Science.gov

Sample records for intravenosa con tramadol

  1. Tramadol

    MedlinePlus

    ... moderate to moderately severe pain. Tramadol extended-release tablets and capsules are only used by people who ... Tramadol comes as a tablet, an extended-release (long-acting) tablet, an extended-release (long-acting) capsule, and an orally disintegrating tablet (tablet that dissolves ...

  2. Tramadol/paracetamol.

    PubMed

    McClellan, Karen; Scott, Lesley J

    2003-01-01

    The orally administered fixed combination tablet of tramadol (centrally-acting opiate) plus paracetamol (acetaminophen; nonopiate, nonsalicylate analgesic) [37.5/325 mg] provides effective analgesia in patients with moderate to severe acute pain and those with chronic painful conditions characterised by intermittent exacerbations of pain. Two tramadol/paracetamol 37.5/325 mg tablets provided greater relief of dental pain over an 8-hour period than either agent alone, with a faster onset of action than tramadol alone and a longer duration of action than either agent as monotherapy. In patients with postoperative dental pain, two tramadol/paracetamol tablets (37.5/325 mg) provided similar analgesia to hydrocodone/paracetamol 10/650 mg over an 8-hour period. The addition of one or two tramadol/paracetamol 37.5/32 5mg tablets (up to four times daily) for 5 days to existing NSAID or cyclo-oxygenase-2 inhibitor analgesic therapy provided effective pain relief in patients with osteoarthritis flare pain. Tramadol/paracetamol 37.5/325 mg provided similar efficacy to that of codeine/paracetamol 30/300 mg in patients with chronic back pain in a 4-week, randomised, double-blind trial (a maximum of 10 tablets or capsules per day of the active drug). PMID:12749738

  3. 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. PMID:7517826

  4. 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. PMID:9075493

  5. Synthetic Origin of Tramadol in the Environment.

    PubMed

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

    2016-01-01

    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. PMID:26473295

  6. 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

  7. 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. PMID:14986689

  8. Tramadol and acetaminophen tablets for dental pain.

    PubMed Central

    Medve, R. A.; Wang, J.; Karim, R.

    2001-01-01

    The purpose of this work was to compare the efficacy and time to analgesia of a new tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. A meta-analysis was performed of 3 separate single-dose, double-blind, parallel-group trials in patients with moderate or severe pain following extraction of 2 or more third molars. Patients in each study were evenly randomized to a single dose of tramadol/APAP (75 mg/650 mg), tramadol 75 mg, APAP 650 mg, ibuprofen 400 mg, or placebo. Active control with ibuprofen was used to determine model sensitivity. Pain relief (scale, 0-4) and pain intensity (scale, 0-3) were reported at 30 minutes after the dose and then hourly for 8 hours. Total pain relief over 8 hours (TOTPAR8) and the sum of pain intensity differences (SPID8) were calculated from the hourly scores. Time to onset of pain relief was determined by the double-stopwatch technique, and patients were advised to wait at least 2 hours before taking supplemental analgesia. Patients assessed overall efficacy (scale, 1-5) upon completion. In all, 1197 patients (age range, 16-46 years) were evaluable for efficacy; treatment groups in each study were similar at baseline. Pain relief was superior to placebo (P < or = .0001) for all treatments. Pain relief provided by tramadol/ APAP was superior to that of tramadol or APAP alone, as shown by mean TOT-PAR8 (12.1 vs 6.7 and 8.6, respectively, P < or = .0001) and SPID8 (4.7 vs 0.9 and 2.7, respectively, P < or = .0001). Estimated onset of pain relief was 17 minutes (95% CI, 15-20 minutes) for tramadol/APAP compared with 51 minutes (95% CI, 40-70 minutes) for tramadol, 18 minutes (95% CI, 16-21 minutes) for APAP, and 34 minutes (95% CI, 28-44 minutes) for ibuprofen. Median time to supplemental analgesia and mean overall assessment of efficacy were greater (P < .05) for the tramadol/APAP group (302 minutes and 3.0, respectively) than for the tramadol (122 minutes and 2.0) or APAP (183 minutes and 2

  9. Tramadol

    MedlinePlus

    ... other condition that caused high pressure inside your skull; difficulty urinating; depression; thoughts about harming or killing ... the following: decreased size of the pupil (the black circle in the center of the eye) difficulty ...

  10. Tramadol for the treatment of fibromyalgia.

    PubMed

    MacLean, Ashley J B; Schwartz, Thomas L

    2015-05-01

    Tramadol is a novel, synthetic opioid receptor agonist with serotonin-norepinephrine reuptake inhibitor properties that is often prescribed acutely for painful conditions. Fibromyalgia (FM) is a chronic painful condition that is difficult to treat and until more recently has had no approved medical treatments. Currently, the only US FDA-approved medications for FM include duloxetine, milnacipran and pregabalin. No opioid is approved for use in the treatment of FM. This paper specifically reviews the literature on tramadol use in FM and concludes that there is a fair evidence base to support its use as a second-line treatment for more resistant cases. PMID:25896486

  11. Mesusage du tramadol par les adolescents et jeunes adultes en situation de rue

    PubMed Central

    Maiga, Djibo Douma; Seyni, Houdou; Moussa, Ali Ousmane; Sidikou, Amadou

    2012-01-01

    L’objectif de cette étude transversale et descriptive était de décrire quelques caractéristiques de l’addiction au Tramadol chez les adolescents et jeunes adultes en situation de rue, rattachés aux centres d’écoute du Service Educatif, Judiciaire et préventif (SEJUP) de Niamey. Le recueil des données a porté sur les variables sociodémographiques et la consommation de tramadol. L’analyse des données a calculé les moyennes, minima, maxima et écarts types. Les résultats indiquent que : trois centres d’écoute sur huit participaient à l’étude. L’échantillon constituait 61 adolescents et jeunes adultes dont l’âge moyen était de 17,49 ans. L’analyse indique que 47 adolescents et jeunes adultes de toutes les catégories sociodémographiques (sexe, niveau d’instruction, provenance familiale ; région de provenance ; antécdents médicaux; antécédents judiciaires) étaient usagers du Tramadol. 46 étaient dépendants du Tramadol. La quantité moyenne consommée était de 1455,31 ± 901,4mg. Le mésusage du tramadol par les jeunes en situation de rue est probablement une des conséquences de la vente illicite et libre des médicaments, dont il est urgent de préciser les données médicales et sociales. PMID:23330046

  12. A double-blind placebo-controlled comparison of tramadol/acetaminophen and tramadol in patients with postoperative dental pain.

    PubMed

    Fricke, James R; Hewitt, David J; Jordan, Donna M; Fisher, Alan; Rosenthal, Norman R

    2004-06-01

    The objective of this study was to compare the analgesic efficacy of tramadol/acetaminophen (APAP) (total dose 75 mg/650 mg) and tramadol (total dose 100 mg) for the control of pain after oral surgery. A total of 456 patients with moderate-to-severe pain within 5 h after extraction of two or more third molars were randomized to receive two identical encapsulated tablets containing tramadol/APAP 37.5 mg/325 mg, tramadol 50 mg, or placebo. Tramadol/APAP was superior to tramadol (P < 0.001) or placebo (P < 0.001) on all efficacy measures: total pain relief (PAR) over 6 h (7.4, 2.5, and 1.5, respectively, on a scale of 0-24); sum of pain intensity differences (PIDs) (3.1, 0.6, and 0.1, respectively, on a scale of -6 to 18); and sum of PAR and PID (10.5, 3.1, and 1.6, respectively, on a scale of -6 to 42). Median times to onset of perceptible and meaningful PAR were 37.6 and 126.5 min, respectively, for the tramadol/APAP group (P < 0.001) for each, compared with tramadol and placebo arms). The most common adverse events with active treatment were nausea, dizziness, and vomiting; these events occurred more frequently in the tramadol group than in the tramadol/APAP group. This study established the superiority of tramadol/APAP 75 mg/650 mg over tramadol 100 mg in the treatment of acute pain following oral surgery. PMID:15157685

  13. Tramadol extended-release in the management of chronic pain

    PubMed Central

    McCarberg, Bill

    2007-01-01

    Chronic, noncancer pain such as that associated with osteoarthritis of the hip and knee is typically managed according to American College of Rheumatology guidelines. Patients unresponsive to first-line treatment with acetaminophen receive nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. However, many patients may have chronic pain that is refractory to these agents, or they may be at risk for the gastrointestinal, renal, and cardiovascular complications associated with their use. Tramadol, a mild opioid agonist and norepinephrine and serotonin reuptake inhibitor, is recommended by current guidelines for the treatment of moderate to moderately severe pain in patients who have not responded to previous oral therapy, or in patients who have contraindications to COX-2 inhibitors and nonselective NSAIDs. An extended-release (ER) formulation of tramadol was approved by the US Food and Drug Administration in September 2005. In contrast with immediate-release (IR) tramadol, this ER formulation allows once-daily dosing, providing around-the-clock analgesia. In clinical studies, tramadol ER has demonstrated a lower incidence of adverse events than that reported for IR tramadol. Unlike nonselective NSAIDs and COX-2 inhibitors, tramadol ER is not associated with gastrointestinal, renal, or cardiovascular complications. Although tramadol is an opioid agonist, significant abuse has not been demonstrated after long-term therapy. It is concluded that tramadol ER has an efficacy and safety profile that warrants its early use for the management of chronic pain, either alone or in conjunction with nonselective NSAIDs and COX-2 inhibitors. PMID:18488071

  14. 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

  15. Unexceptional seizure potential of tramadol or its enantiomers or metabolites in mice.

    PubMed

    Raffa, Robert B; Stone, Dennis J

    2008-05-01

    Tramadol is one of the most widely used centrally acting analgesics worldwide. Because of its multimodal analgesic mechanism (opioid plus nonopioid), the adverse effects profile of tramadol, similar to its analgesic profile, can be atypical compared with single-mechanism opioid analgesics. The comparison is often favorable (e.g., less respiratory depression or abuse), but it is sometimes cited as unfavorable in regard to seizure potential. As part of a broader study of this analgesic, we compared seizure induction in mice produced by administration of tramadol, the enantiomers and metabolites [M1 (O-desmethyl tramadol), M2 (N-desmethyl tramadol), M3 (N,N-didesmethyl tramadol), M4 (O,N,N-tridesmethyl tramadol), and M5 (O,N-didesmethyl tramadol)] of tramadol, and opioid and nonopioid reference compounds. We found that tramadol, its enantiomers, and M1 to M5 metabolites were of intermediate potency in this endpoint (on either a milligram per kilogram or millimole per kilogram basis). The SD50 (estimated dose required to induce seizures in 50% of test group) of tramadol to antinociceptive ED50 ratio was almost identical to that of codeine. The enantiomers of tramadol were about equipotent to tramadol on this endpoint. The M1 to M5 metabolites (and M1 enantiomers) of tramadol were less potent than tramadol. The relative potency of tramadol to opioids was not altered by quinidine (an inhibitor of CYP4502D6), noxious stimulus (48 degrees C hot-plate), multiple dosing, or in reserpinized mice. Tramadol seizures were increased by naloxone, principally at high tramadol doses and due to an effect on the (-)enantiomer that overcame the opposite effect on the (+)enantiomer. No synergistic effect on seizure induction was observed between concomitant tramadol and codeine or morphine. PMID:18292293

  16. 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

  17. Evaluation of Analgesic Effect of Caudal Epidural Tramadol, Tramadol-Lidocaine, and Lidocaine in Water Buffalo Calves (Bubalus bubalis)

    PubMed Central

    Atiba, Ayman; Ghazy, Alaa; Gomaa, Naglaa; Kamal, Tarek; Shukry, Mustafa

    2015-01-01

    Aim of this study was to compare the analgesic effect of tramadol and a combination of tramadol-lidocaine with that produced by lidocaine administration in the epidural space in buffalo calves. In a prospective randomized crossover study, ten male buffalo calves were used to compare the epidural analgesic effect of tramadol (1 mg/kg) and tramadol-lidocaine combination (0.5 mg/kg and 0.11 mg/kg, resp.) with that produced by 2% lidocaine (0.22 mg/kg). Loss of sensation was examined by pin-prick test. Onset time, duration, and degree of analgesia and ataxia were recorded after each treatment. Heart rate (HR), respiratory rate (RR), rectal temperature, and haematobiochemical parameters were recorded after all treatments. Time to onset and duration of analgesia, respectively, were as follows: tramadol 11 ± 2 min and 208 ± 15 min; tramadol-lidocaine 6 ± 2 min and 168 ± 9 min; lidocaine 4 ± 1 min and 67 ± 13 min. Onset time and duration were significantly longer with tramadol than the other treatments. Duration was significantly longer with tramadol-lidocaine than lidocaine. Ataxia was mildly observed in tramadol-lidocaine and was moderate in lidocaine. HR, RR, and rectal temperature did not differ significantly from baseline after any treatment. Haematobiochemical parameters returned to basal levels by 24 h after all treatments. This combination might be clinically useful to provide analgesia in buffalo for long-duration surgical procedures. PMID:26770870

  18. Evaluation of Analgesic Effect of Caudal Epidural Tramadol, Tramadol-Lidocaine, and Lidocaine in Water Buffalo Calves (Bubalus bubalis).

    PubMed

    Atiba, Ayman; Ghazy, Alaa; Gomaa, Naglaa; Kamal, Tarek; Shukry, Mustafa

    2015-01-01

    Aim of this study was to compare the analgesic effect of tramadol and a combination of tramadol-lidocaine with that produced by lidocaine administration in the epidural space in buffalo calves. In a prospective randomized crossover study, ten male buffalo calves were used to compare the epidural analgesic effect of tramadol (1 mg/kg) and tramadol-lidocaine combination (0.5 mg/kg and 0.11 mg/kg, resp.) with that produced by 2% lidocaine (0.22 mg/kg). Loss of sensation was examined by pin-prick test. Onset time, duration, and degree of analgesia and ataxia were recorded after each treatment. Heart rate (HR), respiratory rate (RR), rectal temperature, and haematobiochemical parameters were recorded after all treatments. Time to onset and duration of analgesia, respectively, were as follows: tramadol 11 ± 2 min and 208 ± 15 min; tramadol-lidocaine 6 ± 2 min and 168 ± 9 min; lidocaine 4 ± 1 min and 67 ± 13 min. Onset time and duration were significantly longer with tramadol than the other treatments. Duration was significantly longer with tramadol-lidocaine than lidocaine. Ataxia was mildly observed in tramadol-lidocaine and was moderate in lidocaine. HR, RR, and rectal temperature did not differ significantly from baseline after any treatment. Haematobiochemical parameters returned to basal levels by 24 h after all treatments. This combination might be clinically useful to provide analgesia in buffalo for long-duration surgical procedures. PMID:26770870

  19. 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. PMID:26867125

  20. 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

  1. Analgesic oral efficacy of tramadol hydrochloride in postoperative pain.

    PubMed

    Sunshine, A; Olson, N Z; Zighelboim, I; DeCastro, A; Minn, F L

    1992-06-01

    Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half-life of 5 to 6 hours and peak plasma levels at about 1 1/2 hours. It derives its activity from attachment to the mu-receptor and blockage of norepinephrine reuptake. The purpose of this single-dose, double-blind, placebo-controlled study was to determine the analgesic effectiveness of an oral administration of two dose levels of tramadol hydrochloride (75 or 150 mg) compared with the combination of 650 mg acetaminophen plus 100 mg propoxyphene napsylate in 161 patients with severe postoperative pain after cesarean section. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data. A global rating of the study medication was also used to compare treatments. The three active treatments were effective analgesics, statistically superior to placebo for many hourly and summary measures. A dose response was seen between the two tramadol doses, with the 150 mg dose providing significantly greater analgesia over the lower dose. The 75 mg dose of tramadol was generally more effective than the acetaminophen-propoxyphene combination after hour 2, and significantly so for some hourly time points, as well as for the global rating of the medication. The 150 mg dose of tramadol was significantly more effective than the acetaminophen-propoxyphene combination from hour 2 through hour 6 for the sum of pain intensity differences and total pain relief scores, as well as for the global rating of the medication. Tramadol hydrochloride at both dose levels is an effective analgesic agent and at 150 mg is statistically superior to the acetaminophen-propoxyphene combination. No serious adverse effects were observed; however, dizziness was more frequently reported with 150 mg tramadol. PMID:1351804

  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. PREDICTIVE PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE FLOATING TABLETS.

