in both tests (p<0.05). When gabapentin and tramadol were used in combination, gabapentin had no additive antinociceptive effect except for 300 mg/kg in tail-flick and hot-plate tests. Tail-flick test showed that tramadol produced better antinociceptive effect than gabapentin.

  13. An assessment of the pharmacokinetics of a sustained-release formulation of a tramadol/acetaminophen combination in healthy subjects.

    PubMed

    Im, Yong-Jin; Jeon, Ji-Young; Kim, Eun-Young; Kim, Yunjeong; Oh, Dong-Joon; Yoo, Ji-Seok; Shin, Dae-Hee; Chae, Soo-Wan; Kim, Min-Gul

    2015-02-01

    To provide consistent pain relief and improve convenient sustained release (SR), a fixed-dose combination tramadol/acetaminophen tablet was formulated. This study aimed to evaluate the pharmacokinetic profiles of an SR 75-mg tramadol/650-mg acetaminophen formulation after a single dose compared with an immediate release (IR) 37.5-mg tramadol/325-mg acetaminophen formulation after 2 doses and at steady state and to assess the effect of food on the pharmacokinetic SR formulation profile after a single dose. Two clinical trials were conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen combination tablet) formulation profiles after a single dose and IR (one 37.5-mg tramadol/325-mg acetaminophen combination tablet q6h for 2 doses) formulation profiles after 2 doses and the effect of food intake on healthy male subjects and (2) an open, randomized, 2-period, 2-treatment multiple dose crossover study to evaluate the steady-state pharmacokinetic SR and IR formulation profiles. Safety assessments were performed. Forty-three subjects completed each study protocol. The SR combination tramadol/acetaminophen formulation was clinically and statistically equivalent to the IR combination formulation in the fasting state. When tramadol and acetaminophen tablets were administered with food, the time to peak plasma concentrations and the tramadol/acetaminophen absorption were unaffected. There was no serious adverse event reported. The SR combination tramadol/acetaminophen tablet exhibited similar exposure and absorption rates compared with those of the IR formulation of tramadol, O-desmethyltramadol, and acetaminophen. The SR formulation may be more convenient for patients and has the potential to enhance compliance and pain control. ClinicalTrials.gov identifier: NCT01880125. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  14. Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones.

    PubMed Central

    Sevcik, J.; Nieber, K.; Driessen, B.; Illes, P.

    1993-01-01

    1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and, therefore, presumably additional mechanisms of analgesic action. Tramadol and its main metabolite O-desmethyltramadol were tested on rat central noradrenergic neurones of the nucleus locus coeruleus (LC), which are involved in the modulation of nociceptive afferent stimuli. 2. In pontine slices of the rat brain the spontaneous discharge of action potentials of LC cells was recorded extracellularly. (-)-Tramadol (0.1-100 microM), (+)-tramadol (0.1-100 microM), (-)-O-desmethyl-tramadol (0.1-100 microM) and (+)-O-desmethyltramadol (0.01-1 microM) inhibited the firing rate in a concentration-dependent manner. (+)-O-desmethyltramadol had the highest potency, while all other agonists were active at a similar range of concentrations. 3. (-)-Tramadol (10, 100 microM) was less inhibitory in brain slices of rats pretreated with reserpine (5 mg kg-1, 5 h before decapitation) than in controls. 4. The effect of (-)-tramadol (10 microM) was abolished in the presence of the alpha 2-adrenoceptor antagonist, rauwolscine (1 microM), whilst that of (+)-O-desmethyltramadol (0.3 microM) virtually disappeared in the presence of the opioid antagonist, naloxone (0.1 microM). (+)-Tramadol (30 microM) and (-)-O-desmethyl-tramadol (10 microM) became inactive only in the combined presence of naloxone (0.1 microM) and rauwolscine (1 microM). 5. In another series of experiments, the membrane potential of LC neurones was determined with intracellular microelectrodes. (-)-Tramadol (100 microM) inhibited the spontaneous firing and hyper-polarized the cells; this effect was abolished by rauwolscine (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8220877

  15. Chronic morphine and tramadol re-exposure induced an anti-anxiety effect in prepubertal rats exposed neonatally to the same drugs.

    PubMed

    Gholami, Morteza; Saboory, Ehsan; Khalkhali, Hamid Reza

    2014-10-01

    Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety-like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3-21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re-exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re-exposure to tramadol and this anxiolytic-like behaviour was more dominant in EPM re-exposure in rats that had received higher doses of tramadol. Re-exposure to tramadol elicited a stronger anxiolytic-like behaviour than re-exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re-exposure to these drugs at an immature stage produces considerable anxiolytic-like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long-term changes in the opioid response.

  16. [Effectiveness and tolerance of tramadol with or without an antiemetic and pethidine in obstetric analgesia].

    PubMed

    Kainz, C; Joura, E; Obwegeser, R; Plöckinger, B; Gruber, W

    1992-01-01

    The aim of this prospective, randomised, blind study was to investigate the analgesic potency and tolerance of intramuscular Tramadol compared to a standard obstetric analgesia with Pethidine. Triflupromazine was administrated in combination with the two tested analgesics in order to study its efficacy in alleviating the emetic side effects of the tested analgesics. 66 parturients were randomly assigned to three groups: group A: 100 mg Tramadol (Tramal), group B: 100 mg Tramadol (Tramal) and 10 mg Triflupromazine (Psyquil), group C: 50 mg Pethidine (Alodan) and 10 mg Triflupromazine (Psyquil). No significant differences concerning duration of labour, FHR-alterations, umbilical cord blood gases, respiration pattern and Apgar Scores of the neonate occurred. In all three groups the analgesic effect was equally good. Combination of the analgesic with the antiemetic showed no reduction of the incidence and severity of side effects.

  17. A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride.

    PubMed

    Mužíková, Jitka; Kubíčková, Alena

    2016-09-01

    The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders.

  18. The use of intraarticular tramadol for postoperative analgesia after arthroscopic knee surgery: a comparison of different intraarticular and intravenous doses.

    PubMed

    Alagöl, A; Calpur, O U; Kaya, G; Pamukçu, Z; Turan, F N

    2004-05-01

    We aimed to determine the optimal dose of tramadol when administered intraarticularly after arthroscopic knee surgery under general anesthesia in patients with an American Society of Anesthesiologists (ASA) physical status score of I-II. When the surgical procedure was completed, patients were assigned to one of seven groups ( n=30 for each) in a double-blinded and randomized manner according to a table of random numbers. Group I received 100 mg tramadol, Group II received 50 mg tramadol, Group III received 20 mg tramadol and Group IV received 0.9% NaCl intraarticularly in 20 ml solutions. Group V received 100 mg tramadol, Group VI received 50 mg tramadol and Group VII received 20 mg tramadol intravenously. Pain was evaluated by using the Visual Analogue Scale (VAS) at 0 min (when the patient was cooperated after extubation), 30 min, 1 h, 4 h, 6 h, 12 h, 18 h and 24 h postoperatively. Patients were administered diclofenac sodium 75 mg intravenously (i.m.) when they experienced pain. The intraarticular tramadol groups had longer duration of analgesia than i.v. tramadol groups who were administered the same doses (I vs V; II vs VI; III vs VII; p <0.001). Group I had the longest duration of analgesia ( p<0.001). Group II had a longer time to the first analgesic request than all other groups ( p<0.001) except Group I. Consequently, Group I and II needed less analgesics than other groups ( p<0.001). Pain scores were 0-3 on the VAS in Groups I, II and V at first assessment, in Groups I and II at 30 min and 1 h, and in Group I at 4 h and 6 h postoperatively ( p<0.01). In Group V, vomiting was more a more frequent complication than with other groups ( p<0.05). It is concluded that tramadol provides analgesia with a peripheral mechanism when administered intraarticularly. The side effects of intraarticular 100 mg tramadol were no more severe than those for intraarticular 50 mg tramadol. Moreover, intraarticular 100 mg tramadol provided excellent analgesia after arthroscopic

  19. Tramadol/paracetamol fixed-dose combination: a review of its use in the management of moderate to severe pain.

    PubMed

    Dhillon, Sohita

    2010-01-01

    Tramadol/paracetamol 37.5 mg/325 mg (Tramacet, Zaldiar, Ixprim, Kolibri) is an orally administered fixed-dose combination of the atypical opioid tramadol and paracetamol, which is indicated in the EU for the symptomatic treatment of moderate to severe pain. This article reviews the pharmacological properties, clinical efficacy and tolerability of tramadol/paracetamol in adults with moderate to severe pain. Fixed-dose tramadol/paracetamol is a rapidly-acting, longer-duration, multimodal analgesic, which is effective and generally well tolerated in patients with moderate to severe pain. In several well designed, clinical studies, single- or multiple-dose tramadol/paracetamol was effective in providing pain relief in adult patients with postoperative pain after minor surgery, musculoskeletal pain (acute, subacute or chronic), painful diabetic peripheral neuropathy or migraine pain. It was also effective as an add-on analgesic in patients who were experiencing moderate to severe musculoskeletal pain (e.g. osteoarthritis or rheumatoid arthritis pain) despite ongoing NSAID and/or disease-modifying antirheumatic drug therapy. Moreover, in patients with postoperative pain, ankle sprain pain or subacute lower back pain, the analgesic efficacy of tramadol/paracetamol was better than that of paracetamol, generally similar to, or better than that, of tramadol, and generally similar to that of ibuprofen or the fixed-dose combinations hydrocodone/paracetamol, codeine/paracetamol and codeine/paracetamol/ibuprofen. In addition, the analgesic efficacy of tramadol/paracetamol did not differ significantly from that of gabapentin in patients with chronic pain associated with diabetic peripheral neuropathy. Tramadol/paracetamol had no additional tolerability issues relative to its components and, overall, the tolerability profile of tramadol/paracetamol was generally similar to that of other active comparators (fixed-dose combinations or single-agents); however, incidences of some

  20. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats.

    PubMed

    Moreno-Rocha, Luis Alfonso; López-Muñoz, Francisco Javier; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam

    2016-11-01

    Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P < 0.05). Nevertheless, this effect decreased about 53% after the chronic treatment (3 doses per day, for 4 days). No pharmacokinetic interaction between metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  1. Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

    PubMed Central

    Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

    2013-01-01

    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

  2. Determination of tramadol in hair using solid phase extraction and GC-MS.

    PubMed

    Hadidi, Kamal A; Almasad, Jamal K; Al-Nsour, Thair; Abu-Ragheib, Samih

    2003-08-12

    Tramadol is a centrally acting synthetic analgesic with mu-opioid receptor agonist activity, it is a widely prescribed analgesic used in the treatment of moderate to severe pain and as an alternative to opiates. Tramadol causes less respiratory depression than morphine at recommended doses. Its efficacy and low incidence of side effects lead to its unnecessary prescribing in patients with mild pain. Tramadol was classified as a "controlled drug" long after its approval for use in Jordan. Analysis of drugs of abuse in hair has been used in routine forensic toxicology as an alternative to blood in studying addiction history of drug abusers. A method for the determination of tramadol in hair using solid phase extraction and gas chromatography-mass spectrometry (GC-MS) is presented, the method offers excellent precision (3.5-9.8%, (M)=6.77%), accuracy (6.9-12%, M=9.4%) and limit of detection 0.5 ng/mg. The recovery was in the range of 87-94.3% with an average of 90.75%. The calibration curve was linear over the concentration range 0.5-5.0 ng/mg hair with correlation coefficient of 0.998. The developed method was tested on 11 hair samples taken from patients using tramadol as prescribed by their physician along with other different drugs in treating chronic illnesses. Tramadol was detected in all hair samples at a concentration of 0.176-16.3 ng/mg with mean concentration of 4.41 ng/mg. The developed method has the potential of being applied in forensic drug hair testing. In Jordan, hair drug testing started to draw the attention of legal authorities which stimulated forensic toxicologists in recent years to develop methods of analysis of drugs known or have the potential to be abused.

  3. Latarjet Procedure for Anterior Shoulder Instability Due to Tramadol-Induced Seizures: A Multicenter Study.

    PubMed

    Khater, Ahmad Hany; Sobhy, Mohamed H; Said, Hatem G; Kandil, Ahmed; Reda, Walid; Seifeldin, Ahmed Fouad; Moustafa, Ramez; Elassal, Maher A; Kamel, Ezzat M

    2016-04-01

    Seizures, commonly due to epilepsy, are known to cause shoulder instability. Tramadol addiction has recently been found to induce seizures in patients who exceed the recommended dose. Because of the easy accessibility and low cost of tramadol, an increasingly alarming phenomenon of tramadol abuse has been demonstrated in recent years. The purpose of this multicenter study was to investigate shoulder instability resulting from tramadol-induced seizure (TIS) as well as to recommended management for such shoulder instability. The hypothesis was that TIS leads to anterior shoulder dislocations with major bony defects, which favors bony reconstructive procedures as a suitable method of treatment. Case series; Level of evidence, 4. This prospective case series study was conducted on 73 patients (78 shoulders) who presented with anterior shoulder dislocations and a clear history of tramadol abuse. The mean age of the patients was 26.8 years, and the mean number of dislocations was 14. The mean duration of addiction was 17 months, with a mean dose of 752 mg of tramadol hydrochloride per day. Glenoid and humeral bone loss ranged from 15% to 35% and from 15% to 40%, respectively. The mean follow-up period was 28 months. All patients underwent an open Latarjet procedure. Postoperative mean Rowe score and American Shoulder and Elbow Surgeons score at final follow-up (24 months) improved significantly from 20 to 84 and from 44 to 91, respectively (P < .05). The patient satisfaction rate reached 95%, and the mean period of return to work was 12.8 weeks. Five patients (9%) had postoperative seizures due to relapse of the tramadol abuse, but only 3 patients (5%) had redislocations with nonunion or breakage of the graft or hardware. Tramadol addiction has evolved as an important cause of seizures that can result in shoulder dislocation. Anterior shoulder instability with TIS occurs mainly with higher levels of addiction and results in significant humeral and/or glenoid bone defects

  4. Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery.

    PubMed

    De Benedictis, Giulia Maria; Giorgi, Mario; Depase, Alice; De Vito, Virginia; Della Rocca, Giorgia; Bellini, Luca

    2017-02-06

    To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation. Prospective randomized controlled study. A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy. Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg(-1)). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography. Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes. Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep

  5. Peripheral synergism between tramadol and ibuprofen in the formalin test.

    PubMed

    Chavarria-Bolaños, Daniel; Perez-Urizar, José; Grandfils, Christian; Pozos-Guillén, Amaury

    2014-06-01

    Preclinical Research Analgesics with different mechanisms of action can be combined in order to obtain pharmacological synergism, employing lower doses of each agent, thus diminishing side effects. For instance, an atypical dual analgesic such as tramadol (TMD) and a nonsteroidal anti-inflammatory drug such as ibuprofen (IBU) are good candidates to be evaluated when combined and applied peripherally. The present study was conducted to evaluate possible local synergism between TMD and IBU when combined peripherally using the formalin test in rats. The effects of the individual analgesics and their combinations were evaluated simultaneously using a 5% formalin dilution. Dose-effect curves were determined for TMD (50-400 μg/paw) and IBU (1-100 μg/paw). Experimental effective doses were evaluated and isobolographic analyses were constructed to evaluate TMD-IBU combination synergism. Both drugs produced a dose-dependent analgesic effect when applied separately. Isobolographic analysis showed synergism during phase 1 (0-10 min) and phase 2 (15-60 min) when compared with theoretical doses (P < 0.05), with interaction indexes of 0.06 and 0.09, respectively. The present information supports the peripheral analgesic effect of TMD and IBU, especially when combined at appropriate doses.

  6. Antinociceptive effects of tramadol in co-administration with metamizol after single and repeated administrations in rats.

    PubMed

    Moreno-Rocha, Luis Alfonso; Domínguez-Ramírez, Adriana Miriam; Cortés-Arroyo, Alma Rosa; Bravo, Guadalupe; López-Muñoz, Francisco Javier

    2012-11-01

    Combinations of two analgesic drugs of the same or different class are widely used in clinical therapy to enhance its antinociceptive effects and reduce the side effects. In order to evaluate a possible antinociceptive synergistic interaction of metamizol s.c., a nonsteroidal antiinflammatory drug (NSAID), and tramadol s.c., an atypical opioid (opioid receptor agonist), were administered alone or in combination. In the present study, the antinociceptive efficacy and the possible development of pharmacological tolerance produced by the combination tramadol plus metamizol during a 4-day treatment in rats using the plantar test was evaluated. Male Wistar rats were s.c. injected with tramadol (17.8 mg/kg), metamizol (177.8 mg/kg) or the combination tramadol plus metamizol three times a day for 4 days. Both metamizol and tramadol produced antinociceptive effects with a low rate trend towards tolerance development at the end of the treatment. The antinociceptive efficacy of tramadol and metamizol co-administration gradually decreased after the second injection. These data suggest that when the combination is given in a unique administration it results in an important potentiation of their individual antinociceptive effects. But, the repeated coadministration of tramadol plus metamizol results in a development of tolerance.

  7. Tramadol, an Opioid Receptor Agonist: An Inhibitor of Growth, Morphogenesis, and Biofilm Formation in the Human Pathogen, Candida albicans.

    PubMed

    Kathwate, Gunderao Hanumantrao; Karuppayil, S Mohan

    2016-12-01

    Tramadol is a synthetic, centrally acting low-affinity agonist of μ-opioid receptors in humans. It is used as an analgesic and is shown to have local anesthetic action. In this study, we have tried to explore its anti-Candida potential. Minimum inhibitory concentration (MIC50) and minimum fungicidal concentration (MFC) values were established. MIC50 ranged from 2 to 4 mg/mL, whereas MFC was recorded at 8 mg/mL. Also, the effect of tramadol on germ tube formation, adhesion, and biofilms in Candida albicans was studied. Tramadol impaired in vitro growth of C. albicans. A time-dependent killing assay showed that it kills C. albicans within 24 h of exposure. Tramadol has strong activity against Candida virulence factors such as yeast-to-hyphal form switching and adhesion. C. albicans biofilms, which are notoriously resistant to many antifungals, were sensitive to tramadol. At 8 mg/mL of tramadol, 82% of early stage biofilms and 52.88% of matured biofilms were inhibited. Although our results show that the antifungal effect of tramadol requires concentrations that can be achieved only locally, they may provide potential candidates for development of novel antifungal drugs.

  8. Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep.

    PubMed

    Bortolami, E; Della Rocca, G; Di Salvo, A; Giorgi, M; Kim, T W; Isola, M; De Benedictis, G M

    2015-09-01

    Although sheep are widely used as an experimental model for various surgical procedures there is a paucity of data on the pharmacokinetics and efficacy of analgesic drugs in this species. The aims of this study were to investigate the pharmacokinetics of intravenously (IV) administered tramadol and its active metabolite O-desmethyltramadol (M1) and to assess the mechanical antinociceptive effects in sheep. In a prospective, randomized, blinded study, six healthy adult sheep were given 4 and 6 mg/kg tramadol and saline IV in a cross-over design with a 2-week wash-out period. At predetermined time points blood samples were collected and physiological parameters and mechanical nociceptive threshold (MNT) values were recorded. The analytical determination of tramadol and M1 was performed using high performance liquid chromatography. Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively. Normally distributed data were analysed by a repeated mixed linear model. Plasma concentration vs. time profiles of tramadol and M1 were similar after the two doses. Tramadol and M1 plasma levels decreased rapidly in the systemic circulation, with both undetectable after 6 h following drug administration. Physiological parameters did not differ between groups; MNT values were not statistically significant between groups at any time point. It was concluded that although tramadol and M1 concentrations in plasma were above the human minimum analgesic concentration after both treatments, no mechanical antinociceptive effects of tramadol were reported. Further studies are warranted to assess the analgesic efficacy of tramadol in sheep.

  9. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  10. Local analgesic effect of tramadol is mediated by opioid receptors in late postoperative pain after plantar incision in rats

    PubMed Central

    de Oliveira Junior, José Oswaldo; de Freitas, Milena Fernandes; Bullara de Andrade, Carolina; Chacur, Marucia; Ashmawi, Hazem Adel

    2016-01-01

    Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals’ nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3–L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals’ nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression. PMID:27799813

  11. Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis.

    PubMed

    Shin, Hye Won; Ju, Bum Jun; Jang, Yoo Kyung; You, Hae Seun; Kang, Hyun; Park, Ji Yong

    2017-01-01

    Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA) effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB). This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery. We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs) that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software. We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004), motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003), and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001) compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001) and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010). In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05) but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies. In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and shorten

  12. Efficacy and safety of a fixed combination of tramadol and paracetamol (acetaminophen) as pain therapy within palliative medicine.

    PubMed

    Husic, Samir; Izic, Senad; Matic, Srecko; Sukalo, Aziz

    2015-02-01

    The goal of the research was to determine the efficacy of a fixed combination of tramadol and paracetamol (acetaminophen) in the treatment of pain of patients with the advanced stage of cancer. A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1(st) to December 31(st) 2013. A total of 353 patients who were treated with a fixed combination of tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2 tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8. If the patient during previous day has two or more pain episodes that required a "rescue dose" of tramadol, increased was the dose of fixed combination tramadol and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg paracetamol). Statistical analysis was performed by biomedical software MedCalc for Windows version 9.4.2.0. The difference was considered significant for P<0.05. The average duration of treatment with a fixed combination tramadol and acetaminophen was 57 days (13-330 days). Already after 24 hours of treatment the average pain score was significantly lower (p<0.0001) compared to the admission day [5.00 (4:00 to 8:00) during the first days versus 2.00 (1:00 to 7:00) during the second day of treatment]. The average dose of the fixed combination tramadol and acetaminophen tablets was 4.8 ± 1.8 (180 mg of tramadol and 1560 mg paracetamol). Side effects, in the treatment of pain with a fixed combination tramadol and acetaminophen, were found in 29.18% of patients, with a predominance of nausea and vomiting. Fixed combination of tramadol and acetaminophen can be used as an effective combination in the treatment of chronic cancer pain, with frequent dose evaluation and mild side effects.

  13. A comparison of extradural tramadol and extradural morphine for postoperative analgesia in female dogs undergoing ovariohysterectomy.

    PubMed

    Neves, Celso Sawaya; Balan, Juliana Andrea Osório; Pereira, Diego Roberto; Stevanin, Helaine; Cassu, Renata Navarro

    2012-04-01

    To compare the postoperative analgesic effects of the extradural tramadol or morphine in female dogs undergoing ovariohysterectomy. Sixteen female dogs were randomly assigned to two groups of eight animals each and received morphine (0.1 mg kg(-1) M group) or tramadol (2 mg kg(-1) T group). The pre-anesthetic medication was intravenously (iv) acepromazine (0.05 mg kg(-1)). Anesthesia was induced with propofol (4 mg kg(-1)iv) and maintained with isoflurane. The degree of analgesia was evaluated using a numerical rating scale that included physiologic and behavior variables. Dogs were scored at one, three, six and 12 hours after surgery by one blinded observer. Dogs were treated with morphine (0.5 mg kg(-1)) if their scores were >6. Serum cortisol was measured before the pre-anesthetic medication was administered (basal), at the time of the ovarian pedicle clamping (T0), and at 1 (T1), 6 (T6) and 12 (T12) hours postoperative. The pain score did not differ between morphine and tramadol treatments. Rescue analgesia was administered to one dog in the T treatment group. Serum cortisol did not differ between treatments. The extradural administration of morphine or tramadol is a safe and effective method of inducing analgesia in female dogs undergoing ovariohyterectomy.

  14. Spectrophotometric and spectrofluorimetric methods for analysis of tramadol, acebutolol and dothiepin in pharmaceutical preparations.

    PubMed

    Abdellatef, Hisham E; El-Henawee, Magda M; El-Sayed, Heba M; Ayad, Magda M

    2006-12-01

    Sensitive spectrophotometric and spectrofluorimetric methods are described for the determination of tramadol, acebutolol and dothiepin (dosulepin) hydrochlorides. The two methods are based on the condensation of the cited drugs with the mixed anhydrides of malonic and acetic acids at 60 degrees C for 25-40 min. The coloured condensation products are suitable for the spectrophotometric and spectrofluorimetric determination at 329-333 and 431-434 nm (excitation at 389 nm), respectively. For the spectrophotometric method, Beer's law was obeyed from 0.5 to 2.5 microg ml(-1) for tramadol, dothiepin and 5-25 microg ml(-1) for acebutolol. Using the spectrofluorimetric method linearity ranged from 0.25 to 1.25 microg ml(-1) for tramadol, dothiepin and 1-5 microg ml(-1) for acebutolol. Mean percentage recoveries for the spectrophotometric method were 99.68+/-1.00, 99.95+/-1.11 and 99.72+/-1.01 for tramadol, acebutolol and dothiepin, respectively and for the spectrofluorimetric method, recoveries were 99.5+/-0.844, 100.32+/-0.969 and 99.82+/-1.15 for the three drugs, respectively. The optimum experimental parameters for the reaction has been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drugs in their pharmaceutical preparations with good recoveries. The procedures were accurate, simple and suitable for quality control application.

  15. Efficacy of two doses of tramadol versus bupivacaine in perioperative caudal analgesia in adult hemorrhoidectomy

    PubMed Central

    Farag, Hanan M.; Esmat, Ibrahim M.

    2016-01-01

    Background: The study was conducted to evaluate the perioperative analgesic efficacy of the two doses of caudally administered tramadol versus bupivacaine in adult hemorrhoidectomy. Patients and Methods: A total of 90 patients, aged 20-50 years, undergoing hemorrhoidectomy were randomly scheduled to receive bupivacaine 0.25% in 20 ml (Group B; n = 30), tramadol 1 mg/kg in 20 ml (Group T1; n = 30), tramadol 2 mg/kg in 20 ml (Group T2; n = 30) through caudal route after induction of general anesthesia. Postoperative pain was assessed every hour until the visual analog scale was 6, which is 1st time for rescue analgesia. Postoperative sedation, hemodynamic changes, serum cortisol, and epinephrine levels and incidence of side effects were also evaluated. Results: Duration of analgesia was longer in Group T2 (20 [1.14] h] compared with the Group B (7 [1.2] h) or Group T1 (12 [0.75] h); all P < 0.001. There were no significant hemodynamic changes. There were not incidences of side effects. Conclusion: Caudal tramadol 2 mg/kg provided a longer duration of postoperative analgesia with rapid onset and no incidence of complications or adverse effects in adult hemorrhoidectomy. PMID:27051362

  16. Simultaneous quantitative determination of paracetamol and tramadol in tablet formulation using UV spectrophotometry and chemometric methods.

    PubMed

    Glavanović, Siniša; Glavanović, Marija; Tomišić, Vladislav

    2016-03-15

    The UV spectrophotometric methods for simultaneous quantitative determination of paracetamol and tramadol in paracetamol-tramadol tablets were developed. The spectrophotometric data obtained were processed by means of partial least squares (PLS) and genetic algorithm coupled with PLS (GA-PLS) methods in order to determine the content of active substances in the tablets. The results gained by chemometric processing of the spectroscopic data were statistically compared with those obtained by means of validated ultra-high performance liquid chromatographic (UHPLC) method. The accuracy and precision of data obtained by the developed chemometric models were verified by analysing the synthetic mixture of drugs, and by calculating recovery as well as relative standard error (RSE). A statistically good agreement was found between the amounts of paracetamol determined using PLS and GA-PLS algorithms, and that obtained by UHPLC analysis, whereas for tramadol GA-PLS results were proven to be more reliable compared to those of PLS. The simplest and the most accurate and precise models were constructed by using the PLS method for paracetamol (mean recovery 99.5%, RSE 0.89%) and the GA-PLS method for tramadol (mean recovery 99.4%, RSE 1.69%). Copyright © 2015. Published by Elsevier B.V.

  17. Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study*

    PubMed Central

    Takhtfooladi, Mohammad Ashrafzadeh; Jahanshahi, Amirali; Sotoudeh, Amir; Jahanshahi, Gholamreza; Takhtfooladi, Hamed Ashrafzadeh; Aslani, Kimia

    2013-01-01

    OBJECTIVE: To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR) and ischemia-reperfusion + tramadol (IR+T). The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively). All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v.) immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p.), the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies. RESULTS: Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both). Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group. CONCLUSIONS: On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion. PMID:24068264

  18. Comparsion of Intravenous Lignocaine, Tramadol and Keterolac for Attenuation of Propofol Injection Pain

    PubMed Central

    Singh, Rajinder; Sodhi, Gurdip Singh

    2016-01-01

    Introduction Propofol possesses many characteristics of an ideal intravenous anaesthetic agent, providing a smooth induction and a rapid recovery. However, it has been reported to evoke considerable pain on injection in 10-100% of patients. The cause of pain upon intravenous injection of propofol remains a mystery. Aim To study and compare the efficacy of Lignocaine, Tramadol and Ketorolac in minimizing the propofol injection pain. Materials and Methods Hundred adult patients (ASA grade I and grade II) scheduled for elective surgery under general anaesthesia with propofol as an inducing agent were considered for the study. Patients were randomly divided into 4 groups of 25 patients each Group L (lignocaine) Group T (tramadol) Group K (ketorolac) and Group N (normal saline). Pain scores were measured by the investigator immediately following injection of propofol. All patients’ responses were graded by a verbal pain score. Results All the results were tabulated and analysed using the one-way ANOVA and z-test. There was no statistically significant difference among group L (24%), T (28%) and K (28%) for pain on injection, but significant difference of all 3 groups was there when compared with group N. Conclusion Intravenous lignocaine, tramadol and ketorolac all 3 drugs significantly reduce propofol injection pain. However, lignocaine appears to be more acceptable cause of less pain and fewer side effects as compared to tramadol and ketorolac. PMID:27630928

  19. Submucous tramadol increases the anesthetic efficacy of mepivacaine with epinephrine in inferior alveolar nerve block.

    PubMed

    Isiordia-Espinoza, Mario Alberto; Orozco-Solis, Mariana; Tobías-Azúa, Francisco Javier; Méndez-Gutiérrez, Elsa Patricia

    2012-03-01

    The purpose of this study was to evaluate the effect of submucous tramadol as adjuvant of mepivacaine with epinephrine in inferior alveolar nerve block. A double-blind, randomized, placebo-controlled, crossover clinical trial was conducted. Twenty healthy young volunteers were randomized into two treatment sequences using a series of random numbers. Sequence 1: Group A, 2% mepivacaine with 1:100,000 epinephrine plus submucous tramadol 50mg (1mL of saline) and one week later Group B, 2% mepivacaine with 1:100,000 epinephrine plus submucous placebo (1mL of saline). Sequence 2: Group B and one week later Group A. All treatments were administered 1min after that patient informed anesthesia of lower lip. We evaluated the duration of anesthesia of lower lip, anesthetic efficacy, and local and systemic adverse events. Anesthetic efficacy was better in group receiving submucous tramadol during the first 2h compared with group receiving submucous placebo (P<0.05). Submucous tramadol increased the anesthetic efficacy of mepivacaine with epinephrine of soft tissue in inferior alveolar nerve block.

  20. [Chronic dizziness in a pain patient--pharmacogenomic identification of tramadol as cause].

    PubMed

    Eichhorn, A; Barth, J

    2010-12-01

    This casuistic reports on a 59-year-old pain patient taking normal dosage Tramadol as analgetic drug, who suffered from chronic dizziness leading to immobilisation for more than 9 months. On admission to inpatient rehabilitation Tramadol was removed in exchange for morphine sulphate with the unexpected result of a prompt and lasting stop of dizziness. A molecular-genetic investigation showed a duplication in the CYP2D6 gene. This genetic situation caused a quick metabolizing-status for substances dependent on CYP2D6 like Tramadol, which is a prodrug. The quick metabolizing-status resulted in an increased rate of active Tramadol-metabolites which caused the chronic dizziness. Under morphine sulphate which is metabolized independently of CYP2D6, a sufficient analgetic outcome could be achieved. Dizziness did not appear in the patient any longer, and he could be mobilised during rehabilitation. Pharmacogenomic knowledge has helped develop a sustainable concept for rehabilitation of this seriously ill patient, and to put it into practise successfully.

  1. Simultaneous quantitative determination of paracetamol and tramadol in tablet formulation using UV spectrophotometry and chemometric methods

    NASA Astrophysics Data System (ADS)

    Glavanović, Siniša; Glavanović, Marija; Tomišić, Vladislav

    2016-03-01

    The UV spectrophotometric methods for simultaneous quantitative determination of paracetamol and tramadol in paracetamol-tramadol tablets were developed. The spectrophotometric data obtained were processed by means of partial least squares (PLS) and genetic algorithm coupled with PLS (GA-PLS) methods in order to determine the content of active substances in the tablets. The results gained by chemometric processing of the spectroscopic data were statistically compared with those obtained by means of validated ultra-high performance liquid chromatographic (UHPLC) method. The accuracy and precision of data obtained by the developed chemometric models were verified by analysing the synthetic mixture of drugs, and by calculating recovery as well as relative standard error (RSE). A statistically good agreement was found between the amounts of paracetamol determined using PLS and GA-PLS algorithms, and that obtained by UHPLC analysis, whereas for tramadol GA-PLS results were proven to be more reliable compared to those of PLS. The simplest and the most accurate and precise models were constructed by using the PLS method for paracetamol (mean recovery 99.5%, RSE 0.89%) and the GA-PLS method for tramadol (mean recovery 99.4%, RSE 1.69%).

  2. Comparison of pharmacokinetics of tramadol between young and middle-aged dogs.

    PubMed

    Itami, Takaharu; Saito, Yasuo; Ishizuka, Tomohito; Tamura, Jun; Umar, Mohammed A; Inoue, Hiroki; Miyoshi, Kenjiro; Yamashita, Kazuto

    2016-07-01

    This study aimed to compare the pharmacokinetics of tramadol between young and middle-aged dogs. Tramadol (4 mg/kg) was administered intravenously (IV) to young and middle-aged dogs (2 and 8-10 years, respectively). Plasma concentrations of tramadol were measured using high-performance liquid chromatography (HPLC), and its pharmacokinetics best fit a two-compartment model. The volume of distribution (Vd), elimination half-life (t1/2,β) and total body clearance (CLtot) of the young group were 4.77 ± 1.07 l/kg, 1.91 ± 0.26 hr and 29.9 ± 7.3 ml/min/kg, respectively, while those of the middle-aged group were 4.73 ± 1.43 l/kg, 2.39 ± 0.97 hr and 23.7 ± 5.4 ml/min/kg, respectively. Intergroup differences in the t1/2,β and CLtot were significant (P<0.05). In conclusion, tramadol excretion was significantly prolonged in middle-aged dogs.

  3. Accuracy of dispersing tramadol capsules for oral administration in young children.

    PubMed

    Kluger, M; Penrose, S; Bjorksten, A R; Chalkiadis, G

    2016-11-01

    Tramadol is used in children aged <12 years for analgesia, particularly for those at risk of obstructive sleep apnoea undergoing adenotonsillectomy. The Australian Therapeutic Goods Administration have strongly recommended that oral tramadol drops (100 mg/ml) not be used in children <12 years because of the risk of inadvertent overdose. The total mass of drug in a 10 ml bottle is 1000 mg. The only alternative preparation available is a 50 mg capsule that requires dispersion of a capsule's contents should smaller doses be required. The accuracy of this preparation has not been assessed. Twenty surgical ward nurses were asked to prepare a 15 mg dose of tramadol from a 50 mg capsule. The dose was within ±5% of 15 mg in 13 cases (65%) and within ±10% in 19 cases (95%) (range 13.9-17.1 mg). Despite the dose variability of this method of preparing tramadol, we consider it sufficiently accurate for clinical use. We also consider it safe, as even at the highest dose prepared, the variability would be unlikely to contribute to clinically significant side-effects or toxicity. Moreover, the maximal dose that could be administered is limited to the size of the capsule (50 mg).

  4. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus)

    PubMed Central

    Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose–response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period. PMID:26817983

  5. The impact of black seed oil on tramadol-induced hepatotoxicity: Immunohistochemical and ultrastructural study.

    PubMed

    Omar, Nesreen Moustafa; Mohammed, Mohammed Amin

    2017-06-01

    The natural herb, black seed (Nigella Sativa; NS) is one of the most important elements of folk medicine. The aim was to evaluate the impact of Nigella Sativa Oil (NSO) on the changes induced by tramadol in rat liver. Twenty four albino rats were used. given intraperitoneal and oral saline for 30days. TR-group: given intraperitoneal tramadol (20, 40, 80mg/kg/day) in the first, middle and last 10days of the experiment, respectively. TR+NS group: administered intraperitoneal tramadol in similar doses to TR-group plus oral NSO (4ml/kg/day) for 30days. Immunohistochemical, electron microscopic, biochemical and statistical studies were performed. TR-group displayed disarranged hepatic architecture, hepatic congestion, hemorrhage and necrosis. Apoptotic hepatocytes, mononuclear cellular infiltration and a significant increase in the number of anti-CD68 positive cells were observed. Ultrastructurally, hepatocytes showed shrunken nuclei, swollen mitochondria, many lysosomes and autophagic vacuoles. Activated Ito and Von Kupffer cells were also demonstrated. Elevated serum levels of AST, ALT, ALP and bilirubin were noticed. NSO administration resulted in preservation of hepatic histoarchitecture and ultrastructure and significant reductions in the number of anti-CD68 positive cells and serum levels of liver seromarkers. In conclusion, NSO administration could mitigate the alterations induced by tramadol in rat liver. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Tramadol versus codeine/acetaminophen after pediatric tonsillectomy: A prospective, double-blinded, randomized controlled trial.

    PubMed

    Friedrichsdorf, Stefan J; Postier, Andrea C; Foster, Laurie Pane; Lander, Timothy A; Tibesar, Robert J; Lu, Yi; Sidman, James D

    2015-01-01

    Tonsillectomy is one of the most common pediatric surgical procedures performed in the United States. The postoperative period can be particularly painful, and there is currently no consensus on an optimal analgesic regimen. The objective of this study was to evaluate efficacy and safety of the single drug tramadol versus codeine/acetaminophen post-tonsillectomy. Prospective, double-blinded, randomized controlled trial. Large, Midwestern US pediatric hospital. Eighty-four children aged 4-15 years who underwent a tonsillectomy (with or without adenoidectomy) procedure were randomized and 74 were included in the analysis. Group 1 received liquid codeine/acetaminophen for 10 days post-tonsillectomy (5 days scheduled, followed by 5 days as-needed). Group 2 received liquid tramadol for 10 days post-tonsillectomy (5 days scheduled, followed by 5 days as-needed). Efficacy and side effects were evaluated using a 10-day take-home diary that was completed by parents. Children in both study arms reported adequate post-tonsillectomy pain management without significant differences between groups in pain scores. Oversedation was significantly higher on the day of surgery in the codeine/acetaminophen group, and itching was experienced by significantly more children in the tramadol group during the postoperative period. As part of multimodal analgesia, scheduled plus as-needed tramadol may be considered for children in the postoperative setting due to its analgesic properties, low potential for side effects, and good safety profile.