    PubMed

    Wang, Jianming; Zhang, Yanzhen; Guo, Zhiling; Tao, Qingwen; Wang, Yongjun; Zhou, Wei; Ma, Xiao; Li, Zhihong

    2016-01-01

    The purpose of this study was to propose the effectiveness of convolution approach to predict pharmacokinetics of tramadol hydrochloride floating tablets, prepared by using various ratios of carbopol, HPMC K100M, and Hibiscus rosa Sinensis as excipient. The in vitro dissolution test was conducted using paddle method in 900 mL of HCl buffer with pH 1.2 to simulate the gastric condition. The stirring speed of paddles was set at 70 rpm. Temperature of dissolution medium was adjusted at 37 ± 5 °C. At predetermined time points, 5 mL of dissolution samples were taken with a replacement of same volume using fresh medium. The obtained samples were analyzed at 271 nm using UV visible spectrophotometer. The values of predicted pharmacokinetic parameters like Cmax (maximum blood drug level), Tmax (time required to attain maximum blood drug level), and AUC (area under blood drug concentration curve) ranged between 80.8 ± 3.2-119.6 ± 4.7 ng/mL, 11.4 ± 0.2-12.2 ± 0.2 h, and 1430.5 ± 209.5-1970.6 ± 287.4 ng.h/mL, respectively. This certainly is a desired feature required at the formulation development step, where the formulator requires the development of a formulation using desired in vivo features on the basis of only accessible in vitro data. It can be concluded from the results that convolution method is a practical method for the prediction of drug concentration in blood and for quality control. PMID:27476294

  4. 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. PMID:25955656

  5. Comparison of tapentadol with tramadol for analgesia after cardiac surgery

    PubMed Central

    Iyer, Srinivas Kalyanaraman; Mohan, Gokulakrishnan; Ramakrishnan, Sivakumar; Theodore, Sanjay

    2015-01-01

    Background: Tapentadol is a relatively new analgesic. We decided to compare it with tramadol for their various effects after cardiac surgery. Setting: A study in a tertiary care hospital. Materials and Methods: Sixty adults undergoing cardiac surgery were divided into 2 groups of 30 each by computerized random allotment (Group X = tapentadol 50 mg oral and Group Y = tramadol 100 mg oral). Informed Consent and Institutional Ethics Committee approval were obtained. The patients were given either drug X or drug Y after extubation in this single blinded study, wherein the data collectors and analyzers were blinded to the study. All patients received oral paracetamol qds and either drug X or drug Y tds. The pain score was noted on a Visual Analog Scale before each drug dose, 3 h later and on coughing. Heart rate, respiratory rate, and blood pressure were recorded before the drug dose and 3 h later. Postoperative nausea or vomiting (PONV), temperature, and modified Glasgow Coma Scale readings were recorded. The above readings were obtained for 6 doses (up to 48 h after extubation). Statistics: t-test, Pearson Chi-square test, Fisher exact test, and Mantel–Haenszel test were used for statistics. Results: Tapentadol group patients had significantly better analgesia 3 h after the drug and “on coughing” than tramadol group. The difference in their effects on blood creatinine levels, temperature, hemodynamics, oxygen saturation, and respiratory rate were not clinically significant. Tapentadol produced lesser drowsiness and lesser vomiting than tramadol. Conclusions: Tapentadol, due to its norepinephrine reuptake inhibition properties, in addition to mu agonist, is a better analgesic than tramadol and has lesser PONV. PMID:26139740

  6. 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

    2015-07-01

    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. PMID:25843409

  7. 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

  8. Tramadol Use in Premature Ejaculation: Daily Versus Sporadic Treatment

    PubMed Central

    Khan, Amil H.; Rasaily, Deepa

    2013-01-01

    Aim: Premature ejaculation (PME) is defined as ejaculation with the minimal sexual stimulation before, on or shortly after penetration and or before a person wishes it. It is a function of the time between intra-vaginal penetration and intra-vaginal ejaculation. Tramadol has shown efficacy in PME when used as sporadic basis. In this study, we compared the use of 100 mg of tramadol as sporadic treatment (administered 6-8 h before coitus) versus continued treatment with the objective of evaluating the therapeutic results of both modalities. We assumed our alternative hypothesis that they have similar effects. Materials and Methods: A prospective study was carried out on 60 patients divided into two groups of 30 patients each. Intra-vaginal ejaculation latency time (IELT) and coital frequency were measured both prior to and after the treatment. Group A received tramadol 100 mg daily for 4 weeks and on request (sporadically) for 4 weeks more. Group B was given placebo in the same manner. Results were statistically analyzed using the Student t-test. Results: Mean IELT prior to treatment was 59.2 s in Group A and 58.7 s in Group B. Mean pre-treatment coital frequency was 2.44 times/week for Group A and 2.13 times/week for Group B. Mean IELT was 202.5 s after continued tramadol treatment and 238.2 s after sporadic treatment in Group A. Mean IELT with daily placebo was 94.8 s and with sporadic placebo was 96.6 s. Coital frequency increased to 4.32 times/week with daily tramadol treatment and 4.86 times with sporadic treatment. Coital frequency increased to 2.88 times/week with daily placebo treatment and 3.23 times with sporadic treatment. Conclusions: The results of PME treatment with tramadol are similar with both continued and sporadic administration. The sex life of patients improved and they reported greater satisfaction with the sporadic treatment. PMID:24249927

  9. 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

  10. Kinetic spectrophotometric determination of tramadol hydrochloride in pharmaceutical formulation.

    PubMed

    Abdellatef, Hisham E

    2002-07-31

    Two simple and sensitive kinetic methods for the determination of tramadol hydrochloride are described. The first method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time at 20 min. The absorbance of the colored manganate ions was measured at 610 nm. The second method is based on the reaction of tramadol hydrochloride with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in presence of 0.1 M sodium bicarbonate. The spectrophotometric measurements were recorded by measuring the absorbance at 467 nm, at fixed time at 25 min on thermostated water bath at 90+/-1 degrees C. All variables affecting the development of the colour have been investigated and the conditions were optimised. The absorbance concentration plots in both methods were rectilinear over the range 5-25 and 50-250 microg ml(-1), for the first and second methods, respectively. The two methods have been applied successfully to commercial capsule and ampoule dosage form. The results obtained are compared statistically with those given by the reference spectrophotometric method. The determination of tramadol hydrochloride by the fixed concentration and rate constant methods is feasible with the calibration equations obtained, but the fixed time method proves to be more applicable. PMID:12093516

  11. 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. PMID:25488714

  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. PMID:23843224

  14. 78 FR 2416 - Notice of Issuance of Final Determination Concerning Rybix® (Tramadol Hydrochloride) Tablets

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-11

    ... Border Protection (``CBP'') has issued a final determination concerning the country of origin of Rybix... determination that India is the country of origin of the Rybix (tramadol hydrochloride) tablets for purposes of... the country of origin of Rybix (tramadol hydrochloride) tablets, which may be offered to the...

  15. Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol.

    PubMed

    Gaynes, B I; Barkin, R L

    1999-07-01

    This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established. PMID:10445636

  16. Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol

    PubMed Central

    Malonne, H; Sonet, B; Streel, B; Lebrun, S; De Niet, S; Sereno, A; Vanderbist, F

    2004-01-01

    Aims To compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche-en-Famenne, Belgium) with that of an immediate release capsule (Topalgic® 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability. Methods The first study had an open, single-dose, three-treatment, three-period, six-sequence, randomised, crossover design with at least a five-day wash-out. The second study had an open, steady-state, two-treatment, two-period, two-sequence, randomised crossover design with at least a seven-day wash-out. Both studies contained 30 healthy subjects. Both enantiomers of tramadol and O-demethyl-tramadol (the only active metabolite of tramadol) were assayed in the plasma using an LC-MS/MS method. AUC∞, AUCt, Cmax, Tmax, and T1/2 were estimated. Statistical analysis was performed using univariate anova, the Wilcoxon nonparametric method or Friedman's nonparametric anova where appropriate. Results Tramadol had a significantly lower Cmax and longer Tmax than the conventional formulation. Thus, the mean (± sd) Cmax of tramadol were 646 ± 192 and 300 ± 94 ng ml−1 for Topalgic® 4 × 50mg and Tramadol LP 200 mg, respectively (95% confidence interval on the difference expressed as a percentage 42–51). AUC of tramadol from both formulations was comparable (similar AUC∞ and AUCt). Thus, the mean AUC∞ of (+/–)tramadol obtained after multiple dosing were 4611 ± 1944 and 5105 ± 2101 ngh ml−1 after Topalgic® 4 × 50mg and Tramadol LP 200 mg, respectively (95%CI 102–123%). We also demonstrate that the pharmacokinetics of the drug are not influenced by the intake of food. Thus, the mean AUC∞ of (+/–) tramadol were 5444 ± 1637 and 5169 ± 1580 ngh ml−1 after Tramadol LP 200 mg given in the fasting and fed states, respectively (95%CI = 88–103%). Conclusions The new sustained release form of tramadol

  17. 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

  18. [A comparison of a tramadol/metamizole infusion with the combination tramadol infusion plus ibuprofen suppositories for postoperative pain management following hysterectomy].

    PubMed

    Striebel, H W; Hackenberger, J

    1992-06-01

    Postoperative pain management is still a grossly neglected field. In most cases, antipyretic analgesics alone are insufficient during the early postoperative period. Powerful narcotics are often avoided or underdosed because they are associated with the risk of respiratory depression. Some authors recommend combined infusion of tramadol and metamizole, which is assumed to provide sufficient pain relief without the risk of respiratory depression. However, this regimen has not yet been investigated in a study that meets currently accepted scientific standards. METHODS. Sixty patients who underwent vaginal hysterectomy were included in a randomised, prospective double-blind study. Thirty women received two placebo suppositories immediately after induction of anaesthesia and a postoperative infusion of tramadol and metamizole (400 mg tramadol plus 5 g [= 10 ml] metamizole in 500 ml electrolyte solution). The 30 women of the control group received two ibuprofen suppositories (585.2 mg) preoperatively and a post-operative tramadol infusion (400 mg tramadol plus 10 ml placebo [NaCl 0.9%] in 500 mg electrolyte solution). The patients of both groups received 125 ml of the appropriate infusion solution as a loading dose over 10 min (corresponding to 1.25 mg metamizole and 100 mg tramadol in the metamizole/tramadol group or 100 mg tramadol in the ibuprofen/tramadol group) 10 min after awakening. The remaining solution was administered at an infusion rate of 12.5-25 ml/h (corresponding to 125-250 mg metamizole and 10-20 mg tramadol/h or 10-20 mg tramadol/h). On request or when complaining of stronger pain, the patients received an additional bolus infusion of 125 ml over 10 min. In case of insufficient pain reduction despite repeated infusion of 125-ml boli or consumption of the entire infusion solution, the patients discontinued the study and received demand-adapted intravenous titration of piritramide. Postoperative pain was evaluated on the visual analogue scale (VAS) and

  19. 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. PMID:26056877

  20. 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. PMID:20235455

  1. 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. PMID:21370649

  2. Tramadol state-dependent memory: involvement of dorsal hippocampal muscarinic acetylcholine receptors.

    PubMed

    Jafari-Sabet, Majid; Jafari-Sabet, Ali-Reza; Dizaji-Ghadim, Ali

    2016-08-01

    The effects on tramadol state-dependent memory of bilateral intradorsal hippocampal (intra-CA1) injections of physostigmine, an acetylcholinesterase inhibitor, and atropine, a muscarinic acetylcholine receptor antagonist, were examined in adult male NMRI mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention. Post-training intra-CA1 administration of an atypical μ-opioid receptor agonist, tramadol (0.5 and 1 μg/mouse), dose dependently impaired memory retention. Pretest injection of tramadol (0.5 and 1 μg/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under the influence of post-training tramadol (1 μg/mouse, intra-CA1). A pretest intra-CA1 injection of physostigmine (1 μg/mouse) reversed the memory impairment induced by post-training administration of tramadol (1 μg/mouse, intra-CA1). Moreover, pretest administration of physostigmine (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of tramadol (0.25 μg/mouse, intra-CA1) also significantly restored retrieval. Pretest administration of physostigmine (0.25, 0.5, and 1 μg/mouse, intra-CA1) by itself did not affect memory retention. A pretest intra-CA1 injection of the atropine (1 and 2 μg/mouse) 5 min before the administration of tramadol (1 μg/mouse, intra-CA1) dose dependently inhibited tramadol state-dependent memory. Pretest administration of atropine (0.5, 1, and 2 μg/mouse, intra-CA1) by itself did not affect memory retention. It can be concluded that dorsal hippocampal muscarinic acetylcholine receptor mechanisms play an important role in the modulation of tramadol state-dependent memory. PMID:27089282

  3. The use of tramadol for acute heroin withdrawal: a comparison to clonidine.

    PubMed

    Sobey, Paul W; Parran, Theodore V; Grey, Scott F; Adelman, Christopher L; Yu, Jaehak

    2003-01-01

    Using a retrospective chart review, 59 patients detoxified with tramadol were compared to 85 patients detoxified with clonidine on rates of leaving against medical advice (AMA) and control of withdrawal symptoms. Patients detoxified with tramadol had 23% (95% CI, 0.09-0.59; P < .01) the risk of leaving AMA and scored an average of 0.24 points lower (95% CI, 0.08-0.41; P < .01) on a 0-3 point withdrawal symptom scale compared to patients detoxified with clonidine. This preliminary study indicates that tramadol is more effective in managing withdrawal than clonidine, and may be especially useful in outpatient detoxification. PMID:14723475

  4. 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

  5. Analgesic efficacy of lysine clonixinate plus tramadol versus tramadol in multiple doses following impacted third molar surgery.

    PubMed

    Perez-Urizar, J; Martínez-Rider, R; Torres-Roque, I; Garrocho-Rangel, A; Pozos-Guillen, A

    2014-03-01

    This study compared the analgesic and anti-inflammatory efficacy, trismus control, and tolerability of the combination of lysine clonixinate and tramadol (LCT) versus tramadol (T) alone after surgical removal of impacted mandibular third molars. This study was a double-blind, randomized clinical trial, including two study groups of 20 patients each, who exhibited acute pain subsequent to surgical extraction of two mandibular third molars. Pain intensity was quantified over a 96-h period using a visual analogue scale and a 5-point verbal rating scale. Secondary indicators of analgesic and anti-inflammatory efficacy, trismus control, and tolerability were determined. Patients administered LCT exhibited better therapeutic effects that those administered T. Fifty percent of patients in the LCT group rated this therapy as 'excellent analgesia' compared with only 10% in the T group. The onset of the analgesic effect of LCT was significantly faster, without any therapeutic failures. There were no significant differences between the groups with regard to anti-inflammatory effect or trismus. The results of this study suggest that the postsurgical analgesic efficacy of LCT in combination (LC 125 mg + T 25 mg) is superior to that obtained with T alone, administered at the standard dose of 50 mg, for up to 96 h after the extraction of both impacted mandibular third molars. PMID:24042066

  6. The effect of tramadol hydrochloride on early life stages of fish.

    PubMed

    Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

    2016-06-01

    The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride. PMID:27208654

  7. Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia.

    PubMed

    Ortner, C M; Steiner, I; Margeta, K; Schulz, M; Gustorff, B

    2012-04-01

    Combining tramadol with paracetamol is an established analgesic treatment strategy. However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After Ethics Committee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross-over study. A defined small skin area was irradiated with a UVB source inducing hyperalgesia. Twenty-four hours after irradiation, heat pain-, cold pain threshold (HPPT, CPPT), mechanical pain sensitivity to pin prick (MPS) in the area of pin prick hyperalgesia (AsH) and MPS in the sunburn were determined. In phase I, measurements have been repeated 30 min after receiving cumulative 0.3, 0.6 and 1 mg/kg of intravenous (i.v.) tramadol or active placebo. Only at 1 mg/kg tramadol and solely for MPS in the sunburn a reduction to placebo could be demonstrated (p = 0.024). Accordingly in phase II, the trial has been repeated using 1 mg/kg tramadol and paracetamol or placebo in a cumulative i.v. dose of 330, 660 and 990 mg. Now the addition of 330 mg paracetamol to tramadol reduced thermal hyperalgesia by 1.15 °C (CI 0.55; 1.76). This effect, however, did not increase with higher doses. Tramadol showed week anti-hyperalgesia reducing CPPT, MPS and AsH compared to baseline measurements (p < 0.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti-hyperalgesia. Even adding a small dose paracetamol enhances thermal anti-hyperalgesia. PMID:22396084

  8. Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration.

    PubMed

    Shilo, Y; Britzi, M; Eytan, B; Lifschitz, T; Soback, S; Steinman, A

    2008-02-01

    Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications. PMID:18177320

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

    PubMed Central

    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. PMID:27445626

  10. 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

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

    PubMed Central

    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. PMID:23103596

  12. 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. PMID:23103596

  13. 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

  14. 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

  15. Control of shivering with clonidine, butorphanol, and tramadol under spinal anesthesia: a comparative study

    PubMed Central

    Bansal, Pranav; Jain, Gaurav

    2011-01-01

    Introduction The present study was designed to evaluate the efficacy of clonidine, butorphanol, and tramadol in control of shivering under spinal anesthesia, and to compare their side effects. Methods This randomized, prospective study was conducted in 90 patients who developed shivering under spinal anesthesia during various abdominal or orthopedic surgery procedures. On shivering, patients were randomly allocated to receive an intravenous, 1 mL bolus dose of 50 mg tramadol, or 1 mg butorphanol, or 150 μg clonidine, in a double blinded manner. Control of shivering, time taken for cessation, recurrence, hemodynamic changes, axillary temperatures, and side effects were noted and compared for all 3 groups. Collected data were analyzed using appropriate statistical tests. Results Butorphanol and tramadol were more effective than clonidine in suppressing shivering. Butorphanol, tramadol, and clonidine completely controlled rigors in 83%, 73%, and 53% of cases, respectively, and incompletely suppressed rigors in 16%, 26%, and 46% of cases, respectively. Time taken to terminate rigors was significantly higher for clonidine (3.3 ± 0.9 minutes) than for butorphanol and tramadol (2.1 ± 1.0 minutes and 1.8 ± 0.5 minutes; P < 0.001). Conclusion Butorphanol had an edge over tramadol in controlling shivering with lower chances of recurrence, though both were superior to clonidine for this purpose with an early onset of action. We conclude that both these opioids control rigors better than α-2 agonists. PMID:22915890

  16. Chronic non-cancer pain: Focus on once-daily tramadol formulations

    PubMed Central

    Coluzzi, Flaminia; Mattia, Consalvo

    2007-01-01

    Despite progress in pain management, chronic non-cancer pain (CNCP) represents still a clinical challenge. The efficacy and safety profile of tramadol make it suitable as a long-term treatment in a variety of CNCP conditions. New once-daily (OD) formulations of tramadol have been marketed in various countries, in order to offer the advantage of a reduced dosing regimen and to improve patients’ compliance. This review focuses on the technology, pharmacology, clinical efficacy, and safety of different once-daily tramadol formulations. Hydrophilic vs hydrophobic matrix systems and newer technologies used in once-daily formulations to control drug delivery are discussed. Three randomized controlled trials (RCTs) established OD tramadol analgesic efficacy to be superior to that of placebo for pain management and functional improvement in patients with osteoarthritis. Three RCTs demonstrated similar rates of efficacy between OD tramadol and immediate-release (IR) or sustained-release (SR) formulations, with a better adverse events profile. An open trial on long term tolerability showed that OD tramadol is generally safe in rheumatological pain treatment. PMID:18473006

  17. 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

  18. 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

  19. 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

  20. Previous administration of naltrexone did not change synergism between paracetamol and tramadol in mice.

    PubMed

    Miranda, Hugo F; Noriega, Viviana; Prieto, Juan Carlos

    2012-07-01

    In the treatment of acute and chronic pain the most frequently used drugs are nonsteroidal anti-inflammatory drugs (NSAIDs), e.g., paracetamol; opioids, e.g., tramadol, and a group of drugs called coanalgesics or adjuvants (e.g., antidepressants, anticonvulsants). The aim of this work was to determine the nature of the interaction induced by intraperitoneal or intrathecal coadministration of paracetamol and tramadol. The type of interaction was evaluated by means of isobolographic analysis, using the acetic acid writhing test as an algesiometer in mice. In addition, the involvement of opioid receptors in the interaction was studied using naltrexone, a non-selective opioid receptor antagonist. The administration of paracetamol or tramadol induced a dose-dependent antinociceptive activity in the assay. The dose-response curves were characterized by equal efficacy but different potencies, being i.t. paracetamol 11.84 times more potent than i.p. paracetamol, and i.t. tramadol 3.54 times more potent than the i.p. tramadol. The isobolographic analysis indicates a synergistic interaction between the coadministration of i.p. or i.t. paracetamol with tramadol. The interaction index values were similar for the i.p. and i.t. coadministration with values of 0.414 and 0.364, respectively. The different mechanisms of action of paracetamol and tramadol strongly explain the analgesic synergism between them, in agreement with the general theory of drug interaction. This synergic interaction was not modified by the non selective opioid antagonist, naltrexone. This association could be of clinical significance in the treatment of pain with a reduction of doses and adverse effects. PMID:22465615

  1. 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

  2. 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

  3. 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. PMID:26142521

  4. 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. PMID:25971856

  5. Hypo and hyperglycemia among tramadol overdose patients in Loghman Hakim Hospital, Tehran, Iran.

    PubMed

    Nasouhi, Soheil; Talaie, Haleh; Pajoumand, Abdolkarim; Aghapour, Sevil; Rahimi, Mitra; Khorasani, Ahmad Ghochani; Mashayekhian, Mohammad; Aghabiklooei, Abbas; Razi, Parmis; Mahdavinejad, Arezou

    2015-11-01

    Tramadol is a synthetic and centrally active analgesic. Hypoglycemia as another possible major side effect among abusers has not been known well. Our objective is evaluation of the Blood Glucose Level (BGL) among tramadol-overdosed patients. This prospective cross-sectional study was performed from Feb to June 2013; BGL was measured at the time of admission, 8 and 12 hours later. All patients with hypoglycemia received infusion of 0.5-1 gr/kg of hypertonic dextrose and their BGL was checked every hour until normal BGL. Patients' demographic, clinical and paraclinical data were collected. Totally, 128 patients with a mean (SD) age of 24.5 (6.9) years were recruited; 127 (99.2%) were male. Seizure occurred in 59.4% cases. Mean ± SD admission BGL was 94.88 ± 21.5mg/dL. Fourteen patients experienced hypoglycemia within 12 hours period. Hyperglycemia was experienced in 8 patients (6.25%) on admission day. There was no significant relation between the dose of tramadol and BGL. In conclusion, hypoglycemia must be considered as an important side effect of tramadol-overdose. It is suggested that serial BGL monitoring in cases of Tramadol-overdose should be done for early recognition of hypoglycemia and its timely management. Also hyperglycemia may be revealed. PMID:26639492

  6. A comparative study of intravenous paracetamol and intravenous tramadol for postoperative analgesia in laparotomies

    PubMed Central

    Shahid, Mohammed; Manjula, B. P.; Sunil, B. V.