  7. Comparison of analgesic efficacy of paracetamol and tramadol for pain relief in active labor.

    PubMed

    Kaur Makkar, Jeetinder; Jain, Kajal; Bhatia, Nidhi; Jain, Vanita; Mal Mithrawal, Sanwar

    2015-03-01

    To evaluate the efficacy and safety profile of paracetamol in comparison with tramadol for pain relief during active labor. Prospective, randomized, double-blind study. Maternity Wing of the Postgraduate Institute of Medical Education and Research, Chandigarh. Sixty laboring, primiparous, full-term parturients with uncomplicated, singleton pregnancy in spontaneous labor and cervical dilatation of 3-5 cm. Parturients were randomized into 2 groups to receive either 1 mg/kg of tramadol intramuscularly (group T; n = 29) or 1 g of paracetamol intravenously (group P; n = 30). Same doses of the drugs were repeated after 4 hours of initial dose. Primary outcome of the study was to assess the analgesic efficacy of the 2 drugs as measured by visual analog scale (VAS) score. Secondary outcome recorded was duration of labor, presence of any maternal, or fetal adverse events during the study. Both the groups showed comparable VAS scores at all times of observation. Lower mean VAS scores were reported in both the groups till 120 minutes only. The duration of first stage of labor was shorter in group P (248.00 ± 98.171 vs 340.63 ± 111.592 minutes; P = .003). The duration of second stage of labor was comparable between the 2 groups. Higher incidence of maternal side effects such as nausea/vomiting and sedation was associated with the use of tramadol. Neonatal outcome was comparable. Intravenous paracetamol provides comparable analgesia as intramuscular tramadol during active labor. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 78 FR 2416 - Notice of Issuance of Final Determination Concerning Rybix® (Tramadol Hydrochloride) Tablets

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-11

    ... determination that India is the country of origin of the Rybix (tramadol hydrochloride) tablets for purposes of... India, blended with excipients and packaged into dosage form in France, was not substantially transformed in France, ] such that India is the country of origin of the finished Rybix...

  9. The role of tramadol in current treatment strategies for musculoskeletal pain

    PubMed Central

    Schug, Stephan A

    2007-01-01

    Non-selective and cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) have been the mainstay of treatment for musculoskeletal pain of moderate intensity. However, in addition to gastrointestinal and renal toxicity, an increased cardiovascular risk may be a class effect for all NSAIDs. Despite these safety risks and the acknowledged ceiling effect of NSAIDs, many doctors still use them to treat moderate, mostly musculoskeletal pain. Recent guidelines for treating osteoarthritis and low back pain, issued by numerous professional medical societies, recommend NSAIDs and COX-2 inhibitors only in strictly defined circumstances, at the lowest effective dose and for the shortest possible period of time. These recent guidelines bring more focus to the usage of paracetamol and opioids. But opioids still remain under-utilized, although they are effective with minimal organ toxicity. In this setting, the atypical, centrally acting analgesic tramadol offers important benefits. Its multi-modal effect results from a dual mode of action, ie, opioid and monoaminergic mechanisms, with efficacy in both nociceptive and neuropathic pain. Moreover, fewer instances of side effects such as constipation, respiratory depression, and sedation occur than with traditional opioids, and tramadol has been prescribed for 30 years for a broad range of indications. Tramadol is now regarded as the first-line analgesic for many musculoskeletal indications. In conclusion, it is recommended to better implement the more recent guidelines focusing on pain management and consider the role of tramadol in musculoskeletal pain treatment strategies. PMID:18472996

  10. Comparative efficacy of intravenous dexmedetomidine, clonidine, and tramadol in postanesthesia shivering

    PubMed Central

    Sahi, Shikha; Singh, Mirley Rupinder; Katyal, Sunil

    2016-01-01

    Background and Aims: Postanesthesia shivering continues to be a major challenge in the perioperative care. We compared the efficacy of tramadol, clonidine, and dexmedetomidine in preventing postoperative shivering and its potential adverse effects in patients undergoing laparoscopic cholecystectomy under general anesthesia. Material and Methods: One hundred and twenty American Society of Anesthesiologists I and II patients scheduled for elective laparoscopic cholecystectomy under general anesthesia were divided into four equal groups. Group 1 received clonidine 2 μg/kg, Group 2 received tramadol 1 mg/kg, Group 3 received dexmedetomidine 1 mcg/kg all intravenous diluted in NS to 5 ml, and Group 4 received NS intravenous 5 ml. Parameters analysed included postoperative blood pressure (BP), pulse rate, respiratory rate (RR), arterial saturation, and tympanic membrane temperature. Patients were observed for shivering episodes, sedation, pain, respiratory depression, nausea, and vomiting. Analysis of variance, Tukey's post-hoc comparison, Chi-square test and Bonferroni post-hoc comparison test were performed using SPSS (Statistical analysis by Statistical Package of Social Sciences of Microsoft Windows) Statistics (version 16.0). Results: The incidence of shivering was 10, 3.3, 13.3 and 40% in Groups 1, 2, 3, and 4 respectively. Patients who were given tramadol had significantly less shivering than patients in clonidine and dexmedetomidine groups (P < 0.01). Conclusion: All the three drugs were effective in preventing postoperative shivering. However, tramadol has been found to be more efficacious in preventing postoperative shivering. PMID:27275057

  11. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).

    PubMed

    Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period.

  12. The Effect of Gabapentin and Tramadol in Cancer Pain Induced by Glioma Cell in Rat Femur.

    PubMed

    Corona-Ramos, Janette Nallely; Déciga-Campos, Myrna; Romero-Piña, Mario; Medina, Luis A; Martínez-Racine, Issac; Jaramillo-Morales, Osmar A; García-López, Patricia; López-Muñoz, Francisco Javier

    2017-08-01

    Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (10(5) ) into the rat femur, by perforating the intercodiloid fossa. Painful behavior was evaluated by measuring mechanical allodynia using the Von Frey test while thermal hyperalgesia was assessed in the plantar test. Histopathological features were evaluated and antinociceptive responses were compared using tramadol and gabapentin. The inoculation of cells inside the right femur produced nociceptive behaviors. Tramadol and gabapentin produced an anti-allodynic effect in this condition, but tramadol did not produce an anti-hyperalgesic response. The development of this model will allow us to perform tests to elucidate the pathology of bone metastasis, cancer pain, and in particular the pain produced by glioma. Drug Dev Res 78 : 173-183, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely.

    PubMed

    Ryan, Nicole M; Isbister, Geoffrey K

    2015-07-01

    Tramadol is a commonly used centrally acting analgesic associated with seizures and suspected to cause serotonin toxicity in overdose. This study sought to investigate the effects of tramadol overdose, and included evaluation for serotonin toxicity based on the Hunter Serotonin Toxicity Criteria where the seven clinical features of spontaneous clonus, inducible clonus, ocular clonus, agitation, diaphoresis, tremor and hyperreflexia are examined for in all patients taking serotonergic medications; seizures and central nervous system depression. This was an observational cases series based on a retrospective review of tramadol overdoses (> 400 mg) admitted to a tertiary toxicology unit from November 2000 to June 2013. Demographic details, information on ingestion (dose and co-ingestants), clinical effects, complications (seizures, serotonin toxicity and cardiovascular effects) and intensive care unit (ICU) admission were extracted from a clinical database. There were 71 cases of tramadol overdose (median age: 41 years, range: 17-69 years; and median ingested dose: 1000 mg, interquartile range [IQR]: 800-2000 mg). Seizures were dose related and occurred in 8 patients, one of them co-ingested a benzodiazepine compared with 16 patients without seizures. There were no cases of serotonin toxicity meeting the Hunter Serotonin Toxicity Criteria. Tachycardia occurred in 27 and mild hypertension occurred in 32. The Glasgow Coma Score was < 15 in 29 and < 9 in 5 patients; three co-ingested tricyclic antidepressants and two tramadol alone (3000 mg and 900 mg). Respiratory depression occurred in 13, median dose: 2500 (IQR: 1600-3000) mg which was significantly different (p = 0.003) to patients without respiratory depression, median dose: 1000 (IQR: 750-1475) mg. Eight patients were admitted to ICU, five due to co-ingestant toxicity and three for respiratory depression. Tramadol overdose was associated with a significant risk of seizures and respiratory depression in more severe

  14. Chlorination of tramadol: Reaction kinetics, mechanism and genotoxicity evaluation.

    PubMed

    Cheng, Hanyang; Song, Dean; Chang, Yangyang; Liu, Huijuan; Qu, Jiuhui

    2015-12-01

    Tramadol (TRA) is one of the most detected analgesics in environmental matrices, and it is of high significance to study the reactivity of TRA during chlorination considering its potential toxicity to the environment. The chlorine/TRA reaction is first order with respect to the TRA concentration, and a combination of first-order and second-order with respect to chlorine concentration. The pH dependence of the observed rate constants (kobs) showed that the TRA oxidation reactivity increased with increasing pH. kobs can be quantitatively described by considering all active species including Cl2, Cl2O and HOCl, and the individual rate constants of HOCl/TRA(0), HOCl/TRAH(+), Cl2/TRA and Cl2O/TRA reactions were calculated to be (2.61±0.29)×10(3)M(-1)s(-1), 14.73±4.17M(-1)s(-1), (3.93±0.34)×10(5)M(-1)s(-1) and (5.66±1.83)×10(6)M(-1)s(-1), respectively. Eleven degradation products were detected with UPLC-Q-TOF-MS, and the corresponding structures of eight products found under various pH conditions were proposed. The amine group was proposed to be the initial attack site under alkaline pH conditions, where reaction of the deprotonated amine group with HOCl is favorable. Under acidic and neutral pH conditions, however, two possible reaction pathways were proposed. One is an electrophilic substitution on the aromatic ring, and another is an electrophilic substitution on the nitrogen, leading to an N-chlorinated intermediate, which can be further oxidized. Finally, the SOS/umu test showed that the genotoxicity of TRA chlorination products increased with increasing dosage of chlorine, which was mostly attributed to the formation of some chlorine substitution products.

  15. [Adverse events associated with tramadol and dipirona administration in a level III hospital].

    PubMed

    Montoya, Giovanny Alberto; Vaca, Claudia; Parra, María Fernanda

    2009-09-01

    The efficacy and safety of pharmaceutical drugs such as dipirone and tramadol must be a primary objective in the post-marketing period and as they are used in specific population groups. The frequency of adverse effects (including therapeutic failure) with the medications tramadol and dipirona were described and estimated. At the Hospital Universitario de la Samaritana, Bogotá, D.C., Colombia, adverse events associated with dipirone and tramadol were rigorously tracked in patients hospitalized in the internal medicine, as well as the orthopedics and surgery departments. For a period of six months, data were collected by means of the Instituto Nacional de Vigilancia Médica y Alimentos (INVIMA) standard report form. Direct costs of adverse event treatment to the patient were calculated. Adverse reactions were detected 213 times in 171 (8.4%) of the 2,547 patients admitted to the services (incidence rate. Of these instances, 53.4% were rated as possible for dipirone and 46.82% for tramadol. Of the total, 0.6% (16 cases) were classes as serious adverse events. The gastrointestinal system was the most affected, with the incidences of adverse events for dipirone of 27%) and tramadol of 42.9%. The total cost generated by the medical response to the 213 adverse events was estimated to be US$14,346.53. An unacceptable level of preventable adverse events was described that impacted the well-being of patients, as well as the costs associated with remedial treatment. These data recommend that institutional pharmacovigilance programs be required.

  16. Tramadol-induced hyperalgesia and its prevention by ketamine in rats: A randomised experimental study.

    PubMed

    Abreu, Mariana; Aguado, Delia; Benito, Javier; García-Fernández, Javier; Gómez de Segura, Ignacio A

    2015-10-01

    Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics. The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes. A randomised, experimental study. Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. Thirty-nine adult male Wistar rats. Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg) with or without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P < 0.05; day 7). Ketamine administration prevented both the reduction in MNT and the increase in MAC (P > 0.05). Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.

  17. Coadministration of tramadol and tizanidine in an experimental acute pain model in rat.

    PubMed

    Beltrán-Villalobos, Karla Lizet; Ramírez-Marín, Pamela Monserrat; Cruz, Carlos Alberto Zúñiga; Déciga-Campos, Myrna

    2014-12-01

    Preclinical Research The use of drug combinations to achieve a desired effect is a common practice in pharmacological reaserch and in clinical practice. The present study was designed to evaluate the potential synergistic antinociceptive interactions between tizanidine, an α-2-adrenoceptor agonist and tramadol on formalin-induced nociception in rat using isobolographic analyses. Tramadol (0.1-100 μg/paw) and tizanidine (0.01-10 μg/paw) were injected into the paw prior to formalin injection (1%). Both drugs produced a dose-dependent antinociceptive effect. The EC50 values were estimated for individual drugs, and isobolograms were constructed. Tizanidine (EC50  = 0.125 ± 0.026 μg) was more potent than tramadol (EC50  = 16.45 ± 6.4 μg). The combination of tramadol-tizanidine at fixed ratios of 1:1 (EC50exp  = 67.43 ± 11 μg; EC50teo  = 8.28 ± 3.2 μg) and 3:1 (EC50exp  = 31.25 ± 9.49 μg; CE50teo  = 12.36 ± 4.8 μg) generated subadditivity (antagonism). On the basis of the current preclinical data, the pharmacological profile of the combination of tramadol-tizanidine produced antagonism. Thus, the utmost caution is required during the use of this combination in clinical practice, due to their antagonistic interaction. © 2014 Wiley Periodicals, Inc.

  18. Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort

    PubMed Central

    2014-01-01

    Background Tramadol is an atypical centrally acting analgesic agent available as both oral and parenteral preparations. For patients who are unable to take tramadol orally, the subcutaneous route of administration offers an easy alternative to intravenous or intramuscular routes. This study aimed to characterise the absorption pharmacokinetics of a single subcutaneous dose of tramadol in severely ill patients and in healthy subjects. Methods/design Blood samples (5 ml) taken at intervals from 2 minutes to 24 hours after a subcutaneous dose of tramadol (50 mg) in 15 patients (13 male, two female) and eight healthy male subjects were assayed using high performance liquid chromatography. Pharmacokinetic parameters were derived using a non-compartmental approach. Results There were no statistically significant differences between the two groups in the following parameters (mean ± SD): maximum venous concentration 0.44 ± 0.18 (patients) vs. 0.47 ± 0.13 (healthy volunteers) mcg/ml (p = 0.67); area under the plasma concentration-time curve 177 ± 109 (patients) vs. 175 ± 75 (healthy volunteers) mcg/ml*min (p = 0.96); time to maximum venous concentration 23.3 ± 2 (patients) vs. 20.6 ± 18.8 (healthy volunteers) minutes (p = 0.73) and mean residence time 463 ± 233 (patients) vs. 466 ± 224 (healthy volunteers) minutes (p = 0.97). Conclusions The similar time to maximum venous concentration and mean residence time suggest similar absorption rates between the two groups. These results indicate that the same dosing regimens for subcutaneous tramadol administration may therefore be used in both healthy subjects and severely ill patients. Trial registration ACTRN12611001018909 PMID:24914400

  19. Cost-Effectiveness of Tramadol and Oxycodone in the Treatment of Knee Osteoarthritis.

    PubMed

    Smith, Savannah R; Katz, Jeffrey N; Collins, Jamie E; Solomon, Daniel H; Jordan, Joanne M; Suter, Lisa G; Yelin, Edward H; David Paltiel, A; Losina, Elena

    2017-02-01

    To evaluate the cost-effectiveness of incorporating tramadol or oxycodone into knee osteoarthritis (OA) treatment. We used the Osteoarthritis Policy Model to evaluate long-term clinical and economic outcomes of knee OA patients with a mean age of 60 years with persistent pain despite conservative treatment. We evaluated 3 strategies: opioid-sparing (OS), tramadol (T), and tramadol followed by oxycodone (T+O). We obtained estimates of pain reduction and toxicity from published literature and annual costs for tramadol ($600) and oxycodone ($2,300) from Red Book Online. Based on published data, in the base case, we assumed a 10% reduction in total knee arthroplasty (TKA) effectiveness in opioid-based strategies. Outcomes included quality-adjusted life years (QALYs), lifetime cost, and incremental cost-effectiveness ratios (ICERs) and were discounted at 3% per year. In the base case, T and T+O strategies delayed TKA by 7 and 9 years, respectively, and led to reduction in TKA utilization by 4% and 10%, respectively. Both opioid-based strategies increased cost and decreased QALYs compared to the OS strategy. Tramadol's ICER was highly sensitive to its effect on TKA outcomes. Reduction in TKA effectiveness by 5% (compared to base case 10%) resulted in an ICER for the T strategy of $110,600 per QALY; with no reduction in TKA effectiveness, the ICER was $26,900 per QALY. When TKA was not considered a treatment option, the ICER for T was $39,600 per QALY. Opioids do not appear to be cost-effective in OA patients without comorbidities, principally because of their negative impact on pain relief after TKA. The influence of opioids on TKA outcomes should be a research priority. © 2016, American College of Rheumatology.

  20. Tramadol-Paracetamol Combination for Postoperative Pain Relief in Elective Single-level Microdisectomy Surgery.

    PubMed

    Dogar, Samie A; Khan, Fauzia A

    2017-04-01

    The tramadol and paracetamol combination is used frequently for postoperative pain management. The literature on the use of this combination for vertebral surgery is limited. Our objective was to compare a combination of paracetamol 1 g and a lower dose of tramadol (1 mg/kg: group 1T) with a combination of paracetamol 1 g and a higher dose of tramadol (1.5 mg/kg: group 1.5T) for postoperative pain after microdisectomy surgery. Our main outcome measure was Visual Analogue Scale pain scores for 4 hours postoperatively. This prospective randomized triple-blind clinical trial was conducted at Aga Khan University Hospital, Karachi. Ninety-four patients aged between 18 and 50 years scheduled for elective single-level microdisectomy were allocated randomly into 1 of 2 groups. Twenty minutes before the end of the surgery, patients received the study drugs. There was no significant demographic difference between groups. None of the patients experienced severe pain (VAS>6). There was no significant difference in the mean pain score between groups. The mean score at 4 hours was 2.17 (1.38) in group 1.5T and 1.74 (1.37) in group 1T. The difference was not statistically significant (P=0.14). In group 1.5T, 13 patients reported having nausea and vomiting compared with 2 patients in group 1T. This was a statistically significant difference (P=0.004). The sedation score was similar between groups. The combination of low-dose tramadol (1 mg/kg) and paracetamol has comparable analgesia and a decreased incidence of nausea and vomiting compared with the higher dose of tramadol (1.5 mg/kg) and paracetamol combination.

  1. Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.

    PubMed

    Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Fiorino, Emma; Faggio, Caterina; Svobodova, Zdenka

    2017-08-31

    Pharmaceuticals occur in water bodies as a consequence of their incomplete removal during waste water treatment processes. The occurence of pharmaceuticals in surface waters as well as their possible impact on aquatic vertebrates have received considerable attention in recent years. However, there is still a lack of informations on the chronic effects of widely used drugs as well as their possible mixture toxicity on non-target aquatic vertebrates as well as their possible mixture toxicity. The aim of this study was to assess the effects of naproxen sodium on early life stages of fish and evaluate its mixture toxicity with tramadol hydrochloride, which was assessed in our earlier study as a single substance. Two embryo-larval toxicity tests with common carp (Cyprinus carpio) were performed according to the OECD guideline 210 (Fish, Early-life Stage Toxicity Test) in order to assess the subchronic toxicity of naproxen sodium and tramadol hydrochlorid-naproxen sodium mixture at the concentrations of 10; 50; 100 and 200 μg/L. These experiments were conducted for 32 days. The subchronic exposure to naproxen sodium and naproxen sodium and tramadol hydrochloride mixture had a strong effect on the early life stages of common carp. Hatching, developmental rate, morphology, histopathology and, in the case of the naproxen sodium and tramadol hydrochloride mixture, mortality were influenced. The bioindicators of oxidative stress were also influenced. The LOEC was determined at 10 μg/L for both naproxen sodium and naproxen sodium and tramadol hydrochloride mixture. Copyright © 2017. Published by Elsevier Ltd.

  2. Postoperative analgesic efficacy of epidural tramadol as adjutant to ropivacaine in adult upper abdominal surgeries

    PubMed Central

    Singh, Anil P.; Singh, Dharmraj; Singh, Yashpal; Jain, Gaurav

    2015-01-01

    Background: Postoperative pain control after major abdominal surgery is the prime concern of anesthesiologist. Among various methodologies, epidural analgesia is the most preferred technique because of the excellent quality of analgesia with minimum side-effects. Aim: The present study was designated to compare postoperative analgesic efficacy and safety of epidural tramadol as adjuvant to ropivacaine (0.2%) in adult upper abdominal surgery. Settings and Design: Prospective, randomized-controlled, double-blinded trial. Materials and Methods: Ninety patients planned for upper abdominal surgery under general anesthesia were randomized into three equal groups to receive epidural drug via epidural catheter at start of incisional wound closure: Group R to receive ropivacaine (0.2%); Group RT1 to receive tramadol 1 mg/kg with ropivacaine (0.2%); and RT2 to receive tramadol 2 mg/kg with ropivacaine (0.2%). Duration and quality of analgesia (visual analog scale [VAS] score), hemodynamic parameters, and adverse event were recorded and statistically analyzed. Statistical Analysis: One-way analysis of variance test, Fisher's exact test/Chi-square test, whichever appropriate. A P < 0.05 was considered significant. Results: Mean duration of analgesia after epidural bolus drug was significantly higher in Group RT2 (584 ± 58 min) when compared with RT1 (394 ± 46 min) or R Group (283 ± 35 min). VAS score was always lower in RT2 Group in comparison to other group during the study. Hemodynamic parameter remained stable in all three groups. Conclusion: We conclude that tramadol 2 mg/kg with ropivacaine (0.2%) provides more effective and longer-duration analgesia than tramadol 1 mg/kg with ropivacaine (0.2%). PMID:26712976

  3. Chemical stability of tramadol hydrochloride injection admixed with selected pain drugs

    PubMed Central

    Di Stefano, V; Pitonzo, R; Bavetta, S; Polidori, P; Sidoti, MG

    2011-01-01

    Background: Tramadol hydrochloride (HCl) and ketorolac tromethamine are analgesic drugs, which are commonly used in combination in postoperative pain management. According to some studies, metoclopramide and magnesium sulfate (MgSO4) as adjuvant agents can improve analgesia and decrease the need for other pain drugs. Materials and Methods: The chemical stability of tramadol HCl combined with ketorolac tromethamine and metoclopramide HCl has been studied using a stability-indicating high-performance liquid chromatographic assay method. Calibration curves were produced using linear regression of the peak area against concentration of each drug, with an r2 value ≥ 0.96. Our aim was to investigate the stability of admixture solution of tramadol HCl combined with ketorolac tromethamine and metoclopramide HCl for 48 h (25°C) and 5 days (5°C), with MgSO4, which has never been assessed. Results: Data obtained for admixtures prepared and stored at temperatures of 25°C and 5°C, show that all drugs have reached at least 98% of the initial concentration. Conclusions: For the purpose of pre-preparing drug admixtures to use with confidence, tramadol HCl infusions may be prepared in advance and then thawed before use in clinical units. On the basis of our results, the intravenous mixture of tramadol (7.69 mg/mL), metoclopramide (0.19 mg/mL), ketorolac (1.15 mg/mL), and magnesium sulfate (77 mg/mL) may be considered for a possible commercial formulation. PMID:23071920

  4. A case of respiratory depression in a child with ultrarapid CYP2D6 metabolism after tramadol.

    PubMed

    Orliaguet, Gilles; Hamza, Jamil; Couloigner, Vincent; Denoyelle, Françoise; Loriot, Marie-Anne; Broly, Franck; Garabedian, Erea Noel

    2015-03-01

    We discuss a case of severe respiratory depression in a child, with ultrarapid CYP2D6 genotype and obstructive sleep apnea syndrome, after taking tramadol for pain relief related to a day-case tonsillectomy.

  5. Comparison of the effect of adding remifentanil to patient-controlled tramadol or morphine for postoperative analgesia after major abdominal surgery.

    PubMed

    Unlugenc, Hakki; Tetiker, Sibel; Büyükkurt, Selim; Guler, Tayfun; Isik, Geylan

    2009-01-01

    In this study, the authors investigated the effect of the addition of remifentanil to tramadol or morphine for patient-controlled analgesia (PCA). Prospective, randomized, double-blind, controlled study. University Hospital. The authors randomly allocated 133 patients undergoing major abdominal surgery to receive IV PCA with tramadol alone, tramadol plus remifentanil, morphine alone or morphine plus remifentanil. Bolus doses of tramadol (0.2 mg/kg), tramadol (0.2 mg/kg) plus remifentanil (0.2 microg/kg), morphine (0.02 mg/kg), or morphine (0.02 mg/kg) plus remifentanil (0.2 microg/kg) were available every 10 minutes without time limit or background infusion. Discomfort, sedation, pain scores, side effects, and total and bolus tramadol and morphine consumption were recorded for up to 24 hours after the start of PCA. Pain scores at rest and movement were greater with tramadol alone than in the other groups at 1, 2, and 6 hours (p < 0.0125). The addition of remifentanil reduced cumulative tramadol consumption at 6, 12, and 24 hours, but not morphine consumption. More patients required supplementary rescue analgesia with meperidine, and with greater dosage, with tramadol alone (p < 0.001), and the incidence of nausea was greater with tramadol alone. The addition of remifentanil not only significantly improved discomfort scores in remifentanil groups, but also increased the degree of sedation in morphine-remifentanil group. After major abdominal surgery, adding remifentanil to PCA tramadol resulted in better pain scores, lower analgesic consumption, and fewer side effects when compared with tramadol alone. However, analgesic outcome with remifentanil was not prominent in MR group as much as in TR group.

  6. The association between tramadol hydrochloride misuse and other substances use in an adolescent population: Phase I of a prospective survey.

    PubMed

    Nazarzadeh, Milad; Bidel, Zeinab; Carson, Kristin V

    2014-01-01

    Tramadol hydrochloride is a common prescription pain reliever that is structurally similar to morphine and codeine with its analgesic effects identified as a mu-receptor agonist. Due to its opioid-like stimulant effects, the potential for tramadol misuse is a public health concern. As such, the aim of this investigation is to estimate the prevalence of tramadol misuse in a sample of Iranian adolescents and to assess the relationship between tramadol misuse and other substance use. This is the first phase of a prospective survey examining the prevalence of adolescent smoking status, substances use and related factors in Ilam city, Iran. Grade 10 male and female students (n=2000) were recruited using multistage sampling. Self-administered multiple-choice questionnaires were conducted with data analysed using cross tabulations and logistic regression models. The prevalence of lifetime tramadol misuse was 4.8% (7.6% males; 1.8% females). Adjusted odds ratios and confidence intervals for lifetime tramadol misusers reporting substance use during the past month were 2.2 (1.1-4.4) for alcohol, 5.0 (1.5-21.9) for cannabis, 8.9 (2.7-29.4) for ecstasy, 0.5 (0.03-7.0) for methamphetamine and 2.3 (0.7-7.4) for opium. Tramadol could be a related factor or co-factor for adolescent alcohol, cannabis and ecstasy use. We recommend future longitudinal studies to investigate the possible role of tramadol as a gateway drug in the development of substance abuse. © 2013.

  7. Potentiation of epidural lidocaine by co-administering tramadol by either intramuscular or epidural route in cats

    PubMed Central

    Hermeto, Larissa C.; DeRossi, Rafael; Marques, Beatriz C.; Jardim, Paulo H.A.

    2015-01-01

    This study investigated the analgesic and systemic effects of intramuscular (IM) versus epidural (EP) administration of tramadol as an adjunct to EP injection of lidocaine in cats. Six healthy, domestic, shorthair female cats underwent general anesthesia. A prospective, randomized, crossover trial was then conducted with each cat receiving the following 3 treatments: EP injection of 2% lidocaine [LEP; 3.0 mg/kg body weight (BW)]; EP injection of a combination of lidocaine and 5% tramadol (LTEP; 3.0 and 2.0 mg/kg BW, respectively); or EP injection of lidocaine and IM injection of tramadol (LEPTIM; 3.0 and 2.0 mg/kg BW, respectively). Systemic effects, spread and duration of analgesia, behavior, and motor blockade were determined before treatment and at predetermined intervals afterwards. The duration of analgesia was 120 ± 31 min for LTEP, 71 ± 17 min for LEPTIM, and 53 ± 6 min for LEP (P < 0.05; mean ± SD). The cranial spread of analgesia obtained with LTEP was similar to that with LEP or LEPTIM, extending to dermatomic region T13–L1. Complete motor blockade was similar for the 3 treatments. It was concluded that tramadol produces similar side effects in cats after either EP or IM administration. Our findings indicate that EP and IM tramadol (2 mg/kg BW) with EP lidocaine produce satisfactory analgesia in cats. As an adjunct to lidocaine, EP tramadol provides a longer duration of analgesia than IM administration. The adverse effects produced by EP and IM administration of tramadol were not different. Further studies are needed to determine whether EP administration of tramadol could play a role in managing postoperative pain in cats when co-administered with lidocaine after painful surgical procedures. PMID:26130854

  8. Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects.

    PubMed

    Skinner-Robertson, Sybil; Fradette, Caroline; Bouchard, Sylvie; Mouksassi, Mohamad-Samer; Varin, France

    2015-12-01

    Tramadol is frequently used in geriatric patients; however, pharmacokinetic (PK) publications on tramadol and O-desmethyltramadol (ODM) in elderly patients are rare. Our objective was to characterize the PK of tramadol and ODM, including absorption processes and covariates for tramadol, in elderly and young subjects after single-dose administration of 200-mg extended-release tablets. We conducted a PK study in 15 elderly (aged ≥75 years) subjects with mild renal insufficiency and 20 young (18-40 years) subjects; blood and urine samples were collected for 48 h post-dose. Non-compartmental analysis (NCA) of each tramadol and ODM enantiomer included area under the concentration-time curve (AUC), terminal elimination rate (k el), total body clearance, volume of distribution (V area/ F), and renal clearance (Clr0-48). A one-compartment population model of total tramadol concentration was parameterized with clearance (CL/F), volume of distribution (V/F), and mixed order absorption (first-order and zero-order absorption rate constants with lag times). NCA demonstrated comparable maximum plasma concentration (C max) and AUC between age groups for tramadol enantiomers, but significant differences in V area/ F (mean 34% higher) and k el (mean 28% lower) in the elderly. PK of ODM were significantly different in the elderly for AUC0-inf (mean 35% higher), Clr0-48 (mean 29% lower), and k el (mean 33% lower). The population analysis identified age as a covariate of V/F (young 305 L; elderly 426 L), with a 50% longer mean elimination half-life in the elderly. No differences in absorption processes were observed. Tramadol exposure was similar between the age groups; exposure to ODM was higher in elderly subjects.

  9. Comparison of the effects of curcumin, tramadol and surgical treatments on neuropathic pain induced by chronic constriction injury in rat.

    PubMed

    Ceyhan, Dilek; Kocman, Atacan Emre; Yildirim, Engin; Ozatik, Orhan; Aydin, Sule; Aydan, Kose

    2017-04-04

    Nerve entrapment syndromes are the most common causes of neuropathic pain. Surgical decompression is preferred method of treatment. The goal of the study was to compare the efficacy of curcumin, tramadol and chronic constriction release treatment (CCR), individually or together, in a rat model of sciatic nerve injury. Eighty male-rats were divided into eight study groups. Group 1 was the sham group. Group 2 was the control group with established chronic constriction injury (CCI). CCI was also established in Groups 3-8. Group 3 underwent chronic constriction release (CCR). Groups 4 and 5 received curcumin and tramadol. Groups 6 and 7 also received curcumin (100 mg kg-1 daily, oral) and tramadol (10 mg kg-1 daily, intraperitoneal, 14 days) after CCR, respectively. Combined curcumin-tramadol treatment was applied to Group 8. Behavioral tests (thermal hyperalgesia, dynamic plantar, cold plate test) were performed on days 0, 3, 7, 13, 17, and 21. Tissue tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels were analyzed in the nerve and dorsal root ganglion (DRG) samples on day 21.days. Histopathologic examination was performed on nervous tissue and DRG. Tramadol-CCR and tramadol-curcumin significantly attenuated mechanical allodynia and thermal hyperalgesia. In CCI-CCR-tramadol treatment, TNF-α levels were found significantly lower in the sciatic nerve tissue and DRG, and IL-10 levels were significantly higher in the sciatic nerve tissue. CCI-CCR-tramadol treatment is highly effective in the symptomatic treatment of neuropathic pain. CCR-curcumin is associated with decreased degeneration and increased regeneration of the nerve tissue.

  10. Potentiation of epidural lidocaine by co-administering tramadol by either intramuscular or epidural route in cats.

    PubMed

    Hermeto, Larissa C; DeRossi, Rafael; Marques, Beatriz C; Jardim, Paulo H A

    2015-07-01

    This study investigated the analgesic and systemic effects of intramuscular (IM) versus epidural (EP) administration of tramadol as an adjunct to EP injection of lidocaine in cats. Six healthy, domestic, shorthair female cats underwent general anesthesia. A prospective, randomized, crossover trial was then conducted with each cat receiving the following 3 treatments: EP injection of 2% lidocaine [LEP; 3.0 mg/kg body weight (BW)]; EP injection of a combination of lidocaine and 5% tramadol (LTEP; 3.0 and 2.0 mg/kg BW, respectively); or EP injection of lidocaine and IM injection of tramadol (LEPTIM; 3.0 and 2.0 mg/kg BW, respectively). Systemic effects, spread and duration of analgesia, behavior, and motor blockade were determined before treatment and at predetermined intervals afterwards. The duration of analgesia was 120 ± 31 min for LTEP, 71 ± 17 min for LEPTIM, and 53 ± 6 min for LEP (P < 0.05; mean ± SD). The cranial spread of analgesia obtained with LTEP was similar to that with LEP or LEPTIM, extending to dermatomic region T13-L1. Complete motor blockade was similar for the 3 treatments. It was concluded that tramadol produces similar side effects in cats after either EP or IM administration. Our findings indicate that EP and IM tramadol (2 mg/kg BW) with EP lidocaine produce satisfactory analgesia in cats. As an adjunct to lidocaine, EP tramadol provides a longer duration of analgesia than IM administration. The adverse effects produced by EP and IM administration of tramadol were not different. Further studies are needed to determine whether EP administration of tramadol could play a role in managing postoperative pain in cats when co-administered with lidocaine after painful surgical procedures.

  11. Clinical efficacy of hydrocodone-acetaminophen and tramadol for control of postoperative pain in dogs following tibial plateau leveling osteotomy.

    PubMed

    Benitez, Marian E; Roush, James K; McMurphy, Rose; KuKanich, Butch; Legallet, Claire

    2015-09-01

    To evaluate clinical efficacy of hydrocodone-acetaminophen and tramadol for treatment of postoperative pain in dogs undergoing tibial plateau leveling osteotomy (TPLO). ANIMALS 50 client-owned dogs. Standardized anesthetic and surgical protocols were followed. Each patient was randomly assigned to receive either tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) for analgesia after surgery. The modified Glasgow composite measure pain scale was used to assess signs of postoperative pain at predetermined intervals by an investigator who was blinded to treatment group. Scoring commenced with the second dose of the assigned study analgesic. Pain scores and rates of treatment failure (ie, dogs requiring rescue analgesia according to a predetermined protocol) were compared statistically between groups. 12 of 42 (29%; 5/19 in the hydrocodone-acetaminophen group and 7/23 in the tramadol group) dogs required rescue analgesic treatment on the basis of pain scores. Median pain score for the hydrocodone group was significantly lower than that of the tramadol group 2 hours after the second dose of study analgesic. The 2 groups had similar pain scores at all other time points. Overall, differences in pain scores between dogs that received hydrocodone-acetaminophen or tramadol were minor. The percentage of dogs with treatment failure in both groups was considered unacceptable.

  12. Intraarticular tramadol-bupivacaine combination prolongs the duration of postoperative analgesia after outpatient arthroscopic knee surgery.

    PubMed

    Zeidan, Ahed; Kassem, Rida; Nahleh, Nazih; Maaliki, Hilal; El-Khatib, Mohamad; Struys, Michel M R F; Baraka, Anis

    2008-07-01

    Intraarticular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery. Recently, IA tramadol was also used for the management of these patients. However, the IA combination of local anesthetic and tramadol has not been evaluated in arthroscopic outpatients. Our primary aim in this study was to evaluate the analgesic effect of an IA combination of bupivacaine and tramadol when compared with each drug alone using visual analog scale (VAS) pain scores in patients undergoing day-care arthroscopic knee surgery. Additionally, we assessed analgesic demand. Ninety ASA I/II patients undergoing arthroscopic partial meniscectomy, performed by a single surgeon under general anesthesia, were assigned in a randomized, double-blind manner into three groups: group B (n = 30) received 0.25% bupivacaine, group T (n = 30) received 100 mg tramadol, and group BT (n = 30) received 0.25% bupivacaine and 100 mg tramadol to a total volume of 20 mL by the IA route after surgery. Postoperative pain scores were measured on a VAS, at rest and on mobilization at 0.5, 1, 2, 4, 6, 8, 12, and 24 h. Duration of analgesia, the subsequent 24 h consumption of rescue analgesia, time to ambulation, and time to discharge were evaluated. In addition, the systemic side effects of the IA injected drugs were also assessed. The results showed significantly lower VAS pain scores in group BT (P < 0.1) when compared with groups T and B. Group BT had a later onset of postsurgical pain and longer time to first rescue analgesic than groups B and T. The 24 h consumption of analgesic was significantly less in group BT when compared with the other two groups (26.7% of the patients required rescue analgesia in group BT, whereas this number was 90% in group B and 86.7% in group T). In addition, time in hours to discharge and time to unassisted ambulation were significantly shorter in group BT when compared with groups T and B, and this was not associated with any

  13. Improved cancer pain treatment using combined fentanyl-TTS and tramadol.

    PubMed

    Marinangeli, Franco; Ciccozzi, Alessandra; Aloisio, Luca; Colangeli, Antonello; Paladini, Antonella; Bajocco, Chiara; Coaccioli, Stefano; Varrassi, Giustino

    2007-12-01

    The aim of the study was to facilitate dose escalation of strong opioids. In this randomized open-label study the influence of tramadol on dose adjustment of transdermal fentanyl in advanced cancer pain control was prospectively evaluated. Seventy patients affected by intractable cancer disease with visual analog scale (VAS) score >3 were enrolled. Thirty-five patients were treated conventionally with increasing transdermal fentanyl dosage as required (group F) and 35 patients received oral tramadol added to their transdermal fentanyl before each increment of the transdermal opioid dosage (group T). Pain control was equally satisfactory in the two groups. VAS scores at baseline (T: 4.36 +/- 1.53; F: 4.51 +/- 1.36; n.s.) and at the end of the study (T: 1.8 +/- 1.6; F: 1.6 +/- 1.5; n.s.) did not differ. However, in the tramadol group this level of pain control was achieved with much slower dose escalation of fentanyl. The mean application time of the fentanyl-Transdermal Therapeutic System patch for each dosage (25, 50, 75 microg/hour) was significantly greater in patients receiving tramadol. No patient in group T escalated to the 100 microg/hour patch, while in 12 patients of group F the 100 microg/hour patch was applied after a 75 microg/hour patch mean application period of 18.6 +/- 4.7 days. The number of fentanyl-TTS dosage changes was significantly lower in group T (1.2 +/- 0.4 vs. 2.3 +/- 0.5; P < 0.05). The mean total duration of treatment in group T, was 37.1 +/- 11.6 days. The amount of fentanyl used at study end was 56.6 +/- 11.2 microg/hour plus 141.1 +/- 151.9 mg tramadol per day (median: 200 mg/day) in group T patients compared with 84.1 +/- 12.2 microg/hour in group F patients (P < 0.05). The combination of a strong opioid with a weak opioid to treat severe cancer pain allowed a more gradual increase of analgesic delivery than was possible using fentanyl-TTS alone, minimizing periods of under- and overdosing. In addition, it considerably slowed the

  14. [Constipation after tilidine/naloxone and tramadol in comparison to codeine. A dose response study in human volunteers].