    2015-01-01

    Background: Pain in the perioperative setting or thereafter plays a significant role in delaying an otherwise successful recovery. Hence, mitigation of such postoperative pain assumes importance. Among the various agents employed for such mitigation, opioids and non-steroidal anti-inflammatory drugs have for some time taken center stage. However, alas they are not without their share of adverse effects. This study was undertaken with the purpose of elucidating the efficacy of intravenous (IV) paracetamol as compared to IV tramadol in mitigating postoperative pain while observing its effect on hemodynamic stability and the presence of adverse drug reactions, if any. Materials and Methods: A total of 60 randomized cases aged ranges from 20 to 60 years of both sexes divided into two groups (each for paracetamol and tramadol) scheduled for laparotomies were administered IV paracetamol and tramadol for postoperative pain relief and assessed with visual analog scale (VAS) score and variations in vital parameters to ascertain extent of pain relief and post-operative nausea vomiting (PONV). Results: Data so collected was statistically interpreted, and observations extrapolated. Save for a perceptible decline in PONV with paracetamol group compared with tramadol group with a statistically significant P < 0.001, nothing statistically significant was observed in any other parameter, including VAS scores between either group. Conclusion: IV paracetamol is a safer alternative to tramadol with lesser PONV in the postoperative period translates into the lesser duration of hospitalization and hence earlier discharge. PMID:26712966

  7. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

    PubMed Central

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

    2015-01-01

    Background 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. Objective This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Methods 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. Results 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. Conclusion From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model. PMID:26039663

  8. 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. PMID:27383891

  9. Predictable pulsatile release of tramadol hydrochloride for chronotherapeutics of arthritis.

    PubMed

    Dabhi, Chandu; Randale, Shivsagar; Belgamwar, Veena; Gattani, Surendra; Tekade, Avinash

    2010-07-01

    The present investigation deals with the development of a pH and time-dependent press-coated pulsatile drug delivery system for delivering drugs into the colon. The system consists of a drug containing core, coated by a combination of natural polymer Delonix regia gum (DRG) and hydroxypropyl methylcellulose (HPMC K4M) in various proportions, which controls the onset of release. The whole system was coated with methacrylic acid copolymers, which not only prevents the drug release in the stomach, but also prolongs the lag time. Tramadol HCl was used as a model drug and varying combinations of DRG and HPMC K4M were used to achieve the desired lag time before rapid and complete release of the drug in the colon. It was observed that the lag time depends on the coating ratio of DRG to HPMC and also on press coating weight. Drug release was found to be increased by 15-30% in the presence of colonic microbial flora. The results showed the capability of the system in achieving pulsatile release for a programmable period of time and pH-dependent release to attain colon-targeted delivery. PMID:20524906

  10. Unique action mechanisms of tramadol in global cerebral ischemia-induced mechanical allodynia.

    PubMed

    Matsuura, Wataru; Kageyama, Erika; Harada, Shinichi; Tokuyama, Shogo

    2016-06-15

    Central poststroke pain is associated with specific somatosensory abnormalities, such as neuropathic pain syndrome. Although central poststroke pain is a serious condition, details pertaining to underlying mechanisms are not well established, making current standard treatments only partially effective. Here, we assessed the effects of tramadol, an analgesic drug mediated by opioid receptors, using a mouse model of global cerebral ischemia. Ischemia was induced by bilateral carotid artery occlusion (30 min) in male ddY mice. Development of hind-paw mechanical allodynia was measured 3 days after bilateral carotid artery occlusion using the von Frey test. Mechanical allodynia was significantly and dose dependently suppressed by intraperitoneal tramadol (10 or 20 mg/kg). These effects, which peaked at 10 min and continued for at least 60 min, were inhibited by naloxone (nonselective opioid receptor antagonist, 1 mg/kg, intraperitoneal). Tramadol antinociception was significantly negated by β-funaltrexamine (selective μ-opioid receptor antagonist, 20 mg/kg, intraperitoneal), but not naltrindole (selective δ-opioid receptor antagonist, 5 mg/kg, intraperitoneal) or nor-binaltorphimine (selective κ-opioid receptor antagonist, 10 mg/kg, intraperitoneal) after 5 min, by β-funaltrexamine and nor-binaltorphimine but not naltrindole after 10 min, and by all selective opioid receptor antagonists at 15 and 30 min after tramadol treatment. These results suggested that antinociception induced by tramadol through various opioid receptors was time dependent. Furthermore, it is possible that the opioid receptors involved in tramadol-induced antinociception change over time with the metabolism of this drug. PMID:27171031

  11. Supra-additive effects of tramadol and acetaminophen in a human pain model.

    PubMed

    Filitz, Jörg; Ihmsen, Harald; Günther, Werner; Tröster, Andreas; Schwilden, Helmut; Schüttler, Jürgen; Koppert, Wolfgang

    2008-06-01

    The combination of analgesic drugs with different pharmacological properties may show better efficacy with less side effects. Aim of this study was to examine the analgesic and antihyperalgesic properties of the weak opioid tramadol and the non-opioid acetaminophen, alone as well as in combination, in an experimental pain model in humans. After approval of the local Ethics Committee, 17 healthy volunteers were enrolled in this double-blind and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (29.6+/-16.2 mA) induced spontaneous acute pain (NRS=6 of 10) and distinct areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities as well as the extent of the areas of hyperalgesia were assessed before, during and 150 min after a 15 min lasting intravenous infusion of acetaminophen (650 mg), tramadol (75 mg), a combination of both (325 mg acetaminophen and 37.5mg tramadol), or saline 0.9%. Tramadol led to a maximum pain reduction of 11.7+/-4.2% with negligible antihyperalgesic properties. In contrast, acetaminophen led to a similar pain reduction (9.8+/-4.4%), but a sustained antihyperalgesic effect (34.5+/-14.0% reduction of hyperalgesic area). The combination of both analgesics at half doses led to a supra-additive pain reduction of 15.2+/-5.7% and an enhanced antihyperalgesic effect (41.1+/-14.3% reduction of hyperalgesic areas) as compared to single administration of acetaminophen. Our study provides first results on interactions of tramadol and acetaminophen on experimental pain and hyperalgesia in humans. Pharmacodynamic modeling combined with the isobolographic technique showed supra-additive effects of the combination of acetaminophen and tramadol concerning both, analgesia and antihyperalgesia. The results might act as a rationale for combining both analgesics. PMID:17709207

  12. Postoperative analgesia at home after ambulatory hand surgery: a controlled comparison of tramadol, metamizol, and paracetamol.

    PubMed

    Rawal, N; Allvin, R; Amilon, A; Ohlsson, T; Hallén, J

    2001-02-01

    We compared in a prospective, randomized, double-blinded study the analgesic efficacy of three drugs in 120 ASA I and II patients scheduled to undergo ambulatory hand surgery with IV regional anesthesia. At discharge, oral analgesic tablets were prescribed as follows: tramadol 100 mg every 6 h, metamizol 1 g every 6 h, and paracetamol (acetaminophen) 1 g every 6 h. Rescue medication consisted of oral dextropropoxyphene 100 mg on demand. Analgesic efficacy was evaluated by self-assessment of pain intensity by visual analog score at six different time intervals during the 48-h study period. Patients also recorded global pain relief on a 5-grade scale, total number of study and rescue analgesic tablets, frequency and severity of adverse effects, sleep pattern, and overall satisfaction. None of the study drugs alone provided effective analgesia in all patients. The percentage of patients who required supplementary analgesics was 23% with tramadol, 31% with metamizol, and 42% with acetaminophen. Tramadol was the most effective analgesic, as evidenced by low pain scores, least rescue medication, and fewest number of patients with sleep disturbance. However, the incidence of side effects was also increased with tramadol. Seven patients (17.5%) withdrew from the study because of the severity of nausea and dizziness associated with the use of tramadol. Metamizol and acetaminophen provided good analgesia in about 70% and 60% of patients, respectively, with a decreased incidence of side effects. Despite receiving oral analgesic medication, up to 40% of patients undergoing hand surgery experienced inadequate analgesia in this controlled trial. Although tramadol was more effective, its use was associated with the highest frequency and intensity of adverse effects and the most patient dissatisfaction. Metamizol and acetaminophen provided good analgesia with a small incidence of side effects. For patients undergoing ambulatory hand surgery, postoperative pain can last longer than

  13. Efficacy and Safety of a Fixed Combination of Tramadol and Paracetamol (Acetaminophen) as Pain Therapy Within Palliative Medicine

    PubMed Central

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

    2015-01-01

    Goal: 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. Material and methods: A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1st to December 31st 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. Results: 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. Conclusion: 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. PMID:25870531

  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. PMID:26291914

  15. 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

  16. 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

  17. Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain.

    PubMed

    Stankov, G; Schmieder, G; Zerle, G; Schinzel, S; Brune, K

    1994-01-01

    To investigate the combined analgesic and spasmolytic effect of dipyrone, 104 patients suffering from "severe" or "excruciating" colic pain due to a confirmed calculus in the upper urinary tract were randomized to receive i.v. either 2.5 g dipyrone (36 patients), 100 mg tramadol (35 patients), or 20 mg butylscopolamine (33 patients) in a multicentre, observer-blind, parallel-group study conducted in 8 German centres. The three treatment groups were homogeneous when analyzed by age, sex, height, and baseline pain intensity. Dipyrone was significantly more effective than tramadol in reducing pain for the primary endpoint, pain intensity differences (PID) at 20, 30, and 50 min after drug administration, and was significantly more effective than butylscopolamine at 30 and 50 min for the secondary efficacy endpoint, pain intensity differences on a categorical scale. Dipyrone had the highest SPID0-2 h of the three drugs (P < 0.05). Only 5 patients receiving dipyrone needed "rescue" medication as compared with 13 patients given tramadol and 11 patients receiving butylscopolamine. Adverse events were observed in 4 patients receiving butylscopolamine and in 1 patient each given dipyrone and tramadol. "Distinct" pain relief as assessed on a visual analogue scale (VAS) is a reliable method of determining the onset of analgesic action in the colic pain model. PMID:7951343

  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.

  19. 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%).

  20. 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

  1. 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%). PMID:26774813

  2. 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

  3. 78 FR 65923 - Schedules of Controlled Substances: Placement of Tramadol Into Schedule IV

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ... direct evidence of abuse, it can lead to an inference that a drug has been diverted or abused. 76 FR...-((dimethylamino)methyl)-1-(3- methoxyphenyl)cyclohexanol, its salts, isomers, salts of isomers, and all isomeric configurations of possible forms including tramadol (the term ``isomers'' includes the optical and...

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

    PubMed Central

    ITAMI, Takaharu; SAITO, Yasuo; ISHIZUKA, Tomohito; TAMURA, Jun; UMAR, Mohammed A.; INOUE, Hiroki; MIYOSHI, Kenjiro; YAMASHITA, Kazuto

    2016-01-01

    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. PMID:26875837

  5. 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

  6. 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. PMID:26130854

  7. Tramadol in traumatic brain injury: Should we continue to use it?

    PubMed Central

    Mahmood, Saeed; Al-Thani, Hassan; El-Menyar, Ayman; Alani, Mushrek; Al-Hassani, Ammar; Mathrdikkal, Saji; Peralta, Ruben; Latifi, Rifat

    2015-01-01

    Background and Aims: Tramadol is commonly used to treat moderate to moderately-severe pain in adults. We aimed to analyze the clinical relevance of tramadol use during weaning and extubation in patients with traumatic brain injury (TBI). Material and Methods: A retrospective observational study was conducted and included all the intubated TBI patients at the level I trauma center between 2011 and 2012. Data included patient's demographics, mechanism of injury (MOI), Glasgow Coma Scale (GCS), injury severity score, length of Intensive Care Unit (ICU) stay length of stay (LOS), agitation scale, analgesics, failure of extubation and tracheostomy. Patients were divided into two groups based on whether they received tramadol (Group 1) or not (Group 2) during ventilatory weaning. Chi-square and Student's t-tests were used for categorical and continuous variables; respectively. Logistic regression analysis was performed for predictors of agitation in ICU. Results: The study included 393 TBI patients; the majority (96%) was males with a mean age of 33.6 ± 14 years. The most common MOI were motor vehicle crash (39%), fall (29%) and pedestrian (17%). The associated injuries were mainly chest (35%) and abdominal (16%) trauma. Tramadol was administered in 51.4% of TBI patients. Tracheostomy was performed in 12.4% cases. Agitation was observed in 34.2% cases. Group 1 patients had significantly lower age (31.6 ± 12.4 vs. 35.7 ± 15.6; P = 0.005) and head AIS (3.5 ± 0.8 vs. 3.9 ± 0.9; P = 0.001) compared to Group 2. The incidence of agitation, ICU and hospital LOS were higher in Group 1. Failure of extubation and tracheostomy were reported more frequently in Group 1 (P = 0.001). On multivariate analysis, tramadol use was an independent predictor for agitation (adjusted odds ratio 21; P = 0.001), followed by low GCS. Conclusion: Patients with TBI who received tramadol are more likely to develop agitation, undergo tracheostomy and to have longer hospital LOS. Therefore, an

  8. 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

  9. Schedule of controlled substances: placement of tramadol into schedule IV. Final rule.

    PubMed

    2014-07-01

    With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration places the substance 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (tramadol), including its salts, isomers, and salts of isomers, into schedule IV of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule IV controlled substances on persons who handle (manufacture, distribute, dispense, import, export, engage in research, conduct instructional activities with, or possess) or propose to handle tramadol. PMID:25016619

  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. 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

  12. 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

  13. Effect of submucosal application of tramadol on postoperative pain after third molar surgery.

    PubMed

    Gönül, Onur; Satılmış, Tülin; Bayram, Ferit; Göçmen, Gökhan; Sipahi, Aysegül; Göker, Kamil

    2015-01-01

    The aim of this study was to evaluate the effectiveness of submucosal application of tramadol, for acute postoperative facial pain, following the extraction of impacted third molar teeth. This prospective, double-blind, randomised placebo-controlled study included 60 ASA I-II patients undergoing impacted third molar surgery under local anaesthesia. Following the surgical procedure, patients were randomly divided into two groups; group T (1 mg/kg tramadol) and group S (2-mL saline). Treatments were applied submucosally after surgery. Pain after extraction was evaluated using a visual analogue scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 h postoperatively. The time at which the first analgesic drug was taken, the total analgesic dose used, and adverse tissue reactions were also evaluated. In group T, postoperative VAS scores were significantly lower compared to that in group S (p < 0.05). This study demonstrated that post-operative submucosal application of tramadol is an effective method for reducing acute post-operative facial pain after impacted third molar surgery. PMID:26467984

  14. 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). PMID:23249424

  15. [Evaluation of the peripartum effects of 2 analgesics: meperidine and tramadol, used in labor].