    PubMed

    Freye, E; Rosenkranz, B; Neruda, B

    1996-10-28

    Tramadol, a mixed mu-opioid agonist and a monoamine-reuptake blocking analgesic, has been supposed to have little effect on propulsive gastrointestinal motility. However, this has not been specifically studied in man. Following institutional approval, 18 human volunteers were given 50 mg of tramadol, tilidine/naloxone, and codeine, respectively, in a double-blind randomised cross-over design. Additionally, 12 further volunteers were given 100 mg of each opioid in a double-blind, randomised fashion, followed by measurement of gastrocoecal transit time. Gastrointestinal transit time was measured using the lactulose H(2)-breath test. A threefold increase in end-expiratory hydrogen when compared to the control value was considered the end point of gastrocoecal transit. At the low dose (50 mg) the three opioids did not differ significantly with regard to their effect on gastrointestinal motility. Gastrocoecal transit time was 90.8 (+/- 10.1 SEM) min for tramadol, 100.6 (+/- 9.8 SEM) min for tilidine/naloxone, and 104.2 (+/- 8.7 SEM) min for codeine. Doubling the dose of each opioid resulted in an increase in mean gastrocoecal transit, namely 97.8 (+/- 11.2 SEM) min for tramadol, 129.2 (+/- 12.2 SEM) min for tilidine/naloxone and 135.9 (+/- 9.2 SEM) min for codeine. The increase in gastrocoecal transit time was significant (P < 0.01) for high doses of tilidine/naloxone and codeine in contrast to the effect of the low doses. This lesser constipation effect may be due to the reduced affinity of tramadol to the mu-opioid receptor. Sedation was significantly higher for codeine after 50 mg (P < 0.05) and 100 mg (P < 0.005) than for tilidine/naloxone and tramadol. Vertigo was significantly higher after 50 mg (P < 0.05) and 100 mg (P < 0.005) of tilidine/naloxone and codeine than after tramadol. Perspiration was significantly higher after tramadol 100 mg (P < 0.005) than after tilidine/naloxone and codeine. Sedation is considered a typical symptom of analgesics interacting with

  15. Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

    PubMed Central

    Chandanwale, Ajay S; Sundar, Subramanian; Latchoumibady, Kaliaperumal; Biswas, Swati; Gabhane, Mukesh; Naik, Manoj; Patel, Kamlesh

    2014-01-01

    Objective We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. Methods A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4–6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. Results Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (P<0.0001) as compared with group B. The combination of tramadol-diclofenac resulted in few mild to moderate adverse events (nausea, vomiting, epigastric pain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. Conclusion An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis. PMID:25152629

  16. NMDA receptors in the dorsal hippocampal area are involved in tramadol state-dependent memory of passive avoidance learning in mice.

    PubMed

    Jafari-Sabet, Majid; Mofidi, Hamed; Attarian-Khosroshahi, Mohammad-Sadegh

    2017-08-03

    The neurobiological mechanisms of tramadol abuse underlying the cognitive function are still imprecise. Considering these, the aim of the present study was to examine the possible effects of intra-CA1 injections of NMDA, an N-methyl-D-aspartate glutamate receptor (NMDAR) agonist and DL-AP5, a competitive NMDAR antagonist, on tramadol state-dependent memory. A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice. Post-training i.p. administration of an atypical MOR agonist, tramadol (2.5 and 5 mg/kg) dose dependently induced impairment of memory retention. Pre-test injection of tramadol (2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under post-training administration of tramadol (5 mg/kg) influence. Pre-test intra-CA1 injection of NMDA (10-5 and 10-4 μg/mouse) 5 min before the administration of tramadol (5 mg/kg, i.p.) dose dependently inhibited tramadol state-dependent memory. Pre-test intra-CA1 injection of DL-AP5 (0.25 and 0.5 μg/mouse) reversed the memory impairment induced by post-training administration of tramadol (5 mg/kg). Pre-test administration of DL-AP5 (0.25 and 0.5 μg/mouse) with an ineffective dose of tramadol (1.25 mg/kg) restored the retrieval and induced tramadol state-dependent memory. It can be concluded that dorsal hippocampal NMDARs mechanisms play an important role in the modulation of tramadol state-dependent memory.

  17. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

    PubMed

    Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E; Strain, Eric C

    2017-09-01

    Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P < .001), but no group effects or group × phase interactions. Analyses of area under the

  18. Treatment of neonatal withdrawal with clonidine after long-term, high-dose maternal use of tramadol.

    PubMed

    O'Mara, Keliana; Gal, Peter; Davanzo, Christie

    2010-01-01

    To describe a case of tramadol withdrawal in a neonate and treatment with clonidine after exposure to long-term maternal use of high-dose tramadol. A 34-week gestational age neonate displayed symptoms of tramadol withdrawal within 48 hours of delivery. Due to a confusing initial clinical picture, including presumed congenital Chlamydia, questionable seizures, and an original report of maternal use of ketorolac (Toradol), diagnosis was delayed until day of life 5. Symptoms included jitteriness, myoclonic movements, and irritability. Upon further questioning of the mother, it was revealed that she was actually taking tramadol 600-800 mg daily. The infant was placed on maintenance therapy with oral clonidine (from 1 to 3 microg/kg orally every 3 hours) until discontinuation on day of life 11. After 3 days off treatment, he began to display symptoms of withdrawal again. Clonidine was restarted at 1 microg/kg orally every 8 hours and he was discharged home on maintenance clonidine therapy at 18 days postnatal age. A 7-day tapering regimen was initiated 2 weeks after discharge, and no further withdrawal symptoms occurred. Few published articles are available to guide clinicians on the clinical course and treatment strategies for tramadol dependence and withdrawal. In neonates, the reports are particularly sparse. Traditional agents used in neonatal opioid withdrawal are narcotics (morphine, tincture of opium, methadone), benzodiazepines (diazepam, lorazepam), and phenobarbital. Clonidine use for neonatal abstinence syndrome from narcotics has been shown to be effective alone or in combination with agents such as other opiates and chloral hydrate. Potential benefits of clonidine therapy include shorter duration of therapy, reduced withdrawal symptoms, and decreased length of hospital stay. Withdrawal can be prolonged in infants exposed to maternal tramadol use. Clonidine may be a safe and effective option for managing symptoms of neonatal tramadol abstinence.

  19. Comparison of Efficacy and Safety of Intramuscular Piroxicam and Tramadol for Post-operative Pain in Patients Undergoing Caesarean Delivery

    PubMed Central

    Thippeswamy, Tejashree; Bengalorkar, Girish M; Mariyappa, Narayanaswamy

    2016-01-01

    Introduction Post-caesarean section pain can be both stressful and unfavourable. Effective and rapid reduction of pain facilitates early ambulation and care of the new born. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and opioids are used for pain relief but they are associated with adverse effects both in the mother and the child. Aim To evaluate efficacy and safety of piroxicam and tramadol in post-caesarean section pain. Materials and Methods Primigravidae who underwent elective caesarean section received either piroxicam 20mg or tramadol 100mg intra-muscularly, following recovery from anaesthesia. Severity of pain was assessed using Visual Analogue Scale (VAS) and side-effects to study drugs were noted. Rescue analgesic butorphanol 2mg was administered if VAS score was more than four. Patient’s satisfaction score was assessed at 12 hours post-operatively. Results Mean age in piroxicam and tramadol groups were 23.32±3.43 and 22.03±2.0 years respectively. Significant reduction in pain was observed at 2, 4, 8, 12 and 24 hours in both groups (p<0.001). Pain relief was significant at 2, 4 and 8 hours in piroxicam group compared to tramadol. Twenty-one and 12 patients in tramadol and piroxicam groups received rescue analgesic respectively. Sedation and nausea was significantly higher in tramadol group (p<0.001), 46.66% of patients graded their satisfaction score as good and 15% as excellent in piroxicam group. Conclusion Intra-muscular piroxicam was effective in reducing post-caesarean section pain for 24 hours with minimal side-effects compared to tramadol. PMID:28050391

  20. The role of tramadol in pain management in Latin America: a report by the Change Pain Latin America Advisory Panel.

    PubMed

    Santos Garcia, Joäo Batista; Lech, Osvandré; Campos Kraychete, Durval; Rico, María Antonieta; Hernández-Castro, John Jairo; Colimon, Frantz; Guerrero, Carlos; Sempértegui Gallegos, Manuel; Lara-Solares, Argelia; Flores Cantisani, José Alberto; Amescua-Garcia, César; Guillén Núñez, María Del Rocío; Berenguel Cook, María Del Rosario; Jreige Iskandar, Aziza; Bonilla Sierra, Patricia

    2017-09-01

    Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol's role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol's high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics - mainly controlled drugs (classical opioids) - is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients.

  1. Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients

    PubMed Central

    Coller, Janet K; Michalakas, Jennifer R; James, Heather M; Farquharson, Aaron L; Colvill, Joel; White, Jason M; Somogyi, Andrew A

    2012-01-01

    AIMS To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine methadone and seven buprenorphine maintained subjects received a single 100 mg dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites. RESULTS The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012–0.103)] compared with those taking buprenorphine [0.192 (0.108–0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower in subjects taking methadone compared with buprenorphine (0.069 (0.044–0.093) and 0.126 (0.069–0.187), respectively, P= 0.04, probability score 0.19), M2 was significantly higher in subjects taking methadone compared with buprenorphine (0.048 (0.033–0.085) and 0.033 (0.014–0.049), respectively, P= 0.04, probability score 0.81). Tramadol was similar (0.901 (0.635–1.30) and 0.685 (0.347–1.04), respectively, P= 0.35, probability score 0.65). CONCLUSIONS Methadone inhibited the CYP2D6-mediated metabolism of tramadol to M1. Hence, as the degree of opioid analgesia is largely dependent on M1 formation, methadone maintenance patients may not receive adequate analgesia from oral tramadol. PMID:22369095

  2. Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy.

    PubMed

    Benitez, Marian E; Roush, James K; KuKanich, Butch; McMurphy, Rose

    2015-09-01

    To evaluate the pharmacokinetics of hydrocodone (delivered in combination with acetaminophen) and tramadol in dogs undergoing tibial plateau leveling osteotomy (TPLO). 50 client-owned dogs. Dogs were randomly assigned to receive tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) following TPLO with standard anesthetic and surgical protocols. Blood samples were collected for pharmacokinetic analysis of study drugs and their metabolites over an 8-hour period beginning after the second dose of the study medication. The terminal half-life, maximum serum concentration, and time to maximum serum concentration for tramadol following naïve pooled modeling were 1.56 hours, 155.6 ng/mL, and 3.90 hours, respectively. Serum concentrations of the tramadol metabolite O-desmethyltramadol (M1) were low. For hydrocodone, maximum serum concentration determined by naïve pooled modeling was 7.90 ng/mL, and time to maximum serum concentration was 3.47 hours. The terminal half-life for hydrocodone was 15.85 hours, but was likely influenced by delayed drug absorption in some dogs and may not have been a robust estimate. Serum concentrations of hydromorphone were low. The pharmacokinetics of tramadol and metabolites were similar to those in previous studies. Serum tramadol concentrations varied widely, and concentrations of the active M1 metabolite were low. Metabolism of hydrocodone to hydromorphone in dogs was poor. Further study is warranted to assess variables that affect metabolism and efficacy of these drugs in dogs.

  3. [A prospective, randomized, double-blinded control study on comparison of tramadol, clonidine and dexmedetomidine for post spinal anesthesia shivering].

    PubMed

    Venkatraman, Rajagopalan; Karthik, Krishnamoorthy; Pushparani, Anand; Mahalakshmi, Annadurai

    2017-05-22

    Shivering, a common intraoperative problem under spinal anesthesia increases the oxygen consumption considerably and is uncomfortable and distressing to the patient, anesthesiologist as well as surgeon. The present study was designed to explore the effectiveness of tramadol, clonidine and dexmedetomidine in the treatment of post spinal anesthesia shivering and to look for their adverse effects. This prospective, randomized, double blinded control study was done on 90 patients who developed shivering under spinal anesthesia. They were randomly allocated into three groups with Group T receiving tramadol 1mg.kg(-1), Group C getting clonidine 1mcg.kg(-1) and Group D patients receiving dexmedetomidine 0.5mcg.kg(-1). The time taken to control shivering, recurrence rate, hemodynamic variables, sedation score and adverse effects were observed. Dexmedetomidine was faster in the control of shivering in 5.7±0.79minutes (min) whereas tramadol took 6.76±0.93min and clonidine was slower with 9.43±0.93min. The recurrence rate was much lower in the dexmedetomidine group with 3.3% than for clonidine (10%) and tramadol (23.3%) group. The sedation achieved with dexmedetomidine was better than clonidine and tramadol. The tramadol group had more cases of vomiting (four) and dexmedetomidine group had six cases of hypotension and two cases of bradycardia. Two of the clonidine patients encountered bradycardia and hypotension. Dexmedetomidine is better than tramadol and clonidine in the control of shivering because of its faster onset and less recurrence rate. Though complications are encountered in the dexmedetomidine group, they are treatable. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Comparison between IV Paracetamol and Tramadol for Postoperative Analgesia in Patients Undergoing Laparoscopic Cholecystectomy

    PubMed Central

    Singh, Vivek

    2016-01-01

    Introduction Efforts to use safer drug with minimal side effects for postoperative analgesia are growing day by day for surgeries of shorter duration or which may require day care only, search for ideal agent has been a never ending process. Aim The aim of the present study was to compare the efficacy of intravenous Paracetamol and Tramadol for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Materials and Methods This study was done at Department of Anaesthesiology, Era’s Medical College, Lucknow, India. Sixty ASA-I or II patients between 18-55 years of age, scheduled for laparoscopic cholecystectomy were randomly allocated to two groups of 30 each. Group A received IV infusion of paracetamol 1g in 100 ml solution, while Group B received IV infusion of Tramadol 100 mg in 100 ml NS at 0 (first complain of pain postoperatively), 6, 12 and 18 hours respectively. Pain intensity was measured by a 10 point Visual Analogue Scale (0→no pain and 10→worst imaginable pain) VAS at T(0)→just before analgesic administration, at 0.5, 1.5, 3, 6, 12, 18 and 24 hours thereafter, in addition to HR, SBP, DBP. Statistical Analysis: Chi-square test, Student t-test and p-values <0.05 was considered significant. Results During postoperative follow-up intervals, paracetamol showed significantly lower VAS scores as compared to tramadol at 1.5 hour, 3 hour, 6 hour, 12 hour and 24 hour follow up intervals. One patient in tramadol group had nausea postoperatively (p>0.05). No adverse effect attributable to paracetamol was noticed. Conclusion Intravenous Paracetamol can be advocated as an effective and safe analgesic agent for postoperative pain relief. PMID:27656532

  5. The effect of tramadol plus paracetamol on consumption of morphine after coronary artery bypass grafting.

    PubMed

    Altun, Dilek; Çınar, Özlem; Özker, Emre; Türköz, Ayda

    2017-02-01

    To compare the effects of oral tramadol+paracetamol combination on morphine consumption following coronary artery bypass grafting (CABG) in the patient-controlled analgesia (PCA) protocol. A prospective, double-blind, randomized, clinical study. Single-institution, tertiary hospital. Fifty cardiac surgical patients undergoing primary CABG surgery. After surgery, the patients were allocated to 1 of 2 groups. Both groups received morphine according to the PCA protocol after arrival to the coronary intensive care unit (bolus 1 mg, lockout time 15 minutes). In addition to morphine administration 2 hours before operation and postoperative 2nd, 6th, 12th, 18th, 24th, 30th, 36th, 42th, and 48th hours, group T received tramadol+paracetamol (Zaldiar; 325 mg paracetamol, 37.5 mg tramadol) and group P received placebo. Sedation levels were measured with the Ramsay Sedation Scale, whereas pain was assessed with the Pain Intensity Score during mechanical ventilation and with the Numeric Rating Scale after extubation. If the Numeric Rating Scale score was ≥3 and Pain Intensity Score was ≥3, 0.05 mg/kg morphine was administered additionally. Preoperative patient characteristics, risk assessment, and intraoperative data were similar between the groups. Cumulative morphine consumption, number of PCA demand, and boluses were higher in group P (P<.01). The amount of total morphine (in mg) used as a rescue analgesia was also higher in group P (5.06±1.0), compared with group T (2.37±0.52; P<.001). The patients who received rescue doses of morphine were 8 (32%) in group T and 18 (72%) in group P (P<.001). Duration of mechanical ventilation in group P was longer than group T (P<.01). Tramadol+paracetamol combination along with PCA morphine improves analgesia and reduces morphine requirement up to 50% after CABG, compared with morphine PCA alone. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Spectrophotometric and spectrofluorimetric methods for analysis of tramadol, acebutolol and dothiepin in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Abdellatef, Hisham E.; El-Henawee, Magda M.; El-Sayed, Heba M.; Ayad, Magda M.

    2006-12-01

    Sensitive spectrophotometric and spectrofluorimetric methods are described for the determination of tramadol, acebutolol and dothiepin (dosulepin) hydrochlorides. The two methods are based on the condensation of the cited drugs with the mixed anhydrides of malonic and acetic acids at 60 °C for 25-40 min. The coloured condensation products are suitable for the spectrophotometric and spectrofluorimetric determination at 329-333 and 431-434 nm (excitation at 389 nm), respectively. For the spectrophotometric method, Beer's law was obeyed from 0.5 to 2.5 μg ml -1 for tramadol, dothiepin and 5-25 μg ml -1 for acebutolol. Using the spectrofluorimetric method linearity ranged from 0.25 to 1.25 μg ml -1 for tramadol, dothiepin and 1-5 μg ml -1 for acebutolol. Mean percentage recoveries for the spectrophotometric method were 99.68 ± 1.00, 99.95 ± 1.11 and 99.72 ± 1.01 for tramadol, acebutolol and dothiepin, respectively and for the spectrofluorimetric method, recoveries were 99.5 ± 0.844, 100.32 ± 0.969 and 99.82 ± 1.15 for the three drugs, respectively. The optimum experimental parameters for the reaction has been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drugs in their pharmaceutical preparations with good recoveries. The procedures were accurate, simple and suitable for quality control application.

  7. Frequency of Electrocardiographic Abnormalities in Tramadol Poisoned Patients; a Brief Report

    PubMed Central

    Alizadeh Ghamsari, Anahita; Dadpour, Bita; Najari, Fares

    2016-01-01

    Introduction: Previous studies have raised the probably of cardiac manifestation in tramadol poisoning. However, conclusive information on electrocardiographic (ECG) abnormalities of tramadol overdose remains to be explained. Therefore, the present study aimed to evaluate the epidemiology of ECG abnormalities in tramadol poisoned patients. Methods: In a prospective cross-sectional study, all patients with tramadol poisoning, who were admitted to the emergency department of Loghman Hospital during 2012 – 2013, were evaluated. Patients’ baseline characteristics and ECG findings including axis, rate, rhythm, PR interval, QRS duration, QTc interval, evidence of Brugada pattern, and evidence of blocks were recorded. Obtained Data were descriptively analyzed using SPSS 21.0 statistical software. Results: 1402 patients with the mean age of 24 ± 6 years were studied (71.1% male). Sinus tachycardia was detected in 463 (33%) patients, sinus bradycardia in one patient (0.07%), right axis deviation in 340 (24.2), QRS widening in 91 (6.5%), long QTc interval in 259 (18.4%), dominant S wave in either I or aVL lead in 395 (28.1%), and right bundle branch block in 73 (5.2%). Increased PR interval was not detected in any cases. The evidence of Brugada pattern was observed in 2 (0.14%) patients (100% male), both symptomatized with seizure. All abnormalities had same sex distribution. Conclusion: Based on the results of the present study, the most common types of ECG changes were sinus tachycardia, a deep S wave in leads I and aVL, right axis deviation, and long QTc interval, respectively. Brugada pattern and sinus bradycardia were rarely presented. PMID:27299145

  8. Comparison of tramadol and lornoxicam in intravenous regional anesthesia: a randomized controlled trial.

    PubMed

    Çelik, Hande; Abdullayev, Ruslan; Akçaboy, Erkan Y; Baydar, Mustafa; Göğüş, Nermin

    2016-01-01

    Tourniquet pain is one of the major obstacles for intravenous regional anesthesia. We aimed to compare tramadol and lornoxicam used in intravenous regional anesthesia as regards their effects on the quality of anesthesia, tourniquet pain and postoperative pain as well. After the ethics committee approval 51 patients of ASA physical status I-II aged 18-65 years were enrolled. The patients were divided into three groups. Group P (n = 17) received 3mg/kg 0.5% prilocaine; group PT (n = 17) 3mg/kg 0.5% prilocaine + 2 mL (100mg) tramadol and group PL (n = 17) 3mg/kg 0.5% prilocaine + 2 mL (8 mg) lornoxicam for intravenous regional anesthesia. Sensory and motor block onset and recovery times were noted, as well as tourniquet pains and postoperative analgesic consumptions. Sensory block onset times in the groups PT and PL were shorter, whereas the corresponding recovery times were longer than those in the group P. Motor block onset times in the groups PT and PL were shorter than that in the group P, whereas recovery time in the group PL was longer than those in the groups P and PT. Tourniquet pain onset time was shortest in the group P and longest in the group PL. There was no difference regarding tourniquet pain among the groups. Group PL displayed the lowest analgesic consumption postoperatively. Adding tramadol and lornoxicam to prilocaine for intravenous regional anesthesia produces favorable effects on sensory and motor blockade. Postoperative analgesic consumption can be decreased by adding tramadol and lornoxicam to prilocaine in intravenous regional anesthesia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  9. [Comparison of tramadol and lornoxicam in intravenous regional anesthesia: a randomized controlled trial].

    PubMed

    Çelik, Hande; Abdullayev, Ruslan; Akçaboy, Erkan Y; Baydar, Mustafa; Göğüş, Nermin

    2016-01-01

    Tourniquet pain is one of the major obstacles for intravenous regional anesthesia. We aimed to compare tramadol and lornoxicam used in intravenous regional anesthesia as regards their effects on the quality of anesthesia, tourniquet pain and postoperative pain as well. After the ethics committee approval 51 patients of ASA physical status I-II aged 18-65 years were enrolled. The patients were divided into three groups. Group P (n=17) received 3mg/kg 0.5% prilocaine; group PT (n=17) 3mg/kg 0.5% prilocaine+2mL (100mg) tramadol and group PL (n=17) 3mg/kg 0.5% prilocaine+2mL (8mg) lornoxicam for intravenous regional anesthesia. Sensory and motor block onset and recovery times were noted, as well as tourniquet pains and postoperative analgesic consumptions. Sensory block onset times in the groups PT and PL were shorter, whereas the corresponding recovery times were longer than those in the group P. Motor block onset times in the groups PT and PL were shorter than that in the group P, whereas recovery time in the group PL was longer than those in the groups P and PT. Tourniquet pain onset time was shortest in the group P and longest in the group PL. There was no difference regarding tourniquet pain among the groups. Group PL displayed the lowest analgesic consumption postoperatively. Adding tramadol and lornoxicam to prilocaine for intravenous regional anesthesia produces favorable effects on sensory and motor blockade. Postoperative analgesic consumption can be decreased by adding tramadol and lornoxicam to prilocaine in intravenous regional anesthesia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Fentanyl versus tramadol with levobupivacaine for combined spinal-epidural analgesia in labor

    PubMed Central

    Chatrath, Veena; Khetarpal, Ranjana; Sharma, Sujata; Kumari, Pratibha; Sudha; Bali, Kusum

    2015-01-01

    Background: Neuraxial labor analgesia using new local anesthetics such as levobupivacaine has become very popular by virtue of the safety and lesser motor blockade caused by these agents. Combined spinal-epidural analgesia (CSEA) has become the preferred method for labor analgesia as it combines benefits of both spinal analgesia and flexibility of the epidural catheter. Adding opioids to local anesthetic drugs provide rapid onset and prolonged analgesia but may be associated with several maternal and fetal adverse effects. The purpose of this study is to compare fentanyl and tramadol used in CSEA in terms of duration of analgesia and frequency of the adverse fetomaternal outcome. Materials and Methods: A total of 60 primiparas with a singleton pregnancy in active labor were given CSEA after randomly allocating them in two groups of 30 each. Group I received intrathecal 2.5 mg levobupivacaine + 25 μg fentanyl followed by epidural top ups of 20 ml 0.125% solution of the same combination. Group II received 25 mg tramadol instead of fentanyl. Epidural top ups were given when parturient complained of two painful contractions (visual analogue scale ≥ 4). Data collected were demographic profile of the patients, analgesic qualities, side- effects and the fetomaternal outcome. Results: Patients in Group II had significantly prolonged analgesia (145 ± 9 minutes) than in Group I (95 ± 7 minutes). Patients receiving fentanyl showed rapid onset of analgesia, but there were more incidence of side-effects like shivering, pruritus, transient fetal bradycardia, hypotension, nausea and vomiting. Only side-effect in the tramadol group was nausea and vomiting. During labor, maternal satisfaction was excellent. Conclusions: Adding tramadol to local anesthetic provides prolonged analgesia with minimal side effects. Fentanyl, when used as adjuvant to local anesthetic, has a rapid onset of analgesia but has certain fetomaternal side-effects. PMID:26240543

  11. Intrathecal ropivacaine with or without tramadol for lower limb orthopedic surgeries

    PubMed Central

    Salhotra, Rashmi; Mohta, Medha; Agarwal, Deepti; Sethi, Ashok K.

    2016-01-01

    Background and Aim: Preservative free tramadol has been used as an adjuvant to intrathecal bupivacaine. However, the effect of the addition of tramadol on intrathecal isobaric ropivacaine has never been studied. Material and Methods: This prospective, randomized, double-blind study was conducted in 50 adult male American Society of Anesthesiologists grade I or II patients, aged 18–60 years, being operated for unilateral femur fractures. An epidural catheter was inserted in L2-L3 interspace and subarachnoid block was given in L3-L4 space. The patients were randomized to receive 0.5 mL normal saline (group R) or 0.5 mL (25 mg) preservative free tramadol (group RT) with 2.5 mL of 0.75% intrathecal ropivacaine. Hemodynamic parameters, sensory level, motor block, sedation and side-effects were recorded. Statistical analysis was done using Student's t-test, Chi-square test, Fischer's exact test and repeated measures ANOVA. Results: The time of sensory block onset was 9.2 ± 4.9 min and 8.6 ± 5.3 min (P = 0.714) in group R and group RT, respectively. The motor block onset was also comparable in both the groups (P = 0.112). The duration of sensory block was 147.2 ± 37.4 min in group R and 160.4 ± 40.9 min in group RT (P = 0.252). The median maximum block height achieved in both the groups was T6 and the time to achieve the maximum block was also comparable statistically (P = 0.301). Conclusion: The addition of intrathecal tramadol 25 mg to the isobaric ropivacaine does not alter the block characteristics produced by intrathecal ropivacaine alone. PMID:28096579

  12. Comparison of lornoxicam and low-dose tramadol for management of post-thyroidectomy pain.

    PubMed

    Yücel, Ali; Yazıcı, Alper; Müderris, Togay; Gül, Fatih

    2016-10-01

    The present study sought to compare the analgesic efficacy and adverse effects of intravenous (IV) lornoxicam and tramadol to investigate if lornoxicam is a reasonable alternative to a weak opioid for post-thyroidectomy pain. Fifty patients of American Society of Anesthesiologists class I or II, 18 to 65 years of age, and who underwent thyroidectomy were assigned to 2 groups in a randomized manner. Group L received 8 mg of lornoxicam IV and Group T received 1 mg/kg of tramadol IV at conclusion of the operation. Pain intensity of patients was recorded at 15 and 30 minutes, and at 1, 2, 3, 4, 6, 12, and 24 hours after the initial dose with Numerical Rating Scale (NRS) and Ramsey Sedation Scale. Electrocardiogram, heart rate, systolic/diastolic and average artery pressure and peripheral oxygen saturations were monitored continuously during this period. Patients completed satisfaction questionnaires at 24th hour. Both drugs produced acceptable analgesia; however, significantly fewer patients reported 1 or more adverse events with lornoxicam than with tramadol. Most commonly seen in Group T was nausea/vomiting. NRS scores at 15 minutes, 30 minutes, and 1 hour were lower in Group L than in Group T (p<0.05), but there was no significant difference between groups after postoperative first hour. First analgesic requirement time was significantly longer in Group L compared to Group T (p<0.001). No serious complications were seen in either group. Lornoxicam is a safe and effective analgesic that may be used with fewer complications than low-dose tramadol for treatment of moderate to severe postoperative pain.

  13. Characterizing the Toxicity and Dose-Effect Profile of Tramadol Ingestions in Children.

    PubMed

    Stassinos, Gina L; Gonzales, Lawrence; Klein-Schwartz, Wendy

    2017-02-21

    Tramadol can cause life-threatening toxicity in overdose; however, data on its toxicity in children are lacking. This study investigates toxicity associated with tramadol ingestions in children. The hypothesis is that children will experience dose-related central nervous system and respiratory depression and seizures. A retrospective evaluation of cases from the National Poison Center Data System between January 1, 2000, and December 31, 2013, was performed. Inclusion criteria were age below 6 years and single-substance acute tramadol ingestion. For dose-effect analysis, cases with sufficient dose quantity information were included. There were 7334 cases that met inclusion criteria. Outcomes were 84.8% no effect, 12.6% minor, 2.2% moderate, and 0.4% major effect. There was 1 fatality. Most of the children (36.4%) were treated/released from the emergency department; other management sites were home (36.4%), admission (5.9%), and others (3.2%). In the 1115 children with symptoms, drowsiness (N = 611) and vomiting (N = 178) occurred most frequently. More serious clinical effects included respiratory depression in 36 and seizures in 24 children. Of 2772 children with milligram dose recorded, there were 10 cases of respiratory depression and 6 of seizure. Median doses for respiratory depression and seizure were 225 (range, 50-600 mg) and 525 mg (range, 50-1050 mg), respectively. The minimum weight-based dose for respiratory depression/arrest was 7.9 mg/kg and for seizures, 4.8 mg/kg. Seizure and respiratory depression are uncommon in pediatric tramadol ingestions. Given the small number of patients with dose data and lack of laboratory confirmation of dose, more studies are needed to determine the minimum dose at which medical management is recommended.

  14. [Comparison of the action of 2 effective analgesics. Experimental study: tramadol versus tilidine/naloxone].

    PubMed

    Bromm, B; Herrmann, W M; Scharein, E

    1989-06-10

    In the present study involving healthy test subjects, tilidin/naloxone (Valoron N; VAL) proved to have an analgesic effect roughly twice as pronounced as that of tramadol (TRA). Moreover, the analgesic effect of VAL showed a significantly more rapid onset than did that of TRA. This finding reflects the difference in rate of action of the active substances. In accordance with these findings, VAL is thus the most powerful analgesic presently available on the German market on simple prescription.

  15. Design, development and in vitro-in vivo study of tramadol-paracetamol inlay tablets.

    PubMed

    Kotta, Sabna; Bijumol, C; Anitha, Y; Dileep, K J; Valsala, Kumari

    2014-02-01

    The objective of this work is to formulate, optimize and evaluate in-lay tablets of tramadol-paracetamol. This study investigated the effect of hydrophobic, plastic and hydrophilic types of polymers and their content level on release profile of a highly water-soluble drug tramadol hydrochloride. A 3(2) full factorial design was employed for the optimization of the sustained release (SR) formula of tramadol hydrochloride using ethyl cellulose, eudragit and carbopol. CP9 (66% carbopol and compression load of 6 ton) with a percentage drug release of 89.03 after 12 hours were found to be most comparable to the marketed product in terms of similarity factor and most appropriately fits to zero-order kinetics. Hence, it was selected for in vivo study. Statistical analysis of in vivo studies showed that the plasma drug level after oral administration from the prepared formulation is almost comparable to the marketed product (p < 0.05). Pharmacokinetic analysis of the optimized tablet formulation CP9 were done to find out relevant pharmacokinetic parameters. The results showed that Cmax, tmax, AUC, AUMC, MRT were comparable to the marketed preparation. The formulation exhibited a good in vitro-in vivo correlation (r(2) = 0.971).

  16. Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy.

    PubMed

    Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M

    2013-08-01

    The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. A comparative study of the effect of clonidine and tramadol on post-spinal anaesthesia shivering

    PubMed Central

    Shukla, Usha; Malhotra, Kiran; Prabhakar, T

    2011-01-01

    The aim of this study was to evaluate the efficacy, potency and side effects of clonidine as compared to tramadol in post–spinal anaesthesia shivering. In this prospective double-blind randomized controlled clinical trial, 80 American Society of Anaesthesiologists grade-l (ASAI) patients aged between 18 and 45 years scheduled for various surgical procedures under spinal anaesthesia, who developed shivering were selected.The patients were divided into two groups: Group C (n=40) comprised of patients who received clonidine 0.5mg/kg intravenously (IV) and group patients who received tramadol 0.5 mg/kg IV. Grade of shivering, disappearance of shivering, haemodynamics and side effects were observed at scheduled intervals. Disappearance of shivering was significantly earlier in group C (2.54±0.76) than in group T (5.01±1.02) (P=.0000001). Response rate to treatment in group C was higher (97.5%) than in group T (92.5%), but the difference was not significant. Nausea, vomiting and dizziness were found to be higher in group T (P=0.001, 0.005, 0.001, respectively), while the patients in group C were comparatively more sedated (sedation level, 2; group C, 25%). We conclude that clonidine gives better thermodynamics than tramadol, with fewer side effects. PMID:21808395

  18. Comparative receptor based brain delivery of tramadol-loaded poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Lalani, Jigar; Raichandani, Yogesh; Mathur, Rashi; Lalan, Manisha; Chutani, Krishna; Mishra, Anil Kumar; Misra, Ambikanandan

    2012-12-01

    Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf). Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker. Prepared nanoparticles were characterized for their size, surface charge, drug entrapment, transmission electron microscopy and in vitro drug release. The surface density of Tf and Lf was estimated by protein estimation. The drug distribution in blood, brain and other tissues was studied in mice after intravenous administration. Tf and Lf anchored nanoparticles exhibit enhanced uptake with 2.38 and 3.85 folds higher targeting respectively in the brain when compared with unconjugated nanoparticles. The brain targeting observed for Lf anchored PLGA nanoparticles (Lf-TMD-PLGA-NP) was 1.62 folds that of Tf anchored PLGA nanoparticles (Tf-TMD-PLGA-NP). Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.

  19. Designing and characterizing of tramadol hydrochloride transdermal patches prepared with Ficus carica fruit mucilage and povidone.

    PubMed

    Ahad, Hindustan Abdul; Ishaq, Beludari Mohammed; Shaik, Muneer; Bandagisa, Faheem

    2016-05-01

    The purpose of this investigation was to prepare matrix type transdermal patches of Tramadol HCl using various ratios of Ficus carica fruit mucilage and Povidone. The matrix type transdermal patches were prepared using Tramadol HCl with Ficus carica fruit mucilage and Povidone. The interactions between Tramadol HCl with F. carica fruit mucilage and Povidone were performed by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The prepared patches were examined for physicochemical characterization and in vitro drug permeation studies (using a Keshary-Chien diffusion cell across hairless Albino rat skin), skin irritation studies and accelerated stability studies. The drug was found to be free from negligible interactions with the polymers used. The formulated patches possessed satisfactory physicochemical properties, in vitro drug permeation and devoid of serious skin irritation. The selected formulation (F-5) was retains the characteristics even after the accelerated environmental conditions. The study concludes that F. carica fruit mucilage with Povidone is a good combination for preparing transdermal patches.

  20. Antihyperalgesic effects of clomipramine and tramadol in a model of posttraumatic trigeminal neuropathic pain in mice.

    PubMed

    Alvarez, Pedro; Brun, Aurore; Labertrandie, Anaïs; Lopez, José; Correa, Alejandro; Constandil, Luís; Hernández, Alejandro; Pelissier, Teresa

    2011-01-01

    To develop a behavioral model in mice that is capable of mimicking some distinctive symptoms of human posttraumatic trigeminal neuropathic pain such as spontaneous pain, cold allodynia, and chemical÷inflammatory hyperalgesia, and to use this model to investigate the antinociceptive effects of clomipramine and tramadol, two drugs used for the treatment of neuropathic pain. A partial tight ligature of the right infraorbital nerve by an intraoral access or a sham procedure was performed. Fourteen days later, mice were subcutaneously injected with saline or drugs and the spontaneous nociceptive behavior, as well as the responses to topical acetone and to formalin or capsaicin injected into the ipsilateral vibrissal pad, were assessed. Data were analyzed by ANOVA. Neuropathic mice exhibited an increased spontaneous rubbing÷scratching of the ipsilateral vibrissal pad, together with enhanced responses to cooling (acetone) and the chemical irritants (formalin, capsaicin). Clomipramine and tramadol produced an antihyperalgesic effect on most of these nociceptive responses, but tramadol was ineffective on capsaicin-induced hyperalgesia. Nociceptive responses in this neuropathic pain model in mice exhibited a pattern consistent with the pain described by posttraumatic trigeminal neuropathic patients. The selective antihyperalgesic effect obtained with two commonly used drugs for treating neuropathic pain confirms the validity of this preclinical model.