    PubMed

    Fieni, S; Angeri, F; Kaihura, C T; Ricci, L; Bedocchi, L; Galanti, B; Rossi, T; Benassi, G; Benassi, L

    2000-01-01

    The need for analgesia to overcome pain in labour is highly requested by women today. Various ways either non pharmachologic e.g. Emotional sustain, psycho-prophylactic preparation, yoga and hypnosis or pharmachologic such as epidural blockade or parenteral are used. Therefore in our study we evaluated the efficacy and tolerability of the two opioids usually used today in parenteral analgesia to reduce pain during labour: Tramadol and Meperidine. We studied two groups of patients each made up of 20 women in labour, all at term and with a physiologic course of pregnancy. 75 mg i.m. of Meperidine chloryhydrate were somministered in the first group while in the second group 100 mg i.m. of tramadol chloryhydrate were somministered. Various maternal, fetal and neonatal parameters were then monitored demonstrating--A moderate maternal analgesic effect in both drugs (evaluated through the analogic grading of pain). In the group to whom Meperidine was given, sedative effects on the mother were observed associated with respiratory depression in the newborn (the latter evaluated through the Apgar index at 1st and 5th minute of life and pH of the blood obtained at the umbilical cord. The data obtained permitted us to conclude that Tramadol in accordance to the obtained in literature gives an analogous analgesic effect, with better tolerability for the absence of collateral effects on the mother, fetus and newborn. PMID:11424777

  16. 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. PMID:27166538

  17. "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

  18. 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

  19. 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

  20. Efficacy of tramadol as a preincisional infiltration anesthetic in children undergoing inguinal hernia repair: a prospective randomized study

    PubMed Central

    Numanoğlu, Kemal Varım; Ayoğlu, Hilal; Er, Duygu TatlıEbubekir

    2014-01-01

    Background Preincisional local anesthetic infiltration at the surgical site is a therapeutic option for postoperative pain relief for pediatric inguinal hernia. Additionally, tramadol has been used as an analgesic for postoperative pain in children. Recently, the local anesthetic effects of tramadol have been reported. The aim of this study was to determine both the systemic analgesic and the local anesthetic effects of tramadol and to determine how it differs from bupivacaine when administered preincisionally. Methods Fifty-two healthy children, aged 2–7 years, who were scheduled for elective herniorrhaphy were randomly allocated to receive either preincisional infiltration at the surgical site with 2 mg/kg tramadol (Group T, n=26) or 0.25 mL/kg 0.5% bupivacaine (Group B, n=26). At the time of anesthetic administration, perioperative hemodynamic parameters were recorded. The pain assessments were performed 10 minutes after the end of anesthesia and during the first 6-hour period, using pain scores. The time of first dose of analgesia and need for additional analgesia were recorded. Results Between T and B groups, the anesthesia time, perioperative hemodynamic changes, and pain scores were not statistically different. However, in group B, the postoperative analgesic requirement was higher than in group T. Conclusion Tramadol shows equal analgesic effect to bupivacaine and decreases additional analgesic requirement, when used for preincisional infiltration anesthesia in children undergoing inguinal herniorrhaphy. PMID:25285011

  1. 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

  2. A randomized, double-blind, placebo-controlled, crossover trial of “on-demand” tramadol for treatment of premature ejaculation

    PubMed Central

    Kurkar, Adel; Elderwy, Ahmad A.; Abulsorour, Sherief; Awad, Sara M.; Safwat, Ahmed S.; Altaher, Ahmed

    2015-01-01

    Objectives: The objective of this study is to assess the dose-related effects of tramadol on a group of patients with premature ejaculation (PE). Subjects and Methods: During the period of months between June 2010 and July 2012, 180 PE patients presented to outpatient clinic of our hospital. Patients were randomized in a 1:1:1 fashion to receive different sequences of the three medications: placebo, 50 mg of tramadol and 100 mg of tramadol. Every patient received 10 doses of each medication for 2 months. Intra-vaginal ejaculatory latency time (IELT) was recorded in seconds initially and for each arm. Successful treatment of PE is defined if IELT exceeded 120 s. Side-effects of medications were reported. Results: Of patients enrolled, 125 (69.4%) continued the study. Patients’ age range was 20-55 years with PE complaint of 1 to 10 years duration. Mean IELT was 72 at presentation, 82 for placebo, 150 for tramadol 50 mg, and 272 for tramadol 100 mg (P < 0.001 for all comparisons). PE was successfully treated in only 2.4% of patients with placebo, in contrast to 53.6% and 85.6% with 50 and 100 mg tramadol, respectively (P < 0.001 for all comparisons). On multivariate logistic regression analysis, baseline IELT was the only predictor of successful treatment of PE with both tramadol 50 mg (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.03-1.07, P < 0.001) and tramadol 100 mg (OR: 1.07, 95% CI: 1.04-1.11, P < 0.001). Postmicturition dribble annoyed 12.8% of those who received 50 mg tramadol and 33.6% of those who received 100 mg tramadol (P < 0.001). Weak scanty ejaculation was the main complaint in 7.2% versus 21.6% of those using 50 and 100 mg tramadol, respectively (P = 0.002). Two patients discontinued tramadol 100 mg due to side-effects. Conclusion: Tramadol hydrochloride exhibits a significant dose-related efficacy and side-effects over placebo for treatment of PE. PMID:25835132

  3. 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.

  4. 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.

  5. Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial.

    PubMed

    Rawal, Narinder; Macquaire, Valery; Catalá, Elena; Berti, Marco; Costa, Rui; Wietlisbach, Markus

    2011-01-01

    This randomized, double-blind, double-dummy, multicenter trial compared efficacy and safety of tramadol HCL 37.5 mg/paracetamol 325 mg combination tablet with tramadol HCL 50 mg capsule in the treatment of postoperative pain following ambulatory hand surgery with iv regional anesthesia. Patients received trial medication at admission, immediately after surgery, and every 6 hours after discharge until midnight of the first postoperative day. Analgesic efficacy was assessed by patients (n = 128 in each group, full analysis set) and recorded in a diary on the evening of surgery day and of the first postoperative day. They also documented the occurrence of adverse events. By the end of the first postoperative day, the proportion of treatment responders based on treatment satisfaction (primary efficacy variable) was comparable between the groups (78.1% combination, 71.9% tramadol; P = 0.24) and mean pain intensity (rated on a numerical scale from 0 = no pain to 10 = worst imaginable pain) had been reduced to 1.7 ± 2.0 for both groups. Under both treatments, twice as many patients experienced no pain (score = 0) on the first postoperative day compared to the day of surgery (35.9% vs 16.4% for tramadol/paracetamol and 36.7% vs 18% for tramadol treatment). Rescue medication leading to withdrawal (diclofenac 50 mg) was required by 17.2% patients with tramadol/paracetamol and 13.3% with tramadol. Adverse events (mainly nausea, dizziness, somnolence, vomiting, and increased sweating) occurred less frequently in patients under combination treatment (P = 0.004). Tramadol/paracetamol combination tablets provided comparable analgesic efficacy with a better safety profile to tramadol capsules in patients experiencing postoperative pain following ambulatory hand surgery. PMID:21559356

  6. Sequencing CYP2D6 for the detection of poor-metabolizers in post-mortem blood samples with tramadol.

    PubMed

    Fonseca, Suzana; Amorim, António; Costa, Heloísa Afonso; Franco, João; Porto, Maria João; Santos, Jorge Costa; Dias, Mário

    2016-08-01

    Tramadol concentrations and analgesic effect are dependent on the CYP2D6 enzymatic activity. It is well known that some genetic polymorphisms are responsible for the variability in the expression of this enzyme and in the individual drug response. The detection of allelic variants described as non-functional can be useful to explain some circumstances of death in the study of post-mortem cases with tramadol. A Sanger sequencing methodology was developed for the detection of genetic variants that cause absent or reduced CYP2D6 activity, such as *3, *4, *6, *8, *10 and *12 alleles. This methodology, as well as the GC/MS method for the detection and quantification of tramadol and its main metabolites in blood samples was fully validated in accordance with international guidelines. Both methodologies were successfully applied to 100 post-mortem blood samples and the relation between toxicological and genetic results evaluated. Tramadol metabolism, expressed as its metabolites concentration ratio (N-desmethyltramadol/O-desmethyltramadol), has been shown to be correlated with the poor-metabolizer phenotype based on genetic characterization. It was also demonstrated the importance of enzyme inhibitors identification in toxicological analysis. According to our knowledge, this is the first study where a CYP2D6 sequencing methodology is validated and applied to post-mortem samples, in Portugal. The developed methodology allows the data collection of post-mortem cases, which is of primordial importance to enhance the application of these genetic tools to forensic toxicology and pathology. PMID:26926096

  7. Efficacy of tramadol in preventing postoperative shivering using thiopentone or propofol as induction agent: A randomized controlled trial

    PubMed Central

    Yousuf, Beena; Samad, Khalid; Ullah, Hameed; Hoda, Muhammad Q

    2013-01-01

    Background: Postoperative shivering (POS) is a common and distressing experience occurring in up to 60% patients postoperatively. This study was designed to compare the efficacy of tramadol in preventing POS when used with two different induction agent, propofol or thiopentone. Materials and Methods: One hundred and twenty-four ASA I and II adult patients, aged between 18-60 years, undergoing general anesthesia of intermediate duration (60-240 min) for orthopedic, gynecological, and general surgical procedures were randomly divided to receive either thiopentone or propofol as induction agent. Each group was further subdivided (31 patients in each group) to receive either tramadol or saline 15 min before wound closure. Presence of POS after extubation till discharge from post anesthesia care unit (PACU) was recorded at six different time intervals. Results: The highest incidence of POS was observed in thiopentone-saline (TS) group 77.4%, while the lowest (12.9%) was in propofol-tramadol (PT) group (P > 0.001). Total number of shivering episodes was 122 out of which, 35 (28.7%) were of grade 2 and 3 (significant shivering) requiring treatment. The incidence of significant shivering was similar to the episodes of POS, highest in TS group and lowest being in PT group (P > 0.05). Conclusion: The prophylactic use of tramadol in a dose of 1 mg/kg with propofol as an induction agent significantly reduces the incidence of POS in patients recovering from general anesthesia of intermediate duration. PMID:24249991

  8. Efficacy and safety of flupirtine maleate and tramadol hydrochloride in postoperative pain management--a prospective randomised double blinded study.

    PubMed

    Naser, Syed Mohammed; Sarkar, Niladri; Biswas, Arunava; Kamal, Firdaus; Prakash, Raghu; Rahaman, Q M; Das, Anup Kumar

    2012-03-01

    The study was conducted to evaluate the efficacy and safety of flupirtine maleate 100 mg thrice daily compared to tramadol hydrochloride 50 mg thrice daily as postoperative pain management for 5 days. A total of 113 postoperative patients were recruited for the study. Those who met the inclusion criteria (n = 104) were randomised into two treatment groups. One of the groups received flupirtine maleate and the other tramadol hydrochloride both orally. The pain intensity was assessed by visual analogue scale. Patients were informed to report any adverse effect encountered during the study period. The overall effect of the drug (global assessment of the study medication) on pain and side-effects was assessed by the patients at the end of the trial on a categorical scale. There was significant reduction in pain score (p < 0.001) in the flupirtine group with almost equal efficacy to that of tramadol group but the incidence of adverse effects were much less (7.4%) and didn't need discontinuation of the study. All drugs were assessed as good. Therefore it can be concluded that oral flupirtine can deliver the same analgesic efficacy as oral tramadol for postoperative pain relief, which might be beneficial for avoiding the adverse effects ofopioids and non-steroidal anti-inflammatory drug therapy. PMID:23029946

  9. Analgesia after day case laparoscopic sterilisation. A comparison of tramadol with paracetamol/dextropropoxyphene and paracetamol/codeine combinations.

    PubMed

    Crighton, I M; Hobbs, G J; Wrench, I J

    1997-07-01

    In a prospective, double-blind trial we compared the analgesic efficacy of tramadol during the first 24 h after day case laparoscopic sterilisation with two commonly prescribed combination analgesics. Seventy-five women were allocated randomly to receive oral paracetamol 325 mg/dextropropoxyphene hydrochloride 32.5 mg, tramadol 50 mg or paracetamol 500 mg/codeine phosphate 30 mg as required after a standardised anaesthetic technique. There were no significant differences in average or worst pain, sleep disturbance, mobility, number of tablets taken, satisfaction or preference for stronger analgesia (26.2% of all patients). The incidences of nausea and vomiting were comparable between groups. There was a trend towards a lower incidence of central nervous system side-effects (drowsiness, dizziness, headache) in the paracetamol/codeine group. Tramadol may be considered an alternative analgesic for day case surgery although analgesic regimens of greater efficacy are required for many patients. The relative incidence of side-effects for tramadol and other analgesics requires further evaluation. PMID:9244023

  10. Tramadol Extended-Release for the Management of Pain due to Osteoarthritis

    PubMed Central

    Guetti, Cristiana; Paladini, Antonella; Varrassi, Giustino

    2013-01-01

    Current knowledge on pathogenesis of osteoarticular pain, as well as the consequent several, especially on the gastrointestinal, renal, and cardiovascular systems, side effects of NSAIDs, makes it difficult to perform an optimal management of this mixed typology of pain. This is especially observable in elderly patients, the most frequently affected by osteoarthritis (OA). Tramadol is an analgesic drug, the action of which has a twofold action. It has a weak affinity to mu opioid receptors and, at the same time, can result in inhibition of the reuptake of noradrenaline and serotonin in nociceptorial descending inhibitory control system. These two mechanisms, “opioidergic” and “nonopioidergic,” are the grounds for contrasting certain types of pain that are generally less responsive to opioids, such as neuropathic pain or mixed OA pain. The extended-release formulation of tramadol has good efficacy and tolerability and acts through a dosing schedule that allows a high level of patients compliance to therapies with a good recovery outcome for the patients' functional status. PMID:27335872

  11. Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics.

    PubMed

    Moore, R A; McQuay, H J

    1997-02-01

    The analgesic effectiveness and safety of oral tramadol were compared with standard analgesics using a meta-analysis of individual patient data from randomised controlled trials in patients with moderate or severe pain after surgery or dental extraction. Calculation of %maxTOTPAR from individual patient data, and the use of > 50%maxTOTPAR defined clinically acceptable pain relief. Number-needed-to-treat (NNT) for one patient to have > 50%maxTOTPAR compared with placebo was used to examine the effectiveness of different single oral doses of tramadol and comparator drugs. Eighteen randomised, double-blind, parallel-group single-dose trials with 3453 patients using categorical pain relief scales allowed the calculation of %maxTOTPAR. The use of > 50%maxTOTPAR was a sensitive measure to discriminate between analgesics. Tramadol and comparator drugs gave significantly more analgesia than placebo. In postsurgical pain tramadol 50, 100 and 150 mg had NNTs for > 50%maxTOTPAR of 7.1 (95% confidence intervals 4.6-18), 4.8 (3.4-8.2) and 2.4 (2.0-3.1), comparable with aspirin 650 mg plus codeine 60 mg (NNT 3.6 (2.5-6.3)) and acetaminophen 650 mg plus propoxyphene 100 mg (NNT 4.0 (3.0-5.7)). With the same dose of drug postsurgical patients had more pain relief than those having dental surgery. Tramadol showed a dose-response for analgesia in both postsurgical and dental pain patients. With the same dose of drug postsurgical pain patients had fewer adverse events than those having dental surgery. Adverse events (headache, nausea, vomiting, dizziness, somnolence) with tramadol 50 mg and 100 mg had a similar incidence to comparator drugs. There was a dose response with tramadol, tending towards higher incidences at higher doses. Single-patient meta-analysis using more than half pain relief provides a sensitive description of the analgesic properties of a drug, and NNT calculations allow comparisons to be made with standard analgesics. Absolute ranking of analgesic performance

  12. 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

  13. 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

  14. 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. PMID:26352950

  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. Lornoxicam versus tramadol for post-operative pain relief in patients undergoing ENT procedures

    PubMed Central

    Abdelhalim, Ashraf A.; Al harethy, Sami; Moustafa, Mohamed

    2014-01-01

    Background: Pain following ear-nose and throat surgery is one of the most important complaints for which, several drugs are used. This prospective, randomized, double-blind controlled trial was designed to compare the analgesic effect of tramadol versus lornoxicam for post-operative pain relief in patients undergoing ENT surgical procedures. Methods: One hundred and twenty patients of ASA class I-II, who had undergone elective ENT surgical procedures under general anesthesia, were assigned in a randomized manner into three equal groups. Group L received lornoxicam8 mg IV, Group T received tramadol 1 mg/kg IV and Group C received IV saline after induction of anesthesia before the start of the surgery. Post-operative pain was assessed using the visual analogue scale (VAS) and sedation level was evaluated during stay in the post-anesthesia care unit with a four-point sedation scale. Intraoperative blood loss was estimated using the Five-Point Scale. Adverse events in the first 24 h post-operative were recorded. Results: The VAS pain scores were significantly higher in Group C as compared with those in Groups L and T at 30 min and 1, 2, 4and 6 h post-operatively, with no significant difference between Group L and Group T. The amount of morphine consumption post-operatively was significantly lower in Group L (5.2 ± 2.5 mg) and Group T (5.0 ± 2.0 mg) as compared with that in Group C (7.4 ± 2.3 mg) (P = 0.001). The time for the first analgesic requirement was significantly less in Group L (92.62 ± 24.23 min) and Group T (88 ± 21.43 min) as compared with that in Group C (42.82 ± 25.61 min), with no significant difference between the other two groups. Estimated intraoperative blood loss score by the surgeons showed no significant difference between the three groups. The most frequent side-effects in the three groups were nausea and vomiting, and their incidence was significantly higher in the placebo group as compared with the other two groups. Conclusion: Tramadol 1

  17. Intraperitoneal pre-insufflation of 0.125% bupivaciane with tramadol for postoperative pain relief following laparoscopic cholecystectomy

    PubMed Central

    Jamal, Aslam; Usmani, Hammad; Khan, Mohd Mozaffar; Rizvi, Amjad Ali; Siddiqi, Mohd Masood Hussain; Aslam, Mohammad

    2016-01-01

    Background and Aims: Laparoscopic cholecystectomy is associated with a fairly high incidence of postoperative discomfort which is more of visceral origin than somatic. Studies have concluded that the instillation of local anesthetic with opioid around gall bladder bed provides more effective analgesia than either local anesthetic or opioid alone. Material and Methods: The study included 90 American Society of Anesthesiologists I-II patients of age 16-65 years scheduled for laparoscopic cholecystectomy under general anesthesia. The patients received the study drugs at the initiation of insufflation of CO2 in the intraperitoneal space by the operating surgeon under laparoscopic camera guidance over the gallbladder bed. Patients in Group T received tramadol 2 mg/kg in 30 ml normal saline, in Group B received bupivacaine 30 ml of 0.125% and in Group BT received tramadol 2 mg/kg in 30 ml of 0.125% bupivacaine intraperitoneally. Postoperative pain assessment was done at different time intervals in the first 24 h using Visual Analog Scale of 0-10 (0 = No pain, 10 = Worst pain imagined). Time to first dose of rescue analgesic and total analgesics required in the first 24 h postoperatively were also recorded. The incidence of side effects during the postoperative period was recorded. Results: Reduction in postoperative pain was elicited, at 4 and 8 h postoperatively when Group BT (bupivacaine-tramadol group) was compared with Group T (tramadol group) or Group B (bupivacaine group) (P < 0.01). There was a significantly lower requirement of analgesics during first 24 h postoperatively in Group BT compared to Group B or T but no significant difference in the intake of analgesics was noted between Groups B Group T. Time to first dose of rescue analgesic was also significantly prolonged in Group BT compared to Group B or T. The incidence of nausea and vomiting was comparable in all the study groups. Conclusions: Intraperitoneal application of bupivacaine with tramadol was a more

  18. 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

  19. Enhanced analgesic effects of propacetamol and tramadol combination in rats and mice.

    PubMed

    Zhang, Yuyang; Du, Lili; Pan, He; Li, Li; Su, Xing

    2011-01-01

    Drug combinations have more potential advantage of greater analgesia than monotherapy. By the combination of analgesics with different mechanism, potency of analgesia can be maximized while the incidence of adverse effects is minimized. This study was aimed to assess a possible interaction in the antinociceptive effects between tramadol (T) and propacetamol (P) when administered in combination against nociceptive effects induced by physical or chemical injury in mice and rats. Three series of experiments were performed. The first was to determine effects of P and T alone or in combination in the acetic acid (AA)-induced writhing test in mice. Combination of T/P (3.9/67.5, 7.8/135, 15.6/271 mg/kg, intraperitoneally (i.p.)) elicited dose-dependent antinociception. The second determined whether the antinociceptive effects of the drugs observed in a test of persistent chemical pain could be seen in a test of acute thermal pain and the back-paw licking response was tested on the hot plate. The back-paw licking latency at different times after drugs obtained with the combination (16/270, 32/540 mg/kg, i.p. T/P) was longer than the respective values obtained with the individual agents. The third was designed to compare the antinociceptive effects between the drugs, either alone or in combination in the rat tail-flicks test. Combination of T/P (5.5/96, 11/192 mg/kg i.p.) both showed effects of higher potency than T and P, respectively. The data obtained confirmed that propacetamol is able to enhance the antinociceptive activity of tramadol. PMID:21372383

  20. 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

  1. 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

  2. Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: lessons from tramadol

    PubMed Central

    Epstein, David H.; Preston, Kenzie L.; Jasinski, Donald R.

    2010-01-01

    Assessment of abuse potential of opioid analgesics has a long history in both laboratory animals and humans. This article reviews the methods used in animals and in humans and then presents the data collected in the evaluation of tramadol, an atypical centrally acting opioid analgesic approved for marketing in the United States in 1998. Finally, data on the abuse of tramadol from postmarketing surveillance and case reports are presented. The consistency between animal and human study results and the predictive value of both are discussed. Overall, there was substantial agreement between animal and human data, with each having predictive value. Nonetheless, it is suggested that abuse-potential screening of new medications would benefit from an organized, integrated cross-species program. PMID:16497429

  3. 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

  4. Control of acute pain after major abdominal surgery in 585 patients given tramadol and ketorolac by intravenous infusion.

    PubMed

    Pieri, M; Meacci, L; Santini, L; Santini, G; Dollorenzo, R; Sansevero, A

    2002-01-01

    The aim of this study was to assess the efficacy and safety of postoperative pain relief using tramadol and ketorolac in continuous intravenous infusion. The 585 patients included in the study underwent major surgery according to a protocol involving the parenteral administration of 100 mg tramadol approximately 40 min before the end of surgery. This was followed by the continuous intravenous infusion of 600 mg tramadol and 180 mg ketorolac diluted with physiological solution to a total volume of 96 ml. Delivery was carried out using an elastomeric pump or a syringe pump and administered over a 48-hour period at a constant rate of 2 ml/h. Any further doses consisted of 100 mg tramadol up to a maximum of 300 mg over a 24-h period. Pain was assessed on a verbal numeric scale (VNS). For each patient the intensity of pain was assessed both at rest and on movement (coughing, deep breathing, movement of lower limbs). At the scheduled times (T0-T72, every 6 h), the following parameters were evaluated: hemodynamic stability; respiratory function; the appearance of any side effects; the level of sedation; and the need for any further doses of analgesic. The analysis of the data obtained showed the good quality of postoperative pain relief achieved: pain intensity at rest was, on average, always below VNS level 3, while during movement it always had an average VNS level of 3-4. The only side effects found with any frequency were nausea (22.6%) and vomiting (8.5%); hemodynamic and respiratory parameters remained stable. The method adopted was of limited cost and was well accepted by both patients and staff. On the basis of the data obtained, it is possible to affirm that the post-operative pain protocol proposed is effective, safe, without significant side effects, and of limited cost. Therefore, it is the first choice protocol for our operating unit after major abdominal surgery. PMID:12224377

  5. Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells.

    PubMed

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

    2016-06-01

    Opioid therapy and abuse are increasing, justifying the need to study their toxicity and underlying mechanisms. Given opioid pharmacodynamics at the central nervous system, the analysis of toxic effects in neuronal models gains particular relevance. The aim of this study was to compare the toxicological effects of acute exposure to tramadol and tapentadol in the undifferentiated human SH-SY5Y neuroblastoma cell line. Upon exposure to tramadol and tapentadol concentrations up to 600μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death. Cell death was shown to predominantly occur through necrosis, with no alterations in membrane potential or in cytochrome c release. Both drugs were shown to stimulate glucose uptake and to cause ATP depletion, due to changes in the expression of energy metabolism enzymes. The toxicity mechanisms in such a neuronal model are relevant to understand adverse reactions to these opioids and to contribute to dose adjustment in order to avoid neurological damage. PMID:27317026

  6. 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

  7. Postoperative Pain After Abdominal Hysterectomy: A Randomized, Double-Blind, Controlled Trial Comparing the Effects of Tramadol and Gabapentin as Premedication

    PubMed Central

    Farzi, Farnoush; Naderi Nabi, Bahram; Mirmansouri, Ali; Fakoor, Fereshteh; Atrkar Roshan, Zahra; Biazar, Gelareh; Zarei, Tayyebeh

    2016-01-01

    Background: Uncontrolled postoperative pain, characteristic to abdominal hysterectomy, results in multiple complications. One of the methods for controlling postoperative pain is preemptive analgesia. Gabapentin and tramadol are both used for this purpose. Objectives: This study aims to compare the effects of tramadol and gabapentin, as premedication, in decreasing the pain after hysterectomy. Patients and Methods: This clinical trial was performed on 120 eligible elective abdominal hysterectomy patients, divided in three groups of 40, receiving tramadol, gabapentin and placebo, respectively. Two hours before the surgery, the first group was given 300 mg gabapentin, the second one was given 100 mg tramadol, while the other group was given placebo, with 50 ml water. After the surgery, in case of visual analog pain scale (VAS) > 3, up to 3 mg of diclofenac suppository would be used. Pain score, nausea, vomiting, sedation, patient’s satisfaction and the number of meperidine administered during 24 hours (1 - 4 - 8 - 12 - 16 - 20 - 24 hours) were recorded. If patients had VAS > 3, despite using diclofenac, intravenous meperidine (0.25 mg/kg) would be prescribed. Data were analyzed using SPSS 21 software, chi-square test, general linear model and repeated measurement. Results: The three groups were similar regarding age and length of surgery (up to 2 hours). The average VAS, in the placebo group, was higher than in the other two groups (P = 0.0001) and the average received doses of meperidine during 24-hour time were considerably higher in placebo group, compared to the other two groups (55.62 mg in placebo, 18.75 mg in gabapentin and 17.5 mg in tramadol groups, P = 0.0001). Nausea, vomiting and sedation, in the tramadol group, were higher than in the other two groups, although they were not significant. Patients’ dissatisfaction, in the placebo group, during initial hours, especially in the fourth hour, was higher (P = 0.0001). In the gabapentin and tramadol groups

  8. Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.

    PubMed

    Wilder-Smith, C H; Hill, L; Spargo, K; Kalla, A

    2001-03-01

    Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid

  9. Depressing interleukin-1β contributed to the synergistic effects of tramadol and minocycline on spinal nerve ligation-induced neuropathic pain.

    PubMed

    Mei, Xiao-Peng; Sakuma, Yasushi; Xie, Cheng; Wu, Dan; Ho, Ichinyo; Kotani, Junichiro; Xu, Li-Xian

    2014-01-01

    Our previous study indicated that coadministration of tramadol and minocycline exerted synergistic effects on spinal nerve ligation (SNL)-induced neuropathic mechanical allodynia. However, the underlying mechanisms are still unclear. Recent reports indicated that spinal proinflammatory factor interleukin-1β (IL-1β) contributed to the development of neuropathic pain and the positive feedback communication between neuron and glia. Therefore, the present research is to confirm whether spinal IL-1β-related pathway response contributes to the synergistic effects of tramadol and minocycline on SNL-induced neuropathic pain. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn 3 days after lesion, which could be significantly decreased by tramadol and minocycline coadministration. Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication. Meanwhile, intrathecal administration of p38 inhibitor SB203580 markedly alleviated mechanical allodynia whilst reducing IL-1β and Fos expression induced by SNL. Moreover, intrathecal neutralized antibody of IL-1β could depress SNL-induced mechanical allodynia and Fos expression. These results suggest that depressing SNL-induced aberrant activation of the spinal dorsal horn IL-1β-related pathway contributes to the underlying mechanism of the synergistic effects of tramadol and minocycline coadministration on SNL-induced neuropathic mechanical allodynia. PMID:24157594

  10. A double-blind, placebo-controlled randomized comparison of pre and postoperative administration of ketorolac and tramadol for dental extraction pain

    PubMed Central

    Mishra, Hitesh; Khan, Farhan Ahmad

    2012-01-01

    Objective: To compare the analgesic efficacy and safety of single-dose oral ketorolac and tramadol administered pre and postoperatively for dental extraction pain. Materials and Methods: 74 patients undergoing third molar extraction (impacted or other causes) were recruited into the study, over a period of 1 year. The patients were divided into six groups and they were given ketorolac (20 mg), tramadol (100 mg), or placebo either preoperatively or postoperatively (half an hour before or half an hour after the procedure). Placebo was glucose powder filled in empty capsule. Pain assessment was done using a modified Verbal Rating Scale (VRS) at 30 min, 2, 4, and 6 h after the procedure. A record of whether rescue analgesic (ibuprofen 400 mg) was taken during the 6 h study period, along with the time it was taken, was made. Record of any adverse effects experienced by the patient was also kept. Maximum pain scores for each of the six study groups, over the 6 h study period, were noted. Results: Ketorolac and tramadol were significantly better than placebo in relieving molar tooth extraction pain. Postoperative administration of tramadol was found to be more efficacious than preoperative administration in relieving the pain, whereas the preoperative administration of ketorolac was better than its postoperative administration. Conclusion: This study demonstrated that tramadol is equally effective to ketorolac in relieving pain in the first 6 h after molar extraction and therefore can be tried in patients who are intolerant to nonsteroidal anti-inflammatory drugs. PMID:22557747

  11. 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

  12. Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice.

    PubMed

    Miranda, H F; Puig, M M; Romero, M A; Prieto, J C

    2009-02-01

    The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo-oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re-uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed-dose method GIT. The administration of DEX or TRAM individually induced dose-dependent antinociception in all the algesiometric tests. In the three tests, TRAM was between 5.2 (FT, phase I) and 35 times (FT, Phase II) more potent than DEX. When testing combinations at different potency ratios (1 : 1, 1 : 3, 3 : 1), we could demonstrate synergy in all algesiometric tests, only when drugs were combined in a 1 : 1 proportion. Interestingly, the proportion of the drugs in the combination could change the type of interaction from synergy to antagonism. On the inhibition of GIT, a dose-related inhibition was established for TRAM, but not for DEX. Using a fixed-dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans. PMID:19267773

  13. 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

  14. 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. PMID:25623330

  15. Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study

    PubMed Central

    Singh, Arvinderpal; Sharma, Geeta; Gupta, Ruchi; Kumari, Anita; Tikko, Deepika

    2016-01-01

    Background and Aims: Pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia. Tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice. However, their potential to relieve propofol injection pain still needs to be explored. Material and Methods: A randomized, double-blind, placebo-controlled study was conducted on 90 American Society of Anesthesiologists I and II adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent. Consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each. Group I patients received an injection of normal saline 3 ml intravenously (placebo) while Group II and Group III patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously, respectively. Before induction of anesthesia patients were asked about the intensity of pain on propofol injection by using visual analog scale (VAS) before the loss of consciousness. Descriptive statistics and analysis of variance with Chi-square test were used to analyze the data. The value of P < 0.05 was considered as a significant and P < 0.0001 as highly significant. Results: The incidence of pain in Group I was observed in 80% of the patients, while it was observed in 23.33% and 20% of patients in Group II and III, respectively. Mean VAS scores were 2.27 ± 1.51, 1.14 ± 1.74, and 1.03 ± 1.72 in Group I, II, and Group III patients, respectively. The incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in Group II and III, respectively. Conclusion: Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain. PMID:27006549

  16. 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

  17. 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

    2016-02-01

    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. PMID:26625281

  18. The Effect of Systemic and Regional Use of Magnesium Sulfate on Postoperative Tramadol Consumption in Lumbar Disc Surgery.

    PubMed

    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

  19. Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor.

    PubMed

    Gillen, C; Haurand, M; Kobelt, D J; Wnendt, S

    2000-08-01

    The present study was conducted to characterise the centrally active analgesic drug tramadol hydrochloride [(1RS,2RS)-2-[(dimethyl-amino)-methyl]-1-(3-methoxyphenyl)-cyclohe xanol hydrochloride] and its metabolites M1, M2, M3, M4 and M5 at the cloned human mu-opioid receptor. Membranes from stably transfected Chinese hamster ovary (CHO) cells were used to determine the four parameters of the ligand-receptor interaction: the affinity of (+/-)-tramadol and its metabolites was determined by competitive inhibition of [3H]naloxone binding under high and low salt conditions. The agonist-induced stimulation of [35S]GTPgammaS binding permits the measurement of potency (EC50), efficacy (Emax = maximal stimulation) and relative intrinsic efficacy (effect as a function of receptor occupation). The metabolite (+)-M1 showed the highest affinity (Ki=3.4 nM) to the human mu-opioid receptor, followed by (+/-)-M5 (Ki=100 nM), (-)-M1 (Ki=240 nM) and (+/-)-tramadol (Ki=2.4 microM). The [35S]GTPgammaS binding assay revealed an agonistic activity for the metabolites (+)-M1, (-)-M1 and (+/-)-M5 with the following rank order of intrinsic efficacy: (+)-M1>(+/-)-M5>(-)-M1. The metabolites (+/-)-M2, (+/-)-M3 and (+/-)-M4 displayed only weak affinity (Ki> 10 microM) and had no stimulatory effect on GTPgammaS binding. These data indicate that the metabolite (+)-M1 is responsible for the mu-opioid-derived analgesic effect. PMID:10961373

  20. 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

  1. 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

  2. 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

  3. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

    PubMed Central

    Pergolizzi, Joseph V; van de Laar, Mart; Langford, Richard; Mellinghoff, Hans-Ulrich; Merchante, Ignacio Morón; Nalamachu, Srinivas; O’Brien, Joanne; Perrot, Serge; Raffa, Robert B

    2012-01-01

    Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with

  4. Evaluation of the anti-nociceptive effects of morphine, tramadol, meloxicam and their combinations using the tail-flick test in rats

    PubMed Central

    Foroud, Mehrzad; Vesal, Nasser

    2015-01-01

    The purpose of the present study was to evaluate anti-nociceptive effects of morphine, tramadol, meloxicam and their combinations in rats. Seventy male Wistar rats were divided into seven equal groups and randomly assigned to receive intraperitoneal saline (S) (control group, 1.0 mL kg-1), morphine (MO) (4.0 mg kg-1), tramadol (TR) (12.5 mg kg-1), meloxicam (ML) (1.0 mg kg-1), tramadol- morphine (TR-MO), meloxicam-morphine (ML-MO) and meloxicam-tramadol (ML-TR) at the same doses. Anti-nociception was evaluated using tail flick latency (TFL) test at 45, 60, 75, 90 and 120 min after drug injection. The TFL was significantly higher in TR and MO groups compared to S group for 90 and 120 min, respectively. No significant change in TFL from baseline values was observed at all time points in ML group. Among rats that received combination of analgesics, those that received TR-MO had significantly greater TFL. There was no significant difference in TFL between ML-TR and ML-MO groups. In conclusion, TR, MO and their combination all provided acceptable anti-nociceptive effects in rats. Meloxicam at the given dosage (1.0 mg kg-1) did not demonstrate any anti-nociceptive effect when evaluated by TFL test. PMID:26973767

  5. [Analgesic effect of oral tramadol on transrectal ultrasound-guided needle biopsy of the prostate in a randomized double-blind study].

    PubMed

    Nomi, Hayahito; Azuma, Haruhito; Segawa, Naoki; Inamoto, Teruo; Takahara, Kiyoshi; Komura, Kazumasa; Koyama, Kohei; Ubai, Takanobu; Katsuoka, Yoji

    2011-08-01

    A total of 121 Japanese patients scheduled for prostate biopsy were randomly and double-blindly assigned to be given a single oral dose of 100 mg Tramadol mixed with 20 ml of sugar syrup or placebo, 30 minutes before the procedure. Pain severity was measured by verbal rating scale (VRS) and visual analog scales (VAS). We also analyzed cardio-respiratory parameters and complications. Of 121 patients, 117 replied validly to VRS and VAS ; and 91 of 117 patients replied to the cohort questionnaire for analysis of the late disorder, patient's impression, prolonged pain and past history of hemorrhoid treatment. Tramadol showed no significant effect on pain severity indicated by VRS and VAS, and no change in cardiorespiratory parameters. Furthermore, 70 patients without a history of hemorrhoid treatment, showed no significant analgesic benefits of Tramadol during the biopsy. In total, 3 patients had side effects of vomiting (CTCAE : grade 1)6), which subsided spontaneously. The oral administration of a single dose of 100 mg Tramadol 30 minutes before a transrectal needle biopsy of the prostate was safe, but was not effective to calm down the pain severity. PMID:21894078

  6. Gas chromatographic method using nitrogen-phosphorus detection for the measurement of tramadol and its O-desmethyl metabolite in plasma and brain tissue of mice and rats.