  1. Preemptive analgesic effectiveness of oral ketorolac plus local tramadol after impacted mandibular third molar surgery.

    PubMed

    Isiordia-Espinoza, Mario A; Pozos-Guillén, Amaury J; Martínez-Rider, Ricardo; Herrera-Abarca, Jorge E; Pérez-Urizar, José

    2011-09-01

    The aim of this study was to compare preemptive analgesia of oral ketorolac plus submucous local placebo with oral ketorolac plus submucous local tramadol after impacted mandibular third molar surgery. A double-blind, randomized, placebo-controlled clinical trial was conducted. Patients were randomized into two treatment groups (n = 15 per group): group A, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local placebo (1 mL saline solution); group B, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local tramadol (50 mg diluted in 1 mL saline solution). We evaluated the intensity of pain, time for the first analgesic rescue medication, and total analgesic consumption. Pain intensity, number of patients requiring analgesic rescue medication, number of patients in each group not requiring analgesic rescue medication, and total analgesic consumption showed statistical significance. Preemptive use of oral ketorolac plus submucous local tramadol is an alternative treatment for acute pain after surgical removal of an impacted mandibular third molar.

  2. Use of tramadol in psychiatric care: A comprehensive review and report of two cases.

    PubMed

    Rougemont-Bücking, Ansgar; Gamma, Franziska; Panksepp, Jaak

    2017-05-10

    Tramadol is widely prescribed for treating acute and chronic forms of pain. It is a weak mu-receptor opioid agonist and also increases concentrations of serotonin and noradrenaline within the limbic system of the brain. The therapeutic range of tramadol is relatively wide. Compared with other opioid agonists, there is little risk for developing tolerance and for abuse. Recent models of depression emphasise the subjective experience of a depressive mood as being, in part, a psychologically painful state. It is well established that psychological stress due to social separation/loss, disruption or be-trayal of pre-existent significant interpersonal bonds is mediated by the activation of the mammalian PANIC (separation-distress) system. It is also known that this kind of stress can be soothed very effectively by very low doses of endogenous or exogenous opioid receptor agonists. These observations raise the question of whether tramadol can be an effective and safe treat-ment option for some forms of anxiety and depression in which elements of social loss or betrayal are in-volved. In support of this possibility, two clinical cases are presented, and ideas for development of new ap-proaches targeting the endogenous opioidergic system in clinical practice are discussed.

  3. Comparative analysis of preemptive analgesic effect of tramadol chlorhydrate and nimesulide following third molar surgery.

    PubMed

    da Costa Araújo, Fábio Andrey; de Santana Santos, Thiago; de Morais, Hécio Henrique Araújo; Laureano Filho, José Rodrigues; de Oliveira E Silva, Emanuel Dias; Vasconcellos, Ricardo José Holanda

    2012-12-01

    The aim of this prospective, randomized, controlled, paired trial was to perform a comparative analysis of the preemptive analgesic effect of nimesulide and tramadol chlorhydrate during third molar surgery. The study was carried out between March and November 2009, involving 94 operations in 47 male and female patients with bilateral impacted lower third molars in comparable positions. The sample was divided into two groups. Group A received an oral dose of 100 mg of nimesulide 1 h prior to surgery. Group B received an oral dose of 100 mg of tramadol chlorhydrate 1 h prior to surgery. The following aspects were evaluated in the postoperative period: adverse effects of the drugs; amount of rescue medication used (acetaminophen 750 mg); and pain 5, 6, 24, 36, 48, 60, 72 and 84 h after surgery using a visual analog pain scale. Peak pain occurred 5 h after surgery in both groups, with a mean pain score of 2.3 in Group A and 3.0 in Group B; this difference did not achieve statistical significance (p > 0.141). Based on the sample studied, nimesulide and tramadol chlorhydrate demonstrate similar preemptive analgesic effects when used in lower third molar surgeries.

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

    PubMed Central

    Cardozo, Alejandro; Silva, Carlos; Dominguez, Luis; Botero, Beatriz; Zambrano, Paulo; Bareno, Jose

    2014-01-01

    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 five 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. PMID:25548601

  5. Development and validation of a new GC-MS method for the detection of tramadol, O-desmethyltramadol, 6-acetylmorphine and morphine in blood, brain, liver and kidney of Wistar rats treated with the combination of heroin and tramadol.

    PubMed

    Mahdy, Tarek; El-Shihi, Taha H; Emara, Mostafa M; Chericoni, Silvio; Giusiani, Mario; Giorgi, Mario

    2012-10-01

    Heroin is one of the most dangerous abused drugs in the world. Tramadol is an additive recently found at high concentration levels in street heroin seizures in Egypt. This substance could affect the usual analytical method for the detection of heroin and metabolites, as well as the pharmacokinetic and disposition of single analytes. One shortfall regarding this issue is present in the literature. This study describes a validated, simple, sensitive and selective method to determine tramadol, O-desmethyltramadol, 6-acetylmorphine and free morphine in the blood, brain, liver and kidney of Wistar rats, intraperitoneally treated with a combination of heroin and tramadol (10 and 70 mg/kg, respectively) using liquid-liquid extraction and gas chromatography-mass spectrometry detection. The calibration curves of tramadol, O-desmethyltramadol and 6-acetylmorphine in blood were linear in the concentration range from 25-5,000 ng/mL and morphine was found in the concentration range 50-5,000 ng/mL. The analytes were detected in all tested matrices, except 6-acetylmorphine, which was not detected in liver. The highest concentrations of tramadol and O-desmethyltramadol were observed in kidney (22,9381 and 28,498 ng/g), while 6-acetylmorphine and morphine were found at the highest levels in brain (3,280 and 3,899 ng/g, respectively). The present method is simple, rapid and sensitive and can be used to study the pharmacokinetics, disposition and interaction of these drugs in several animal models.

  6. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment.

    PubMed

    Zhou, Xiao; Liu, Ji

    2015-01-01

    This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval) of the test drug/reference drug for tramadol were 100.2% (95.3%-103.4%) for the area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration, 99.6% (94.2%-102.7%) for the AUC from administration to infinite time, and 100.8% (93.1%-106.4%) for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules) were bioequivalent.

  7. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

    PubMed Central

    Zhou, Xiao; Liu, Ji

    2015-01-01

    This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval) of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4%) for the area under the plasma concentration–time curve (AUC) from time zero to the last measurable concentration, 99.6% (94.2%–102.7%) for the AUC from administration to infinite time, and 100.8% (93.1%–106.4%) for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules) were bioequivalent. PMID:25750519

  8. Gas chromatography-mass spectrometry designation and prediction of metabolic dealkylation and hydroxylation reactions in xenobiotics exemplified by tramadol.

    PubMed

    El-Haj, Babiker; Al-Amri, Abdulkader; Ali, Heyam

    2009-01-01

    Metabolic dealkylation and hydroxylation reactions in xenobiotics are common and may take place at different sites in the molecules. Sometimes confusion may arise as to the nature and site of the resulting metabolic change when there is more than one potential site. The use of GC-MS in resolving the problem has been demonstrated by using tramadol as example. Human urine samples containing tramadol and its metabolites were extracted under basic pH conditions and analyzed by GC-MS, in the electron impact and chemical ionization modes, before and after trimethylsilyl (TMS) derivatization. By recognizing the mass-to-charge ratios of molecular and base-peak ions in the mass spectra, it was possible to predict and designate sites of demethylation and hydroxylation in tramadol metabolites. In addition to the designation of the known tramadol metabolites, the practice has led to the tentative characterization of hydroxytramadol and norhydroxytramadol as new metabolites of tramadol in humans. Possible extension of the modus operandi to other xenobiotics was discussed.

  9. Colon specific drug delivery of tramadol HCl for chronotherapeutics of arthritis

    PubMed Central

    Kadiyam, Rajyalakshmi; Muzib, Y. Indira

    2015-01-01

    Objective: The objective of present work is to develop and evaluate a matrix system for Chronotherapeutic delivery of centrally acting of opioid analgesic (tramadol HCl) to treat nocturnal symptoms of arthritis using almond gum as carrier. Materials and Methods: Matrix tablets of tramadol HCl were prepared by using 30, 40, 50, 60 and 70% w/w of tablet of gum badam as carrier by wet granulation technique. These tablets were compression coated with eudragit S100 to prevent drug release in stomach. All formulations were evaluated for hardness, friability, weight variation, drug content, in vitro and in vivo studies. The almond gum was characterized by viscosity measurements and Fourier transform infrared analysis. The coated (FC1 to FC5) and uncoated tablets (F1 to F5) were evaluated for in vitro release of tramadol HCl after sequential exposure to pH 1.2, pH 7.4 and pH 6.8 respectively for 2 h, 3 h and 19 h in the absence as well as presence of rat caecal content and the corresponding data was fitted to popular release kinetic equations in order to evaluate the release mechanisms-kinetics. The selected formulation was subjected to in vivo targeting efficacy studies by roentgenography technique. Results and Discussion: In vitro release studies indicated that the matrix tablets (F1 to F5) failed to control the drug release in the physiological environment of stomach and small intestine. On the other hand, compression coated formulations were able to protect the tablet cores from premature drug release. Presence of rat caecal content enhances the drug release from the tablets as the concentration of polymer increased, drug release was found to be retarded. The release of tramadol from all the formulation followed zero order with non fickian diffusion. X-ray studies confirmed that the tablet successfully reached colon without getting disintegrated in upper gastrointestinal tract. Conclusion: Based on the results, selective delivery of tramadol HCl to the colon could be

  10. Tramadol chronic abuse: an evidence from hair analysis by LC tandem MS.

    PubMed

    Verri, Patrizia; Rustichelli, Cecilia; Palazzoli, Federica; Vandelli, Daniele; Marchesi, Filippo; Ferrari, Anna; Licata, Manuela

    2015-01-01

    Hair analysis, as complementary matrix, has expanded across the spectrum of toxicological investigations for misuse drug monitoring. Hair has become an important matrix for drug analysis, owing to the possibility to detect target analytes for long time periods, depending on hair length. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitation of tramadol, a widely used centrally acting analgesic, and its main metabolites in hair (ODMT, NDMT, NOT). Hair samples were decontaminated and incubated overnight in diluted hydrochloric acid; the extracts were purified by mixed-mode solid phase cartridges and analyzed by LC-MS/MS in positive ionization mode monitoring two transitions per analyte. The procedure was fully validated in terms of linearity, limit of detection and lower limit of quantitation (LLOQ), accuracy, precision, recovery, matrix effect and selectivity. The linear regression analysis was calibrated by deuterated internal standards; for all analytes, responses were linear over the range 0.04-40.00 ng/mg hair, with R(2) values of at least 0.995. The method offered satisfactory precision (RSD < 10%), accuracy (90-110%) and recovery (> 90%) values. The found LLOQ values for tramadol and metabolites were in the range 0.010-0.030 ng/mg hair. The proposed procedure was successfully applied to quantify tramadol and metabolites in real hair samples submitted to our laboratory: three cases of tramadol assumption within the therapeutic dosage (3 × 2 segments) and one case of tramadol abuse in a binge pattern (8 segments). The ranges found for TRAM, ODMT, NDMT and NOT were markedly higher in the abuse case (63.42-107.30, 3.76-6.26, 24.88-45.66, 0.22-1.18 ng/mg hair, respectively) compared to the other case reports (3.29-20.12, 0.28-1.87, 0.45-4.32, 0.07-0.80 ng/mg, respectively); also the values of NMDT/ODMT ratio differed significantly. According to the obtained data, we hypothesized that the binge pattern may

  11. Metabolic Patterns of Fentanyl, Meperidine, Methylphenidate, Tapentadol and Tramadol Observed in Urine, Serum or Plasma.

    PubMed

    Wu, Fang; Slawson, Matthew H; Johnson-Davis, Kamisha L

    2017-05-01

    Drug testing is a useful tool to identify drug use or monitor adherence to prescription drugs. The interpretation of drug results can be complicated based on the pattern and proportional concentrations of drugs and/or drug metabolite(s). The purpose of this retrospective study was to detect the positivity rates and metabolic patterns of five prescription drugs, including fentanyl, meperidine, methylphenidate, tapentadol and tramadol. Retrospective data were retrieved from the laboratory information system in a national reference laboratory. Drug testing was performed using four mass spectrometry methods that were validated for clinical use. For urine specimens, the positivity rate was the highest for methylphenidate (62.3%, n = 2,489), followed by tramadol (43.7%, n = 3,483), fentanyl (41.9%, n = 4,657), tapentadol (37.9%, n = 736) and meperidine (8.3%, n = 138). Among positive samples, both parent drug and metabolite(s) was detectable in 94.9% of meperidine samples, 94.5% of tramadol samples, 93.8% of fentanyl samples, 89.9% of methylphenidate and 86.6% of tapentadol samples. For serum or plasma specimens, the positivity rate was the highest for tapentadol (75.0%, n = 39), followed by methylphenidate (74.2%, n = 569), fentanyl (53.6%, n = 113), meperidine (41.9%, n = 18) and tramadol (28.9%, n = 213). Similar metabolic patterns were found in serum or plasma. Of positive results, both parent drug and metabolite(s) were found in 94.7% of fentanyl samples, 83.3% of meperidine samples, 79.6% of methylphenidate samples, 53.8% of tapentadol samples and 44.1% of tramadol samples. Our data demonstrates the metabolic patterns of five drugs from a random urine or serum/plasma collection in patients that have been prescribed these medications. The data presented can be used to guide clinicians in determining drug adherence by assessing the positivity rates of the parent drug and corresponding metabolite(s). © The Author 2017. Published by Oxford University Press. All rights

  12. Influence of tramadol on acute thermal and mechanical cutaneous nociception in dogs.

    PubMed

    Schütter, Alexandra F; Tünsmeyer, Julia; Kästner, Sabine B R

    2017-03-01

    The aim of the study was to evaluate the influence of tramadol on acute nociception in dogs. Experimental, blinded, randomized, crossover study. Six healthy laboratory Beagle dogs. Dogs received three treatments intravenously (IV): isotonic saline placebo (P), tramadol 1 mg kg(-1) (T1) and tramadol 4 mg kg(-1) (T4). Thermal thresholds were determined by ramped contact heat stimulation (0.6 °C second(-1)) at the lateral thoracic wall. Mechanical thresholds (MT) were measured using a probe containing three blunted pins which were constantly advanced over the radial bone, using a rate of force increase of 0.8 N second(-1). Stimulation end points were defined responses (e.g. skin twitch, head turn, repositioning, vocalization) or pre-set cut-out values (55 °C, 20 N). Thresholds were determined before treatment and at predetermined time points up to 24 hours after treatment. At each measurement point, blood was collected for determination of O-desmethyltramadol concentrations. The degree of sedation and behavioural side effects were recorded. Data were analysed by one-way anova and two-way anova for repeated measurements. Thermal nociception was not influenced by drug treatment. Mechanical nociception was significantly increased between P and T1 at 120 and 240 minutes, and between P and T4 at 30, 60, 240 and 420 minutes. T1 and T4 did not differ. O-desmethyltramadol (M1) maximum plasma concentrations (Cmax) were 4.2±0.8 ng mL(-1) and 14.3±2.8 ng mL(-1) for T1 and T4, respectively. Times to reach maximum plasma concentrations (Tmax) were 27.6±6.3 minutes for T1 and 32.1±7.8 minutes for T4. No sedation occurred. There were signs of nausea and mild to moderate salivation in both groups. Tramadol was metabolized marginally to O-desmethyltramadol and failed to produce clinically relevant acute antinociception. Therefore, the use of tramadol for acute nociceptive pain is questionable in dogs. Copyright © 2017 Association of Veterinary Anaesthetists and

  13. "Weak" opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine.

    PubMed

    2016-02-01

    So-called weak opioid analgesics are often used to treat severe pain, or when paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) proves inadequate. But are weak opioids any more effective than paracetamol or NSAIDs on nociceptive pain, and are they better tolerated than morphine? To answer these questions, we conducted a review of literature using the standard Prescrire methodology. The potency of codeine and tramadol is strongly influenced by the cytochrome P450 isoenzyme CYP2D6 genotype, which varies widely from one person to another. This explains reports of overdosing or underdosing after administration of standard doses of the two drugs. The potency of morphine and that of buprenorphine, an opioid receptor agonist-antagonist, appears to be independent of CYP2D6 activity. All "weak" opioids can have the same dose-dependent adverse effects as morphine. There is no evidence that, at equivalent analgesic efficacy, weak opioids carry a lower risk of addiction than low-dose morphine. Respiratory depression can occur in ultrarapid metabolisers after brief exposure to standard doses of codeine or tramadol. Similar cases have been reported with dihydrocodeine in patients with renal failure. In addition, tramadol can cause a serotonin syndrome, hypoglycaemia, hyponatraemia and seizures. Several trials have compared different weak opioids in patients with post-operative pain. A single dose of a weak opioid, possibly combined with paracetamol, has greater analgesic efficacy than paracetamol alone but is not more effective than an NSAID alone. There is a dearth of evidence on weak opioids in patients with chronic pain. Available trials fail to show that a weak opioid has markedly superior analgesic efficacy to paracetamol or an NSAID. Sublingual buprenorphine at analgesic doses appears less likely to cause respiratory depression, but it seems to have weak analgesic efficacy. In practice, when opioid therapy is needed, there is no evidence that codeine

  14. The effect of ondansetron on the efficacy of postoperative tramadol: a systematic review and meta-analysis of a drug interaction.

    PubMed

    Stevens, A J; Woodman, R J; Owen, H

    2015-02-01

    Several studies have investigated the presence of a drug interaction between tramadol and ondansetron that reduced the efficacy of tramadol postoperatively. Most of these studies were small and the results inconsistent, so we performed a systematic review and meta-analysis of randomised controlled trials comparing the cumulative dose of tramadol administered by patient-controlled analgesia within the first 24 h after surgery between subjects receiving tramadol alone and those who received tramadol with ondansetron. Six studies, with a total of 340 participants, met the selection criteria and were included in the meta-analysis. There was an increased tramadol requirement in patients receiving ondansetron. The standardised mean difference in tramadol requirements, expressed in terms of standard deviations (95% CI), was 1.03 (0.54-1.53) (p < 0.001) at 4 h, 0.66 (0.06-1.25) (p = 0.03) at 8 h, 0.86 (0.41-1.31) (p < 0.001) at 12 h and 0.45 (0.01-0.90) (p = 0.046) at 24 h postoperatively, where the mean pooled standard deviations were 79.5, 157.7, 238.1 and 289.4 mg at 4, 8, 12 and 24 h, respectively. There was a significant linear time effect over the 24 h, indicating that the effect of ondansetron on tramadol consumption diminished with time. The results support the presence of a drug interaction between tramadol and ondansetron in the early postoperative period that potentially decreases the effectiveness of tramadol.

  15. [Combination Therapy of Pregabalin with Tramadol for Treatment of Peripheral Neuropathy in Patients with Gynecological Cancer Receiving Taxane Containing Chemotherapy].

    PubMed

    Nishikawa, Tadaaki; Hasegawa, Kosei; Shintani, Daisuke; Yano, Yuri; Sato, Sho; Yabuno, Akira; Kurosaki, Akira; Yoshida, Hiroyuki; Fujiwara, Keiichi

    2017-03-01

    Taxane-based regimens are often used in gynecologic cancer chemotherapy. Chemotherapy-induced peripheral neuropathy( CIPN)is one of the typical side effects caused by taxanes. Grade 2 or higher CIPN is observed in 5% to 30% of ovarian cancer patients who are treated with paclitaxel, which is recognized as one of the unmanageable side effects leading to treatment interruption. We retrospectively investigated the significance of combination therapy of pregabalin with tramadol for CIPN in patients with gynecological cancer. In the current study, 19 patients(19/22; 86%)were administered pregabalin with tramadol orally for at least 1week, and we observed improvement of the CIPN in 15 patients(15/19; 79%).We suggest that the combination therapy of pregabalin with tramadol has a positive impact on the CIPN in patients under a taxane-based chemotherapy.

  16. Comparing the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery.

    PubMed

    Jazayeri, Seyed Mohammad; Mosaffa, Faramarz; Abbasian, Mohammadreza; Hosseinzadeh, Hamid Reza

    2012-01-01

    Intra-articular analgesia is a pain reliever that is frequently administered following arthroscopic knee surgery. The purpose of this study was to compare the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery. For this randomized double blinded clinical trial, 132 patients undergoing minor arthroscopic knee surgery were randomly assigned to receive either; 5 mg morphine or 50 mg tramadol intra-articularly. Pain was evaluated by means of the verbal pain rating score (VRS) preoperatively (at rest and on movement of the knee joint) and postoperatively at 0, 1, 2, 3, 4, 6, 12 and 24 hours. Meanwhile, the time of the first analgesic request and need for supplemental analgesic were also recorded. There was no statistically significant difference in VRS scoring between the two groups during the preoperative period either at rest or on knee movement. Meanwhile, VRS scores did not differ significantly between the morphine and tramadol treated groups postoperatively, except for in the one-hour post-operative scores in which the tramadol-treated group experienced less pain (P < 0.007). Post-operative VRS scores at 6, 12, and 24 hours were significantly decreased when compared with previous scores in both morphine and tramadol prescribed subjects (P < 0.001), hence, both local analgesics can significantly reduce pain after minor knee surgery. We have found a postoperative analgesic effect of intra-articularly administered morphine and tramadol following minor arthroscopic knee surgeries with a maximum effect 6 hours post injection.

  17. The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder.

    PubMed

    Kim, Kyung-Hee; Suh, Jung-Woo; Oh, Ki Young

    2017-08-03

    Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.

  18. Comparing the Efficacy of Intra-Articular Application of Morphine and Tramadol on Postoperative Pain After Arthroscopic Knee Surgery

    PubMed Central

    Jazayeri, Seyed Mohammad; Mosaffa, Faramarz; Abbasian, Mohammadreza; Hosseinzadeh, Hamid Reza

    2012-01-01

    Background: Intra-articular analgesia is a pain reliever that is frequently administered following arthroscopic knee surgery. Objectives: The purpose of this study was to compare the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery. Patients and Methods: For this randomized double blinded clinical trial, 132 patients undergoing minor arthroscopic knee surgery were randomly assigned to receive either; 5 mg morphine or 50 mg tramadol intra-articularly. Pain was evaluated by means of the verbal pain rating score (VRS) preoperatively (at rest and on movement of the knee joint) and postoperatively at 0, 1, 2, 3, 4, 6, 12 and 24 hours. Meanwhile, the time of the first analgesic request and need for supplemental analgesic were also recorded. Results: There was no statistically significant difference in VRS scoring between the two groups during the preoperative period either at rest or on knee movement. Meanwhile, VRS scores did not differ significantly between the morphine and tramadol treated groups postoperatively, except for in the one-hour post-operative scores in which the tramadol-treated group experienced less pain (P < 0.007). Post-operative VRS scores at 6, 12, and 24 hours were significantly decreased when compared with previous scores in both morphine and tramadol prescribed subjects (P < 0.001), hence, both local analgesics can significantly reduce pain after minor knee surgery. Conclusions: We have found a postoperative analgesic effect of intra-articularly administered morphine and tramadol following minor arthroscopic knee surgeries with a maximum effect 6 hours post injection. PMID:24223330

  19. Use of oral tramadol to prevent perianesthetic shivering in patients undergoing transurethral resection of prostate under subarachnoid blockade

    PubMed Central

    Tewari, Anurag; Dhawan, Ira; Mahendru, Vidhi; Katyal, Sunil; Singh, Avtar; Garg, Shuchita

    2014-01-01

    Context: Under regional anesthesia, geriatric patients are prone to shivering induced perioperative complications that Anesthesiologists should prevent rather than treat. Aim: We investigated the prophylactic efficacy of oral tramadol 50 mg to prevent the perioperative shivering after transurethral resection of prostate (TURP) surgery under subarachnoid blockade (SAB). Shivering is usually overlooked in patients undergoing urological surgery under spinal anesthesia and may result in morbidity, prolonged hospital stay and increased financial burden. Use of prophylactic measures to reduce shivering in geriatric patients who undergo urological procedures could circumvent this. Oral formulation of tramadol is a universally available cost-effective drug with the minimal side-effects. Settings and Design: Prospective, randomized, double-blinded, placebo-controlled study. Patients and Methods: A total of 80 patients who were scheduled for TURP surgery under subarachnoid block were randomly selected. Group I and II (n = 40 each) received oral tramadol 50 mg and placebo tablet respectively. After achieving subarachnoid block, the shivering, body temperature (tympanic membrane, axillary and forehead), hemodynamic parameters and arterial saturation were recorded at regular intervals. Statistical Analysis Used: T-test, analysis of variance test, Z-test and Fisher exact test were utilized while Statistical Product and Service Solutions, IBM, Chicago (SPSS statistics (version 16.0)), software was used for analysis. Results: Incidence of shivering was significantly less in patients who received tramadol (7.5% vs. 40%; P < 0.01). The use of tramadol was associated with clinically inconsequential side-effects. Conclusion: We conclude that the use of oral tramadol 50 mg is effective as a prophylactic agent to reduce the incidence, severity and duration of perioperative shivering in patients undergoing TURP surgery under SAB. PMID:24665233

  20. Effects of Intraoperative Magnesium Sulfate Administration on Postoperative Tramadol Requirement in Liver Transplantation: A Prospective, Double-Blind Study.

    PubMed

    Gucyetmez, B; Atalan, H K; Aslan, S; Yazar, S; Polat, K Y

    2016-10-01

    Magnesium is an N-methyl-d-aspartate receptor blocker and is known to have analgesic effect. Hypomagnesemia can often be seen in liver transplantation and may be associated with higher morbidity and mortality. The objective of this study was to investigate the effects of intraoperative magnesium sulfate administration on postoperative tramadol requirement in liver transplant patients. Liver transplant patients >18 years of age were screened prospectively from October 2014 to April 2015. Of these, 35 randomly selected patients with normal blood magnesium level (≥1.8 mmol/L) were included in a control group and another 35 randomly selected patients with low magnesium level (<1.8 mmol/L) were given 50 mg/kg intravenous magnesium sulfate replacement in the last 30 minutes of the operation. All patients received standard anesthesia induction and maintenance. Patient's age, sex, body mass index, Model for End-Stage Liver Disease and Acute Physiology and Chronic Health Evaluation II scores, 24-hour tramadol requirement, mechanical ventilation duration, and time of 1st tramadol need were recorded. In the magnesium group, mean 24-hour total tramadol requirement (3.7 mg/kg/d) and duration of mechanical ventilation (6.3 h) were significantly lower and time of 1st tramadol need (17.5 h) was significantly higher than in the control group (P < .001 for each). In the multivariate analysis, duration of mechanical ventilation was decreased by the usage of magnesium sulfate (P < .001). Intraoperative use of magnesium sulfate in liver transplantation reduces the need for postoperative tramadol and duration of mechanical ventilation and therefore it is a candidate to be adjuvant agent. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Metoclopramide improves the quality of tramadol PCA indistinguishable to morphine PCA: a prospective, randomized, double blind clinical comparison.

    PubMed

    Pang, Weiwu; Liu, Yu-Cheng; Maboudou, Edgard; Chen, Tom Xianxiu; Chois, John M; Liao, Cheng-Chun; Wu, Rick Sai-Chuen

    2013-09-01

    Multimodal analgesia has been effectively used in postoperative pain control. Tramadol can be considered "multimodal" because it has two main mechanisms of action, an opioid agonist and a reuptake inhibitor of norepinephrine and serotonin. Tramadol is not as commonly used as morphine due to the increased incidence of postoperative nausea and vomiting (PONV). As metoclopramide is an antiemetic and an analgesic, it was hypothesized that when added to reduce PONV, metoclopromide may enhance the multimodal feature of tramadol by the analgesic property of metoclopramide. Therefore, the effectiveness of postoperative patient-controlled analgesia (PCA) with morphine was compared against PCA with combination of tramadol and metoclopramide. A prospective, randomized, double blind clinical trial. Academic pain service of a university hospital. Sixty patients undergoing elective total knee arthroplasty with general anesthesia. Sixty patients were randomly divided into Group M and Group T. In a double-blinded fashion, Group M received intraoperative 0.2 mg/kg morphine and postoperative PCA with 1 mg morphine per bolus, whereas Group T received intraoperative tramadol 2.5 mg/kg and postoperative PCA with 20 mg tramadol plus 1 mg metoclopramide per bolus. Lockout interval was 5 minutes in both groups. Pain scale, satisfaction rate, analgesic consumption, PCA demand, and side effects were recorded by a blind investigator. These two groups displayed no statistically significant difference between the items and variables evaluated. This combination provides analgesia equivalent to that of morphine and can be used as an alternative to morphine PCA. Wiley Periodicals, Inc.

  2. Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems

    PubMed Central

    Chen, Fu-chao; Zhu, Jun; Li, Bin; Yuan, Fang-jun; Wang, Lin-hai

    2016-01-01

    Background Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Materials and methods Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. Results All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Conclusion Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C. PMID:27350741

  3. Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems.

    PubMed

    Chen, Fu-Chao; Zhu, Jun; Li, Bin; Yuan, Fang-Jun; Wang, Lin-Hai

    2016-01-01

    Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C.

  4. Tramadol and the risk of fracture in an elderly female population: a cost utility assessment with comparison to transdermal buprenorphine.

    PubMed

    Hirst, Alexander; Knight, Chris; Hirst, Matt; Dunlop, Will; Akehurst, Ron

    2016-03-01

    Opioid treatment for chronic pain is a known risk factor for falls and/or fractures in elderly patients. The latter cause a significant cost to the National Health Service and the Personal Social Services in the UK. Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population. A model was developed to assess the cost effectiveness of tramadol compared with transdermal buprenorphine over a 1-year time horizon and a patient population of high-risk patients (female patients age 75 or older). To estimate the total cost and quality-adjusted life years (QALYs) of treatment, published odds ratios are used in combination with the published incidence rates of four types of fracture: hip, wrist, humerus and other. The model shows tramadol to be associated with 1,058 more fractures per 100,000 patients per year compared with transdermal buprenorphine, resulting in transdermal buprenorphine being cost-effective with an incremental cost-effectiveness ratio of less than £7,000 compared with tramadol. Sensitivity analysis found this result to be robust. In the UK data, there is uncertainty regarding the transdermal buprenorphine odds ratios for fractures. Odds ratios published in Danish and Swedish studies show similar point estimates but are associated with less uncertainty. Transdermal buprenorphine is cost-effective compared to tramadol at a willingness-to-pay threshold of £20,000 per QALY.

  5. Epidural tramadol via intraoperatively placed catheter as a standalone analgesic after spinal fusion procedure: An analysis of efficacy and cost.

    PubMed

    Ilangovan, Vijaysundar; Vivakaran, Thanga Tirupathi Rajan; Gunasekaran, D; Devikala, D

    2017-01-01

    This was a prospective analysis of epidural tramadol as a single analgesic agent delivered through intraoperatively placed epidural catheter for postoperative pain relief after spinal fusion procedures in terms of efficacy and cost. Twenty patients who underwent spinal fusion procedures were included in the study. After completion of the procedure, an epidural catheter was placed at the highest level of exposed dura and brought out through a separate tract. Postoperatively, tramadol was infused into the epidural space via the catheter at a dose of 1 mg/kg diluted in 10 ml of saline. The dosage frequency was arbitrarily fixed at every 6 h during the first 2 days and thereafter reduced to every 8 h after the first 2 days till day 5. Conventional intravenous analgesics were used only if additional analgesia was required as assessed by visual analog scale (VAS). Patients' VAS score was assessed every 4 h from the day of surgery. Patients with a VAS score of 6 or more were given additional analgesia in the form of intravenous paracetamol. Of the twenty patients, eight patients needed additional analgesia during the first 24 h and none required additional analgesia after the first 24 h. The median VAS score was 7 within the first 24 h and progressively declined thereafter. Epidural tramadol was noted to be many times cheaper than conventional parenteral analgesics. Epidural tramadol infusion is safe and effective as a standalone analgesic after open spinal fusion surgery, especially after the 1(st) postoperative day. Intraoperative placement of the epidural catheter is a simple way of delivering tramadol to the epidural space. The cost of analgesia after spinal fusion surgery can be reduced significantly using epidural tramadol alone.

  6. Epidural tramadol via intraoperatively placed catheter as a standalone analgesic after spinal fusion procedure: An analysis of efficacy and cost

    PubMed Central

    Ilangovan, Vijaysundar; Vivakaran, Thanga Tirupathi Rajan; Gunasekaran, D.; Devikala, D.

    2017-01-01

    Objective: This was a prospective analysis of epidural tramadol as a single analgesic agent delivered through intraoperatively placed epidural catheter for postoperative pain relief after spinal fusion procedures in terms of efficacy and cost. Materials and Methods: Twenty patients who underwent spinal fusion procedures were included in the study. After completion of the procedure, an epidural catheter was placed at the highest level of exposed dura and brought out through a separate tract. Postoperatively, tramadol was infused into the epidural space via the catheter at a dose of 1 mg/kg diluted in 10 ml of saline. The dosage frequency was arbitrarily fixed at every 6 h during the first 2 days and thereafter reduced to every 8 h after the first 2 days till day 5. Conventional intravenous analgesics were used only if additional analgesia was required as assessed by visual analog scale (VAS). Results: Patients’ VAS score was assessed every 4 h from the day of surgery. Patients with a VAS score of 6 or more were given additional analgesia in the form of intravenous paracetamol. Of the twenty patients, eight patients needed additional analgesia during the first 24 h and none required additional analgesia after the first 24 h. The median VAS score was 7 within the first 24 h and progressively declined thereafter. Epidural tramadol was noted to be many times cheaper than conventional parenteral analgesics. Conclusion: Epidural tramadol infusion is safe and effective as a standalone analgesic after open spinal fusion surgery, especially after the 1st postoperative day. Intraoperative placement of the epidural catheter is a simple way of delivering tramadol to the epidural space. The cost of analgesia after spinal fusion surgery can be reduced significantly using epidural tramadol alone. PMID:28149082

  7. Glomerular filtration rate after tramadol, parecoxib and pindolol following anaesthesia and analgesia in comparison with morphine in dogs.

    PubMed

    Kongara, Kavitha; Chambers, Paul; Johnson, Craig B

    2009-01-01

    To compare the effects of morphine, parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol on nociceptive thresholds in awake animals and their effect on glomerular filtration rate (GFR) in dogs subjected to 30 minutes of anesthesia. Eight adult mixed breed experimental dogs. Randomized, controlled trial. Dogs received 0.05 mg kg(-1) acepromazine subcutaneously (SC) as anaesthetic pre-medication. Thirty to sixty minutes later, they received either tramadol 3 mg kg(-1) intravenously, (IV), parecoxib (1 mg kg(-1) IV), a combination of tramadol 3 mg kg(-1) (IV), parecoxib 1 mg kg(-1) (IV) and pindolol 5 microg kg(-1) (SC), morphine (0.1 mg kg(-1) (IV) or 0.9% saline (2 mL). Anaesthesia was then induced with IV propofol to effect (2.9 +/- 0.8 mg kg(-1)) and maintained with halothane in oxygen for 30 minutes. Systolic arterial blood pressure was maintained above 90 mmHg with IV fluids and by adjusting the inspired halothane concentration. Post-treatment nociceptive thresholds to mechanical stimuli, expressed as percent of pre-treatment values, were compared between the treatments to assess the analgesic efficacy of the drugs. Plasma iohexol clearance (ICL), a measure of GFR, was estimated both before and 24 hours after induction of anaesthesia to study the drugs' effects on renal perfusion. Nociceptive threshold and GFR data were compared using mixed model analysis in SAS 9.1. Both tramadol and parecoxib produced similar analgesia, which was less than that of morphine. Their combination with pindolol produced analgesia comparable with morphine. None of the test drugs, either alone or in combination, reduced GFR. Tramadol and parecoxib (either alone or in combination) can increase nociceptive thresholds in awake dogs and have minimal effects on renal perfusion in normotensive dogs subjected to anaesthesia.

  8. Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals.

    PubMed

    Knych, H K; Steffey, E P; White, A M; McKemie, D S

    2016-01-01

    Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Experimental. Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasions at ages 6–8, 13–15, 20–22 and 40–43 days. Blood samples were collected prior to administration and at multiple times until 48 h post administration. Blood samples were analysed for tramadol and metabolite concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed. The average volume of distribution was 5.10, 4.63, 4.02 and 3.84 l/kg bwt and clearance 3.44, 3.08, 3.14 and 2.69 l/h/kg bwt when foals were aged 6–8, 13–15, 20–22 and 40–43 days, respectively. There was not a significant difference in the elimination half-life between age groups (1.52, 1.73, 1.13 and 1.51 for ages 6–8, 13–15, 20–22 and 40–43 days, respectively). The metabolites produced were the same as in mature horses; however, glucuronidation capability, appeared to increase with increasing age. Tramadol administration was well tolerated at all ages studied with sedation noted in the 3 older age groups. Tramadol appears to be consistently well tolerated following i.v. administration of 3 mg/kg bwt to foals ranging in age from 1 to 6 weeks. Although analgesic concentrations in foals have yet to be established, the results of this study support further study of tramadol for clinical use in foals.