    PubMed

    Tao, Q; Stone, D J; Borenstein, M R; Jean-Bart, V; Codd, E E; Coogan, T P; Desai-Krieger, D; Liao, S; Raffa, R B

    2001-11-01

    A method that allows the measurement of plasma and brain levels of the centrally-acting analgesic tramadol and its major metabolite (O-desmethyl tramadol) in mice and rats was developed using gas chromatography equipped with nitrogen-phosphorus detection (GC-NPD). Plasma samples were extracted with methyl tert.-butyl ether (MTBE) and were injected directly into the GC system. Brain tissue homogenates were precipitated with methanol, the resulting supernatant was dried then acidified with hydrochloric acid. The aqueous solution was washed with MTBE twice, alkalinized, and extracted with MTBE. The MTBE layer was dried, reconstituted and injected into the GC system. The GC assay used a DB-1 capillary column with an oven temperature ramp (135 to 179 degrees C at 4 degrees C/min). Dextromethorphan was used as the internal standard. The calibration curves for tramadol and O-desmethyl tramadol in plasma and brain tissue were linear in the range of 10 to 10000 ng/ml (plasma) and ng/g (brain). Assay accuracy and precision of back calculated standards were within +/- 15%. PMID:11710575

  7. Comparative study in patients with symptomatic internal derangements of the temporomandibular joint: analgesic outcomes of arthrocentesis with or without intra-articular morphine and tramadol.

    PubMed

    Sipahi, A; Satilmis, T; Basa, S

    2015-04-01

    Our aim was to find out whether pain was better controlled if morphine or tramadol was injected intra-articularly after arthrocentesis with Ringer's lactate in patients with painful temporomandibular joints (TMJ). This placebo-controlled, double-blind study involved 30 patients who had not responded to conservative treatment and who were divided randomly into 3 groups of 10 patients each. All patients had arthrocentesis, and the drugs were given as intra-articular injections immediately after the procedure. One group was give 5% Ringer's lactate 1ml, the second morphine 1mg, and the third tramadol 50mg. Visual analogue scales (VAS) for pain were recorded at maximum mouth opening and at rest before intra-articular injection and after 15 and 30min; at 1, 2, 3, 8, 12, 24, 36 and 48h; and at 1, 3, and 6 monthly follow-up. The mean (SD) VAS decreased from 6.90 (1.45) to 2.6 (2.5) in the control group, from 7.30 (1.64) to 1.20 (0.79) in the morphine group (p=0.005), and from 7.10 (1.73) to 1.50 (1.78) in the tramadol group (p=0.005). We conclude that morphine given by intra-articular injection after arthrocentesis gives a significant, sustained (6 months) improvement in pain relief compared with simple arthrocentesis alone. The effect was similar with tramadol except that it was shorter lived. PMID:25623934

  8. Adsorption mechanisms of emerging micro-pollutants with a clay mineral: Case of tramadol and doxepine pharmaceutical products.

    PubMed

    Thiebault, Thomas; Guégan, Régis; Boussafir, Mohammed

    2015-09-01

    A sodium exchanged smectite clay mineral (Mt) was used as geo-sorbent for the adsorption of tramadol and doxepin: two pharmaceutical products (PPs) defined as emerging pollutants due to their presence at significant concentration in numerous water compartments. The adsorption isotherms for both the temperatures of 20 and 40°C and the derived data determined through the fitting procedure by using Langmuir, Freundlich and Dubinin-Radushkevich equation models explicitly pointed out that the sorption of both tramadol and doxepin is mainly driven by electrostatic interaction. The studied PPs are intercalated in a monolayer arrangement within the interlayer space through a cation exchange in stoichiometric proportion with the Na(+) cations leading to adsorbed PPs amounts that match the cation exchange capacity (CEC) of Mt. Due to their hydrophobic character, additional doxepin molecules could be adsorbed by weak molecular interaction driving to an increase of the adsorbed amount beyond the CEC at low temperature (20°C). The confinement of PPs within the interlayer space of Mt confirms the use of clay minerals as potential material for the wastewater treatment as well as it drives to an amorphous or glassy state, which can find echo in biopharmaceutical applications for a controlled release of PPs. PMID:25950945

  9. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    PubMed

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol. PMID:25006518

  10. Electrochemical oxidation of tramadol in low-salinity reverse osmosis concentrates using boron-doped diamond anodes.

    PubMed

    Lütke Eversloh, Christian; Schulz, Manoj; Wagner, Manfred; Ternes, Thomas A

    2015-04-01

    The electrochemical treatment of low-salinity reverse osmosis (RO) concentrates was investigated using tramadol (100 μM) as a model substance for persistent organic contaminants. Galvanostatic degradation experiments using boron-doped diamond electrodes at different applied currents were conducted in RO concentrates as well as in ultra-pure water containing either sodium chloride or sodium sulfate. Kinetic investigations revealed a significant influence of in-situ generated active chlorine besides direct anodic oxidation. Therefore, tramadol concentrations decreased more rapidly at elevated chloride content. Nevertheless, reduction of total organic carbon (TOC) was found to be comparatively low, demonstrating that transformation rather than mineralization was taking place. Early stage product formation could be attributed to both direct and indirect processes, including demethylation, hydroxylation, dehydration, oxidative aromatic ring cleavage and halogenation reactions. The latter led to various halogenated derivatives and resulted in AOX (adsorbable organic halogens) formation in the lower mg/L-range depending on the treatment conditions. Characterisation of transformation products (TPs) was achieved via MS(n) experiments and additional NMR measurements. Based on identification and quantification of the main TPs in different matrices and on additional potentiostatic electrolysis, a transformation pathway was proposed. PMID:25660808

  11. 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

  12. Postmortem Attraction of Sarcosaprophagous Diptera to Tramadol-Treated Rats and Morphometric Aspects of the Developed Larvae.

    PubMed

    AbouZied, E M

    2016-06-01

    The presence of some specific drugs in animal tissues may affect the time of minimal postmortem intervals estimated during forensic entomological investigations. To test the effects of a specific drug on decomposition, a field study was conducted at Fayoum University campus, Egypt, from March to May 2013, using tramadol, a synthetic analgesic opioid used to treat moderate to severe pain in humans. Albino rats were used as the animal model during this study. The duration of the fresh stage of tramadol treated rat (Ttr) carcasses was significantly shorter (2.4 ± 0.27 days) compared to tramadol free rat (Tfr) carcasses (6.4 ± 0.49 days). The dry carcass stage of Ttr lasted longer (10.3 ± 0.99 days) as compared to (7.4 ± 0.18 days) the Tfr carcass. The decomposition process of the (Ttr) carcass was not significantly faster (24.9 ± 1.58 days) as compared to (Tfr) carcasses (29.5 ± 1.69). Lucilia cuprina (Wiedemann), Chrysomya albiceps (Wiedemann), and Musca domestica L. were less attracted to Ttr carcass-baited traps than traps with Tfr carcasses. However, females of Sarcophaga spp. showed a greater attraction to Ttr carcasses. Females of another sarcophagid fly, Wohlfahrtia spp. exhibited similar attraction tendencies to both types of trap baits. Larvae of S. argyrostoma (Robineau-Desvoidy) collected from Ttr carcasses developed to a significantly longer total body length (10.4 ± 0.04 mm) as compared to the average length of the larvae collected from Tfr carcasses (8.9 ± 0.34 mm). During days 9-13 after rat death, the relative lengths of larvae from Ttr carcasses were not significantly different from Tfr carcasses. Larvae fed on Ttr carcasses pupated 2 days later than the control larvae. PMID:26931613

  13. Serotonin syndrome after the use of tramadol and ziprasidone in a patient with a deep brain stimulator for Parkinson disease.

    PubMed

    El-Okdi, Nasser Samir; Lumbrezer, Daniel; Karanovic, Djuro; Ghose, Abhimanyu; Assaly, Ragheb

    2014-01-01

    Serotonin syndrome (SS) is a life-threatening adverse reaction that can result from the therapeutic use of serotonergic drugs or accidental drug interactions. Tramadol is a drug that is widely prescribed because of its low abuse potential, but physicians need to be aware of its significant potential to cause SS because it inhibits serotonin reuptake. Ziprasidone is an atypical antipsychotic that can also cause dangerous interactions to cause SS because it is not only a potent 5-HT1A agonist but also has been reported to inhibit serotonin reuptake with an affinity similar to tricyclic antidepressants, in addition to inhibiting reuptake of norepinephrine. We are describing the clinical characteristics of a gentleman with bipolar disorder and Parkinson disease who presented with SS, despite having a deep brain stimulator in the subthalamic nucleus, which decreases central serotonin levels, and a discussion of the factors that contributed to his presentation. PMID:24158007

  14. Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems.

    PubMed

    Vazzana, M; Andreani, T; Fangueiro, J; Faggio, C; Silva, C; Santini, A; Garcia, M L; Silva, A M; Souto, E B

    2015-03-01

    Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration. PMID:25776506

  15. Tramadol/acetaminophen combination as add-on therapy in the treatment of patients with ankylosing spondylitis.

    PubMed

    Chang, Jhi-Kai; Yu, Chen-Tung; Lee, Ming-Yung; Yeo, Kj; Chang, I-Chang; Tsou, Hsi-Kai; Wei, James Cheng-Chung

    2013-03-01

    This study aimed to determine the safety and efficacy of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (Ultracet®) in patients with ankylosing spondylitis (AS). This was a 12-week, randomized, double-blind, placebo-controlled study. Sixty patients with active AS according to the Modified New York Criteria were enrolled. Active disease was defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for more than 3 at randomization. Subjects were randomized equally into two groups: the treatment group received aceclofenac plus Ultracet® one tablet twice a day, and the control group received aceclofenac plus placebo for 12 weeks. The primary endpoint was a difference of Assessment in Ankylosing Spondylitis (ASAS20) response criteria between two groups at week 12. At week 12, ASAS20 was achieved by 53.3 % of the aceclofenac plus Ultracet group and 31 % of the aceclofenac alone group (p = 0.047). For the pain visual analogue scale at week 12, there was a reduction of 45.6 % in aceclofenac plus Ultracet group and 25.7 % in the aceclofenac alone group (p = 0.087). There was no statistically significant difference between two groups in BASDAI, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Global Index, Physician Global Assessment, spinal mobility, ESR, hs-CRP, and Ankylosing Spondylitis Quality of Life Questionnaire. A slight increase in total adverse events was noted with dizziness (7.5 vs 1.5 %), vertigo (4.5 vs 1.5 %), and nausea/vomiting (6 vs 0 %) in the Ultracet arm compared to placebo. The tramadol 37.5 mg/acetaminophen 325 mg combination tablet (Ultracet®) might has additional effect to nonsteroidal anti-inflammatory drugs in the treatment of patients with ankylosing spondylitis. It showed marginal benefit in pain and disease activity. However, a slight increase in minor adverse events was noted. PMID:23192419

  16. Novel analgesic combination of tramadol, paracetamol, caffeine and taurine in the management of moderate to moderately severe acute low back pain

    PubMed Central

    Madhusudhan, Santhosh Kumar

    2013-01-01

    Background Acute low back pain is one the leading cause of doctor's visit in our country with innumerable medication for treatment. Finding an ideal analgesic medication with better efficacy and least adverse effects is always a challenging task to the treating doctor. Methods In this study we compared the efficacy and safety profile of a fixed dose combination of novel analgesic tramadol 37.5 mg/paracetamol 325 mg/caffeine 30 mg/taurine 250 mg with commonly used tramadol 37.5 mg/paracetamol 325 mg tablet in the treatment of moderate to moderately severe acute low back pain. Patients attending 50 clinics throughout India were enrolled in either of the above group and were asked to take one tablet every 6th hour for five consecutive days. The pain evaluation in both groups was done with verbal pain relief scale and pain intensity scale at end of treatment. Results Proportion of patients in novel combination group compared to tramadol/paracetamol only group responding to treatment based on treatment satisfaction (good and excellent) and mean pain intensity (no pain or mild pain), were 81% Vs 45%, (p < 0.001) and 83% Vs 66% (p < 0.001) respectively. Common expected adverse drug reaction like nausea, vomiting and dizziness occurred with far less frequency in patients under novel combination group. Conclusion We conclude that significantly more patients in novel combination drug group compared to tramadol/paracetamol only group had a superior analgesic effect with lesser adverse reactions. PMID:24396231

  17. On-demand use of tramadol, sildenafil, paroxetine and local anaesthetics for the management of premature ejaculation: A randomised placebo-controlled clinical trial

    PubMed Central

    Gameel, Tarek A.; Tawfik, Ahmad M.; Abou-Farha, Mohamed O.; Bastawisy, Mohamed G.; El-Bendary, Mohamed A.; El-Gamasy, Abd El-Naser

    2013-01-01

    Objectives To compare the clinical efficacy of the on-demand use of four drugs in the management of patients with premature ejaculation (PE), as the off-label use of selective serotonin-reuptake inhibitors and topical penile anaesthetics is frequently indicated for the management of patients with PE, and tramadol HCl and sildenafil citrate were also tried for managing this disorder, but with recommendations based on weak evidence. Patients and methods This was a single-centre, single-blind, placebo-controlled clinical trial conducted on 150 patients who had PE for >1 year. Patients were randomised equally into five groups. On-demand tramadol, sildenafil, paroxetine, local lidocaine gel or placebo was given for patients in groups 1–5, respectively. During the month before treatment, the intravaginal ejaculation latency time (IELT) and sexual satisfaction scores (on a 0–5-point scale) were measured and compared to the mean IELT and sexual satisfaction scores recorded during 4 weeks of on-demand drug administration, with monitoring of any possible side-effects. Results Tramadol-treated patients had a significantly longer mean (SD) IELT, of 351 (119) s, than the other groups. Local anaesthetic was significantly better than paroxetine in prolonging the IELT, at 278 (111) vs. 186 (65) s, respectively. The improvement in sexual satisfaction was significantly better in the sildenafil group, with a mean (SD) improvement of 2.9 (1) points, than in the paroxetine and local anaesthetic groups, at 2.2 (0.9) and 1.9 (0.9) points, respectively. Conclusions The four drugs significantly improved IELT values over placebo. Tramadol was associated with significantly longer IELT values, whilst sildenafil induced significantly better sexual satisfaction than the other drugs. The four drugs had tolerable side-effects. PMID:26558110

  18. Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain.

    PubMed

    Edwards, Jayne E; McQuay, Henry J; Moore, R Andrew

    2002-02-01

    The primary aims of this study were to assess the analgesic efficacy and adverse effects of single-dose oral tramadol plus acetaminophen in acute postoperative pain and to use meta-analysis to demonstrate the efficacy of the combination drug compared with its components. Individual patient data from seven randomized, double blind, placebo controlled trials of tramadol plus acetaminophen were supplied for analysis by the R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey, USA. All trials used identical methods and assessed single-dose oral tramadol (75 mg or 112.5 mg) plus acetaminophen (650 mg or 975 mg) in adult patients with moderate or severe postoperative pain. Summed pain intensity and pain relief data over six and eight hours and global evaluations of treatment effect after eight hours were extracted. Number-needed-to-treat (NNT) for one patient to obtain at least 50% pain relief was calculated. NNTs derived from pain relief data were compared with those derived from pain intensity data and global evaluations. Information on adverse effects was collected. Combination analgesics (tramadol plus acetaminophen) had significantly lower (better) NNTs than the components alone, and comparable efficacy to ibuprofen 400 mg. This could be shown for dental but not postsurgical pain, because more patients were available for the former. Adverse effects were similar for the combination drugs and the opioid component alone. Common adverse effects were dizziness, drowsiness, nausea, vomiting, and headache. In sum, this meta-analysis demonstrated analgesic superiority of the combination drug over its components, without additional toxicity. PMID:11844632

  19. Physico-chemical stability of butorphanol-tramadol and butorphanol-fentanyl patient-controlled analgesia infusion solutions over 168 hours.

    PubMed

    Chen, Fuchao; Fang, Baoxia; Li, Peng; Zhu, Xuesong; Zhou, Benhong

    2014-08-01

    This study was to investigate the physical and chemical compatibility of butorphanol with tramadol or fentanyl in 0.9% sodium chloride injections for patient controlled analgesia administration. The solutions were prepared in polyvinyl chloride (PVC) infusion bags and stored without protected from light exposure at room temperature (25 degrees C) or refrigerated (4 degrees C). Over a period of 168 hours, stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography (HPLC) assay of drug concentrations. At both temperatures, admixtures of butorphanol-tramadol and butorphanol-fentanyl were clear in appearance, and no color change or precipitation was observed during the study period. The maximum losses obtained were lower than 5% for the three drugs after 168 hours of storage. The results indicate that, at ambient or refrigerated storage conditions, the drug mixtures of butorphanol-tramadol and butorphanol-fentanyl in 0.9% sodium chloride injections were physically and chemically stable for at least 168 hours when stored in PVC syringes. PMID:25158568

  20. Photocatalytic degradation kinetics, mechanism and ecotoxicity assessment of tramadol metabolites in aqueous TiO2 suspensions.

    PubMed

    Αntonopoulou, Μ; Hela, D; Konstantinou, I

    2016-03-01

    This study investigated for the first time the photocatalytic degradation of three well-known transformation products (TPs) of pharmaceutical Tramadol, N-desmethyl-(N-DES), N,N-bidesmethyl (N,N-Bi-DES) and N-oxide-tramadol (N-OX-TRA) in two different aquatic matrices, ultrapure water and secondary treated wastewater, with high (10mgL(-1)) and low (50μgL(-1)) initial concentrations, respectively. Total disappearance of the parent compounds was attained in all experiments. For initial concentration of 10mgL(-1), the target compounds were degraded within 30-40min and a mineralization degree of more than 80% was achieved after 240min of irradiation, while the contained organic nitrogen was released mainly as NH4(+) for N-DES, N,N-Bi-DES and NO3(-) for N-OX-TRA. The degradation rates of all the studied compounds were considerably decreased in the wastewater due to the presence of inorganic and organic constituents typically found in effluents and environmental matrices which may act as scavengers of the HO(•). The effect of pH (4, 6.7, 10) in the degradation rates was studied and for N-DES-TRA and N,N-Bi-DES-TRA, the optimum pH value was 6.7. In contrast, N-OX-TRA showed an increasing trend in the photocatalytic degradation kinetic in alkaline solutions (pH 10). The major transformation products were identified by high resolution accurate mass spectrometry coupled with liquid chromatography (HR-LC-MS). Scavenging experiments indicated for all studied compounds the important role of HO(•) in the photocatalytic degradation pathways that included mainly hydroxylation and further oxidation of the parent compounds. In addition, Microtox bioassay (Vibrio fischeri) was employed for evaluating the ecotoxicity of photocatalytically treated solutions. Results clearly demonstrate the progressive decrease of the toxicity and the efficiency of the photocatalytic process in the detoxification of the irradiated solutions. PMID:26760268

  1. Implantable biodegradable sponges: effect of interpolymer complex formation of chitosan with gelatin on the release behavior of tramadol hydrochloride.