  9. Incidence of tramadol shopping behavior in a retrospective cohort of chronic non-cancer pain patients in France.

    PubMed

    Chenaf, Chouki; Kabore, Jean-Luc; Delorme, Jessica; Pereira, Bruno; Mulliez, Aurélien; Roche, Lucie; Eschalier, Alain; Delage, Noémie; Authier, Nicolas

    2016-09-01

    Opioid analgesic use in chronic non-cancer pain (CNCP) is increasingly prevalent, but the benefits and risks are inadequately understood. In France, tramadol is one of the most used prescription opioids, but studies on its misuse liability in CNCP are still lacking. The aim was to assess the incidence of tramadol shopping behavior in CNCP patients and to identify the associated risk factors. A retrospective cohort of CNCP patients aged 18 years and older treated by tramadol for at least six consecutive months between 2005 and 2013 from a sample of the French Health Insurance database was established. Doctor shopping was defined as at least 1 day of overlapping prescriptions written by two or more different prescribers and filled in at least three different pharmacies. A total of 3505 CNCP patients were included with a majority of women (66.4%) and a mean age of 66.4 ± 14.7 years. The median tramadol treatment duration was 260 [interquartile range: 211-356] days. The 1-year incidence rate of tramadol shopping behavior was 1.0% [95%CI: 0.7-1.5]. On multivariate analysis, risk factors associated with tramadol shopping behavior were age (hazard ratio [HR] = 7.4 [95%CI: 2.8-19.7] for age <40, HR = 2.8 [95%CI: 1.0-7.7] for 40 ≤ age < 50, versus age ≥50), low-income status (HR = 8.5 [95%CI: 3.6-20.5]), and prior use of strong opioids (HR = 5.7 [95%CI: 1.9-17.0]). Tramadol shopping behavior incidence appears low in CNCP patients but may represent a public health concern given the widespread use of tramadol. Education and best monitoring of high-risk patients are needed to reduce doctor shopping. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. The Investigation of Tramadol Dependence with No History of Substance Abuse: A Cross-Sectional Survey of Spontaneously Reported Cases in Guangzhou City, China

    PubMed Central

    Zhang, Haoran; Liu, Zhimin

    2013-01-01

    The study was to survey and assess the drug dependence and abuse potential of tramadol with no history of substance abuse. Subjects of tramadol dependence with no prior history of substance abuse were surveyed by interview. Physical dependence of tramadol was assessed using 10 items opiate withdrawal scale (OWS), and psychological dependence was assessed by Addiction Research Center Inventory—Chinese Version (ARCI-CV). Twenty-three male subjects (the median age was 23.4 ± 4.1 years) referred to the addiction unit in Medical Hospital of Guangzhou with tramadol abuse problems were included in this cross-sectional study. The control group included 87 heroin addicts, 60 methamphetamine (MA) abusers, and 50 healthy men. The scores of OWS of tramadol were 0.83–2.30; the mean scores of identifying euphoric effects–MBG, sedative effects–PCAG, and psychotomimetic effects–LSD of ARCI were 8.96 ± 3.08, 6.52 ± 3.25, and 6.65 ± 2.50, respectively, F = 4.927, P < 0.001. Scores of MBG scale in tramadol did not differ from those in heroin and MA groups (P > 0.05) but were higher than those in healthy men (P < 0.05). Tramadol with no history of substance abuse has a clear risk of producing high abuse potential under the long-term infrequent abuse and the high doses. PMID:24151592

  11. Isobolographic analysis of the antinociceptive interaction between ursolic acid and diclofenac or tramadol in mice.

    PubMed

    Déciga-Campos, Myrna; Cortés, Alejandra; Pellicer, Francisco; Díaz-Reval, Irene; González-Trujano, María Eva

    2014-02-01

    It is considered that natural products used in folk medicine can potentiate the effect of drugs. The aim of this study was to evaluate the pharmacological interaction between ursolic acid, a triterpene isolated from herbal medicines to treat pain, and the analgesics diclofenac or tramadol. Individual dose-response curves of the antinociceptive effect of these compounds were built to calculate the ED50, as well as the pharmacological interaction, by using isobolographic analysis. All treatments decreased significantly and in a dose-dependent manner the writhing behavior with ED50 values of 103.50 ± 19.66, 20.54 ± 6.05, and 9.60 ± 1.69 mg/kg, for ursolic acid, diclofenac, and tramadol, respectively. An isobolographic analysis allowed the characterization of the pharmacological interaction produced by a fixed ratio combination of 1 : 1 and 1 : 3 of equi-effective doses of these compounds. Theoretical antinociceptive ED50 values of ursolic acid-diclofenac were 62.12 ± 10.28 and 41.43 ± 6.69 mg/kg, respectively, not statistically different from those obtained experimentally (44.52 ± 5.25 and 44.89 ± 49.05 mg/kg, respectively), reporting an additive interaction. Theoretical antinociceptive ED50 values of ursolic acid-tramadol (56.56 ± 9.87 and 33.08 ± 5.07 mg/kg, respectively) were significantly lower than those observed experimentally (138.36 ± 49.05 and 67.34 ± 18.98 mg/kg, respectively) reporting antagonism in this interaction. Antinociceptive response obtained from isobolograms in the writhing test was corroborated by using formalin test in mice. Adverse effects such as gastric damage in the ursolic acid-diclofenac combination did not increase in an additive form similarly as with antinociception. Conversely, sedative response was significantly increased in the ursolic acid-tramadol combination. As observed in the formalin test, the antagonism on the antinociceptive response between ursolic acid

  12. A comparison of fentanyl with tramadol during propofol-based deep sedation for pediatric upper endoscopy.

    PubMed

    Bedirli, Nurdan; Egritas, Odul; Cosarcan, Kaan; Bozkirli, Fusun

    2012-02-01

    This study was conducted to compare the efficacy and safety of tramadol with those of fentanyl and to evaluate the impact of age in pediatric patients undergoing upper gastrointestinal endoscopy (UGIE). Eighty patients with ASA I-II, aged 1-16 years, undergoing UGIE were included in this study. Baseline anesthesia was maintained with 1 mg·kg(-1) propofol, and then, the patients were randomly assigned to receive 2 μg·kg(-1) fentanyl (group F, n = 40) or 2 mg·kg(-1) tramadol (group T, n = 40). Additional propofol, 0.5-1 mg·kg(-1), was administered when needed. Heart rate, mean arterial pressure, oxygen saturation (SpO(2)), and sedation scores were recorded at baseline, induction, and every 5 min. Endoscopy duration, recovery time, and adverse effects were recorded. The data were separated for subgroup analyses based on the age of 0-2, 2-12, and over 12 years. Fentanyl significantly decreased the saturation at induction, 5th min and 10th min in patients of 0-2 years; at 5th and 10th min in 2-12 years; and at 5th min in >12 years. In all age subgroups, sedation scores at 10th, 15th, and 20th min, the overall frequency of adverse effects, and the recovery time were significantly lower in group T compared with group F. Tramadol in pediatric patients undergoing UGIE provided sedation as efficient as fentanyl with a better hemodynamic and respiratory stability and provided a superior safety and tolerance in younger children. © 2011 Blackwell Publishing Ltd.

  13. Theoretical investigation on functional monomer and solvent selection for molecular imprinting of tramadol

    NASA Astrophysics Data System (ADS)

    Fonseca, Matheus C.; Nascimento, Clebio S.; Borges, Keyller B.

    2016-02-01

    The purpose of this Letter was to study for the first time the interaction process of tramadol (TRM) with distinct functional monomers (FM) in the formation of molecular imprinted polymer (MIP), using density functional theory (DFT) calculations at B3LYP/6-31G(d,p). As result we were able to establish that the best MIP synthesis conditions are obtained with acrylic acid as FM in 1:3 molar ratio and with chloroform as solvent. This condition presented the lowest stabilization energy for the pre-polymerization complexes. Besides, the intermolecular hydrogen bonds found between the template molecule and functional monomers play a primary role to the complex stability.

  14. Evaluation of clonidine as an adjuvant to brachial plexus block and its comparison with tramadol

    PubMed Central

    Kelika, Prakash; Arun, Jamkar Maya

    2017-01-01

    Background and Aims: It has been reported that clonidine when used as an additive in a dose of 90 μg in adults increases the duration of peripheral nerve blocks. Hence, this study was conducted to evaluate the effect of clonidine in brachial plexus blocks and to compare it with tramadol. Material and Methods: Ninety patients posted for upper limb orthopedic surgery were divided randomly into three groups. 40 mL of local anesthetic solution was prepared using 15 mL of 2% lignocaine-adrenaline-sodium bicarbonate solution, 15 mL of 0.5% bupivacaine, and 10 mL distilled water. Patients received a supraclavicular brachial plexus block with 0.7 mL/kg of this solution to which either 1 mg/kg tramadol, 1 μg/kg clonidine, or 1.5 μg/kg clonidine was added. The onset and duration of sensory and motor block and the duration of postoperative analgesia were recorded. Pulse rate, blood pressure, respiratory rate, saturation, sedation, and any side effect were monitored. Results were statistically analyzed using analysis of variance F-test and unpaired t-test. Results: There was a statistically significant difference in the onset of both the sensory and motor components of the block with the fastest onset seen when clonidine was used in a dose of 1.5 μg/kg. The block also lasted statistically significantly longer with clonidine as compared with tramadol although there was no statistically significant increase in the duration of the block when a higher dose of clonidine was used. The time for rescue analgesia was the longest in patients who received 1.5 μg/kg of clonidine (491.8 ± 33.9 min). This duration was also statistically significant. Patients who received tramadol reported a statistically significant higher incidence of nausea. Conclusion: Clonidine in a dose of 1.5 μg/kg body weight provided the fastest onset of sensory as well as motor block and the longest duration of postoperative analgesia and thus is a good additive to local anesthetic solutions for brachial

  15. Evaluation of clonidine as an adjuvant to brachial plexus block and its comparison with tramadol.

    PubMed

    Kelika, Prakash; Arun, Jamkar Maya

    2017-01-01

    It has been reported that clonidine when used as an additive in a dose of 90 μg in adults increases the duration of peripheral nerve blocks. Hence, this study was conducted to evaluate the effect of clonidine in brachial plexus blocks and to compare it with tramadol. Ninety patients posted for upper limb orthopedic surgery were divided randomly into three groups. 40 mL of local anesthetic solution was prepared using 15 mL of 2% lignocaine-adrenaline-sodium bicarbonate solution, 15 mL of 0.5% bupivacaine, and 10 mL distilled water. Patients received a supraclavicular brachial plexus block with 0.7 mL/kg of this solution to which either 1 mg/kg tramadol, 1 μg/kg clonidine, or 1.5 μg/kg clonidine was added. The onset and duration of sensory and motor block and the duration of postoperative analgesia were recorded. Pulse rate, blood pressure, respiratory rate, saturation, sedation, and any side effect were monitored. Results were statistically analyzed using analysis of variance F-test and unpaired t-test. There was a statistically significant difference in the onset of both the sensory and motor components of the block with the fastest onset seen when clonidine was used in a dose of 1.5 μg/kg. The block also lasted statistically significantly longer with clonidine as compared with tramadol although there was no statistically significant increase in the duration of the block when a higher dose of clonidine was used. The time for rescue analgesia was the longest in patients who received 1.5 μg/kg of clonidine (491.8 ± 33.9 min). This duration was also statistically significant. Patients who received tramadol reported a statistically significant higher incidence of nausea. Clonidine in a dose of 1.5 μg/kg body weight provided the fastest onset of sensory as well as motor block and the longest duration of postoperative analgesia and thus is a good additive to local anesthetic solutions for brachial plexus blocks.

  16. Incorporation of tramadol drug into Li-fluorohectorite clay: A preliminary study of a medical nanofluid

    NASA Astrophysics Data System (ADS)

    Valdés, L.; Hernández, D.; de Ménorval, L. Ch.; Pérez, I.; Altshuler, E.; Fossum, J. O.; Rivera, A.

    2016-07-01

    During the last years, clays have been increasingly explored as hosts for drugs. In the present paper, we have been able to host the non-steroidal anti-inflammatory drug, Tramadol, into the clay Li-fluorohectorite (Li-Fh). We preliminary evaluate its incorporation by means of UV spectroscopy and X ray diffraction. Our results indicate that the clay hosts the drug molecule in its interlayer space. We suggest a set of parameters to guarantee an efficient incorporation process. Future studies will concentrate on the release of the drug from the clay nanofluid.

  17. The effect of intraarticular combinations of tramadol and ropivacaine with ketamine on postoperative pain after arthroscopic meniscectomy.

    PubMed

    Ayoglu, Hilal; Altunkaya, Hanife; Bayar, Ahmet; Turan, Isil Ozkocak; Ozer, Yetkin; Ege, Ahmet

    2010-03-01

    The purpose of this prospective randomized study was to evaluate the effects of intraarticular combinations of tramadol and ropivacaine with ketamine in postoperative pain control of patients undergoing arthroscopic meniscectomy. We randomly divided 80 patients into four groups to receive intraarticular 50 mg tramadol (Group T), 50 mg tramadol with 0.5 mg kg(-1) ketamine (Group TK), 75 mg ropivacaine (Group R), 75 mg ropivacaine with 0.5 mg kg(-1) ketamine (Group RK) in 20 ml normal saline at the end of surgery. Postoperative analgesia was provided with patient-controlled analgesia with morphine. Postoperative pain scores, total morphine consumption amount and side effects were recorded at intervals of 0, 1, 2, 4, 8, 12 and 24 h after the operation. Pain scores were higher in Group T when compared with Group R and Group RK at second and fourth hours, also compared with Group RK at zeroth, first, second, fourth and eighth hours. Total morphine consumption amount was found to be higher in Group T when compared to Group TK at eighth and twelfth hours and Group RK at eighth hours (P < 0.05). Total morphine consumption was lowest in Group TK (P < 0.05). There were no significant differences among the study groups regarding side effects. Administration of intraarticular tramadol-ketamine combination was found to be more effective in decreasing postoperative daily analgesic consumption.

  18. Effects of different doses of tramadol added to levobupivacaine in continuous wound infusion for postoperative pain treatment following cesarean section.

    PubMed

    Ekmekçi, Perihan; Çağlar, Gamze S; Yilmaz, Hakan; Kazbek, Baturay K; Gursoy, Asli Yarci; Kiseli, Mine; Tüzüner, Filiz

    2017-02-01

    The aim of this study was to compare the effects of two different doses of tramadol added to levobupivacaine as continuous wound infusion, on VAS scores following cesarean section. The study was conducted in an University Hospital and was approved by the Local Ethical Committee. Sixty-five ASA I-II parturients, between 18 and 45 years were enrolled. The participants were randomized to three groups. Group T1 (n = 21) was given the study solution consisting of levobupivacaine 0.25% + tramadol 1 mg/kg. Group T2 (n = 21) was given levobupivacaine 0.25% + tramadol 2 mg/kg and Group L (n = 21) was given levobupivacaine 0.25%, subcutaneously, alone. Each patient who delivered by cesarean section was applied a triple orifice epidural catheter above rectus fascia for continious wound infiltration. VAS at rest and with 20 degrees leg lift, time to first additional analgesic, total additional analgesic consumption, side effects, and sedation scores were recorded. There were no statistically significant differences among groups, concerning VAS scores at rest and VAS scores at leg lift. Total amount of additional analgesics and sedation scores were also similar for three groups. Different doses of tramadol as adjunct to local anesthetics in continuous wound infiltration following cesarean section do not seem to provide superior analgesia.

  19. [Serious adverse drug reactions with tramadol reported to the French pharmacovigilance database between 2011 and 2015].

    PubMed

    Moulis, Florence; Rousseau, Vanessa; Abadie, Delphine; Masmoudi, Kamel; Micallef, Joëlle; Vigier, Caroline; Pierre, Sabrina; Dautriche, Anne; Montastruc, François; Montastruc, Jean-Louis

    2017-06-29

    Tramadol is an opioid and a serotonin reuptake inhibitor drug. It is approved for moderate to severe pain in adults. The aim of this study was to assess tramadol safety through a national pharmacovigilance study in France since dextropropoxyphen withdrawal in 2011. We described all serious adverse drug reactions (SADRs) reported with tramadol in adults in the French National PharmacoVigilance Database from August 1st, 2011 to December 31st, 2015. We identified 1512 SADRs during the study period. The most frequently reported SADRs were neurological (29.4%, including troubles of consciousness [13.2%] and seizures [6.7%]), psychiatric (22.8%, including confusions [14.6%] and hallucinations [7.3%]) and gastrointestinal (17.0%, mostly nausea and vomiting [9.6%]). Unexpected SADRs were also reported: hyponatremia, cholestatic hepatitis, serotonin syndrome. This study demonstrates new unexpected hepatic and metabolic SADRs. Tramadol alone can induce serotonin syndrome in overdose situations. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  20. Effect of combining tramadol and morphine in adult surgical patients: a systematic review and meta-analysis of randomized trials.

    PubMed

    Martinez, V; Guichard, L; Fletcher, D

    2015-03-01

    The role for tramadol in multimodal postsurgical analgesic strategies remains unclear. We undertook a systematic review to evaluate the utility of combining tramadol with morphine after surgery. We searched the MEDLINE, EMBASE, LILAC, Cochrane, and Clinical Trial Register databases for randomized, controlled studies comparing tramadol with placebo or active control in patients undergoing surgery. Fourteen studies (713 patients) were included. There was a limited but significant postoperative morphine-sparing effect, with a weighted mean difference (WMD) of -6.9 (95% confidence interval -11.3 to -2.5) mg. This effect was not associated with a decrease in morphine-related adverse effects. No difference in the incidence of nausea, vomiting, sedation, or shivering was observed. There was no decrease in pain intensity at 24 h; the WMD was -0.9 (-7.2; 5.2) on a 100 mm visual analogue scale at 24 h. We found no significant clinical benefit from the combination of i.v. tramadol and morphine after surgery.

  1. Analgesic Effects and Safety of Desmopressin, Tramadol and Indomethacin in Patients with Acute Renal Colic; A Randomized Clinical Trial

    PubMed Central

    Shirazi, Mehdi; Salehipour, Mehdi; Afrasiabi, Mohammad Amin; Aminsharifi, Alireza

    2015-01-01

    Objective: To compare the efficacy of desmopressin (DDAVP), tramadol and indomethacin on pain intensity of patients with acute renal colic caused by urolithiasis. Methods: This prospective, randomized clinical trial was conducted between July 2005 and July 2006 including 120 patients (70 men and 50 women, mean age 38.2±5.8 years) referring to emergency room of Shahid Faghihi hospital with renal colic caused by urolithiasis without any previous treatment. The patients were randomly assigned to three groups: group A received tramadol 50mg intramuscularly (n=40), group B received desmopressin 40 µg intranasally (n=40) and group C received indomethacin 100mg rectally (n=40). The pain was assessed both on admission and 30 minutes after the intervention. The pain intensity and the side effects were compared between two study groups. Results: There was no significant difference between two study groups regarding the baseline characteristics. The intensity of pain of presentation was almost similar in all groups. In group A, 30 patients (75%), in group B, 15 patients (37.5%) and in group C, 19 patients (47.5%) had complete pain relief. The pain intensity decreased significantly after the intervention within all three groups (p<0.001). Conclusion: According to the results of the current study, rectal indomethacin, intramuscular tramadol and intranasal desmopressin are effective and safe routs of controlling pain in acute renal colic secondary to urolithiasis. Tramadol was the most effective agent in controlling the pain. PMID:27162901

  2. Evaluation of the route dependency of the pharmacokinetics and neuro-pharmacokinetics of tramadol and its main metabolites in rats.

    PubMed

    Sheikholeslami, Behjat; Gholami, Mahdi; Lavasani, Hoda; Rouini, Mohammadreza

    2016-09-20

    Tramadol hydrochloride is a centrally acting analgesic used for the treatment of moderate-to-severe pain. It has three main metabolites: O-desmethyltramadol (M1), N-desmethyltramadol (M2), and N,O-didesmethyltramadol (M5). Because of the frequent use of tramadol by patients and drug abusers, the ability to determine the parent drug and its metabolites in plasma and cerebrospinal fluid is of great importance. In the present study, a pharmacokinetic approach was applied using two groups of five male Wistar rats administered a 20mg/kg dose of tramadol via intravenous (i.v.) or intraperitoneal (i.p.) routes. Plasma and CSF samples were collected at 5-360min following tramadol administration. Our results demonstrate that the plasma values of Cmax (C0 in i.v. group) and area under the curve (AUC)0-t for tramadol were 23,314.40±6944.85 vs. 3187.39±760.25ng/mL (Cmax) and 871.15±165.98 vs. 414.04±149.25μg·min/mL in the i.v. and i.p. groups, respectively (p<0.05). However, there were no significant differences between i.v. and i.p. plasma values for tramadol metabolites (p>0.05). Tramadol rapidly penetrated the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) (5.00±0.00 vs. 10.00±5.77min in i.v. and i.p. groups, respectively). Tramadol and its metabolites (M1 and M2) were present to a lesser extent in the cerebrospinal fluid (CSF) than in the plasma. M5 hardly penetrated the CSF, owing to its high polarity. There was no significant difference between the AUC0-t of tramadol in plasma (414.04±149.25μg·min/mL) and CSF (221.81±83.02μg·min/mL) in the i.p. group. In addition, the amounts of metabolites (M1 and M2) in the CSF showed no significant differences following both routes of administration. There were also no significant differences among the Kp,uu,CSF(0-360) (0.51±0.12 vs. 0.63±0.04) and Kp,uu,CSF(0-∞) (0.61±0.10 vs. 0.62±0.02) for i.v. and i.p. pathways, respectively (p>0.05). Drug targeting efficiency (DTE) values of tramadol

  3. [The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison].

    PubMed

    Freye, E; Latasch, L; Von Bredow, G; Neruda, B

    1998-02-28

    Tramadol, an analgesic with mean potency one tenth that of morphine is used regularly for the treatment of chronic and postoperative pain. Previous reports have indicated that tramadol may induce seizure activity when given together with a selective serotonin reuptake inhibitor (SSRI). Therefore, its major mode of action may be questioned which purportedly is due to binding with the opioid receptor and partly due to the inhibition of monoamine reuptake. We therefore set out to study its potential in inducing seizure activity and to quantify its effect on EEG-power spectra and on the central modulation of sensory afferents in awake and trained dogs (n=7). In order to demonstrate if opioid receptors mediated these effects, incremental doses of tramadol were given which was followed by naloxone for possible reversal. After a wash-out period the same animals were exposed to graded doses of alfentanil, a pure mu-receptor agonist. Again this was followed by the opioid antagonist naloxone for reversal.The electroencephalogram (EEG) and the event-related evoked potentials (SEP) were used to demonstrate possible excitatory effects. In order to derive the SEP the front paw was stimulated electrically (Digi Stim II trade mark ) while the evoked potentials were picked up contralaterally from the somatosensory cortex using stick-on electrodes. 256 sweeps were averaged (Lifescan) and the peak-to-peak amplitude was measured to demonstrate CNS excitation compared to control (%). Additionally, the raw electroencephalogram was viewed for epileptogenic changes and its power computed into the various power bands alpha, beta, delta und theta using FFT over a time epoch of 60 s. Following control, graded doses of either tramadol (2-5-10 mg/kg i.v.) or alfentanil (10-30-60 microg/kg i.v.) were given every 15 min while the EEG and the SEP were recorded. Thereafter naloxone (20 microg/kg i.v.) was injected for reversal. Tramadol did not suppress the amplitude of the SEP at any dose. High

  4. Tramadol loading, release and iontophoretic characteristics of ion-exchange fiber.

    PubMed

    Gao, Yanan; Yuan, Jing; Liu, Hongzhuo; Yang, Yang; Hou, Yanlong; Li, Sanming

    2014-04-25

    The objective of this study was to investigate the drug loading, release and iontophoretic characteristics of strong acidic ion-exchange fiber, using tramadol hydrochloride as a model drug. The complex of charged model drug and ion-exchange fiber was studied as a new approach to achieve controlled drug delivery. Structural characterization of the fiber was elucidated through different approaches including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM) and infrared spectroscopy (IR). And the mechanism of drug binding into ion-exchange fibers was validated to be ion-exchange. The drug loading into and release from ion-exchange fiber were affected by the concentration, volume and valence of the counter-ions in the external solution. Iontophoresis could significantly increase the delivery rate and amount of transdermal drug, and the iontophoretic dose could be easily controlled by adjusting the current intensity and the amount of release medium. The tramadol could be steadily released both from the drug-loaded fiber and drug solution when applied the iontophoretic method, which was in disagreement with the previous publications. As a drug reservoir, ion-exchange fiber has good regularity of drug loading, release and iontophoretic characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Design and development of nasal mucoadhesive microspheres containing tramadol HCl for CNS targeting.

    PubMed

    Belgamwar, Veena S; Patel, Hitesh S; Joshi, Ashwini S; Agrawal, Anshuman; Surana, Sanjay J; Tekade, Avinash R

    2011-07-01

    In the present study, tramadol HCl microspheres were designed in order to accomplish rapid delivery of drug to the brain. For this purpose, lower viscosity grade HPMC (E15) was chosen as mucoadhesive polymer and used at different drug/polymer ratios in the microspheres formulations. The spray-dried microspheres were evaluated with respect to the production yield, incorporation efficiency, particle size, mucoadhesive property, in vitro drug release, histopathological study, and radio imaging study in rabbits. DSC and XRD study showed molecular dispersion and conversion of the drug into amorphous form. Size and surface morphology of microspheres was analyzed by SEM and found to be spherical in shape with smooth surface. It was found that the particle size, swelling ability, and incorporation efficiency of microspheres increase with increasing drug-to-polymer ratio. Microspheres show adequate mucoadhesion and do not have any destructive effect on nasal mucosa. In vitro drug release of optimized formulation was found to be 94% after 90 min. The radio imaging study indicated localization of drug in the brain. Hence, tramadol HCl microspheres based on a HPMC E15 may be a promising nasal delivery system for CNS targeting.

  6. [Pharmaceutical care of serious bleeding induced by tramadol-warfarin interaction: a case report].

    PubMed

    Dong, Shu-jie; Zhang, Ting; Li, Yan; Zhai, Suo-di

    2014-10-18

    Warfarin is a high-alert medication, which may result in bleeding if used improperly. In our case, one elderly female with atrial fibrillation had taken warfarin for more than half a year, and her international normalized ratio (INR) was maintained within the therapeutic range. The patient began to take tramadol to alleviate her shoulder pain. Three days later she presented hematuresis and had ecchymosis in her right upper arm, and in the meantime her INR rose to 10.04. Clinical pharmacists analyzed the cause for bleeding by searching relevant literature, and finally discovered the interaction between warfarin and tramadol. On the basis of that, the clinical pharmacists provided pharmaceutical care, offered specific medication education, as well as assisted the physicians to establish the medication plan for warfarin reuse. Eventually, her INR declined to reference ranges, and her hematuresis and ecchymosis were alleviated significantly. This successful case reveals that clinical pharmacy services contribute to better treatment outcomes. Clinical pharmacists can play an active role in anticoagulation management in healthcare team.

  7. Comparison of analgesia provided by lidocaine, lidocaine-morphine or lidocaine-tramadol delivered epidurally in dogs following orchiectomy.

    PubMed

    Almeida, Ricardo M; Escobar, André; Maguilnik, Samara

    2010-11-01

    To evaluate and compare the postoperative analgesia provided by epidural lidocaine, lidocaine/morphine or lidocaine/tramadol in dogs following elective orchiectomy. Prospective experimental trial. Thirty-six mongrel dogs aged 2-8 years old, weighing 6.6-22 kg. The dogs received 6.0 mg kg(-1) of lidocaine combined with 1.0 mg kg(-1) of tramadol, 0.1 mg kg(-1) of morphine or 0.01 mL kg(-1) of 0.9% NaCl epidurally. Analgesia was assessed at 4, 8, 12, 18 and 24 hours (T4, T8, T12 and T24) after the offset of lidocaine using a scale composed of physiologic and behavioral parameters. Rescue analgesia with morphine (0.2 mg kg(-1) , IM) was performed if the evaluation score exceeded 10 during the postoperative period. The scores over time were analyzed using the Friedman's two-way analysis of variance and the comparison between groups was made by the Kruskal-Wallis test with statistical significances accepted if p ≤ 0.05. There were no differences in the pain scores between the morphine and tramadol groups over time and no rescue analgesia was administered. In the NaCl group, rescue analgesia was needed at T4, T8 and T12. Within this group, the final evaluation times (T18 and T24) had lower pain scores than at T4, T8 and T12. Epidural lidocaine/tramadol provided an analgesic effect comparable to that of epidural lidocaine/morphine during the first 12 hours after surgical castration without substantial side effects, suggesting that tramadol may be an effective postoperative analgesic in dogs submitted to this surgical procedure. © 2010 The Authors. Veterinary Anaesthesia and Analgesia © 2010 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  8. EFFECTS OF TRAMADOL ON THE MINIMUM ANESTHETIC CONCENTRATION OF ISOFLURANE IN WHITE-EYED PARAKEETS (PSITTACARA LEUCOPHTHALMUS).

    PubMed

    Escobar, André; da Rocha, Rozana Wendler; Midon, Monica; de Almeida, Ricardo Miyasaka; Filho, Darcio Zangirolami; Werther, Karin

    2017-06-01

    The aim of this study was to determine the minimum anesthetic concentration (MAC) of isoflurane, and to investigate if tramadol changes the isoflurane MAC in white-eyed parakeets (Psittacara leucophthalmus). Ten adult birds weighing 157 ± 9 g were anesthetized with isoflurane in oxygen under mechanical ventilation. Isoflurane concentration for the first bird was adjusted to 2.2%, and after 15 min an electrical stimulus was applied in the thigh area to observe the response (movement or nonmovement). Isoflurane concentration for the subsequent bird was increased by 10% if the previous bird moved, or decreased by 10% if the previous bird did not move. This procedure was performed serially until at least four sequential crossover events were detected. A crossover event was defined as a sequence of two birds with different responses (positive or negative) to the electrical stimulus. Isoflurane MAC was calculated as the mean isoflurane concentration value at the crossover events. After 1 wk, the same birds were reanesthetized with isoflurane and MAC was determined at 15 and 30 min after intramuscular administration of 10 mg/kg of tramadol using the same method. A paired t-test (P < 0.05%) was used to detect significant differences for MAC between treatments. Isoflurane MAC in this population of white-eyed parakeets was 2.47 ± 0.09%. Isoflurane MAC values 15 and 30 min after tramadol administration were indistinguishable from each other (pooled value was 2.50 ± 0.18%); they were also indistinguishable from isoflurane MAC without tramadol. The isoflurane MAC value in white-eyed parakeets is higher than reported for other bird species. Tramadol (10 mg/kg, i.m.) does not change isoflurane MAC in these birds.

  9. Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol.

    PubMed

    Guedes, A; Knych, H; Hood, D

    2016-07-01

    Laminitis is a painful disease for which adequate pain management remains a challenging and largely unmet medical need. To investigate plasma concentrations, analgesic and physiological effects of 2 doses of tramadol in horses with chronic laminitis. Nonrandomised trial. Four horses with naturally occurring chronic laminitis received 5 mg/kg bwt and then 10 mg/kg bwt tramadol orally every 12 h for one week with a one-week washout between. Noninvasive arterial blood pressure, heart and respiratory rates, intestinal sounds and forelimb off-loading frequency were evaluated before and during treatments. Plasma tramadol and metabolite (M1 and M2) concentrations were measured on predetermined days and times after the morning dosing. Forelimb off-loading frequency decreased significantly with 10 mg/kg bwt (40%, P = 0.02) but not with 5 mg/kg bwt (9%, P = 0.4). Physiological variables did not change significantly with either treatment. For 5 and 10 mg/kg bwt treatments, respectively, individual maximum plasma concentrations (μg/l) ranged from 329 to 728 and 628 to 1330 (tramadol), 12-24 and 32-80 (M1), and 90-157 and 239-362 (M2). Respective median area under the concentration vs. time curves (h μg/l) were 727 and 1426, 33 and 88, 303 and 1003. Twice daily oral tramadol at 10 mg/kg bwt may produce analgesic plasma levels in horses with chronic laminitis. © 2015 EVJ Ltd.

  10. Managing Postoperative Analgesic Failure: Tramadol Versus Morphine for Refractory Pain in the Post-Operative Recovery Unit.

    PubMed

    Byrne, Kelly; Nolan, Aoife; Barnard, John; Tozer, Megan; Harris, David; Sleigh, Jamie

    2017-02-01

    This study aimed to discover whether co-analgesia with tramadol or additional morphine was more effective for patients who still had severe pain despite being given 10 mg intravenous morphine in the post-anesthesia care unit (PACU). All eligible patients were consented and recruited to the trial pre-operatively, but only a small subgroup – whose pain was not successfully controlled (pain score 6/10 or more) after receiving 10 mg of morphine in the PACU—were then randomized to enter the trial and receive, in a double blinded fashion, the analgesic study drug; which consisted of either a further 10 mg of morphine, or 100 mg of tramadol, titrated intravenously to control their pain. The groups were compared as to: the time to readiness for discharge, the patient’s pain scores over time, and the presence of side effects. There was no statistically significant difference in any of the outcomes measured. The time to readiness for discharge from PACU was 119 minutes in the morphine group and 120 minutes in the tramadol group. However in approximately half the cases who entered the trial (i.e., where pain had not been controlled with the pre-enrollment baseline 10 mg of morphine in PACU) neither a further 10 mg of morphine nor 100 mg of tramadol effectively relieved the patient’s pain. We found no difference between additional morphine and co-analgesia with tramadol in this study. Patients who don’t respond to reasonable doses of opioids in PACU are very likely to be unresponsive to further opioids, and other non-opioid analgesic techniques (such as regional anesthesia) should be considered early in this group of patients.

  11. Prevention of Propofol Injection Pain in Children: A Comparison of Pretreatment with Tramadol and Propofol-Lidocaine Mixture

    PubMed Central

    Borazan, Hale; Sahin, Osman; Kececioglu, Ahmet; Uluer, M.Selcuk; Et, Tayfun; Otelcioglu, Seref

    2012-01-01

    Background: The pain on propofol injection is considered to be a common and difficult to eliminate problem in children. In this study, we aimed to compare the efficacy of pretreatment with tramadol 1 mg.kg-1and propofol-lidocaine 20 mg mixture for prevention of propofol induced pain in children. Methods: One hundred and twenty ASA I-II patients undergoing orthopedic and otolaryngological surgery were included in this study and were divided into three groups with random table numbers. Group C (n=39) received normal saline placebo and Group T (n=40) received 1 mg.kg-1 tramadol 60 sec before propofol (180 mg 1% propofol with 2 ml normal saline) whereas Group L (n=40) received normal saline placebo before propofol-lidocaine mixture (180 mg 1% propofol with 2 ml %1 lidocaine). One patient in Group C was dropped out from the study because of difficulty in inserting an iv cannula. Thus, one hundred and nineteen patients were analyzed for the study. After given the calculated dose of propofol, a blinded observer assessed the pain with a four-point behavioral scale. Results: There were no significant differences in patient characteristics and intraoperative variables (p>0.05) except intraoperative fentanyl consumption and analgesic requirement one hr after surgery among the groups (p<0.05). Both tramadol 1 mg.kg-1 and lidocaine 20 mg mixture significantly reduced propofol pain when compared with control group. Moderate and severe pain were found higher in control group (p<0.05). The incidence of overall pain was 79.4% in the control group, 35% in tramadol group, 25% in lidocaine group respectively (p<0.001). Conclusions: Pretreatment with tramadol 60 sec before propofol injection and propofol-lidocaine mixture were significantly reduced propofol injection pain when compared to placebo in children. PMID:22927775

  12. Significant Efficacy of Tramadol/Acetaminophen in Elderly Patients with Chronic Low Back Pain Uncontrolled by NSAIDs: An Observational Study

    PubMed Central

    Imamura, Toshihiro

    2015-01-01

    Chronic low back pain (LBP) is a common condition and is generally treated using non-steroidal anti-inflammatory drug (NSAID); however, chronic NSAID use can decrease renal function. Tramadol, a weak opioid agonist, may improve chronic LBP and disability, while avoiding adverse effects such as gastrointestinal and renal toxicity. However, few studies have evaluated the short-term efficacy of opioids in Asian patients with chronic LBP. In this study, 24 patients with chronic LBP unresponsive to NSAIDs (10 men, 14 women; mean age, 65.1 ± 12.1 years) were prescribed tramadol/acetaminophen (37.5 mg/325 mg; four tablets daily) for 1 month. Then, the following parameters were assessed at baseline and after 1 week and 1 month of treatment: leg pain and LBP (Visual Analog Score [VAS]); activity of daily life (Roland-Morris Disability Questionnaire [RDQ]); and disability (Oswestry Disability Index [ODI]). Leg pain resolved within 1 week (p = 0.00093); however, LBP was relieved only at 1 month (p = 0.00034). The mean RDQ (p = 0.015) and ODI (p = 0.0032) scores were improved at 1 month. A total 41.6% of patients reported nausea and floating sensation beginning tramadol/acetaminophen treatment, and 12.5% (four patients) discontinued treatment as a result. LBP did not improve in 25% of patients administered tramadol/acetaminophen. Because this was an observational study, rather than a comparative study, further investigation is needed to evaluate the long-term efficacy of tramadol/acetaminophen in elderly patients with chronic LBP unresponsive to NSAIDs. PMID:26157527

  13. Comparative Study of the Effect of Intravenous Paracetamol and Tramadol in Relieving of Postoperative Pain after General Anesthesia in Nephrectomy Patients.

    PubMed

    Manne, Venkata Sesha Sai Krishna; Gondi, Srinivasa Rao

    2017-01-01

    The aim of this study was to compare the effect of intravenous paracetamol and tramadol in relieving of postoperative pain after general anesthesia for nephrectomy in prospective donor patients for kidney transplantation. A randomized study was conducted on 100 adult patients scheduled for nephrectomy aged from 35 to 55 years of both sexes and divided into two groups and were administered intravenous paracetamol and tramadol for postoperative pain relief and assessed with visual analog scale score and variations in vital parameters to assess extent of pain relief. After statistical interpretation of collected data, the observations were extrapolated. There was a statistically significant difference in the pain intensity scores obtained between the paracetamol and tramadol groups. On the basis of the present study, it is concluded that tramadol due to its lesser onset of action time was superior to paracetamol in providing acute postoperative pain relief.

  14. Comparative Study of the Effect of Intravenous Paracetamol and Tramadol in Relieving of Postoperative Pain after General Anesthesia in Nephrectomy Patients

    PubMed Central

    Manne, Venkata Sesha Sai Krishna; Gondi, Srinivasa Rao

    2017-01-01

    Aim: The aim of this study was to compare the effect of intravenous paracetamol and tramadol in relieving of postoperative pain after general anesthesia for nephrectomy in prospective donor patients for kidney transplantation. Materials and Methods: A randomized study was conducted on 100 adult patients scheduled for nephrectomy aged from 35 to 55 years of both sexes and divided into two groups and were administered intravenous paracetamol and tramadol for postoperative pain relief and assessed with visual analog scale score and variations in vital parameters to assess extent of pain relief. Results: After statistical interpretation of collected data, the observations were extrapolated. There was a statistically significant difference in the pain intensity scores obtained between the paracetamol and tramadol groups. Conclusion: On the basis of the present study, it is concluded that tramadol due to its lesser onset of action time was superior to paracetamol in providing acute postoperative pain relief. PMID:28298768

  15. Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats

    PubMed Central

    Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

    2015-01-01

    Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

  16. An evaluation of analgesic efficacy and clinical acceptability of intravenous tramadol as an adjunct to propofol sedation for third molar surgery.

    PubMed Central

    Shipton, E. A.; Roelofse, J. A.; Blignaut, R. J.

    2003-01-01

    This article details a double-blind, randomized, placebo-controlled pilot study evaluating the analgesic efficacy and clinical acceptability of intravenous tramadol in patients undergoing surgical removal of an impacted third molar tooth under local anesthesia and intravenous sedation with propofol. Forty-five ASA status 1 dental outpatients were randomly allocated to 2 groups of 22 (group A) and 23 (group B) patients each (n = 45). Group A (T/P) received intravenous tramadol 1.5 mg/kg injected over 2 minutes, followed by a bolus dose of intravenous propofol 0.4 mg/ kg. Maintenance consisted of a continuous infusion of propofol 3 mg/kg/h, with an additional bolus dose of 0.4 mg/kg intravenously 2-3 minutes prior to the infiltration of the local anesthetic solution. Group B (P/P) patients received no tramadol but instead a saline placebo solution and an identical amount of propofol. Overall, in this study, postoperative pain was much better controlled in the group receiving tramadol 1.5 mg/kg intravenously despite there being no significant difference in the dose of propofol administered in both groups. Intravenous tramadol, when given with propofol, did not affect the cardiovascular, respiratory, and sedative effects of propofol. Following tramadol, despite being an opioid, no nausea and vomiting were reported in the early postoperative period, indicating the value of using tramadol with propofol. Thus, this pilot study demonstrated the potential use of intravenous tramadol with propofol in day-case dento-alveolar surgery. PMID:14558587

  17. PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    PubMed

    Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

    2015-09-01

    Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

  18. Mitochondrial impairments contribute to spatial learning and memory dysfunction induced by chronic tramadol administration in rat: Protective effect of physical exercise.

    PubMed

    Mehdizadeh, Hajar; Pourahmad, Jalal; Taghizadeh, Ghorban; Vousooghi, Nasim; Yoonessi, Ali; Naserzadeh, Parvaneh; Behzadfar, Ladan; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

    2017-10-03

    Despite the worldwide use of tramadol, few studies have been conducted about its effects on memory and mitochondrial function, and controversial results have been reported. Recently, there has been an increasing interest in physical exercise as a protective approach to neuronal and cognitive impairments. Therefore, the aim of this study was to investigate the effects of physical exercise on spatial learning and memory and brain mitochondrial function in tramadol-treated rats. After completion of 2-week (short-term) and 4-week (long-term) treadmill exercise regimens, male Wistar rats received tramadol (20, 40, 80mg/kg/day) intraperitoneally for 30days. Then spatial learning and memory was assessed by Morris water maze test (MWM). Moreover, brain mitochondrial function was evaluated by determination of mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release from mitochondria. Chronic administration of tramadol impaired spatial learning and memory as well as brain mitochondrial function as indicated by increased ROS level, MMP collapse, increased mitochondrial swelling and cytochrome c release from mitochondria. Conversely, treadmill exercise significantly attenuated the impairments of spatial learning and memory and brain mitochondrial dysfunction induced by tramadol. The results revealed that chronic tramadol treatment caused memory impairments through induction of brain mitochondrial dysfunction. Furthermore, pre-exposure to physical exercise markedly mitigated these impairments through its positive effects on brain mitochondrial function. Copyright © 2017. Published by Elsevier Inc.

  19. Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors.

    PubMed

    Sun, Hong-Lei; Zheng, Ji-Wang; Wang, Keng; Liu, Rui-Ke; Liang, Jian-Hui

    2003-01-31

    Tramadol, an atypical opioid analgesic, stimulates both opiatergic and serotonergic systems. Here we have investigated the effect of tramadol in mice on 5-hydroxyptrytophan (5-HTP)-induced head twitch response (HTR), which is an animal model for the activation of the CNS 5-HT(2A) receptors in mice. Tramadol attenuated 5-HTP-induced HTR in a dose-dependent manner as morphine. Furthermore, the nonselective opioid receptor antagonists, naloxone and diprenorphine (M5050), reversed the effect of tramadol on 5-HTP-induced HTR dose-dependently. Interestingly, in contrast to the selective delta opioid receptor antagonist NTI, beta-FNA, a selective mu receptor antagonist, and nor-BNI, a selective kappa opioid receptor antagonist, antagonized the attenuation of 5-HTP-induced HTR by tramadol. In conclusion, administration of tramadol systemically inhibits 5-HTP-induced HTR in mice by activating opiatergic system in the CNS. Our findings show that mu and kappa opioid receptors, but not delta opioid receptor, play an important role in the regulation of serotonergic function in the CNS.

  20. Tramadol versus Celecoxib for reducing pain associated with outpatient hysteroscopy: a randomized double-blind placebo-controlled trial.

    PubMed

    Hassan, A; Wahba, A; Haggag, H

    2016-01-01

    Which is better, Tramadol or Celecoxib, in reducing pain associated with outpatient hysteroscopy? Both Tramadol and Celecoxib are effective in reducing pain associated with outpatient hysteroscopy but Celecoxib may be better tolerated. Pain is the most common cause of failure of outpatient hysteroscopy. A systematic review and meta-analysis showed that local anaesthetics were effective in reducing pain associated with hysteroscopy but there was insufficient evidence to support the use of oral analgesics, opioids and non-steroidal anti-inflammatory drugs, to reduce hysteroscopy-associated pain and further studies were recommended. This was a randomized double-blind placebo-controlled trial with balanced randomization (allocation ratio 1:1:1) conducted in a university hospital from May 2014 to November 2014. Two hundred and ten women who had diagnostic outpatient hysteroscopy were randomly divided into three equal groups: Group 1 received oral Tramadol 100 mg, group 2 received Celecoxib 200 mg and group 3 received an oral placebo. All the drugs were given 1 h before the procedure. A patient's perception of pain was assessed during the procedure, immediately afterwards and 30 min after the procedure with the use of a visual analogue scale (VAS). There was a significant difference in the pain scores among the groups during the procedure, immediately afterwards and 30 min after the procedure (P< 0.001, 0.001, <0.001 respectively). Tramadol had significantly lower pain scores when compared with the placebo during the procedure (mean difference = 1.54, 95% confidence interval (CI) (0.86, 2.22), P < 0.001), immediately after the procedure (mean difference = 1.09; 95% CI (0.5, 1.68), P < 0.001) and 30 min later (mean difference = 0.95, 95% CI (0.48, 1.41), P < 0.001). Celecoxib administration also led to significantly lower pain scores than the placebo during the procedure (mean difference = 1.28, 95% CI (0.62, 1.94), P < 0.001), immediately after the procedure (mean

  1. Multimodal Analgesia With Ketamine or Tramadol in Combination With Intravenous Paracetamol After Renal Surgery

    PubMed Central

    Khajavi, Mohammad Reza; Sabouri, Seyed Mehdi; Shariat Moharari, Reza; Pourfakhr, Pejman; Najafi, Atabak; Etezadi, Farhad; Imani, Farsad

    2016-01-01

    Background Opioids are generally the preferred analgesic agents during the early postoperative period. Objectives The present study was designed to assess and compare the multimodal analgesic effects of ketamine and tramadol in combination with intravenous acetaminophen after renal surgery. Patients and Methods This randomized, double-blinded, clinical trial was conducted on 80 consecutive patients undergoing various types of kidney surgeries in Sina hospital in Tehran in 2014 - 2016. After extubation, the patients were randomly assigned to receive intravenous paracetamol (1 gr) plus tramadol (0.7 mg/kg) (PT group) or paracetamol (1 gr) plus ketamine (0.5 mg/kg) (PK group) within ten minutes. Pain severity was assessed by the visual analog scale (VAS), and the level of agitation was assessed by the Ramsey sedation scale (RSS). Morphine consumption was assessed within the first six hours after drug injection, and hemodynamic parameters were assessed at 5, 10, and 20 minutes after infusion, at the time of transfer from recovery to the ward, and also at one and six hours after transfer to the ward. Results Postoperative pain scores were significantly lower in the PK group than in the PT group during all study time points. The mean dose of morphine needed at recovery in the PK group was lower compared with the PT group (0.47 ± 0.94 mg versus 1.50 ± 1.35 mg/P = 0.001). The level of agitation based on the RSS score was significantly lower in the PK group than in the PT group at 10 and 20 minutes after drug administration. The total postoperative complication rate in the PK group was lower than in the PT group (20% versus 53.3%, P = 0.007). In this regard, catheter bladder discomfort was more frequent in the PT group than in the PK group (43.3% versus 3.3%, P < 0.001). Conclusions The combination of intravenous paracetamol 1 gr and ketamine 0.5 mg/kg resulted in an overall reduction in pain scores, decreased postoperative analgesic requirements, and lower agitation

  2. The release behavior and kinetic evaluation of tramadol HCl from chemically cross linked Ter polymeric hydrogels

    PubMed Central

    2013-01-01

    Background and the purpose of the study Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels. Methods Ter-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA) were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol% EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism. Results and major conclusion Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n) derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n > 0.5 > 1) showing swelling controlled mechanism. The mechanical strength and controlled release capability of the

  3. Evaluating the Efficacy of Tramadol as an Adjuvant to Intrathecal Isobaric Levobupivacaine for Elective Infraumbilical Surgeries.

    PubMed

    Singh, Dewan Roshan; Mohamed, Hajer; Krishnaveni, N; Nag, Kusha

    2017-01-01

    Long-acting local anesthetics are used in subarachnoid block to increase the duration of anesthesia. Adjuvants are added to improve the duration of analgesia. Randomized controlled trial was conducted in the Department of Anesthesiology in a tertiary care hospital. The objective of this study was to evaluate the efficacy of low-dose tramadol as an intrathecal adjuvant to levobupivacaine in terms of duration of analgesia, onset of sensory blockade, onset of motor blockade, and duration of motor blockade. After obtaining the Institutional Ethics Committee approval and informed consent, sixty patients posted for infraumbilical surgeries were recruited. Randomization was done using a sealed envelope technique. Patients were divided into two groups: LT received 3 ml of 0.5% isobaric levobupivacaine with tramadol 10 mg (0.2 ml) and LS received 3 ml of 0.5% isobaric levobupivacaine with 0.2 ml of normal saline. Duration of analgesia, onset of sensory blockade, and onset and duration of motor blockade were recorded. There was no statistical difference in demographic data between the two groups. The mean onset time of sensory blockade in Group LS was 12.7 ± 9.81 min and for Group LT was 12.9 ± 0.81 min, which was not statistically significant between two groups (P = 0.93). The mean onset time of motor blockade in Group LS was 13.4 ± 10 min and for Group LT was 14.4 ± 10 min, which was no statistically significant between the two groups (P = 0.71). The mean time duration of analgesia in Group LS was 170.3 ± 59 min and for LT was 198.9 ± 57.33 min. There was mild prolongation of analgesia in Group LT, but it was not statistically significant (P = 0.0615). The mean duration of motor blockade in Group LS was 170.23 ± 58 min and Group LT was 190.76 ± 4 min, which was not statistically significant between the two groups (P = 0.14). Low-dose tramadol as an adjuvant to isobaric intrathecal levobupivacaine does not prolong analgesia significantly.

  4. Evaluating the Efficacy of Tramadol as an Adjuvant to Intrathecal Isobaric Levobupivacaine for Elective Infraumbilical Surgeries

    PubMed Central

    Singh, Dewan Roshan; Mohamed, Hajer; Krishnaveni, N.; Nag, Kusha

    2017-01-01

    Background: Long-acting local anesthetics are used in subarachnoid block to increase the duration of anesthesia. Adjuvants are added to improve the duration of analgesia. Settings: Randomized controlled trial was conducted in the Department of Anesthesiology in a tertiary care hospital. Aims and Objectives: The objective of this study was to evaluate the efficacy of low-dose tramadol as an intrathecal adjuvant to levobupivacaine in terms of duration of analgesia, onset of sensory blockade, onset of motor blockade, and duration of motor blockade. Methodology: After obtaining the Institutional Ethics Committee approval and informed consent, sixty patients posted for infraumbilical surgeries were recruited. Randomization was done using a sealed envelope technique. Patients were divided into two groups: LT received 3 ml of 0.5% isobaric levobupivacaine with tramadol 10 mg (0.2 ml) and LS received 3 ml of 0.5% isobaric levobupivacaine with 0.2 ml of normal saline. Duration of analgesia, onset of sensory blockade, and onset and duration of motor blockade were recorded. Results: There was no statistical difference in demographic data between the two groups. The mean onset time of sensory blockade in Group LS was 12.7 ± 9.81 min and for Group LT was 12.9 ± 0.81 min, which was not statistically significant between two groups (P = 0.93). The mean onset time of motor blockade in Group LS was 13.4 ± 10 min and for Group LT was 14.4 ± 10 min, which was no statistically significant between the two groups (P = 0.71). The mean time duration of analgesia in Group LS was 170.3 ± 59 min and for LT was 198.9 ± 57.33 min. There was mild prolongation of analgesia in Group LT, but it was not statistically significant (P = 0.0615). The mean duration of motor blockade in Group LS was 170.23 ± 58 min and Group LT was 190.76 ± 4 min, which was not statistically significant between the two groups (P = 0.14). Conclusion: Low-dose tramadol as an adjuvant to isobaric intrathecal

  5. Comparison of topical tramadol and ketamine in pain treatment after tonsillectomy.

    PubMed

    Tekelioglu, Umit Y; Apuhan, Tayfun; Akkaya, Akcan; Demirhan, Abdullah; Yildiz, Isa; Simsek, Tugce; Gok, Uzeyir; Kocoglu, Hasan

    2013-06-01

    The primary objective of this study is to evaluate the effects of topically applied ketamine or tramadol on early postoperative pain scores in children undergoing tonsillectomy. The secondary aim of the study is to assess nausea, vomiting, difficulty in swallowing, and sore throat characteristics of the patients. Tonsillectomy surgery is frequently associated with postoperative pain, which usually requires substantial consumption of analgesics including opioids. Safe and effective post-tonsillectomy pain control is still a clinical dilemma, in spite of the use of various surgical and anesthetic techniques. A total of 60 children, aged between 4 and 10 years, scheduled for tonsillectomy, were randomly assigned to one of three groups. Study drugs were administered to both tonsillar fossae for 5 min. In 5 ml artificial saliva, Group K (n = 20) received 0.4 ml (20 mg) ketamine and Group T (n = 20) received 0.8 ml tramadol HCl solution. Group C (n = 20) received only 5 ml saline as a control. Ramsay Sedation Scale and FACES PRS Score, nausea, vomiting, difficulty in swallowing, and sore throat were evaluated. There was no difference among the groups in terms of baseline characteristics, including age, sex, and ASA profile (P > 0.05 for all). Systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, respiratory rate, and saturation of peripheral oxygen (SpO2 ) values were not significantly different among the groups in all time points (P > 0.05 for all). There was a statistically significant difference among the groups according to Ramsay Sedation Scales in 40th minute (P < 0.001). There were statistically significant differences among the groups in terms of Wong-Baker FACES Pain Rating Scale Score in all time points (P < 0.004 for all). There was a statistically significant difference among the groups in terms of rescue analgesia necessity in 5th and 10th minute (P < 0.001 and P = 0.003). There was a statistically

  6. Comparing the effects of peritonsillar infiltration of tramadol before and after the surgery on post-tonsillectomy pain.

    PubMed

    Maryam, Hatami; Amin, Jesmani; Sedighe, Vaziribozorg; Vida, Ayatollahi

    2017-03-01

    The aim of the study was to compare the effects of peritonsillar infiltration of tramadol before and after the surgery on post-tonsillectomy pain. In this double-blinded clinical trial study, 80 children aged 5-12 years old with ASA (American Society of Anesthesiologists) class I or II undergoing tonsillectomy involved. In group A (n = 40), after anesthesia induction and before starting the surgery, tramadol 2 mg/kg diluted in normal saline up to 2 cc total volume was injected into the tensile bed by the anesthesiologist using a 25 gauge needle. Surgery began 3 min later and the tonsils were removed using the sharp dissection method. In children of group B (n = 40), anesthesia induction was performed. When surgery was completed, tramadol 2 mg/kg diluted in normal saline up to 2 cc total volume was injected at the site of removing each tonsil using a 25 gauge needle by the anesthesiologist. Using the CHEOPS (Children's Hospital of Eastern Ontario Pain Scale) Scale, pain recorded at different times. Patient sedation was recorded using the RAMSAY Sedation Scale. All the data were analyzed using SPSS 17 statistical software. Two groups significantly felt different pain intensities at different times following the surgery. At the three times, the mean sedation score in the group receiving tramadol infiltration before surgery was a little higher compared to the other group, but this difference was not significant (p > 0.05). As for the relative frequency of nausea and vomiting, the difference was not significant (p = 0.793). Request for analgesics between the groups was not significant (p = 0.556). The mean time of the first feeding after the surgery was not significant between the groups (p = 0.062). Surgical duration was almost the same for both groups (p > 0.05). Systolic blood pressures (before surgery, before extubation, and after extubation) were statistically the same in both groups (p < 0.05). Furthermore, systolic blood

  7. Crise convulsive chez les abuseurs de Tramadol et caféine: à propos de 8 cas et revue de la littérature

    PubMed Central

    Maiga, Djibo Douma; Seyni, Houdou; Sidikou, Amadou; Azouma, Alfazazi

    2012-01-01

    Nous rapportons Huit cas de crises convulsives diagnostiquées comme maladie épileptique après ingestion de Tramadol et d'autres substances psychotropes dont la Caféine dans une région ou maladie épileptique et addiction au café sont fréquentes. L'objectif de ce travail était d'informer les praticiens sur le risque de convulsion lié à la consommation du Tramadol seul ou en association avec d'autres psychotropes en s'appuyant sur les données de la littérature. Il s'agissait d'une étude rétrospective et exhaustive de patients vus en consultation ambulatoire pour crise convulsive et consommation de Tramadol et de caféine de janvier à mai 2012. Les données collectées étaient les caractéristiques sociodémographiques et de la consommation de Tramadol. Le diagnostic de crise convulsive a été posé sur les renseignements obtenus à l'anamnèse. Tous les patients ont été soumis à un examen neurologique et aux critères de dépendance du Diagnostic and Statistical Manual of Mental Disorders (DSMIV)-R par rapport à leur consommation de Tramadol. Nous n'avons pas trouvé dans la littérature médicale de cas de consommation concomitante de Tramadol et de Caféine. Les données expérimentales suggèrent une action synergique du Tramadol et de la Caféine sur la douleur et le seuil épileptogène. Nos observations plaident également en faveur d'une synergie d'action de ces deux molécules dans la survenue des crises convulsives. La fréquence des crises convulsives suite à une intoxication par le Tramadol et la caféine est susceptible d'augmenter en Afrique en raison du mésusage croissant de ces substances. Une étude comparative usagers de Tramadol associé à la Caféine et usagers du Tramadol seul devrait permettre d’évaluer le risque. PMID:23308329

  8. Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain.

    PubMed

    Stachtari, Chrysoula C; Thomareis, Olympia N; Tsaousi, Georgia G; Karakoulas, Konstantinos A; Chatzimanoli, Foteini I; Chatzopoulos, Stavros A; Vasilakos, Dimitrios G

    The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain. Prospective randomized trial assessing the individual or combined application of intraperitoneal tramadol (10 mg/kg) and the selective cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress stimulus. Pharmacological specificity was established by antagonizing tramadol with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120) minutes after incision. Blood samples for plasma IL-6 and IL-2 level determination were obtained 2 hours after incision. Data from 42 rats were included in the final analyses. Significant augmentation of thermal threshold was observed at all time points, after administration of either tramadol or (R,S)-AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively). The combination of (R,S)-AM1241 plus tramadol promoted the induced antinociception in an important manner compared with control (P = 0.002) and (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P = 0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241 administration in a significant manner (P = 0.001) at all time points. Similarly, naloxone plus SR144528 also blocked the effects of the combination of (R,S)-AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241 plus tramadol group was significantly attenuated compared with control group (P = 0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups. It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may

  9. Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

    PubMed Central

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of −0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables. PMID:21179349

  10. Formulation and development of matrix tablets of tramadol using katira gum as release modifier.

    PubMed

    Singh, Inderbir; Kumar, Pradeep; Kumar, Sanjeev; Rana, Vikas

    2010-09-01

    The present study was aimed to study the drug release retardant property of katira gum in matrix tablets containing tramadol as a model drug. Katira gum was characterized in terms of pH, viscosity and swelling index. The tablets were evaluated for various physical tests viz. hardness, friability, tensile strength and drug content. In vitro dissolution studies were performed and different empirical models were applied to drug release data for evaluating the drug release mechanisms and kinetics. Owing to good swelling properties (swelling index 340% and 480% after 6 and 24 h hydration) of the gum, the n values (as computed from Korsmeyer-Peppas model) were found to be ranging between 0.453 to 0.710 indicating involvement of both polymeric hydration and relaxation in the diffusion of drug from the matrix tablet.

  11. Population pharmacokinetic/pharmacodynamic modelling of the analgesic effects of tramadol in pediatrics.

    PubMed

    Garrido, María J; Habre, Walid; Rombout, Ferdinand; Trocóniz, Iñaki F

    2006-09-01

    The efficacy of tramadol (T) in children is not clearly understood because it is still unknown the ability of that population to form the active metabolite O-demethyltramadol (M1) and, whether or not the parent compound has a contribution to the efficacy. The aim was to develop a population pharmacokinetic/pharmacodynamic model for T in pediatrics, identifying the main active components. One hundred four children, mean age (4.55 years) received intravenously 1 mg/kg dose of T over 2.5 min at the end of surgery. If pain relief was inadequate, then an additional 0.33 mg/kg dose was given at 15, 30 and/or 45 min. Plasma samples and analgesic responses such as crying and movement were measured during a 6-h period. The estimates of the apparent volumes of distribution of the central compartment and at steady state and total plasma clearance of T were 8 l, 46.2 l, and 15.2 l/h, respectively. M1 formation clearance represented only a minor elimination pathway of T. Effect site concentrations of T and M1 were found to be the best predictors of the movement and crying responses, respectively. Steady-state plasma concentration levels of T and M1 of 100 and 15 ng/ml were associated with a 95% probability of adequate pain relief. Children have the ability to produce enough M1 to achieve proper pain relief. The response variables investigated give further evidence that not only the opioid effects of the metabolite are relevant, also the non-opiod effects of tramadol seem to give a significant contribution in its clinical use.

  12. Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin

    PubMed Central

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-01-01

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 μm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs. PMID:20631867

  13. Ketamine and tramadol for the prevention of shivering during spinal anaesthesia.

    PubMed

    Hidayah, M N; Liu, C Y; Joanna, O S M

    2014-01-01

    Anaesthesia and surgery promote significant thermal disorder in the human body. Spinal anaesthesia causes lower limb vasodilation and redistribution of body heat from central to the peripheral compartments. This was a prospective, randomised, double-blind clinical study to compare the effectiveness of IV ketamine and tramadol in the prevention of shivering associated with spinal anaesthesia. We prospectively studied 150 ASA classification I and II patients between 18 and 70 years old scheduled for any elective surgery performed under spinal anaesthesia. Patients were randomly allocated to receive either prophylactic IV ketamine 0.5 mg/kg (Group K), IV tramadol 0.5 mg/kg (Group T) or normal saline as control (Group P) after intrathecal injection of 0.5% hyperbaric bupivacaine 12.5 mg (2.5 ml) and 25 mcg fentanyl. The frequency and degree of shivering, haemodynamic parameters, core body temperature and side effects of the studied drugs were recorded for the first 30 minutes. The incidence of shivering was 8% in Group K, 16% in Group T and 24% in Group P. This result was statistically significant between Groups K and P. Patients from Group K also exhibited significantly higher mean arterial blood pressure and heart rate at 5 and 15 minutes post intrathecal injection while their mean core temperature was also significantly higher. Side effects such as nausea, vomiting, hallucination, agitation and sweating were comparable between all three groups. Patients from Group K however, had significant higher incidence of behavioural changes (blunted affect or catatonic state) and nystagmus. Prophylactic use of IV ketamine 0.5 mg/kg significantly reduced the frequency and the intensity of perioperative shivering associated with spinal anaesthesia but also exhibited some side effects of the drug. Lower doses of prophylactic ketamine should be studied.

  14. Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.

    PubMed

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-05-26

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

  15. Tramadol overdose and apnea in hospitalized children, a review of 20 cases

    PubMed Central

    Hassanian-Moghaddam, Hossein; Farnaghi, Fariba; Rahimi, Mitra

    2015-01-01

    We aimed to determine the clinical manifestations of tramadol intoxication in children and to find its potential poor prognostic factors. In a retrospective study, from 1363 cases of admitted pediatric poisoning, all tramadol-exposed hospitalized patients younger than 12 years were included in the study. They were hospitalized between March 2010 and April 2012 to the only referral hospital for pediatric poisoned patients in Tehran, Iran. Data including age, weight, gender, ingested dose (determined by history), pupil size, seizure, apnea, treatment interventions, and laboratory results was collected using chart review of the hospitalized intoxicated children. Twenty children with a mean age of 3.7 ± 2.9 years were identified amongst children during this 26-month period of whom, 14 (70%) had a decreased level of consciousness, 3 (15%) experienced apnea, and four (20%) had nausea and vomiting. Witnessed seizure did not occur in any of these patients. All patients were referred to hospital within 10.5 h of the exposure. The mean ingested dose was 9.6 ± 5.5 mg/kg. There was no significant relation between apnea and the estimated toxic dose. Apnea was more common in children who had presented with respiratory acidosis (Relative risk = 3.8, 95% CI = 1.6, 8.7, P = 0.043). All patients survived. Patients with apnea were managed conservatively by naloxone and recovered without need for intubation. Respiratory depression might occur at doses just above the therapeutic dose. We recommend an observation time of 12 h for all asymptomatic children who have ingested any dose greater than the therapeutic one. PMID:26779274

  16. Intrathecal injection of codeine, buprenorphine, tilidine, tramadol and nefopam depresses the tail-flick response in rats.

    PubMed

    Bernatzky, G; Jurna, I

    1986-01-14

    The effect of intrathecal (i.t.) injection of the analgesic agents, codeine, buprenorphine, tilidine and one of its metabolites, nortilidine, tramadol and nefopam, was determined in the tail-flick test performed on rats. ED50 values were derived from the dose-response lines. The relative potency ranking established from the ED50 values is buprenorphine (0.4 nM) greater than nortilidine (29 nM) = tramadol (26 nM) = nefopam (34 nM) greater than codeine (42 nM) greater than tilidine (118 nM). An i.t. injection of the opiate antagonist, naloxone (5 micrograms), prevented the antinociceptive effect of all analgesic agents administered at the highest dose tested. It is concluded that these analgesic agents, like morphine, exert their effect at least in part through a spinal site of action.

  17. Rates of abuse of tramadol remain unchanged with the introduction of new branded and generic products: results of an abuse monitoring system, 1994-2004.

    PubMed

    Cicero, Theodore J; Inciardi, James A; Adams, Edgar H; Geller, Anne; Senay, Edward C; Woody, George E; Muñoz, Alvaro

    2005-12-01

    The analgesic Tramadol HCl (Ultram) was approved in 1994 as a non-scheduled drug under the CSA provided that a novel risk-management program would be developed by an Independent Steering Committee (ISC). The risk-management program began in 1995 with the launch of Ultram, and has been modified over the past decade to accommodate Ultracet (Ultram and acetaminophen) in 2001 and generic tramadol in 2002. This provided a unique opportunity to study the potential changes in abuse as the generic and combination products became available. To proactively detect cases of abuse and diversion, the ISC developed a comprehensive questionnaire which was completed quarterly by an extensive network of drug abuse experts (n = 309) and police agencies (n = 100) who were asked to indicate how many diversion cases involving Ultram, Ultracet, and generic tramadol were identified during the preceding 3 months and what were the ten most commonly diverted drugs in their catchment area during that period. The data generated demonstrate that the abuse of tramadol remained very low despite new branded and generic formulations. Contrary to the hypothesis that cheaper generic drugs would lead to higher rates of abuse, we found no increase in abuse with the introduction of generic tramadol. Ultracet abuse rates, unlike those found with other widely used hydrocodone and oxycodone combination products, have been even lower than that observed for tramadol. Since the FDA has now mandated that proactive risk-management plans be implemented for new drugs, the tramadol risk-management plan may be useful as a prototypic model which can be modified to accommodate other drugs with abuse potential. Copyright (c) 2005 John Wiley & Sons, Ltd.

  18. Intraoperative administration of tramadol for postoperative nurse-controlled analgesia resulted in earlier awakening and less sedation than morphine in children after cardiac surgery.

    PubMed

    Chu, Ya-Chun; Lin, Su-Man; Hsieh, Ying-Chou; Chan, Kwok-Hon; Tsou, Mei-Yung

    2006-06-01

    In adults, intraoperative administration of tramadol could result in earlier recovery and less sedation than morphine. In this controlled, randomized, double-blind study, we investigated whether an intraoperative initial dose of tramadol could cause more rapid awakening from general anesthesia, less sedation, and earlier tracheal extubation than morphine in children during the immediate postoperative period. Forty children aged 1-6 yr, scheduled for atrial or ventricular septal defect repair and tracheal extubation in the pediatric intensive care unit, were randomly allocated to receive morphine, initial dose 0.2 mg/kg, or tramadol 2 mg/kg given at the end of sternal closure, followed by nurse-controlled analgesia (bolus 0.02 mg/kg of morphine and 0.2 mg/kg of tramadol) with background infusions (0.015 mg x kg(-1) x h(-1) for morphine and 0.15 mg x kg(-1) x h(-1) for tramadol). Postoperatively, children receiving tramadol had earlier awakening from general anesthesia (P = 0.02) and were less sedated at 1 and 2 h postoperatively (P = 0.03 and P = 0.01, respectively). Tracheal extubation was earlier in the tramadol group (P = 0.01). Lengths of pediatric intensive care unit stay did not differ between groups. Times to first trigger of nurse-controlled analgesia bolus and objective pain scores during the 48 h observation period were comparable between groups. The incidence of desaturation and emesis were similar between groups. The patients ate well and did not differ on Day 1 or Day 2.

  19. Carprofen provides better post-operative analgesia than tramadol in dogs after enucleation: A randomized, masked clinical trial

    PubMed Central

    Delgado, Cherlene; Bentley, Ellison; Hetzel, Scott; Smith, Lesley J

    2015-01-01

    Objective To compare analgesia provided by carprofen or tramadol in dogs after enucleation. Design Randomized, masked trial Animals Forty-three dogs Procedures Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for pain at baseline, and postoperatively at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥9, if there was a score ≥ 3 in any one category, or if the visual analog scale score (VAS) was ≥35 combined with a palpation score of >0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. Characteristics between groups were compared with a Student’s t-test and Fisher’s exact test. The incidence of rescue was compared between groups using a log rank test. Pain scores and VAS scores between groups were compared using repeated measures ANOVA. Results There was no difference in age (p=0.493), gender (p=0.366) or baseline pain scores (p=0.288) between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21) compared to dogs receiving carprofen (1/22; p=0.035). Pain and VAS scores decreased linearly over time (p=0.038, p<0.001, respectively). There were no significant differences in pain (p=0.915) or VAS scores (p=0.372) between groups at any time point (dogs were excluded from analysis after rescue). Conclusions and Clinical Relevance This study suggests that carprofen, with opioid premedication, provides more effective post-operative analgesia than tramadol in dogs undergoing enucleation. PMID:25459482

  20. Comparison of caudal ketamine with lidocaine or tramadol administration for postoperative analgesia of hypospadias surgery in children.

    PubMed

    Gunduz, M; Ozalevli, M; Ozbek, H; Ozcengiz, D

    2006-02-01

    This study was designed to investigate whether the addition of tramadol or lidocaine to ketamine would enhance the quality of intra- and postoperative analgesia for hypospadias surgery in children. Sixty-two ASA PS I or II children, between 1 and 10 years of age, scheduled for hypospadias surgery were recruited. Anesthesia was induced with 6-8% sevoflurane and maintained with 0.5-2.5% sevoflurane-50% N2O in oxygen. Children were allocated randomly to receive one of two study drugs. Children in group KL received caudal ketamine (0.25 mg.kg(-1)) plus lidocaine (2%, 2 mg.kg(-1)) and in group KT ketamine (0.25 mg.kg(-1)) plus tramadol (1 mg.kg(-1)). Systemic blood pressure, heart rate, peripheral O2 saturation, sedation, and pain scores (CHEOPS) were recorded at 1, 5, 10, 15, 30, 45 min and 1, 2, 3 h following recovery from anesthesia. Duration of analgesia was similar in the two groups (P > 0.05). CHEOPS in group KL was lower than in group KT during the study period, except at first 15 min. Sedation scores were higher in group KL than group KT in the first 10 min (P < 0.05). Incidence of postoperative nausea and vomiting was similar in the two groups (P > 0.05) Sevoflurane concentration required was significantly lower in group KL than group KT peroperatively (P < 0.001). Caudal ketamine (0.25 mg.kg(-1)), plus lidocaine (2% 2 mg.kg(-1)) significantly reduced sevoflurane concentration compared with ketamine (0.25 mg.kg(-1)) + tramadol (1 mg.kg(-1)). We suggested that both ketamine + lidocaine and ketamine + tramadol provided very effective and long duration of analgesia, similarly. However, analgesia quality is superior in the ketamine-lidocaine group postoperatively.

  1. [The effect of tramadol and other analgesics on the pain threshold in human dental pulp (author's transl)].

    PubMed

    Rost, A; Schenck, E G

    1978-01-01

    In 60 young, healthy volunteers the analgesic efficacy of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal), dextropropoxyphene and a commercial drug mixture (acetylsalicylic acid 200 mg; phenacetin 200 mg; codeine phosphor. 10 mg; caffeine anhydr. 50 mg; phenobarbital 25 mg) was investigated by determining the pain threshold in dental pulp. All three drugs increased the pain threshold considerably but there was no difference in the analgesic effect of the three drugs.

  2. A Comparative Assessment of Postoperative Analgesic Efficacy of Lornoxicam versus Tramadol after Open Reduction and Internal Fixation of Mandibular Fractures.

    PubMed

    Jain, Ankesh Dilip; Vsm, Ravisankar; Ksn, Siva Bharani; Km, Sudheesh; Tewathia, Nisha

    2017-09-01

    Pain after any surgical procedure is inevitable but can be controlled by administration of analgesics in most cases. Postoperative pain after surgical treatment of mandibular fractures can be treated by nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. The purpose of this study is to critically compare the postoperative analgesic efficacy of small doses of intravenous TRAMADOL (opioid analgesic) versus LORNOXICAM (NSAID) in patients with mandibular trauma undergoing open reduction and internal fixation (ORIF) and to assess the presence of any adverse effects due to NSAID or opioid use. Forty adult ASA grade I-II patients with mandibular trauma, scheduled for ORIF under general anesthesia in the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, were selected for the study. The patients were randomly assigned into a tramadol group (Group T) and a lornoxicam group (Group L) and were administered intravenous tramadol 50 mg and intravenous lornoxicam 8 mg, respectively, at specific postoperative intervals. Pain intensity was quantitatively assessed at the 2nd, 4th, 6th, 12th, and 24th postoperative hours using a visual analog scale of 10 cm. Adverse effects of the analgesics were also recorded and compared. Both the drugs resulted in a significant decrease in pain intensity from 2nd to 24th postoperative hours, but better pain control was observed in Group L at 24th postoperative hour. Only two patients experienced nausea and vomiting in Group T and one patient experienced gastric acidity in Group L. The comparative results clearly demonstrate that pain control by intravenous lornoxicam is significantly better than by intravenous tramadol at 24th postoperative hour after ORIF of mandibular trauma. Side effects produced by both the drugs were minor and had no apparent effect on the study results.

  3. Local Infiltration of Tramadol versus Bupivacaine for Post Cesarean Section Pain Control: A Double-Blind Randomized Study.

    PubMed

    Sahmeddini, Mohammad Ali; Azemati, Simin; Motlagh, Ehsan Masoudi

    2017-05-01

    Postoperative pain control after cesarean section (C/S) is important because inadequate postoperative pain control can result in a prolonged hospital stay. In this study, we compared postoperative somatic wound pain control between patients receiving tramadol and bupivacaine, infiltrated at the wound site. In this randomized clinical trial, 98 patients, eligible for elective C/S under general anesthesia, were randomly allocated to 2 groups. Before wound closure, 20 cc of 0.025% bupivacaine and 2 mg/kg of tramadol, diluted to 20 cc, were infiltrated at the wound site in groups A and B, respectively. After surgery, the pain score was measured using the visual analogue scale (VAS). Additionally, 24-hour total morphine consumption, nausea and vomiting, and respiratory depression were compared after 2, 4, 8, 16, and 24 hours between the 2 groups. The data were analyzed using SPSS with the Student independent t test, χ(2) test, Fisher exact test, and repeated measure test. Postoperatively, there was no significant difference between these 2 groups in their VAS scores until 16 hours (P>0.05). However, at the 16(th) and 24(th) hours, the mean VAS scores were 3.20±2.24 and 2.51±2.55 in the bupivacaine group and 2.51±0.99 and 1.40±0.88 in the tramadol group, respectively (P<0.05). There was no difference in nausea and vomiting during the 24-hour period between the 2 groups. Also, no respiratory depression was detected in the both groups. Local infiltration of tramadol (2 mg/kg) at the incision site of C/S was effective in somatic wound pain relief without significant complications. IRCT2013070111662N2.

  4. Local Infiltration of Tramadol versus Bupivacaine for Post Cesarean Section Pain Control: A Double-Blind Randomized Study

    PubMed Central

    Sahmeddini, Mohammad Ali; Azemati, Simin; Motlagh, Ehsan Masoudi

    2017-01-01

    Background: Postoperative pain control after cesarean section (C/S) is important because inadequate postoperative pain control can result in a prolonged hospital stay. In this study, we compared postoperative somatic wound pain control between patients receiving tramadol and bupivacaine, infiltrated at the wound site. Methods: In this randomized clinical trial, 98 patients, eligible for elective C/S under general anesthesia, were randomly allocated to 2 groups. Before wound closure, 20 cc of 0.025% bupivacaine and 2 mg/kg of tramadol, diluted to 20 cc, were infiltrated at the wound site in groups A and B, respectively. After surgery, the pain score was measured using the visual analogue scale (VAS). Additionally, 24-hour total morphine consumption, nausea and vomiting, and respiratory depression were compared after 2, 4, 8, 16, and 24 hours between the 2 groups. The data were analyzed using SPSS with the Student independent t test, χ2 test, Fisher exact test, and repeated measure test. Results: Postoperatively, there was no significant difference between these 2 groups in their VAS scores until 16 hours (P>0.05). However, at the 16th and 24th hours, the mean VAS scores were 3.20±2.24 and 2.51±2.55 in the bupivacaine group and 2.51±0.99 and 1.40±0.88 in the tramadol group, respectively (P<0.05). There was no difference in nausea and vomiting during the 24-hour period between the 2 groups. Also, no respiratory depression was detected in the both groups. Conclusion: Local infiltration of tramadol (2 mg/kg) at the incision site of C/S was effective in somatic wound pain relief without significant complications. Trial Registration Number: IRCT2013070111662N2 PMID:28533571

  5. Tramadol vs dexmedetomidine for emergence agitation control in pediatric patients undergoing adenotonsillectomy with sevoflurane anesthesia: prospective randomized controlled clinical study.