    PubMed

    Foda, Nagwa H; El-laithy, Hanan M; Tadros, Mina I

    2007-01-01

    The effect of interpolymer complex formation between positively charged chitosan and negatively charged gelatin (Type B) on the release behavior of tramadol hydrochloride from biodegradable chitosan-gelatin sponges was studied. Mixed sponges were prepared by freeze-drying the cross-linked homogenous stable foams produced from chitosan and gelatin solutions where gelatin acts as a foam builder. Generation of stable foams was optimized where concentration, pH of gelatin solution, temperature, speed and duration of whipping process, and, chitosan-gelatin ratio drastically affect the properties and the stability of the produced foams. The prepared sponges were evaluated for their morphology, drug content, and microstructure using scanning electron microscopy, mechanical properties, uptake capacity, drug release profile, and their pharmacodynamic activity in terms of the analgesic effect after implantation in Wistar rats. It was revealed that whipping 7% (w/w) gelatin solution, of pH 5.5, for 15 min at 25 degrees C with a stirring speed of 1000 rpm was the optimum conditions for stable gelatin foam generation. Moreover, homogenous, uniform chitosan-gelatin foam with small air bubbles were produced by mixing 2.5% w/w chitosan solution with 7% w/w gelatin solution in 1:5 ratio. Indeed, polyionic complexation between chitosan and gelatin overcame the drawbacks of chitosan sponge mechanical properties where, pliable, soft, and compressible sponge with high fluid uptake capacity was produced at 25 degrees C and 65% relative humidity without any added plasticizer. Drug release studies showed a successful retardation of the incorporated drug where the t50% values of the dissolution profiles were 0.55, 3.03, and 4.73 hr for cross-linked gelatin, un-cross-linked chitosan-gelatin, and cross-linked chitosan-gelatin sponges, respectively. All the release experiments followed Higuchi's diffusion mechanism over 12 hr. The achieved drug prolongation was a result of a combined effect

  2. The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

    PubMed

    Corona-Ramos, Janette Nallely; De la O-Arciniega, Minarda; Déciga-Campos, Myrna; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

    2016-08-01

    Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc. PMID:27300150

  3. Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice.

    PubMed

    Miranda, Hugo F; Romero, Maria Asunción; Puig, Margarita M

    2012-06-01

    Preclinical studies have demonstrated antinociceptive synergism between dexketoprofen (DEX) and tramadol (TRM) in acute animal models of nociception. The aim of the present study was to investigate the type of interaction between DEX and TRM in a chronic musculoskeletal pain model in mice, which fairly replicates the characteristics of chronic osteoarticular pain in humans. Inflammation was induced by a subplantar injection of complete Freund's adjuvant (CFA) in male CF1 mice. Nociceptive thresholds were evaluated using the hot plate, the nocifensive spontaneous behavior and the acetone tests, while plasma extravasation (PE) was assessed with Evan's blue. We used the following experimental groups: control (no inflammation), acute (1 day after CFA injection), and chronic inflammation (7 days after CFA). Dose-response curves for DEX and TRM, individually and combined in a 1 : 1 proportion based on their potency were obtained, and the doses that produced a 50% inhibition calculated. The isobolographic analysis revealed that in all groups of study (no inflammation, acute, and chronic inflammation), the combination of DEX : TRM was synergistic, for both the inhibition of nociception and the PE. The results suggest that the DEX : TRM (1 : 1) combination could be useful in the management of acute and chronic inflammatory musculoskeletal pains in humans; in addition, the synergistic interaction between the drugs observed both during acute and chronic inflammation suggests that less doses would be required of each drug to obtain effective analgesia. PMID:22081874

  4. Spectroscopic investigations of the interactions of tramadol hydrochloride and 5-azacytidine drugs with human serum albumin and human hemoglobin proteins.

    PubMed

    Tunç, Sibel; Cetinkaya, Ahmet; Duman, Osman

    2013-03-01

    The interactions of tramadol hydrochloride (THC) and 5-azacytidine (AZA) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins were investigated by fluorescence, UV absorption and circular dichroism (CD) spectroscopy at pH 7.4 and different temperatures. The UV absorption spectra and the fluorescence quenching of HSA and HMG proteins indicated the formation of HSA-THC and HMG-THC complexes via static quenching mechanism. AZA did not interact with HSA and HMG proteins. It was found that the formation of HMG-THC complex was stronger than that of HSA-THC complex. The stability of HSA-THC and HMG-THC complexes decreased with increasing temperature. The number of binding site was found as one for HSA-THC and HMG-THC systems. Negative enthalpy change (ΔH) and Gibbs free energy change (ΔG) and positive entropy change (ΔS) values were obtained for these systems. The binding of THC-HSA and HMG proteins was spontaneous and exothermic. In addition, electrostatic interactions between protein and drug molecules played an important role in the binding processes. The results of CD analysis revealed that the addition of THC led to a significant conformational change in the secondary structure of HSA protein, on the contrary to HMG protein. PMID:23428887

  5. Tramadol/Paracetamol Fixed-Dose Combination for Chronic Pain Management in Family Practice: A Clinical Review

    PubMed Central

    Morón Merchante, Ignacio; Pergolizzi, Joseph V.; van de Laar, Mart; Mellinghoff, Hans-Ulrich; O'Brien, Joanne; Perrot, Serge; Raffa, Robert B.

    2013-01-01

    The family practitioner plays an important role in the prevention, diagnosis, and early management of chronic pain. He/she is generally the first to be consulted, the one most familiar with the patients and their medical history, and is likely the first to be alerted in case of inadequate pain control or safety and tolerability issues. The family practitioner should therefore be at the center of the multidisciplinary team involved in a patient's pain management. The most frequent indications associated with chronic pain in family practice are of musculoskeletal origin, and the pain is often multimechanistic. Fixed-dose combination analgesics combine compounds with different mechanisms of action; their broader analgesic spectrum and potentially synergistic analgesic efficacy and improved benefit/risk ratio might thus be useful. A pain specialist meeting held in November 2010 agreed that the fixed-dose combination tramadol/paracetamol might be a useful pharmacological option for chronic pain management in family practice. The combination is effective in a variety of pain conditions with generally good tolerability. Particularly in elderly patients, it might be considered as an alternative to conventional analgesics such as NSAIDs, which should be used rarely with caution in this population. PMID:24959571

  6. Application of HPLC for the Simultaneous Determination of Aceclofenac, Paracetamol and Tramadol Hydrochloride in Pharmaceutical Dosage Form

    PubMed Central

    Chandra, Preeti; Rathore, Atul Singh; Lohidasan, Sathiyanarayanan; Mahadik, Kakasaheb Ramoo

    2012-01-01

    A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of aceclofenac (ACF), paracetamol (PCM) and tramadol hydrochloride (TRM) in pharmaceutical dosage form. The chromatographic separation was achieved on a HiQ-Sil™ HS C18 column (250×4.6 mm i.d., 5 μm particle size), kromatek analytical column at ambient temperature. The mobile phase consisted of 40: 60 (v/v); phosphate buffer (pH 6.0): methanol. The flow rate was set to 1.0 mL min−1 and UV detection was carried out at 270 nm. The retention time (tR) for ACF, PCM and TRM were found to be 14.567 ± 0.02, 3.133 ± 0.01 and 7.858 ± 0.02 min, respectively. The validation of the proposed method was carried out for linearity, precision, robustness, limit of detection, limit of quantitation, speci city, accuracy and system suitability. The linear dynamic ranges were from 40–160 μg mL−1 for ACF, 130–520 μg mL−1 for PCM and 15–60 μg mL−1 for TRM. The developed method can be used for routine quality control analysis of titled drugs in pharmaceutical dosage form. PMID:22896821

  7. Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

    PubMed Central

    Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent

  8. Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study

    PubMed Central

    Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

    2014-01-01

    This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse. PMID:25550769

  9. Comprehensive quantum chemical and spectroscopic (FTIR, FT-Raman, 1H, 13C NMR) investigations of O-desmethyltramadol hydrochloride an active metabolite in tramadol - An analgesic drug

    NASA Astrophysics Data System (ADS)

    Arjunan, V.; Santhanam, R.; Marchewka, M. K.; Mohan, S.

    2014-03-01

    O-desmethyltramadol is one of the main metabolites of tramadol widely used clinically and has analgesic activity. The FTIR and FT-Raman spectra of O-desmethyl tramadol hydrochloride are recorded in the solid phase in the regions 4000-400 cm-1 and 4000-100 cm-1, respectively. The observed fundamentals are assigned to different normal modes of vibration. Theoretical studies have been performed as its hydrochloride salt. The structure of the compound has been optimised with B3LYP method using 6-31G** and cc-pVDZ basis sets. The optimised bond length and bond angles are correlated with the X-ray data. The experimental wavenumbers were compared with the scaled vibrational frequencies determined by DFT methods. The IR and Raman intensities are determined with B3LYP method using cc-pVDZ and 6-31G(d,p) basic sets. The total electron density and molecular electrostatic potential surfaces of the molecule are constructed by using B3LYP/cc-pVDZ method to display electrostatic potential (electron + nuclei) distribution. The electronic properties HOMO and LUMO energies were measured. Natural bond orbital analysis of O-desmethyltramadol hydrochloride has been performed to indicate the presence of intramolecular charge transfer. The 1H and 13C NMR chemical shifts of the molecule have been anlysed.

  10. The effects of tramadol on norepinephrine and MHPG releasing in locus coeruleus in formalin test in rats: a brain stereotaxic study

    PubMed Central

    Mobasher, Mohammad Ali; Sajedianfard, Javad; Jamshidzadeh, Akram; Naghdi, Naser; Namvaran, Mohammad Mehdi

    2014-01-01

    Objective(s): The relationship between tramadol, as an antinociceptive drug, and locus coeruleus (LC), the main noradrenergic nucleus of the brain that affects regulation and modulation of pain through descending noradrenergic pathways was investigated. Materials and Methods: Male Sprague-Dawley rats were divided into four groups of 10 rats. The rats were fixed in stereotaxic instrument and then a probe was inserted into LC. Pain was induced by subcutaneous injection of 50 μl of 2.5% formalin 40 minutes after initiation of microdialysis in right hind paw, and nociceptive pain scores were calculated every 5 minutes. Subsequently noradrenaline (NA) and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were collected and measured by microdialysis of locus coeruleus in freely moving rats every 15 minutes during formalin injection. Results: Nociceptive pain scores observed in formalin test had the highest nociceptive sensation 5 minutes after injection. Significant rises in concentrations of NA and MHPG, in samples taken between 30 and 45 min after initiation of the locus coeruleus microdialysis, coincided with the peak of the pain after injection of formalin. Conclusion: According to concurrency of the highest nociceptive sensation and peak of NE and MHPG concentrations, tramadol can indirectly affect the LC by blocking the pain signals from different parts of the brain such as periaqueductal gray mater, central nucleus of amygdale or the spinal cord. PMID:25140203

  11. Hair analysis to demonstrate administration of amitriptyline, temazepam, tramadol and dihydrocodeine to a child in a case of kidnap and false imprisonment.

    PubMed

    Chatterton, Craig; Kintz, Pascal

    2014-03-01

    Amitriptyline, temazepam, tramadol and dihydrocodeine are prescription-only-medications that are rarely prescribed to children. Each of these drugs has a sedative effect on the central nervous system; their combined use could cause an exacerbation of the sedative effects. Amitriptyline (a tricyclic antidepressant) can be prescribed to treat nocturnal enuresis; temazepam (a hypnotic) can be used as a premedicant in inpatient and day-case surgery; tramadol (a synthetic opioid analgesic) is used to treat moderate or severe pain, though it is not recommended for children under the age of 12 years and dihydrocodeine (opioid analgesic), which is available in combination with acetaminophen (Co-dydramol), is not recommended for children under the age of 4 years; in children over 4 years, a reduced dose is necessary. The North West Forensic Science Service Laboratory, Euxton, Lancashire, was asked by a British police force to analyze three separate hair samples, which had been collected from a young child following their discovery as a result of a large scale kidnap and false imprisonment investigation. After decontamination and segmentation (20 x 1-cm section), two of the three hair specimens were analyzed by liquid chromatography coupled with tandem mass spectrometry after alkaline (pH 9.5) extraction using methylene chloride/isopropanol/n-heptane (25:10:65, v/v/v). The entire length of each hair specimen tested positive for amitriptyline and nortriptyline (7-314 pg/mg amitriptyline; 7-318 pg/mg nortriptyline), temazepam (2-29 pg/mg), tramadol (60-2000 pg/mg) and dihydrocodeine (10-90 pg/mg) demonstrating that the child had ingested these drugs on more than one occasion prior to the kidnap. In this case, the child's mother and the mothers' partner were found guilty of kidnap, false imprisonment and perverting the course of justice. There are very few studies citing the concentrations of these drugs in children - especially children's hair samples. This case demonstrates

  12. Nam Con Son Basin

    SciTech Connect

    Tin, N.T.; Ty, N.D.; Hung, L.T.

    1994-07-01

    The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

  13. A retro-biosynthetic approach to the prediction of biosynthetic pathways from position-specific isotope analysis as shown for tramadol

    PubMed Central

    Romek, Katarzyna M.; Nun, Pierrick; Remaud, Gérald S.; Silvestre, Virginie; Taïwe, Germain Sotoing; Lecerf-Schmidt, Florine; Boumendjel, Ahcène; De Waard, Michel; Robins, Richard J.

    2015-01-01

    Tramadol, previously only known as a synthetic analgesic, has now been found in the bark and wood of roots of the African medicinal tree Nauclea latifolia. At present, no direct evidence is available as to the biosynthetic pathway of its unusual skeleton. To provide guidance as to possible biosynthetic precursors, we have adopted a novel approach of retro-biosynthesis based on the position-specific distribution of isotopes in the extracted compound. Relatively recent developments in isotope ratio monitoring by 13C NMR spectrometry make possible the measurement of the nonstatistical position-specific natural abundance distribution of 13C (δ13Ci) within the molecule with better than 1‰ precision. Very substantial variation in the 13C positional distribution is found: between δ13Ci = −11 and −53‰. Distribution is not random and it is argued that the pattern observed can substantially be interpreted in relation to known causes of isotope fractionation in natural products. Thus, a plausible biosynthetic scheme based on sound biosynthetic principals of precursor–substrate relationships can be proposed. In addition, data obtained from the 18O/16O ratios in the oxygen atoms of the compound add support to the deductions made from the carbon isotope analysis. This paper shows how the use of 13C NMR at natural abundance can help with proposing a biosynthetic route to compounds newly found in nature or those difficult to tackle by conventional means. PMID:26106160

  14. Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) as a drug carrier for controlled release of tramadol hydrochloride

    PubMed Central

    Subramanian, Kaliappa gounder; Vijayakumar, Vediappan

    2011-01-01

    Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic acid and characterized by FT-IR, thermogravimetry and swelling in simulated biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug–polymer interaction. But differential scanning calorimetric studies indicated a probable drug–polymer interaction at a scale >100 nm level. The observed Korsmeyer–Peppas’s power law exponents (0.19–1.21) for the in vitro release profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an anomalous drug release mechanism. The decreased release rates for the grafted chitosan and the enhanced release rate for the grafts with increasing itaconic acid content in the feed were more likely attributed to the enhanced drug–matrix interaction and polymer–SBF interactions, respectively. The different release profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the different chemical structures of drugs. The above features suggest the graft copolymer’s candidature for use as a promising oral drug delivery system. PMID:23960799

  15. Comparison of dexmedetomidine and midazolam for monitored anesthesia care combined with tramadol via patient-controlled analgesia in endoscopic nasal surgery: A prospective, randomized, double-blind, clinical study

    PubMed Central

    Karaaslan, Kazim; Yilmaz, Fahrettin; Gulcu, Nebahat; Colak, Cemil; Sereflican, Murat; Kocoglu, Hasan

    2007-01-01

    Abstract Background Monitored anesthesia care (MAC) may be applied for septoplasty or endoscopic sinus surgery in which an adequate sedation and analgesia without respiratory depression are desired for comfort of both the patient and the surgeon. Several combinations with different agents have been used for this purpose in these patients. However, analgesic properties for these agents have not been reported. Objective The aim of this study was to investigate the analgesic and sedative effects of dexmedetomidine or midazolam infusion combined with tramadol that was used via patient-controlled analgesia (PCA), and to document the effects of these drugs on early cognitive functions. Methods This prospective, randomized, double-blind, clinical study enrolled patients undergoing septoplasty or endoscopic sinus surgery at the Abant Izzet Baysal University Hospital, Bolu, Turkey, between February and September 2006. Patients were randomly allocated in a 1:1 ratio into 1 of 2 groups: the dexmedetomidine group (group D) patients received IV dexmedetomidine 1 μg/kg for 10 minutes followed by continuous infusion of 0.5 μg/kg · h−1; and the midazolam group (group M) patients were administered a loading dose of IV midazolam 40 μg/kg for 10 minutes followed by infusion at the rate of 50 μg/kg · h−1. A 1-minute bolus dose of IV tramadol (1.5 mg/kg) was administered in both groups 10 minutes after the administration of the primary drug, and continued via infusion using a PCA device. After baseline measurements, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), oxygen saturation, and rate of respiration were recorded after the loading dose of study drug, after the bolus tramadol dose, at 10-minute intervals during the operation, and twice in the recovery rooms; 5 minutes after arrival and 5 minutes before discharge. Verbal rating score (VRS) and Ramsay sedation score were determined at baseline (after

  16. Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor knock out mice brain.