    PubMed

    Bedirli, Nurdan; Akçabay, Mehmet; Emik, Ulku

    2017-03-11

    This study was designed to compare the efficacy of an intraoperative single dose administration of tramadol and dexmedetomidine on hemodynamics and postoperative recovery profile including pain, sedation, emerge reactions in pediatric patients undergoing adenotonsillectomy with sevoflurane anesthesia. Seventy-seven patient, aged 2-12, undergoing adenotonsillectomy with sevoflurane anesthesia was enrolled in this study. Patients were randomly assigned to receive either intravenous 2 mg/kg tramadol (Group T; n = 39) or 1 μg/kg dexmedetomidine (Group D; n = 38) after intubation. Heart rates (HR), mean arterial pressure (MAP) were recorded before induction, at induction and every 5 min after induction. Observational pain scores (OPS), pediatric anesthesia emergence delirium (PAED) scores, percentage of patients with OPS ≥ 4 or PAED scale items 4 or 5 with an intensity of 3 or 4, and Ramsay sedation scores (RSS) were recorded on arrival to the postoperative care unit (PACU) and at 5, 10, 15, 30, 45, 60 min. Extubation time and time to reach Alderete score > 9 were recorded. Dexmedetomidine significantly decreased the HR and MAP 10 and 15 min after induction; increased the RSS 15, 30 and 45 min after arrival to PACU. OPS and PAED scores and percentage of patients with OPS ≥ 4 or PAED scale items 4 or 5 with an intensity of 3 or 4 in both groups did not show any significant difference. Extubation time and time to have Alderete score > 9 was significantly longer in Group D. Both tramadol and dexmedetomidine were effective for controlling pain and emergence agitation. When compared with tramadol intraoperative hypotension, bradycardia and prolonged sedation were problems related with dexmedetomidine administration. Retrospectively registered, registration number: ISRCTN89326952 registration date: 14.07.2016.

  6. Effects of tramadol on viscero-visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis.

    PubMed

    Lopopolo, Mariangela; Affaitati, Giannapia; Fabrizio, Alessandra; Massimini, Francesca; Lapenna, Domenico; Giamberardino, Maria Adele; Costantini, Raffaele

    2014-06-01

    The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14-18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). All were video-taped 24 h nonstop for 7 days before and 4 days after stone formation (14-25th day postendometriosis) to record ureteral and pelvic pain behaviors. Lumbar sensitivity (L1) was tested bilaterally, daily over the same period, by verifying presence/absence of vocalization upon muscle pinching at a predefined pressure (calibrated forceps). Additional fifty endo + stone rats underwent the same protocol, except that treatment was performed on 21st-25th day (poststone treatment). Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose-dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from 'viscero-visceral hyperalgesia' in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities.

  7. [Non-steroidal anti-inflammatory drugs and tramadol in the treatment of osteoarthrosis deformans in patients with arterial hypertension].

    PubMed

    Lazebnik, L B; Kotsiubinskaia, O B; Konev, Iu V; Drozdov, V N

    2004-01-01

    The prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can be manifested by the decreased efficiency of antihypertensive therapy. The tactics of their differential use in relation to the its effect on blood pressure (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not been developed for the most effective and safe therapy. In this connection, it is extremely urgent to study the comparative safety of used NSAIDs as to their prohypertensive effect and to work out the management of patients with AH and OA. Ninety-eight patients with second-third degree OA of the knee and hip joints concurrent with the pain syndrome and first-second grade AH were followed up. Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a control group, the analgesic tramadol was supplemented to the therapy. AH was controlled by enalapril monotherapy. In groups of patients receiving diclofenac, arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the prohypertensive effect of these drugs; this trend was most pronounced in the diclofenac and arthrotec groups. Despite its marked prohypertensive effect, nimesulide did not impair circadian BP variations. The central-acting analgesic tramadol exerted no prohypertensive effect and it did not increase BP values. The prohypertensive effect of the tested NSAIDs and tramadol increases in the following order: tramadol, ketoprofen, meloxicam, nimesulide, arthrotec, diclofenac.

  8. The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal

    PubMed Central

    Karrasch, Nicole M.; Lerche, Phillip; Aarnes, Turi K.; Gardner, Heather L.; London, Cheryl A.

    2015-01-01

    This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period. PMID:26246627

  9. Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

    PubMed

    Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

    2015-05-01

    Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

  10. Formulation and dissolution kinetics study of hydrophilic matrix tablets with tramadol hydrochloride and different co-processed dry binders.

    PubMed

    Komersová, Alena; Lochař, Václav; Myslíková, Kateřina; Mužíková, Jitka; Bartoš, Martin

    2016-12-01

    The aim of this study is to present the possibility of using of co-processed dry binders for formulation of matrix tablets with drug controlled release. Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and different co-processed dry binders were prepared by direct compression method. Hypromelloses Methocel™ K4M Premium CR or Methocel™ K100M Premium CR were used as controlled release agents and Prosolv® SMCC 90 or Disintequik™ MCC 25 were used as co-processed dry binders. Homogeneity of the tablets was evaluated using scanning electron microscopy and energy dispersive X-ray microanalysis. The release of tramadol hydrochloride from prepared formulations was studied by dissolution test method. The dissolution profiles obtained were evaluated by non-linear regression analysis, release rate constants and other kinetic parameters were determined. It was found that matrix tablets based on Prosolv® SMCC 90 and Methocel™ Premium CR cannot control the tramadol release effectively for >12h and tablets containing Disintequik™ MCC 25 and Methocel™ Premium CR >8h. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Comparison of single-dose nalbuphine versus tramadol for postoperative pain management in children: a randomized, controlled trial.

    PubMed

    Liaqat, Naeem; Dar, Sajid Hameed

    2017-04-01

    Acute postoperative pain control in children is an essential component of postoperative care, particularly in daycare procedures. Giving patients continuous narcotic analgesics can be risky; however, a single dose may be sufficient. This study used a prospective, randomized controlled design and was conducted at the Pediatric Surgery Unit, Services Hospital, Lahore. In total, 150 patients who underwent inguinal herniotomy (age range: 1-12 years) were randomly assigned to two groups: group A (nalbuphine) and group B (tramadol). Patients were given a single dose of either nalbuphine (0.2 mg/kg) or tramadol (2 mg/kg) immediately after surgery and pain was measured at 0, 1, 2, 4, and 8 h. The demographic characteristics were similar between the two groups. The mean pain score was lower in group A than in group B at 0 and 1 h (P < 0.05). However, at 4 h and 8 h, the pain scores in group A were still lower, but not significantly. In all, 9 patients (12.0%) required rescue analgesics in group A compared to 16 patients (21.3%) in group B (P = 0.051). The mean time for requirement of rescue analgesics was 6.5 ± 0.5 h in group A and 5.3 ± 1.7 h in group B (P = 0.06). A single dose of nalbuphine is sufficient, and superior to tramadol, for postoperative pain management in children who have undergone daycare procedures.

  12. The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal.

    PubMed

    Karrasch, Nicole M; Lerche, Phillip; Aarnes, Turi K; Gardner, Heather L; London, Cheryl A

    2015-08-01

    This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period.

  13. Effects of tramadol, morphine or their combination in dogs undergoing ovariohysterectomy on peri-operative electroencephalographic responses and post-operative pain.

    PubMed

    Kongara, K; Chambers, J P; Johnson, C B

    2012-03-01

    To compare the peri-operative electroencephalogram (EEG) responses and post-operative analgesic efficacy of pre-operative morphine or tramadol with a combination of low-dose pre-operative morphine and post-operative tramadol, in dogs undergoing ovariohysterectomy. Dogs undergoing routine ovariohysterectomy were treated with either pre-operative morphine (0.5 mg/kg S/C, n=8), or tramadol (3 mg/kg S/C, n=8), or pre-operative low-dose morphine (0.1 mg/kg S/C) and post-operative tramadol (3 mg/kg I/V, n=8). All dogs received routine pre-anaesthetic medication, and anaesthesia was induced with I/V thiopentone to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO₂ tension (EtCO₂) were monitored throughout surgery. The EEG was recorded continuously in a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) of the EEG power spectra were compared during different 100-second periods of surgery: prior to and during skin incision, ligation of each ovarian pedicle, ligation of uterine body and skin closure. Post-operatively, pain was assessed using the short form of the Glasgow composite measure pain scale (CMPS-SF). There was no difference in F50 or Ptot of the EEG between baseline and noxious surgical events within each treatment group, or between the three groups (p>0.05). The mean F95 was higher during the first three periods of surgery for dogs administered tramadol and low-dose morphine than those that received 0.5 mg/kg morphine (p=0.001). Dogs that received low-dose morphine and tramadol had lower CMPS-SF pain scores after ovariohysterectomy than those that received either tramadol or morphine alone (p=0.001). There was no difference in pain scores between dogs in the latter two groups. Tramadol and morphine administered pre-operatively provided an equal degree of post-operative analgesia in dogs after ovariohysterectomy. A combination

  14. Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk

    PubMed Central

    Ilett, Kenneth F; Paech, Michael J; Page-Sharp, Madhu; Sy, Sherwin K; Kristensen, Judith H; Goy, Raymond; Chua, Sebastian; Christmas, Tracey; Scott, Karen L

    2008-01-01

    AIMS To investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant. METHODS Tramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2–4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac-tramadol and rac-O-desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied. RESULTS At steady-state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac-tramadol and 2.8 (2.5, 3.1) for rac-O-desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) μg kg−1 day−1 and 30 (28, 32) μg kg−1 day−1, and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac-tramadol and rac-O-desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores. CONCLUSIONS The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. WHAT THIS STUDY ADDS We have provided quantitative data on the absolute and relative infant doses of rac-tramadol and it rac-O-desmethyl metabolite for the breastfed infant. We have also demonstrated a novel sparse sampling data collection method for investigating infant

  15. Effect of epidural tramadol and lignocaine on physiological and behavioural changes in goats subjected to castration with a high tension band.

    PubMed

    Ajadi, R A; Owanikin, A O; Martins, M M; Gazal, O S

    2012-11-01

    To compare the effect of a single epidural injection of either lignocaine or tramadol on behavioural changes, anaesthetic indices, leucocyte parameters, erythrocyte sedimentation rates and concentration of cortisol in plasma in goats subjected to castration by high tension band. Ten male goats weighing 14.4 (SD 0.7) kg were randomly allocated to anaesthesia with epidural injections of tramadol (3 mg/kg), or lignocaine (4 mg/kg). Following anaesthesia, a rubber ring was applied and tensioned to the scrotal neck of each goat. Behavioural changes were noted as they occurred, and the onset of drug action (time between epidural injection and loss of pedal reflex) and duration of antinociception (time interval between disappearance and reappearance of pedal withdrawal reflex) were determined. Hearts rates, respiratory rates and rectal temperatures were determined every 15 minutes for a 90-minute period, while blood was obtained for determination of white cell counts, erythrocyte sedimentation rates and concentrations of cortisol. Anaesthetic indices were compared using Student's t-test, while physiological parameters were compared using an ANOVA for repeated measurements. Goats treated with epidural tramadol were not recumbent and continued rumination while goats treated with epidural lignocaine were recumbent and did not continue rumination. The onset of analgesia was longer (p=0.01) in goats treated with epidural tramadol (5.0 minutes; SD 1.2) than goats treated with epidural lignocaine (3.0 minutes; SD 1.1), while duration of analgesia was shorter (p=0.003) in goats treated with epidural tramadol (47.2 minutes; SD 13.1) than goats treated with epidural lignocaine (89.8 minutes; SD 23.1). There was no significant difference in heart rates, respiratory rates and erythrocyte sedimentation rates, while the concentration of cortisol in plasma differed (p<0.05) between goats treated with epidural tramadol and lignocaine. Epidural lignocaine injection produced longer

  16. Involvement of nitric oxide and ATP-sensitive potassium channels in the peripheral antinoceptive action of a tramadol-dexketoprofen combination in the formalin test.

    PubMed

    Isiordia-Espinoza, Mario A; Pozos-Guillén, Amaury; Pérez-Urizar, José; Chavarría-Bolaños, Daniel

    2014-11-01

    Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)-cyclic guanosine monophosphate pathway and ATP-sensitive K(+) channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin-injured mouse paw and the antinociceptive effect evaluated. ED50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction during the second phase of the formalin test. Pretreatment with NO antagonists, including l-NG-nitroarginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, or the ATP-sensitive K(+) channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol-dexketoprofen combination, suggesting that NO and ATP-sensitive K(+) channels were involved. © 2014 Wiley Periodicals, Inc.

  17. Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial

    PubMed Central

    Isiordia-Espinoza, Mario-Alberto; Martinez-Rider, Ricardo; Perez-Urizar, Jose

    2016-01-01

    Background Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. Material and Methods A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Results Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. Conclusions According to the VAS and AUC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery. Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. PMID:27475688

  18. The addition of a small-dose ketamine infusion to tramadol for postoperative analgesia: a double-blinded, placebo-controlled, randomized trial after abdominal surgery.

    PubMed

    Webb, Ashley R; Skinner, Bradley S; Leong, Samuel; Kolawole, Helen; Crofts, Tyron; Taverner, Murray; Burn, Sara J

    2007-04-01

    There are few data on combining ketamine with tramadol for postoperative analgesia in humans. We tested the hypothesis that adding ketamine to tramadol would improve analgesia after major abdominal surgery. In this double-blind, randomized, controlled trial, adult patients (n = 120) having elective laparotomy were randomly assigned to a ketamine group (intraoperative ketamine 0.3 mg/kg and postoperative infusion at 0.1 mg x kg(-1) x h(-1) or control group (equivalent volume/rate of normal saline). All patients received intraoperative tramadol 3 mg/kg and a tramadol infusion (0.2 mg x kg(-1) x h(-1) for 48 h postoperatively and had morphine patient-controlled analgesia available for rescue analgesia. The ketamine group had less pain at rest (P = 0.01) and with movement (P = 0.02) and required less morphine (P = 0.003) throughout the 48-h study period. In the 0-24 h period, ketamine improved subjective analgesic efficacy (P = 0.008), was less sedating (P = 0.03), and required fewer physician interventions to manage severe pain (P = 0.01). Hallucinations were more common in ketamine patients, but other side effects were similar. Small-dose ketamine was a useful addition to tramadol and morphine after major abdominal surgery.

  19. Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial.

    PubMed

    Ayatollahi, Vida; Behdad, Shokoufeh; Hatami, Maryam; Moshtaghiun, Hossein; Baghianimoghadam, Behnam

    2012-04-01

    To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects. The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery. Tramadol group had significantly lower pain scores (P=0.005), significantly longer time to the first request for analgesic (P=0.001), significantly shorter time to the beginning of liquid regimen (P=0.001), and lower hemodynamic parameters such as blood pressure (P=0.001) and heart rate (P=0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting. Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects.

  20. Evaluation of analgesic efficacy of intra-articular bupivacaine, bupivacaine plus fentanyl, and bupivacaine plus tramadol after arthroscopic knee surgery.

    PubMed

    Mitra, Sukanya; Kaushal, Harpreet; Gupta, Ravi K

    2011-12-01

    To compare the efficacy of intra-articular (IA) bupivacaine, bupivacaine-fentanyl, and bupivacaine-tramadol for relief of postoperative pain after arthroscopic knee surgery. In a randomized double-blind design, 60 adult American Society of Anesthesiologists class I or class II patients undergoing elective arthroscopic knee surgery under general anesthesia were randomized to 3 groups: all received 30 mL of 0.25% bupivacaine, plus either 1 mL of normal saline solution (group I), 1 mL (50 μg) of fentanyl (group II), or 1 mL (50 mg) of tramadol (group III). Pain was assessed by use of a 100-mm visual analog scale (VAS) at 0, 1, 2, 4, 6, and 8 hours postoperatively. Intramuscular diclofenac sodium was used as rescue analgesic. Postoperative adverse effects were noted. The mean VAS pain scores were the lowest for group II, intermediate for group III, and highest for group I. There was a significant main effect for group differences on pain scores (F = 41.138, P < .001). The main effect for the time factor was also significant (F = 6.097, P < .001). However, both group II and group III were comparable and both were superior to group I with regard to supplementary analgesia in terms of (1) number of patients receiving it, (2) total consumption during the study period, and (3) time to first supplementary analgesic requirement. The incidence of adverse event was comparable among the 3 groups. On the primary outcome measure (VAS pain score), both bupivacaine with fentanyl and bupivacaine with tramadol were better than IA bupivacaine, and bupivacaine with fentanyl was better than that with tramadol. However, both the combinations were comparable to each other with regard to the secondary outcome measure (supplementary analgesic requirement). Thus IA bupivacaine-fentanyl appears to be the best combination for relief of postoperative pain in patients undergoing arthroscopic knee surgery, followed by IA bupivacaine-tramadol. Level I, randomized controlled trial. Copyright

  1. Effects of tramadol or morphine in dogs undergoing castration on intra-operative electroencephalogram responses and post-operative pain.

    PubMed

    Kongara, K; Chambers, J P; Johnson, C B; Dukkipati, V S R

    2013-11-01

    To compare the effects of pre-operatively administered tramadol with those of morphine on electroencephalographic responses to surgery and post-operative pain in dogs undergoing castration. Dogs undergoing castration were treated with either pre-operative morphine (0.5 mg/kg S/C, n = 8) or tramadol (3 mg/kg S/C, n = 8). All dogs also received 0.05 mg/kg acepromazine and 0.04 mg/kg atropine S/C in addition to the test analgesic. Anaesthesia was induced with thiopentone administered I/V to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO2 tension (EtCO2) were monitored throughout surgery. Electroencephalograms (EEG) were recorded continuously using a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) derived from EEG power spectra recorded before skin incision (baseline) were compared with those recorded during ligation of the spermatic cords of both testicles. Post-operatively, pain was assessed after 1, 3, 6 and 9 h using the short form of the Glasgow composite measure pain scale (CMPS-SF). Dogs premedicated with tramadol had higher mean F50 (12.2 (SD 0.2) Hz) and lower Ptot (130.39 (SD 12.1) µv(2)) compared with those premedicated with morphine (11.5 (SD 0.2) Hz and 161.8 (SD 15.1) µv(2), respectively; p<0.05) during ligation of testicle 1. There were no differences in EEG responses between the two treatment groups during ligation of testicle 2 (p>0.05). The F95 of the EEG did not differ between the two groups during the ligation of either testicle (p > 0.05). Post-operatively, no significant differences in the CMPS-SF score were found between animals premedicated with tramadol and morphine at any time during the post-operative period. No dog required rescue analgesia. Tramadol and morphine administered pre-operatively provided a similar degree of post-operative analgesia in male dogs at the doses tested.

  2. Comparative evaluation of pre-emptive analgesic efficacy of intramuscular ketorolac versus tramadol following third molar surgery.

    PubMed

    Shah, Ashwin V; Arun Kumar, K V; Rai, Kirthi Kumar; Rajesh Kumar, B P

    2013-06-01

    Pre-emptive analgesia aims at preventing the central nervous system from reaching a hyper-excitable state known as central sensitization, in which it responds excessively to afferent inputs. The clinical implication would be more effective pain management, thereby reducing post-operative pain and analgesic requirements. This study aimed at investigating the existence of pre-emptive analgesia and to compare the pre-emptive analgesic efficacy of im ketorolac [NSAID] versus tramadol [SYNTHETIC OPIOD] for post-operative pain management following third molar surgery. Fifty patients under the age group of 16-25 years with asymptomatic, symmetrically impacted mandibular third molars were equally divided into 2 groups and underwent third molar surgery under local anesthesia. Ketorolac 30 mg and tramadol 50 mg were used in the study group, while sodium chloride 0.9 % was used in the control group. Study parameters included pain intensity scores for 12 post-operative hours, time to 1st rescue analgesia, total number of analgesics consumed during the 5 post-operative days and patients' self assessment of efficacy of the surgery with regardsto no pain. Statistically, the data are presented as the mean values with their standard deviations and a 95 % confidence interval [p is significant, if p < 0.05] for the mean are applicable. Incidences of adverse events like pain on injection of the study drug, local reactions, nausea and vomiting were noted. Patients in the study group significantly performed better than the control group in terms of all the parameters; while among the study group, ketorolac fared better than tramadol. All the drug related complications were mild and did not require any intervention. Pre-operative ketorolac or tramadol in comparison to placebo resulted in a significantly better post-operative pain management. However as against tramadol, ketorolac is a better choice as a pre-emptive analgesic agent for the post-operative pain management following

  3. Anti-nociceptive and sedative effects of romifidine, tramadol and their combination administered intravenously slowly in ponies.

    PubMed

    Costa, Giovanna L; Cristarella, Santo; Quartuccio, Marco; Interlandi, Claudia

    2015-03-01

    To evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies. Within-subject blinded. Twenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg). On separate occasions, each pony received one of the following three treatments IV; romifidine 50 μg kg(-) (R) tramadol 3 mg kg(-1) given over 15 minutes (T) or tramadol 3 mg kg(-1) followed by romifidine 50 μg kg(-1) (RT). Physiologic parameters and caecal borborygmi (CB) were measured and sedation and response to electrical stimulation of the coronary band assessed before and up to 120 minutes following drugs administration. Results were analyzed using the Friedman's test and 2 way anova as relevant. When compared to baseline, heart (HR, beats minute(-1) ) and respiratory rates (fR , breaths minute(-1) ) increased with treatment T (highest mean ± SD, HR 43 ± 1; fR 33 ± 2) and decreased with R (lowest HR 29 ± 1 and fR 10 ± 4) and RT (lowest HR 32 ± 1 and fR 9 ± 3). There were no changes in other measured physiological variables. The height of head from the ground was lower following treatments R and TR than T. There was slight ataxia with all three treatments. No excitatory behavioural effects were observed. The response to electrical stimulation was reduced for a prolonged period relative to baseline following all three treatments, the effect being significantly greatest with treatment RT. Tramadol combined with romifidine at the stated doses proved an effective sedative and anti-nociceptive combination in ponies, with no unacceptable behavioural or physiologic side effects. Slow controlled administration of tramadol should reduce the occurrence of adverse behavioural side effects. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  4. Impact of fraction unbound, CYP3A, and CYP2D6 in vivo activities, and other potential covariates to the clearance of tramadol enantiomers in patients with neuropathic pain.

    PubMed

    de Moraes, Natália V; Lauretti, Gabriela R; Coelho, Eduardo B; Godoy, Ana Leonor P C; Neves, Daniel V; Lanchote, Vera L

    2016-04-01

    The pharmacokinetics of tramadol is characterized by a large interindividual variability, which is partially attributed to polymorphic CYP2D6 metabolism. The contribution of CYP3A, CYP2B6, fraction unbound, and other potential covariates remains unknown. This study aimed to investigate the contribution of in vivo activities of cytochrome P450 (CYP) 2D6 and 3A as well as other potential covariates (CYP2B6 genotype to the SNP g.15631G>T, fraction unbound, age, body weight, creatinine clearance) to the enantioselective pharmacokinetics of tramadol. Thirty patients with neuropathic pain and phenotyped as CYP2D6 extensive metabolizers were treated with a single oral dose of 100 mg tramadol. Multiple linear regressions were performed to determine the contribution of CYP activities and other potential covariates to the clearance of tramadol enantiomers. The apparent total clearances were 44.9 (19.1-102-2) L/h and 55.2 (14.8-126.0) L/h for (+)- and (-)-tramadol, respectively [data presented as median (minimum-maximum)]. Between 79 and 83% of the overall variation in apparent clearance of tramadol enantiomers was explained by fraction unbound, CYP2D6, and CYP3A in vivo activities and body weight. Fraction unbound explained 47 and 41% of the variation in clearance of (+)-tramadol and (-)-tramadol, respectively. Individually, CYP2D6 and CYP3A activities were shown to have moderate contribution on clearance of tramadol enantiomers (11-16% and 11-18%, respectively). In conclusion, factors affecting fraction unbound of drugs (such as hyperglycemia or co-administration of drugs highly bound to plasma proteins) should be monitored, because this parameter dominates the elimination of tramadol enantiomers. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  5. Binary Solvents Dispersive Liquid—Liquid Microextraction (BS-DLLME) Method for Determination of Tramadol in Urine Using High-Performance Liquid Chromatography

    PubMed Central

    2014-01-01

    Background Tramadol is an opioid, synthetic analog of codeine and has been used for the treatment of acute or chronic pain may be abused. In this work, a developed Dispersive liquid liquid microextraction (DLLME) as binary solvents-based dispersive liquid-liquid microextraction (BS-DLLME) combined with high performance liquid chromatography (HPLC) with fluorescence detection (FD) was employed for determination of tramadol in the urine samples. This procedure involves the use of an appropriate mixture of binary extraction solvents (70 μL CHCl3 and 30 μL ethyl acetate) and disperser solvent (600 μL acetone) for the formation of cloudy solution in 5 ml urine sample comprising tramadol and NaCl (7.5%, w/v). After centrifuging, the small droplets of extraction solvents were precipitated. In the final step, the HPLC with fluorescence detection was used for determination of tramadol in the precipitated phase. Results Various factors on the efficiency of the proposed procedure were investigated and optimized. The detection limit (S/N = 3) and quantification limit (S/N = 10) were found 0.2 and 0.9 μg/L, respectively. The relative standard deviations (RSD) for the extraction of 30 μg L of tramadol was found 4.1% (n = 6). The relative recoveries of tramadol from urine samples at spiking levels of 10, 30 and 60 μg/L were in the range of 95.6 – 99.6%. Conclusions Compared with other methods, this method provides good figures of merit such as good repeatability, high extraction efficiency, short analysis time, simple procedure and can be used as microextraction technique for routine analysis in clinical laboratories. PMID:24495475

  6. Pharmacokinetic/pharmacodynamic assessments of 10 mg/kg tramadol intramuscular injection in yellow-bellied slider turtles (Trachemys scripta scripta).

    PubMed

    Giorgi, M; Salvadori, M; De Vito, V; Owen, H; Demontis, M P; Varoni, M V

    2015-10-01

    In reptiles, administration of opioid drugs has yielded unexpected results with respect to analgesia. The aims of this study were to assess the pharmacokinetic/pharmacodynamic (PK/PD) properties of tramadol and its active metabolite M1 and to evaluate the effect of the renal portal system on the PK/PD parameters in yellow-bellied slider turtles. Turtles (n = 19) were randomly assigned to four treatment groups, according to a masked, single-dose, four-treatment, unpaired, four-period crossover design. Group A (n = 5) received a single i.m. dose of tramadol (50 mg/mL) at 10 mg/kg in the proximal hindlimb. Group B (n = 5) received the same i.m. dose but in the forelimb. Groups C (n = 5) and D (n = 4) received a single i.m. injection of saline (NaCl 0.9%) of equivalent volume to the volumes of tramadol injected in the hind- and forelimb, respectively. Groups were rotated (1-month washout period) until the completion of the crossover study. Tramadol plasma concentrations were evaluated by a validated HPLC-FL method. An infrared thermal stimulus was applied to the plantar surface of the turtles' hindlimbs to evaluate the thermal withdrawal latency (TWL). The two PK profiles of tramadol differed in the first 2 h following administration, but overlapped in the elimination phases. The metabolite M1 was formed in both the treatment groups, showing similar pharmacokinetic trends, although the amount of M1 was significantly higher (20%) in the hindlimb vs. forelimb group. Turtles given tramadol in the hind- and forelimb showed a significant increase in TWL over the periods of 0.5-48 and 8-48 h, respectively. The calculated % maximal possible response (% MPR) was low (about 24%). The PK/PD correlations between M1 plasma concentrations vs. % MPR appeared to show a counterclockwise hysteresis loop shape.

  7. Sublingual ketorolac versus sublingual tramadol for moderate to severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial.

    PubMed

    Neri, Elena; Maestro, Alessandra; Minen, Federico; Montico, Marcella; Ronfani, Luca; Zanon, Davide; Favret, Anna; Messi, Gianni; Barbi, Egidio

    2013-09-01

    To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children. A double-blind, randomised, controlled, non-inferiority trial was conducted in the paediatric emergency department of a research institute. One hundred and thirty-one children aged 4-17 years with suspected bone fracture or dislocation were enrolled. Eligible children were randomised to ketorolac (0.5 mg/kg) and placebo, or to tramadol (2 mg/kg) and placebo by sublingual administration, using a double-dummy technique. Pain was assessed by the patients every 20 min, for a maximum period of 2 h, using the McGrath scale for patients up to 6 years of age, and the Visual Analogue Scale for those older than 6 years of age. The mean pain scores fell significantly from eight to four and five in the ketorolac and tramadol groups, respectively, by 100 min (Wilcoxon sign rank test, p<0.001). The mean pain scores for ketorolac were lower than those for tramadol, but these differences were not significant at any time point (Mann-Whitney U Test, p values: 0-20 min: 0.167; 20-40 min: 0.314; 40-60 min: 0.223; 60-80 min: 0.348; 80-100 min: 0.166; 100-120 min: 0.08). The rescue dose of paracetamol-codeine was administered in 2/60 children in the ketorolac group versus 8/65 in the tramadol group (Fisher exact test, p=0.098). There were no statistically significant differences between the two groups in the frequency of adverse effects. Both sublingual ketorolac and tramadol were equally effective for pain management in children with suspected fractures or dislocations.

  8. Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice.

    PubMed

    Fox, Meredith A; Jensen, Catherine L; Murphy, Dennis L

    2009-09-01

    The serotonin syndrome is a potential side-effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioural responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wild-type (+/+), heterozygous (+/-) and knockout (-/-) mice. Comparisons were made with SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviours in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT-/- mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT-/- mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs that dangerous side-effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT+/- mice.

  9. Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Multiple-Ascending-Dose Study.

    PubMed

    DeLemos, Byron; Richards, Henry M; Vandenbossche, Joris; Ariyawansa, Jay; Natarajan, Jaya; Alexander, Binu; Ramakrishna, Tage; Murtaugh, Thomas; Stahlberg, Hans-Jürgen

    2017-09-07

    This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUCtau,ss of tramadol increased approximately 2.2- and 3.6-fold for the (+) enantiomer and 2.0- and 3.5-fold for the (-) enantiomer with increasing dose from 200 to 400  and 600 mg/day, whereas the Cmax,ss increased 2.1- and 3.3-fold for the (+) enantiomer and 2.0- and 3.2-fold for the (-) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment-emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study. © 2017, The American College of Clinical Pharmacology.

  10. Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

    PubMed

    Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

    2014-09-01

    Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (P<0.001). Tramadol increased the PWT by 336% in CCI rats (P<0.001) and by 16% in sham (P<0.05). On the EPM, CCI rats spent 45% less time than sham on the open arms of the maze (P<0.05). Tramadol increased the time spent on the open arms of CCI rats by 67% (P<0.05) and had no significant effect on sham. During the FST, CCI rats showed 28% longer immobility than sham (P<0.01). Tramadol reduced the immobility time in CCI rats by 22% (P<0.001), while having no effect on sham. Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP.

  11. Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: role of nitric oxide and oxidative stress.

    PubMed

    Abdel-Zaher, Ahmed O; Abdel-Rahman, Mahran S; Elwasei, Fahmy M

    2011-12-01

    Nigella sativa seed extracts and its oil have been exploited for their various health benefits. In this study, the effects of N. sativa oil on tramadol-induced tolerance and dependence and possible mechanism(s) of these effects were investigated, for the first time, in mice. Repeated administration of N. sativa oil (4 ml/kg, p.o.) along with tramadol (50mg/kg, s.c.) inhibited the development of tramadol tolerance, as measured by the hot plate test, and dependence as assessed by naloxone (5mg/kg, i.p.)-precipitated withdrawal manifestations. Concomitantly, nitric oxide overproduction and increase in brain malondialdehyde level induced by repeated administration of tramadol to mice or by administration of naloxone to tramadol-dependent mice were inhibited by co-administration of the oil. Also, the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments was inhibited by co-administration of the oil. The increase in brain glutamate level induced by both treatments was not inhibited by concurrent administration of the oil. The inhibitory effect of N. sativa oil on tramadol-induced tolerance and dependence was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine (0.25mg/kg). Also, the inhibitory effect of the oil on naloxone-induced biochemical alterations in tramadol-dependent mice was enhanced by concurrent administration of dizocilpine. Similarly, concurrent i.p. administration of the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (10mg/kg) or the antioxidant, N-acetylcysteine (50mg/kg) enhanced these inhibitory effects of N. sativa oil. On the other hand, these effects were antagonized by concurrent i.p. administration of the NO precursor, L-arginine (300 mg/kg). These results provide evidence that N. sativa oil appears to have a therapeutic potential in tramadol tolerance and dependence through blockade of NO overproduction and oxidative stress induced by

  12. Impact of tramadol and morphine abuse on the activities of acetylcholine esterase, Na+/K+-ATPase and related parameters in cerebral cortices of male adult rats

    PubMed Central

    El-Hamid Mohamed Elwy, Abd; Tabl, Ghada

    2017-01-01

    Objective To determine the effect of the most commonly abused drugs (tramadol and morphine), on acetylcholine esterase (AChE), Na+/K+-ATPase activities and related parameters, Na+ and K+ as biomarkers of neurotoxicity. Methods Tramadol - as a weak μ opioid receptor agonist- and morphine - as opiate analgesic drugs, were chosen for the present study. Four series of experimental animals were conducted for either tramadol or morphine: control series; repeated single equal doses (therapeutic dose) series; cumulative increasing doses series and delay (withdrawal) series (96 hours withdrawal period after last administration), at time period intervals 7, 14 and 21 days. Acetylcholine esterase (AChE), Na+/K+-ATPase activities and related parameters, Na+ and K+ were measured in cerebral cortices of experimental rats. Results Acetylcholine esterase (AChE) activity in the brain cerebral cortex increased after the administration of therapeutic repeated doses of either tramadol (20 mg/kg b.w.) or morphine (4 mg/kg b.w.) in different groups. The daily intraperitoneal injection of cumulative increasing dose levels of either tramadol 20, 40 and 80 mg/kg or morphine 4, 8 and 12 mg/kg revealed a significant increase in the mean of acetylcholine esterase activities. The withdrawal groups of either tramadol or morphine showed significant decreases in their levels. Na+/K+ ATPase activity in the brain cerebral cortex of either repeated therapeutic doses of tramadol (20 mg/kg) or morphine repeated therapeutic doses (4 mg/kg) for 21 consecutive days at different intervals 7, 14 and 21 days, induced a significant decrease in the levels of Na+/K+-ATPase in all groups. Withdrawal groups showed a significant decrease in Na+/K+-ATPase level. Furthermore, the daily intraperitoneal injection of cumulative increasing dose levels of either tramadol (20, 40 and 80 mg/kg b.w.) or morphine (4, 8 and 12 mg/kg b.w.) induced significant decreases in Na+/K+-ATPase levels in all studied groups. Regarding

  13. [Treating pain after dental surgery: a randomised, controlled, double-blind trial to assess a new formulation of paracetamol, opium powder and caffeine versus tramadol or placebo].

    PubMed

    Borel, Jean-François; Deschaumes, Christophe; Devoize, Laurent; Huard, Cédric; Orliaguet, Thierry; Dubray, Claude; Baudet-Pommel, Martine; Dallel, Radhouane

    2010-05-01

    The aim of this study was to evaluate the analgesic efficacy and the safety of the association, paracetamol, opium prepared and caffeine, in two different dosages as compared to the conventional analgesic tramadol hydrochloride, on acute postoperative dental pain. We conducted a randomised, double-blind, multicentre, parallel-group clinical trial to test the efficacy and safety of single doses of two associations; paracetamol 500 mg, caffeine 50mg, opium prepared 25, and paracetamol 500 mg, caffeine 50mg, opium prepared 50mg, as compared to tramadol hydrochloride 100mg (called hereafter tramadol 100), and placebo, in the control of postoperative pain following the removal of 2 ipsilateral impacted third molars. The primary efficacy criterion was the sum of pain intensity differences as assessed every 30 minutes within 3 hours after the baseline assessment and administration of study treatment (SPID(0-3h)). Of the 232 randomised patients, 228 (98%) completed the study. Analysis of the primary efficacy criterion (SPID(0-3h)) established: (i) the superiority of the 3 active study treatments vs. placebo (p<0.005); (ii) non-inferiority of paracetamol, caffeine, and opium 25mg, and paracetamol, caffeine, and opium 50mg vs. tramadol. Besides, both formulations of paracetamol, caffeine, and opium showed: (i) a faster onset of analgesic effect as compared to tramadol 100; (ii) a significantly stronger analgesic efficacy than tramadol 100, as measured 1 hour after the treatment intake; this superiority lasted all over the study duration for paracetamol, caffeine, and opium 50mg but not for paracetamol, caffeine, and opium 25mg. No unexpected safety concerns occurred, the two formulations of paracetamol, caffeine, and opium showed a good safety profile especially with paracetamol, caffeine, and opium 25mg as compared to tramadol. This study evidenced the non-inferiority of the paracetamol, caffeine, and opium 25mg or 50mg vs. tramadol 100, and even though the strengths of the

  14. Impact of tramadol and morphine abuse on the activities of acetylcholine esterase, Na+/K+-ATPase and related parameters in cerebral cortices of male adult rats.

    PubMed

    El-Hamid Mohamed Elwy, Abd; Tabl, Ghada

    2017-03-01

    To determine the effect of the most commonly abused drugs (tramadol and morphine), on acetylcholine esterase (AChE), Na(+)/K(+)-ATPase activities and related parameters, Na(+) and K(+) as biomarkers of neurotoxicity. Tramadol - as a weak μ opioid receptor agonist- and morphine - as opiate analgesic drugs, were chosen for the present study. Four series of experimental animals were conducted for either tramadol or morphine: control series; repeated single equal doses (therapeutic dose) series; cumulative increasing doses series and delay (withdrawal) series (96 hours withdrawal period after last administration), at time period intervals 7, 14 and 21 days. Acetylcholine esterase (AChE), Na(+)/K(+)-ATPase activities and related parameters, Na(+) and K(+) were measured in cerebral cortices of experimental rats. Acetylcholine esterase (AChE) activity in the brain cerebral cortex increased after the administration of therapeutic repeated doses of either tramadol (20 mg/kg b.w.) or morphine (4 mg/kg b.w.) in different groups. The daily intraperitoneal injection of cumulative increasing dose levels of either tramadol 20, 40 and 80 mg/kg or morphine 4, 8 and 12 mg/kg revealed a significant increase in the mean of acetylcholine esterase activities. The withdrawal groups of either tramadol or morphine showed significant decreases in their levels. Na(+)/K(+) ATPase activity in the brain cerebral cortex of either repeated therapeutic doses of tramadol (20 mg/kg) or morphine repeated therapeutic doses (4 mg/kg) for 21 consecutive days at different intervals 7, 14 and 21 days, induced a significant decrease in the levels of Na(+)/K(+)-ATPase in all groups. Withdrawal groups showed a significant decrease in Na(+)/K(+)-ATPase level. Furthermore, the daily intraperitoneal injection of cumulative increasing dose levels of either tramadol (20, 40 and 80 mg/kg b.w.) or morphine (4, 8 and 12 mg/kg b.w.) induced significant decreases in Na(+)/K(+)-ATPase levels in all studied groups

  15. Simultaneous determination of tramadol and O-desmethyltramadol in human plasma using HPLC-DAD.

    PubMed

    Hilal, Maha A; Mohamed, Khaled M

    2014-01-01

    A sensitive and accurate method for the extraction and quantification of tramadol (T) and its active metabolite, O-desmethyltramadol (ODT) in human plasma with high-performance liquid chromatography-diode array detection was developed and validated. The analytes were extracted from plasma samples by tert-butylmethyl ether in the presence of ammonium hydroxide as alkaline medium and back extraction with 1.0 M hydrochloric acid. Propranolol was used as internal standard. The extraction efficiencies of T and ODT were 83.51 and 78.72%, respectively. The calibration curves were linear (r(2) > 0.99) in the concentration range of 250-2000 ng/mL for T and ODT. Limits of detection and quantification were 125 and 250 ng/mL for both analytes. Intra- and interassay precision for T and ODT were ranged from 1.89 to 10.91% and 2.16 to 5.85%, respectively. Intra- and interassay accuracy for T and ODT were ranged from -13.07 to 4.99% and -2.03 to -6.98%, respectively. The method was successfully applied to quantify T and ODT from authentic plasma samples received from Hospital Sohag University. The method was completely validated and can be of interest to clinical and forensic laboratories. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Effects of opioids on local anesthesia in the rat: a codeine and tramadol study.

    PubMed

    Carnaval, Talita Girio; Sampaio, Roberta Moura; Lanfredi, Camila Bernadeli; Borsatti, Maria Aparecida; Adde, Carlos Alberto

    2013-01-01

    Opioids are central analgesics that act on the CNS (central nervous system) and PNS (peripheral nervous system). We investigated the effects of codeine (COD) and tramadol (TRAM) on local anesthesia of the sciatic nerve. Eighty Wistar male rats received the following SC injections in the popliteal fossa: local anesthetic with epinephrine (LA); local anesthetic without vasoconstrictor (LA WV); COD; TRAM; LA + COD; LA + TRAM; COD 20 minutes prior to LA (COD 20' + LA) or TRAM 20 minutes prior to LA (TRAM 20' + LA). As a nociceptive function, the blockade was considered the absence of a paw withdraw reflex. As a motor function, it was the absence of claudication. As a proprioceptive function, it was the absence of hopping and tactile responses. All data were compared using repeated-measures analysis of variance (ANOVA). Opioids showed a significant increase in the level of anesthesia, and the blockade duration of LA + COD was greater than that of the remaining groups (p < 0.05). The associated use of opioids improved anesthesia efficacy. This could lead to a new perspective in controlling dental pain.

  17. Optimization of Carboxymethyl-Xyloglucan-Based Tramadol Matrix Tablets Using Simplex Centroid Mixture Design

    PubMed Central

    Madgulkar, Ashwini R.; Bhalekar, Mangesh R.; Padalkar, Rahul R.; Shaikh, Mohseen Y.

    2013-01-01

    The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan (X1), HPMC K100M (X2), and dicalcium phosphate (X3) were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour (Y1) and at 8th hour (Y2). Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P > 0.05). The statistical models developed for optimization were found to be valid. PMID:26555977

  18. A simple colorimetric method for estimation of tramadol hydrochloride in pure and tablet dosage forms.

    PubMed

    Thomas, Scaria P; Sankar, Hari K N

    2016-01-01

    The objective of this study was to develop and validate a simple method for estimation of tramadol hydrochloride (TH) in pure and pharmaceutical dosage forms using a colorimeter. TH on reaction with Eriochrome Black T in the presence of acetate buffer at pH 3.5 forms a colored complex. This complex was extracted with a fixed volume of chloroform. The optical density of this colored complex was measured against reagent blank using a colorimeter at 520 nm. Beer's law was obeyed with a good correlation coefficient (0.999) in the concentration range of 2.5 μg/ml to 10 μg/ml. Drug content estimation and recovery studies carried out on commercial tablet dosage forms demonstrated the accuracy of the method and that excipients do not cause interference. Precision and robustness were measured and found to be acceptable (% relative standard deviation <2%). The proposed method can be used for the rapid determination of TH content in tablets at a health-care provider level using already available staff and equipment.

  19. Effects of intra-articular levobupivacaine, fentanyl-levobupivacaine and tramadol-levobupivacaine for postoperative pain in arthroscopic knee surgery.

    PubMed

    Sayın, Pınar; Dobrucalı, Hale; Türk, Hacer Şebnem; Totoz, Tolga; Işıl, Canan Tülay; Hancı, Ayşe

    2015-01-01

    The aim of this study was to compare the postoperative analgesic efficacy of intra-articularly injected levobupivacaine, levobupivacaine-fentanyl, and levobupivacaine-tramadol combinations. Eighty patients scheduled for elective knee arthroscopy were divided randomly into 4 groups of 20 patients each. Group 1 (the control group) received intra-articular saline, Group 2 received levobupivacaine 2.5 mg/ml, Group 3 received levobupivacaine 2.5 mg/ml + tramadol 50 mg, and Group 4 received levobupivacaine 2.5 mg/ml + fentanyl l50 mcg. All patients were operated on under general anesthesia, and a total of 20 ml study solution was injected: 7 ml subcutaneously before surgery and 13 ml intra-articularly upon completion of surgery. For postoperative, pain visual analogue scale (VAS) was assessed at the 1st, 2nd, 4th, 8th, 12th, and 24th hours postoperatively. Patients with a VAS score over 5 received diclofenac sodium, and the need for rescue analgesics was recorded. At the 1st, 2nd, 4th, 8th, 12th, and 24th postoperative hours, Group 3 and Group 4 had statistically significant lower VAS scores of pain (p<0.01). Postoperative rescue analgesic requirements were different among the groups. The postoperative 1st hour analgesic requirement was statistically significantly lower in Group 3 and Group 4 when compared to the other groups (p<0.01). At the postoperative 2nd and 4th hours, analgesic requirements were statistically significantly lower in Group 3 than in the other groups (p<0.01). Analgesic requirements were statistically significantly lower in Group 3 and Group 4 than in the other groups (p<0.01). Analgesic requirements at the 12th and 24th postoperative hours did not show any statistically significant difference (p>0.05). The results indicated that levobupivacaine combined with either fentanyl or tramadol decreased rescue analgesic requirements when compared to levobupivacaine alone.

  20. The preoperative analgesic effect of 3-in-1 block on postoperative pain and tramadol consumption in total hip arthroplasty.

    PubMed

    Köroğlu, Süleyman; Takmaz, Suna Akin; Kaymak, Cetin; Narli, Altuğ; Karalezli, Kubilay; Dikmen, Bayazit

    2008-01-01

    We studied the effect of preoperative 3-in-1 block for total hip replacement surgery on postoperative pain and tramadol consumption during patient-controlled analgesia. Thirty ASA I-II patients undergoing elective total hip arthroplasty (THA) were included in the study. Patients were randomly divided into 2 groups; Group I: Patients who received 3-in-1 block with 40 ml of 0.25% bupivacaine 30-minutes before surgery and later received general anesthesia, Group II: Patients who received only a simple needle puncture at the operation site 30-minutes before surgery and later received general anesthesia. All patients received intravenous tramadol at the end of surgery via a PCA device. Pain was evaluated at 0,1/2,1,4,8,12,24 and 48 h at rest and on movement of the hip, using a 10 cm VAS. The average intraoperative fentanyl consumption was lower in Group I than in Group II. VAS scores were significantly lower in group I, both at rest and during movement at all timepoints over in the first postoperative 12 h and also during movement 24 h postoperatively. However differences in VAS scores weren't clinically significant after 4 hours. In the recovery room, Group I VAS scores were only a third of Group II, both at rest and movement (p=0.0001). Total tramadol consumption was lower in Group I (633.0+/-119.3 mg) than in Group II (991.1+/-41.0 mg). Patient satisfaction scores were higher in Group I than in Group II. We concluded that preoperative 3-in-1 block with 40 ml-0,25% bupivacaine provides effective postoperative pain relief for elective THA, reducing intra-and postoperative analgesic consumption without increase in side effects.

  1. Ultra low-dose naloxone and tramadol/acetaminophen in elderly patients undergoing joint replacement surgery: a pilot study.

    PubMed

    Imasogie, Ngozi N; Singh, Sudha; Watson, James T; Hurley, Debbie; Morley-Forster, Patricia

    2009-01-01

    A pilot study was conducted to assess whether both the rationale and feasibility exist for future randomized clinical trials to evaluate the combined use of naloxone infusion and tramadol/acetaminophen as opioid-sparing drugs in elderly patients undergoing lower extremity joint replacement surgery. Ten patients 70 years of age or older undergoing either total knee (n=7) or total hip (n=3) arthroplasty were treated prospectively. Each patient received two tablets of tramadol/acetaminophen (Tramacet; Janssen-Ortho Inc, Canada) preoperatively and every 6 h postoperatively, as well as a naloxone infusion started preoperatively at 0.25 microg/kg/h and continued up to 48 h postoperatively. In addition, standard intraoperative care was provided with 0.2 mg of intrathecal morphine, 1.4 mL of 0.75% bupivacaine, and an intra-articular infiltration of 100 mL of 0.3% ropivacaine and 30 mg of ketorolac, as well as standard postoperative morphine via patient-controlled analgesia orders and celecoxib 200 mg twice daily for five days. Compared with seven historical controls, also 70 years of age or older, who had undergone either a total knee (n=4) or total hip (n=3) arthroplasty, postoperative opioid use was reduced by 80%. Except for transient nausea and vomiting in 40% and 20% of patients, respectively, the 10 patients on tramadol/acetaminophen and naloxone tolerated the new regimen without difficulty. Consequently, a randomized, double-blinded clinical trial comparing standard therapy versus standard therapy plus these two drugs seems warranted. In such a trial, it would require approximately 20 subjects per treatment arm to detect a 80% decrease in morphine use.

  2. The comparison of intraarticular morphine-bupivacaine and tramadol-bupivacaine in postoperative analgesia after arthroscopic anterior cruciate ligament reconstruction.

    PubMed

    Hosseini, Habibollah; Abrisham, Seyyed Mohammad Jalil; Jomeh, Hossein; Kermani-Alghoraishi, Mohammad; Ghahramani, Rahil; Mozayan, Mohammad Reza

    2012-09-01

    To compare intraarticular morphine-bupivacaine and tramadol-bupivacaine as postoperative analgesics in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction. A randomized, double blind, controlled trial study of 60 ASA I-II patients undergoing arthroscopic ACL reconstruction was performed under general anesthesia. Patients were randomly allocated into three groups. The MB group (n = 20) received 10 mg morphine and 0.5% bupivacaine; the TB group (n = 20) received 100 mg tramadol and 0.5% bupivacaine; and the control group (n = 20) received isotonic saline intraarticularly in a total volume of 20 ml after the operation. Postoperative pain was assessed with visual analogue scale (VAS) at 0, 30, 60, 90 min and 2, 4, 6, 12, 24 h being at rest. Analgesic duration as defined was the time of first request for analgesics, the first 24 h analgesic consumption, time to unassisted ambulation, discharge time and incidence of side effects were also evaluated. The VAS scores at 30, 60, 90 min and 2, 4, 12, 24 h were significantly less in the MB and TB groups in comparison with the control group (P < 0.05); VAS scores also decreased significantly in the MB group compared to the TB group at 2, 4 and 24 h (P < 0.05). Analgesic duration was longer and analgesic consumption was substantially less in the MB group (P < 0.05). Moreover, unassisted ambulation time and discharge time were significantly shorter in the MB group than the TB and control groups (P < 0.05). Side effects were similar among the groups. Intraarticular morphine-bupivacaine provides effective pain relief, longer analgesic duration, less analgesic requirement, shorter unassisted ambulation and discharge time were compared with intraarticular tramadol-bupivacaine after ACL reconstruction arthroscopy. I.

  3. Ultra low-dose naloxone and tramadol/acetaminophen in elderly patients undergoing joint replacement surgery: A pilot study

    PubMed Central

    Imasogie, Ngozi N; Singh, Sudha; Watson, James T; Hurley, Debbie; Morley-Forster, Patricia

    2009-01-01

    OBJECTIVE: A pilot study was conducted to assess whether both the rationale and feasibility exist for future randomized clinical trials to evaluate the combined use of naloxone infusion and tramadol/acetaminophen as opioid-sparing drugs in elderly patients undergoing lower extremity joint replacement surgery. DESIGN: Ten patients 70 years of age or older undergoing either total knee (n=7) or total hip (n=3) arthroplasty were treated prospectively. Each patient received two tablets of tramadol/acetaminophen (Tramacet; Janssen-Ortho Inc, Canada) preoperatively and every 6 h postoperatively, as well as a naloxone infusion started preoperatively at 0.25 μg/kg/h and continued up to 48 h postoperatively. In addition, standard intraoperative care was provided with 0.2 mg of intrathecal morphine, 1.4 mL of 0.75% bupivacaine, and an intra-articular infiltration of 100 mL of 0.3% ropivacaine and 30 mg of ketorolac, as well as standard postoperative morphine via patient-controlled analgesia orders and celecoxib 200 mg twice daily for five days. OUTCOME MEASURES: Compared with seven historical controls, also 70 years of age or older, who had undergone either a total knee (n=4) or total hip (n=3) arthroplasty, postoperative opioid use was reduced by 80%. Except for transient nausea and vomiting in 40% and 20% of patients, respectively, the 10 patients on tramadol/acetaminophen and naloxone tolerated the new regimen without difficulty. CONCLUSION: Consequently, a randomized, double-blinded clinical trial comparing standard therapy versus standard therapy plus these two drugs seems warranted. In such a trial, it would require approximately 20 subjects per treatment arm to detect a 80% decrease in morphine use. PMID:19532850

  4. Intraarticular tramadol plus pericapsular incisional bupivacaine provides better analgesia than intraarticular plus pericapsular incisional bupivacaine after outpatient arthroscopic partial meniscectomy.

    PubMed

    Beyzadeoglu, Tahsin; Yilmaz, Cemil; Bekler, Halil; Gokce, Alper; Sayin, Murat M

    2007-05-01

    Postoperative analgesic effects of intraarticular tramadol plus periarticular bupivacaine, and intraarticular plus periarticular bupivacaine injections after day-case arthroscopic partial meniscectomy were compared. Seventy-four ASA I/II patients undergoing arthroscopic partial meniscectomy, performed by a single surgeon under general anesthesia were assigned in a randomized, double-blinded manner into two groups: Group TB (n = 41) received intraarticular 100 mg of tramadol in 20 ml normal saline and periarticular incisional injection of 10 ml bupivacaine 0.5%. Group BB (n = 33) received intraarticular 20 ml 0.25% and periarticular incisional 10 ml 0.5% bupivacaine injections. The injections were performed immediately after the portal closures. Pain was assessed with visual analog scale (VAS) at 0, 15, 30 min and at 1, 2, 4 h at rest and active 90 degrees knee flexion by a blinded observer. The first additional analgesic requirement time was recorded. The patients were discharged the same day with a prescription for paracetamol as required, up to six tablets a day and questioned for analgesic use and pain score at 24 h. VAS scores at rest at 15, 30 min and at movement at 0, 15, 30 min were lower in group TB (P < 0.05). First time requiring additional analgesia was lower in group TB (17.1 +/- 21.9, 33.8 +/- 26.6) (P < 0.05) and total paracetamol dose at the end of 24 h was 1.2 +/- 1.5 g in group BB and 0.9 +/- 1.3 g in group TB (P < 0.05). Intraarticular tramadol plus periarticular bupivacaine combination provides better pain relief and less analgesic requirement following arthroscopic outpatient partial meniscectomy surgery.

  5. The Effect of Systemic and Regional Use of Magnesium Sulfate on Postoperative Tramadol Consumption in Lumbar Disc Surgery

    PubMed Central

    Demiroglu, Melek; Ün, Canan; Ornek, Dilsen Hatice; Kıcı, Oya; Yıldırım, Ali Erdem; Horasanlı, Eyup; Başkan, Semih; Fikir, Emel; Gamli, Mehmet; Dikmen, Bayazit

    2016-01-01

    Aim. To investigate the effect of magnesium administered to the operative region muscle and administered systemically on postoperative analgesia consumption after lumbar disc surgery. Material and Method. The study included a total of 75 ASA I-II patients aged 18–65 years. The patients were randomly allocated into 1 of 3 groups of 25: the Intravenous (IV) Group, the Intramuscular (IM) Group, and the Control (C) Group. At the stage of suturing the surgical incision site, the IV Group received 50 mg/kg MgSO4 intravenously in 150 mL saline within 30 mins. In the IM Group, 50 mg/kg MgSO4 in 30 mL saline was injected intramuscularly into the paraspinal muscles. In Group C, 30 mL saline was injected intramuscularly into the paraspinal muscles. After operation patients in all 3 groups were given 100 mg tramadol and 10 mg metoclopramide and tramadol solution was started intravenously through a patient-controlled analgesia device. Hemodynamic changes, demographic data, duration of anesthesia and surgery, pain scores (NRS), the Ramsay sedation score (RSS), the amount of analgesia consumed, nausea- vomiting, and potential side effects were recorded. Results. No difference was observed between the groups. Nausea and vomiting side effects occurred at a rate of 36% in Group C, which was a significantly higher rate compared to the other groups (p < 0.05). Tramadol consumption in the IM Group was found to be significantly lower than in the other groups (p < 0.05). Conclusion. Magnesium applied to the operative region was found to be more effective on postoperative analgesia than systemically administered magnesium. PMID:27022607

  6. Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.

    PubMed

    Haage, Pernilla; Kronstrand, Robert; Carlsson, Björn; Kugelberg, Fredrik C; Josefsson, Martin

    2016-02-05

    The analgesic drug tramadol and its metabolites are chiral compounds, with the (+)- and (-)-enantiomers showing different pharmacological and toxicological effects. This novel enantioselective method, based on LC-MS/MS in reversed phase mode, enabled measurement of the parent compound and its three main metabolites O-desmethyltramadol, N-desmethyltramadol and N,O-didesmethyltramadol simultaneously. Whole blood samples of 0.5g were fortified with internal standards (tramadol-(13)C-D3 and O-desmethyl-cis-tramadol-D6) and extracted under basic conditions (pH 11) by liquid-liquid extraction. Chromatography was performed on a chiral alpha-1-acid glycoprotein (AGP) column preceded by an AGP guard column. The mobile phase consisted of 0.8% acetonitrile and 99.2% ammonium acetate (20mM, pH 7.2). A post-column infusion with 0.05% formic acid in acetonitrile was used to enhance sensitivity. Quantitation as well as enantiomeric ratio measurements were covered by quality controls. Validation parameters for all eight enantiomers included selectivity (high), matrix effects (no ion suppression/enhancement), calibration model (linear, weight 1/X(2), in the range of 0.25-250ng/g), limit of quantitation (0.125-0.50ng/g), repeatability (2-6%) and intermediate precision (2-7%), accuracy (83-114%), dilution integrity (98-115%), carry over (not exceeding 0.07%) and stability (stable in blood and extract). The method was applied to blood samples from a healthy volunteer administrated a single 100mg dose and to a case sample concerning an impaired driver, which confirmed its applicability in human pharmacokinetic studies as well as in toxicological and forensic investigations. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol.

    PubMed

    Varrassi, Giustino; Hanna, Magdi; Macheras, Giorgos; Montero, Antonio; Montes Perez, Antonio; Meissner, Winfried; Perrot, Serge; Scarpignato, Carmelo

    2017-06-01

    Untreated and under-treated pain represent one of the most pervasive health problems, which is worsening as the population ages and accrues risk for pain. Multiple treatment options are available, most of which have one mechanism of action, and cannot be prescribed at unlimited doses due to the ceiling of efficacy and/or safety concerns. Another limitation of single-agent analgesia is that, in general, pain is due to multiple causes. Combining drugs from different classes, with different and complementary mechanism(s) of action, provides a better opportunity for effective analgesia at reduced doses of individual agents. Therefore, there is a potential reduction of adverse events, often dose-related. Analgesic combinations are recommended by several organizations and are used in clinical practice. Provided the two agents are combined in a fixed-dose ratio, the resulting medication may offer advantages over extemporaneous combinations. Dexketoprofen/tramadol (25 mg/75 mg) is a new oral fixed-dose combination offering a comprehensive multimodal approach to moderate-to-severe acute pain that encompasses central analgesic action, peripheral analgesic effect and anti-inflammatory activity, together with a good tolerability profile. The analgesic efficacy of dexketoprofen/tramadol combination is complemented by a favorable pharmacokinetic and pharmacodynamic profile, characterized by rapid onset and long duration of action. This has been well documented in both somatic- and visceral-pain human models. This review discusses the available clinical evidence and the future possible applications of dexketoprofen/tramadol fixed-dose combination that may play an important role in the management of moderate-to-severe acute pain.

  8. Anisotropic (spherical/hexagon/cube) silver nanoparticle embedded magnetic carbon nanosphere as platform for designing of tramadol imprinted polymer.

    PubMed

    Patra, Santanu; Roy, Ekta; Parui, Retwik; Madhuri, Rashmi; Sharma, Prashant K

    2017-11-15

    Shape specific nanoparticles are getting a tremendous research interests due to their change in property with the shape. As far our knowledge, the impact of change in the shape of nanoparticle used as platform during synthesis of molecularly imprinted polymers (MIPs) has not been reported or tried. Herein, we have studied the effect of shape of silver nanoparticles (AgNPs) on the performance of MIPs. For this, different shaped (spherical, hexagon and cube) AgNPs were prepared by green-synthesis approach, modified with vinyl group, embedded into the shell of magnetic carbon nanoparticles and used as one of the functional monomer during tramadol imprinted polymer synthesis. The resulting MIP@Ag/C@Fe3O4 was used for adsorption, removal and detection of tramadol, which is gaining importance due to their recent ban in several countries. The change in behaviour of resulting MIPs, with the change in shape of the incorporated nanoparticles was studied in terms of electrocatalytic activity, surface area, adsorption capacity, and removal efficiency. Among their different shaped colleagues cube shaped AgNPs win the MIP race and exhibited the best performance owing to the presence of more facets in comparison to the others. Furthermore, the cube shaped AgNPs based MIP (MIP@Cube-Ag/C@Fe3O4) was successfully applied for the detection of tramadol in human sera and pharmaceutical samples without any cross-reactivity. In addition to the advantages of low cost, high selectivity, sensitivity, good adsorption and removal properties, the resulting MIP format is biodegradable too i.e. the material will not create any environmental hazards after their use and could be very easily disposed off from the medium. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A comparison of ropivacaine, ropivacaine with tramadol and ropivacaine with midazolam for post-operative caudal epidural analgesia

    PubMed Central

    Krishnadas, A; Suvarna, K; Hema, VR; Taznim, M

    2016-01-01

    Background and Aims: Caudal epidural analgesia is the most commonly used method of post-operative analgesia in children undergoing subumbilical surgeries. Many additive drugs have been used to prolong the post-operative analgesia. The aim of this study was to compare the efficacy of tramadol or midazolam addition to caudal ropivacaine for post-operative analgesia in children undergoing subumbilical surgeries. Methods: In this prospective, randomised, double-blinded comparative study, sixty children of either gender, in the age group of 1–5 years and scheduled for elective subumbilical surgeries were randomly divided into three groups of twenty each. Children in Group R received an epidural injection of 1 mL/kg of 0.2% plain ropivacaine whereas children in Group RT received an epidural injection of 2 mg/kg of tramadol plus 1 mL/kg of 0.2% ropivacaine and Group RM received an epidural injection of 50 μg/kg midazolam plus 1 mL/kg of 0.2% ropivacaine. The primary outcome variable was the duration of time to rescue analgesia. The secondary outcome variables were motor block, sedation score and urinary retention. Statistical comparison among the three groups was performed using one-way ANOVA with post hoc analysis using Bonferroni. For qualitative variables, Chi-square test was used. Statistical significance was defined as P < 0.05. Results: The mean duration of time to rescue analgesia was significantly longer (P < 0.001) in Group RT (913 ± 315.5 min) and Group RM (769.2 ± 331.9 min) compared to Group R (437.75 ± 75.68 min). However, there was no significant difference in the duration of time to rescue analgesia between RT and RM groups. Motor block and sedation scores were comparable between groups. Conclusions: The addition of tramadol or midazolam to caudal epidural ropivacaine prolongs the duration of analgesia without causing significant side effects. PMID:27942056

  10. Comparison of caudal tramadol versus caudal fentanyl with bupivacaine for prolongation of postoperative analgesia in pediatric patients

    PubMed Central

    Solanki, NM; Engineer, SR; Jansari, DB; Patel, RJ

    2016-01-01

    Background and Aims: Caudal block is a common technique for pediatric analgesia for infraumblical surgeries. Because of the short duration of analgesia with bupivacaine alone various additive have been used to prolong the action of bupivacaine. The present study was aimed to evaluate the analgesic effect of tramadol or fentanyl added to bupivacaine for infraumblical surgeries in pediatric patients. Materials and Methods: We conducted a prospective, randomized, single-blind controlled trial. After written informed consent from parents, 100 patients belonging to American Society of Anesthesiologist physical status I-II, in the age group of 1-12 years, of either sex undergoing infraumblical surgery under general anesthesia were divided into two groups. Group BT received 1 ml/kg of 0.25% bupivacaine with tramadol 2 mg/kg in normal saline and Group BF received 1 ml/kg of 0.25% bupivacaine with fentanyl 2 μg/kg in normal saline with maximum volume of 12 ml in both groups. All patients were assessed intraoperatively for hemodynamic changes, the requirement of sevoflurane concentration, as well as postoperatively for pain by using FLACC (F = Face, L = Leg, A = Activity, C = Cry, C = Consolability), pain score and for sedation by using four point sedation score. Results: The mean duration of analgesia was 10–18 h in Group BT while in Group BF it was 7-11 h. The postoperatively period up to 1½ h, Group BF had higher sedation score up to two as compared to that below one on Group BT. Conclusion: Caudal tramadol significantly prolongs the duration of analgesia as compared to caudal fentanyl without any side effects. PMID:27051365

  11. Anaesthetic effects in the ferret of alfaxalone alone and in combination with medetomidine or tramadol: a pilot study.

    PubMed

    Giral, M; García-Olmo, D C; Gómez-Juárez, M; Gómez de Segura, I A

    2014-10-01

    Alfaxalone is a neurosteroid with anaesthetic effects and it has been used successfully in several animal species. However, there are no data, to our knowledge, about its efficacy and safety in ferrets (Mustela putorius furo). We evaluated a variety of anaesthetic regimens in ferrets, namely, alfaxalone at 20, 10 and 5 mg/kg (n = 1, 10 and 9, respectively; intravenously); medetomidine at 20 µg/kg (n = 3; intramuscularly); medetomidine (20 µg/kg, intramuscularly) plus alfaxalone (2.5 mg/kg, intravenously; n = 7); and tramadol (5 mg/kg, intramuscularly) plus alfaxalone (5 mg/kg, intravenously; n = 2). Two animals treated with alfaxalone at 10 mg/kg and 20 mg/kg, respectively, died. At 5 mg/kg alfaxalone produced anaesthesia with a similar onset but a shorter duration of anaesthesia and analgesia than alfaxalone at 10 mg/kg. The medetomidine-alfaxalone combination produced anaesthesia and analgesia of a longer duration than alfaxalone administered alone at 5 mg/kg (P < 0.0001 and P < 0.001, respectively). Under this anaesthetic regimen, there was a progressive decrease in pulse rate during the first 30 min before the pulse rate stabilized. Respiratory parameters were maintained at acceptable levels. When tramadol was administered, all the animals exhibited a strong excitation reaction and in no case was the toe-pinch reflex clearly abolished. Thus, alfaxalone plus medetomidine provided safe and effective anaesthesia in ferrets. Alfaxalone, alone or in combination with tramadol, did not produce satisfactory results for use as an anaesthetic for this species.

  12. CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.

    PubMed

    Nasare, Namita Vilas; Banerjee, Basu Dev; Suryakantrao Deshmukh, Pravin; Mediratta, Pramod Kumari; Saxena, Ashok Kumar; Ahmed, Rafat Sultana; Bhattacharya, Sambit Nath

    2016-01-01

    Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN

  13. Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial.

    PubMed

    Isiordia-Espinoza, M-A; Pozos-Guillen, A; Martinez-Rider, R; Perez-Urizar, J

    2016-09-01

    Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. According to the VAS and UAC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery.

  14. A comparative study evaluating the prophylactic efficacy of oral clonidine and tramadol for perioperative shivering in geriatric patients undergoing transurethral resection of prostate

    PubMed Central

    Tewari, Anurag; Dhawan, Ira; Mahendru, Vidhi; Katyal, Sunil; Singh, Avtar; Narula, Navneet

    2014-01-01

    Background and Aims: Perioperative shivering, in geriatric patients undergoing urological surgery under central neuraxial blockade is a common complication. Prophylactic measures to reduce shivering are quintessential to decrease the morbidity and mortality. Believing that oral formulation will bring down the cost of treatment, we decided to compare the efficacy of oral clonidine and tramadol, as premedication, in prevention of shivering in patients undergoing transurethral resection of prostate (TURP) under spinal anesthesia in a prospective and double-blind manner. Materials and Methods: The patients were randomly allocated into three groups (40 patients each). Group I received oral clonidine 150 μg, Group II received oral tramadol 50 mg, while Group III received a placebo. Number of patients having shivering, their grades and duration, hemodynamic changes, and side-effects in the form of sedation were recorded. Data were analyzed using analysis of variance, Student's t-test, Z test as and when appropriate. Results: In group I and II, 38 patients (95%) and 37 patients (92.5%) did not shiver, respectively. Although in the group III, 24 patients (60%) exhibited no grade of shivering, the shivering was of significantly severe intensity and lasted for a longer duration. No, clinically significant collateral effects were observed in patients who were administered clonidine or tramadol. Conclusions: Oral clonidine and tramadol were comparable in respect to their effect in decreasing the incidence, intensity, and duration of shivering when used prophylactically in patients who underwent TURP under subarachnoid blockade. PMID:25190940

  15. Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations.

    PubMed

    Brvar, Nina; Mateović-Rojnik, Tatjana; Grabnar, Iztok

    2014-10-01

    This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics. Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers. Tramadol plasma concentration-time data were described by an inverse Gaussian function to model the complete input process linked to a two-compartment disposition model with first-order elimination. Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model. The final model estimated parameters with reasonable precision and was able to estimate the interindividual variability of all parameters except for the relative bioavailability of PR vs. IR formulation. Validity of the model was further tested using the nonparametric bootstrap approach. Finally, the model was applied to assess absorption kinetics of tramadol and predict steady-state pharmacokinetics following administration of both types of formulations. For both formulations, the final model yielded a stable estimate of the absorption time profiles. Steady-state simulation supports switching of patients from IR to PR formulation.

  16. Development of solid-phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer.

    PubMed

    Habibi-Khorasani, Monireh; Mohammadpour, Amir Hooshang; Mohajeri, Seyed Ahmad

    2017-02-01

    In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid-phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid-phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL(-1) ) and 10 ppm (10 μg mL(-1) ) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12-107.54% in aqueous solution and 76.16-91.20% in rabbit brain tissue. The inter- and intra-day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost-effective sample analysis. Copyright © 2016 John Wiley & Sons, Ltd.

  17. First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose.

    PubMed

    Meyer, Markus R; Rosenborg, Staffan; Stenberg, Marta; Beck, Olof

    2015-12-01

    Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48 h using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8-24 h. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB and OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug and active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Combined Ketamine-Tramadol Subcutaneous Wound Infiltration for Multimodal Postoperative Analgesia: A Double-Blinded, Randomized Controlled Trial after Renal Surgery

    PubMed Central

    Khajavi, Mohammad Reza; Navardi, Marzieh; Shariat Moharari, Reza; Pourfakhr, Pejman; Khalili, Narjes; Etezadi, Farhad; Imani, Farsad

    2016-01-01

    Background Pain is an important consideration after renal surgery. A multimodal approach to postoperative pain management could enhance analgesia by risking fewer side effects after surgery. Objectives The aim of this study was to evaluate the clinical efficacy of the subcutaneous infiltration of ketamine and tramadol at the incision site to reduce postoperative pain. Methods Sixty-four patients between 18 and 80 years old who were scheduled for elective renal surgery were enrolled in a double-blind randomized controlled study. At the end of the surgery, patients were divided into four groups with 16 patients in each group: the saline group, who were treated with 10 mL of saline solution; the K group, who were treated with 1 mg/kg etamine in 10 mL of saline solution; the T group, who were treated with 1 mg/kg tramadol in 10 mL of saline solution; and the K/T group, who were treated with 0.5 mg/kg ketamine with 0.5 mg/kg tramadol in 10 mL of saline solution. In each group, the solution was infiltrated subcutaneously at the incision site. The postoperative pain scores and rescue analgesic consumption of the patients in each group were recorded for 24 hours and compared. The primary goal of the study was to compare the results of patients treated with a combined ketamine and tramadol subcutaneous wound infiltration, patients treated with a tramadol subcutaneous wound infiltration, and patients treated with a ketamine subcutaneous wound infiltration. Results Sixty-four patients were enrolled in the study. Pain intensity and cumulative meperidine consumption were significantly lower in the K/T group (27 mg; 95% confidence interval, 25.2 - 53.2) in comparison with the group that received a saline infusion during the first 24 hours after surgery (P < 0.001). The sedation score of the K, T, and K/T groups were significantly higher than the saline group (P < 0.001). Conclusions The combined subcutaneous infiltration of ketamine and tramadol at the incision site produces

  19. Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty.

    PubMed

    McQuay, H J; Moore, R A; Berta, A; Gainutdinovs, O; Fülesdi, B; Porvaneckas, N; Petronis, S; Mitkovic, M; Bucsi, L; Samson, L; Zegunis, V; Ankin, M L; Bertolotti, M; Pizà-Vallespir, B; Cuadripani, S; Contini, M P; Nizzardo, A

    2016-02-01

    The aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen (25 mg) and tramadol (100 mg) in moderate-to-severe acute pain after total hip arthroplasty. This was a randomized, double-blind, parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery, compared with placebo at first administration to validate the pain model. The study drug was administered orally every 8 h throughout a 5 day period. Rescue medication, metamizole 500 mg, was available during the treatment period. The evaluation of efficacy was based on patient assessments of pain intensity and pain relief. The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h (SPID8). Overall, 641 patients, mean age 62 (range 29-80) yr, were analysed; mean (sd) values of SPID8 were 247 (157) for dexketoprofen/tramadol, 209 (155) for dexketoprofen, 205 (146) for tramadol, and 151 (159) for placebo. The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg (P=0.019; 95% confidence interval 6.4-73) and tramadol 100 mg (P=0.012; 95% confidence interval 9.5-76). The single components were superior to placebo (P<0.05), confirming model sensitivity. Most secondary analyses supported the superiority of the combination. The incidence of adverse drug reactions was low and similar among active treatment groups. The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components, even at higher doses (tramadol), with a safety profile fully in line with that previously known for these agents in monotherapy. EudraCT 2012-004548-31 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004548-31);ClinicalTrials.gov NCT01902134 (https://www.clinicaltrials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1). © The Author 2016. Published by Oxford University Press on

  20. Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty

    PubMed Central

    McQuay, H. J.; Moore, R. A.; Berta, A.; Gainutdinovs, O.; Fülesdi, B.; Porvaneckas, N.; Petronis, S.; Mitkovic, M.; Bucsi, L.; Samson, L.; Zegunis, V.; Ankin, M. L.; Bertolotti, M.; Pizà-Vallespir, B.; Cuadripani, S.; Contini, M. P.; Nizzardo, A.

    2016-01-01

    Background. The aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen (25 mg) and tramadol (100 mg) in moderate-to-severe acute pain after total hip arthroplasty. Methods. This was a randomized, double-blind, parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery, compared with placebo at first administration to validate the pain model. The study drug was administered orally every 8 h throughout a 5 day period. Rescue medication, metamizole 500 mg, was available during the treatment period. The evaluation of efficacy was based on patient assessments of pain intensity and pain relief. The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h (SPID8). Results. Overall, 641 patients, mean age 62 (range 29–80) yr, were analysed; mean (sd) values of SPID8 were 247 (157) for dexketoprofen/tramadol, 209 (155) for dexketoprofen, 205 (146) for tramadol, and 151 (159) for placebo. The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg (P=0.019; 95% confidence interval 6.4–73) and tramadol 100 mg (P=0.012; 95% confidence interval 9.5–76). The single components were superior to placebo (P<0.05), confirming model sensitivity. Most secondary analyses supported the superiority of the combination. The incidence of adverse drug reactions was low and similar among active treatment groups. Conclusion. The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components, even at higher doses (tramadol), with a safety profile fully in line with that previously known for these agents in monotherapy. Clinical trial registration. EudraCT 2012-004548-31 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004548-31); ClinicalTrials.gov NCT01902134 (https://www.clinicaltrials.gov/ct2/show/NCT01902134?term

  1. The pharmacokinetics of the effervescent vs. conventional tramadol/paracetamol fixed-dose combination tablet in patients after total gastric resection.

    PubMed

    Szałek, Edyta; Karbownik, Agnieszka; Murawa, Dawid; Połom, Karol; Urbaniak, Bartosz; Grabowski, Tomasz; Wolc, Anna; Więckiewicz, Aleksandra; Grześkowiak, Edmund; Kokot, Zenon J; Murawa, Paweł; Burchardt, Paweł; Cieśla, Sławomir

    2014-02-01

    Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy. The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients received two tramadol/paracetamol fixed-dose combination tablets in a single orally administered dose of 75/650 mg (2 × 37.5/325 mg). The patients were subjected to one of the two study drug group with: I. effervescent tablet (ET) (n = 14; mean [SD] age, 63.4 [10.1] years; weight, 75.5 [15.3]kg; and BMI, 26.0 [4.6]kg/m(2)) and II. conventional tablet (CT) (n = 12; mean [SD] age, 66.8 [7.7] years; weight, 79.8 [17.8]kg; and BMI, 27.4 [5.3]kg/m(2)). Blood samples were collected within 10 h after the drug administration. The plasma concentrations of tramadol