    PubMed

    Höcker, Jan; Weber, Bernd; Tonner, Peter H; Scholz, Jens; Brand, Philipp-Alexander; Ohnesorge, Henning; Bein, Berthold

    2008-03-17

    alpha(2)-adrenoceptor agonists like clonidine or dexmedetomidine increase the sedative and analgesic actions of opioids. Furthermore opioids like meperidine show potent anti-shivering effects like alpha(2)-adrenoceptor agonists. The underlying molecular mechanisms of these effects are still poorly defined. The authors therefore studied the ability of four different opioids (meperidine, remifentanil, sufentanil and tramadol) to interact with different alpha(2)-adrenoceptor subtypes in mice lacking individual alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptors (alpha(2)-adrenoceptor knock out (alpha(2)-AR KO) mice)). The interaction of opioids with alpha(2)-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]-paraiodoclonidine ([(125)I]-PIC) from alpha(2)-adrenoceptors in different brain regions by increasing opioid concentrations was measured, and binding affinity of the analysed opioids to alpha(2)-adrenoceptor subtypes in different brain regions was quantified. Meperidine, remifentanil and tramadol but not sufentanil provoked dose dependent displacement of specifically bound [(125)I]-PIC from all alpha(2)-adrenoceptor subtypes in cortex, cerebellum, medulla oblongata, thalamus, hippocampus and pons. Required concentrations of meperidine and remifentanil for [(125)I]-PIC displacement from alpha(2B)- and alpha(2C)-adrenoceptors were lower than from alpha(2A)-adrenoceptors, indicating higher binding affinity for alpha(2B)- and alpha(2C)-adrenoceptors. In contrast, [(125)I]-PIC displacement by tramadol indicated higher binding affinity to alpha(2A)-adrenoceptors than to alpha(2B)- and alpha(2C)-adrenoceptors. Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C

  17. Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

    PubMed Central

    dos Santos, Ana Claudia Mendonça; Akkari, Alessandra Cristina Santos; Ferreira, Iasmin Rosanne Silva; Maruyama, Cintia Rodrigues; Pascoli, Monica; Guilherme, Viviane Aparecida; de Paula, Eneida; Fraceto, Leonardo Fernandes; de Lima, Renata; Melo, Patrícia da Silva; de Araujo, Daniele Ribeiro

    2015-01-01

    In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407–PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug–micelle interaction studies showed the formation of PL 407–PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407–PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%–45% of the gel dissolved, reaching ~80%–90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower Krel values were observed for PL 407 (20%, Krel =112.9±10.6 μg·h−1/2) and its binary systems PL 407–PL 188 (25%–5% and 25%–10%, Krel =80.8±6.1 and 103.4±8.3 μg·h−1/2, respectively) in relation to TR solution (Krel =417.9±47.5 μg·h−1/2, P<0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes) and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects (>72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain. PMID:25848258

  18. Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation.

    PubMed

    dos Santos, Ana Claudia Mendonça; Akkari, Alessandra Cristina Santos; Ferreira, Iasmin Rosanne Silva; Maruyama, Cintia Rodrigues; Pascoli, Monica; Guilherme, Viviane Aparecida; de Paula, Eneida; Fraceto, Leonardo Fernandes; de Lima, Renata; Melo, Patrícia da Silva; de Araujo, Daniele Ribeiro

    2015-01-01

    In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407-PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug-micelle interaction studies showed the formation of PL 407-PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407-PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%-45% of the gel dissolved, reaching ~80%-90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower K(rel) values were observed for PL 407 (20%, K(rel) = 112.9 ± 10.6 μg · h(-1/2)) and its binary systems PL 407-PL 188 (25%-5% and 25%-10%, K(rel) =80.8 ± 6.1 and 103.4 ± 8.3 μg · h(-1/2), respectively) in relation to TR solution (K(rel) =417.9 ± 47.5 μg · h(-1/2), P<0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes) and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects (>72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain. PMID:25848258

  19. Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

    PubMed

    Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

    2016-04-01

    A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable. PMID:27209697

  20. Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effects of main active metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, in rats.

    PubMed

    Valle, M; Garrido, M J; Pavón, J M; Calvo, R; Trocóniz, I F

    2000-05-01

    The pharmacokinetics and pharmacodynamics of the two main metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, were studied in rats. Pharmacodynamic endpoints evaluated were respiratory depression, measured as the change in arterial blood pCO(2), pO(2), and pH levels; and antinociception, measured by the tail-flick technique. The administration of 10 mg/kg (+)-O-desmethyltramadol in a 10-min i.v. infusion significantly altered pCO(2), pO(2), and pH values in comparison with baseline and lower-dose groups (P <.05). However, 2 mg/kg administered in a 10-min i.v. infusion was enough to achieve 100% antinociception without respiratory depression. Moreover, the beta-funaltrexamine pretreatment completely eliminated the antinociception of the 2-mg/kg dose, suggesting that such an effect is due to mu-opioid receptor activation. To describe and adequately characterize the in vivo antinociceptive effect of the drug, (+)-O-desmethyltramadol was given at different infusion rates of varying lengths (10-300 min). Pharmacokinetics was best described by a two-compartmental model. The time course of response was described using an effect compartment associated with a linear pharmacodynamic model. The estimates of the slope of the effect versus concentration relationship were significantly decreased (P <. 05) as the length of infusion was increased, suggesting the development of tolerance. Doses of up to 8 mg/kg (-)-O-desmethyltramadol given in 10-min i.v. infusion did not elicit either antinociception in the tail-flick test or respiratory effects. These in vivo results are in accordance with the opiate and nonopiate properties reported for these compounds in several in vitro studies. PMID:10773040

  1. Comprehensive quantum chemical and spectroscopic (FTIR, FT-Raman, 1H, 13C NMR) investigations of O-desmethyltramadol hydrochloride an active metabolite in tramadol--an analgesic drug.

    PubMed

    Arjunan, V; Santhanam, R; Marchewka, M K; Mohan, S

    2014-03-25

    O-desmethyltramadol is one of the main metabolites of tramadol widely used clinically and has analgesic activity. The FTIR and FT-Raman spectra of O-desmethyl tramadol hydrochloride are recorded in the solid phase in the regions 4000-400 cm(-1) and 4000-100 cm(-1), respectively. The observed fundamentals are assigned to different normal modes of vibration. Theoretical studies have been performed as its hydrochloride salt. The structure of the compound has been optimised with B3LYP method using 6-31G(**) and cc-pVDZ basis sets. The optimised bond length and bond angles are correlated with the X-ray data. The experimental wavenumbers were compared with the scaled vibrational frequencies determined by DFT methods. The IR and Raman intensities are determined with B3LYP method using cc-pVDZ and 6-31G(d,p) basic sets. The total electron density and molecular electrostatic potential surfaces of the molecule are constructed by using B3LYP/cc-pVDZ method to display electrostatic potential (electron+nuclei) distribution. The electronic properties HOMO and LUMO energies were measured. Natural bond orbital analysis of O-desmethyltramadol hydrochloride has been performed to indicate the presence of intramolecular charge transfer. The (1)H and (13)C NMR chemical shifts of the molecule have been anlysed. PMID:24316546

  2. Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

    PubMed Central

    Devarakonda, Krishna; Kostenbader, Kenneth; Giuliani, Michael J; Young, Jim L

    2015-01-01

    Objective To characterize the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP), IR HB/ibuprofen, and IR tramadol HCl/APAP. Methods In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1) a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose) on day 1, followed by two tablets every 12 hours (q12h) beginning on day 3; 2) a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6), followed by one tablet every 6 hours (q6h) beginning on day 3; 3) a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6), followed by one tablet q6h beginning on day 3; and 4) a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose) on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored. Results The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg) vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures were similar between treatments. Adverse events were similar for each treatment and typical of low-dose combination opioid analgesics. With dosing q12h, IR/ER HB/APAP had half as many concentration peaks and troughs as the comparators treated q6h. Conclusion With dosing q12h, IR/ER HB/APAP provided similar peak and total steady-state hydrocodone

  3. Development and validation of a sensitive UHPLC-MS/MS method for the simultaneous analysis of tramadol, dextromethorphan chlorpheniramine and their major metabolites in human plasma in forensic context: application to pharmacokinetics.

    PubMed

    Heneedak, Hala M; Salama, Ismail; Mostafa, Samia; El-Kady, Ehab; El-Sadek, Mohamed

    2015-07-01

    The prerequisites for forensic confirmatory analysis by LC/MS/MS with respect to European Union guidelines are chromatographic separation, a minimum number of two MS/MS transitions to obtain the required identification points and predefined thresholds for the variability of the relative intensities of the MS/MS transitions (MRM transitions) in samples and reference standards. In the present study, a fast, sensitive and robust method to quantify tramadol, chlorpheniramine, dextromethorphan and their major metabolites, O-desmethyltramadol, dsmethyl-chlorpheniramine and dextrophan, respectively, in human plasma using ibuprofen as internal standard (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction method using ethyl acetate-diethyl-ether (1:1). Extracted samples were analyzed by ultra-high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase containing acetonitrile, water and formic acid (89.2:11.7:0.1) for 2.0 min at a flow rate of 0.25 μL/min into a Hypersil-Gold C18 column, 20 × 2.0 mm (1.9 µm) from Thermoscientific, New York, USA. The calibration curve was linear for the six analytes. The intraday precision (RSD) and accuracy (RE) of the method were 3-9.8 and -1.7-4.5%, respectively. The analytical procedure herein described was used to assess the pharmacokinetics of the analytes in 24 healthy volunteers after a single oral dose containing 50 mg of tramadol hydrochloride, 3 mg chlorpheniramine maleate and 15 mg of dextromethorphan hydrobromide. PMID:25417559

  4. Synthetic slings: pros and cons.

    PubMed

    Staskin, David R; Plzak, Louis

    2002-10-01

    Historically, the choice of sling material for the treatment of urinary incontinence has been based on the surgeon's preference and experience. In general, pelvic surgeons have not differentiated artificial graft materials by their inherent qualities or for biocompatibility in the female pelvis and vaginal wall. The introduction of new artificial graft materials and new methods of implantation for the correction of genuine stress incontinence has generated renewed interest in the "pros and cons" associated with nonabsorbable material use. In this review, we discuss and differentiate sling materials and techniques. We consider some of the physical and biologic qualities of artificial graft materials, present theories and practices associated with the successful use of permanent grafts, and discuss the natural evolution of artificial graft slings to the current use of the tension-free vaginal tape and Suprapubic Arc Sling System (American Medical Systems, Minneapolis, MN). PMID:12354353

  5. Galaxias australes con núcleo doble

    NASA Astrophysics Data System (ADS)

    Gimeno, G.; Díaz, R.; Carranza, G.

    Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

  6. InterCon Travel Health: Case B

    ERIC Educational Resources Information Center

    Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

    2010-01-01

    InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

  7. Ependimoma myxopapilar sacro gigante con osteolisis

    PubMed Central

    Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

    2014-01-01

    Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

  8. conF and conJ contribute to conidia germination and stress response in the filamentous fungus Aspergillus nidulans.

    PubMed

    Suzuki, Satoshi; Sarikaya Bayram, Özlem; Bayram, Özgür; Braus, Gerhard H

    2013-07-01

    Light induces various responses in fungi including formation of asexual and sexual reproductive structures. The formation of conidia in the filamentous fungus Aspergillus nidulans is regulated by red and blue light receptors. Expression of conidia associated con genes, which are widely spread in the fungal kingdom, increases upon exposure to light. We have characterized the light-inducible conF and conJ genes of A. nidulans which are homologs of con-6 and con-10 of Neurospora crassa. con genes are expressed during conidia formation in asexual development. Five minutes light exposure are sufficient to induce conF or conJ expression in vegetative mycelia. Similar to N. crassa there were no significant phenotypes of single con mutations. A double conF and conJ deletion resulted in significantly increased cellular amounts of glycerol or erythritol. This leads to a delayed germination phenotype combined with increased resistance against desiccation. These defects were rescued by complementation of the double mutant strain with either conF or conJ. This suggests that fungal con genes exhibit redundant functions in controlling conidia germination and adjusting cellular levels of substances which protect conidia against dryness. PMID:23644150

  9. Somatic cell nuclear transfer: pros and cons.

    PubMed

    Sumer, Huseyin; Liu, Jun; Tat, Pollyanna; Heffernan, Corey; Jones, Karen L; Verma, Paul J

    2009-01-01

    Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both genetically unmodified autologous pluripotent stem cells for transplantation and for the production of cloned animals. In this review we will discuss the pros and cons of SCNT, drawing comparisons with other reprogramming methods. PMID:20232594

  10. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  11. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  12. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  13. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  14. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  15. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  16. Energy Star program benefits Con Edison

    SciTech Connect

    1995-05-01

    Impressed with savings in energy costs achieved after upgrading the lighting and air conditioning systems at its Manhattan headquarters, Home Box Office (HBO) wanted to do more, James Flock, vice president for computer and office systems, contacted Con Edison Co. of New York in March 1991 to determine what the company could do to save money by reducing energy consumed by personal computers. Arthur Kressner, Con Edison Research and Development manager contacted industry organizations and manufacturers for advice, but was told only to shut off computers at night and on weekends. Kressner arranged a series of meetings with IBM and the Electric Power Research Institute (EPRI) to discuss the issue, then approached the U.S. Environmental Protection Agency (EPA), which was designing a program to promote the introduction and use of energy-efficient office equipment. In 1992, the EPA announced the Energy Star program for PCs, enabling manufacturers to display the Energy Star logo on machines meeting program criteria, including the ability to enter a sleep mode in which neither the computer nor monitor consume more than 30 W or electricity. Industry experts estimate national energy consumption by office equipment could double by the year 2000, but Energy Star equipment is expected to improve efficiency and help maintain electric loads.

  17. Cervical disc arthroplasty: Pros and cons

    PubMed Central

    Moatz, Bradley; Tortolani, P. Justin

    2012-01-01

    Background: Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Conclusion: Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing. PMID:22905327

  18. Breath Analysis Science at PittCon 2012, Orlando, Florida

    EPA Science Inventory

    Breath analysis science was featured in three organized sessions at this year’s Pittsburgh Conference and Exposition, or ‘PittCon 2012’ (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

  19. RoboCon: A general purpose telerobotic control center

    SciTech Connect

    Draper, J.V.; Noakes, M.W.; Schempf, H.; Blair, L.M.

    1997-02-01

    This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices.

  20. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  1. ProCon - PROteomics CONversion tool.

    PubMed

    Mayer, Gerhard; Stephan, Christian; Meyer, Helmut E; Kohl, Michael; Marcus, Katrin; Eisenacher, Martin

    2015-11-01

    With the growing amount of experimental data produced in proteomics experiments and the requirements/recommendations of journals in the proteomics field to publicly make available data described in papers, a need for long-term storage of proteomics data in public repositories arises. For such an upload one needs proteomics data in a standardized format. Therefore, it is desirable, that the proprietary vendor's software will integrate in the future such an export functionality using the standard formats for proteomics results defined by the HUPO-PSI group. Currently not all search engines and analysis tools support these standard formats. In the meantime there is a need to provide user-friendly free-to-use conversion tools that can convert the data into such standard formats in order to support wet-lab scientists in creating proteomics data files ready for upload into the public repositories. ProCon is such a conversion tool written in Java for conversion of proteomics identification data into standard formats mzIdentML and Pride XML. It allows the conversion of Sequest™/Comet .out files, of search results from the popular and often used ProteomeDiscoverer® 1.x (x=versions 1.1 to1.4) software and search results stored in the LIMS systems ProteinScape® 1.3 and 2.1 into mzIdentML and PRIDE XML. This article is part of a Special Issue entitled: Computational Proteomics. PMID:26182917

  2. Combinación de radioterapia con quimioterapia mejora la supervivencia con raro cáncer cerebral

    Cancer.gov

    Los resultados de dos estudios clínicos de seguimiento a largo plazo confirman que ciertos pacientes viven substancialmente más si se les trata con una combinación de quimioterapia y radioterapia en comparación con radioterapia solamente.

  3. Pro/con a precessional geodynamo

    NASA Astrophysics Data System (ADS)

    Vanyo, J.

    2003-04-01

    The modest amount of research that exists on the ability, or lack of ability, of mantle precession to power a geodynamo developed mostly during the last half of the 1900s. Papers by Roberts and Stewartson (1965) and by Busse (1968) studied precession generally without a pro/con conclusion. Malkus in the late 1960s attempted to advance a positive role for precession through experiments and analysis. His experiments have survived criticism, but his analyses were discounted, especially by Rochester, Jacobs, Smylie, and Chong (1975) and by Loper (1975). Rochester, et al. critiqued existing analyses of precession, including those of Malkus, but did not reach a strong position either pro or con a precessional geodynamo. Loper argued emphatically that precession was not capable of powering the geodynamo. Explicit analyses that either critique or support Loper’s arguments have yet to appear in the literature. During the 1970s, Vanyo and associates studied energy dissipation during precession of satellite liquid fuels and its effect on satellite attitude stability. Engineers and scientists in every country that has launched satellites completed similar research. Some is published in the aerospace literature, more is available in company and government reports. Beginning in 1981, Vanyo and associates applied this knowledge to the very similar problem of energy dissipation and flow patterns in precessing mechanical models scaled geometrically and dynamically to the Earth’s liquid core. Energy experiments indicate massive amounts of mechanical energy are dissipated at the CMB, and flow experiments show complex motions within the boundary layer and axial flows with helicity throughout the interior. Analysis of Earth core precession also advanced, especially in several papers by Kerswell and by Tilgner in the late 1990s. Detail numerical models have yet to appear. Although progress in understanding the role of precession in Earth core motions has advanced, there remains a

  4. 53. SECONDARY CONNING STATION AFT LOOKING FORWARD ON CENTERLINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. SECONDARY CONNING STATION - AFT LOOKING FORWARD ON CENTERLINE SHOWING ENGINE ORDER TELEGRAPH, HELM, RADAR, GYRO REPEATERS, PORTHOLE WITH BATTLE PORTS CLOSED. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  5. 52. SECONDARY CONNING STATION FORWARD LOOKING AFT ON CENTERLINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. SECONDARY CONNING STATION - FORWARD LOOKING AFT ON CENTERLINE SHOWING ENGINE ORDER TELEGRAPH, HELM, RADAR, GYRO REPEATERS, PORTHOLE WITH BATTLE PORTS CLOSED. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  6. View forward of interior of conning tower and steering station; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View forward of interior of conning tower and steering station; helmsman or observer viewed action through narrow opening at top of photo. (p57) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

  7. [Cement augmentation of pedicle screws : Pros and cons].

    PubMed

    Schnake, K J; Blattert, T R; Liljenqvist, U

    2016-09-01

    Cement augmentation of pedicle screws biomechanically increases screw purchase in the bone. However, clinical complications may occur. The pros and cons of the technique are discussed from different clinical perspectives. PMID:27514827

  8. Planificación Neuroquirúrgica con Software Osirix

    PubMed Central

    Jaimovich, Sebastián Gastón; Guevara, Martin; Pampin, Sergio; Jaimovich, Roberto; Gardella, Javier Luis

    2014-01-01

    Introducción: La individualidad anatómica es clave para reducir el trauma quirúrgico y obtener un mejor resultado. Actualmente, el avance en las neuroimágenes ha permitido objetivar esa individualidad anatómica, permitiendo planificar la intervención quirúrgica. Con este objetivo, presentamos nuestra experiencia con el software Osirix. Descripción de la técnica: Se presentan 3 casos ejemplificadores de 40 realizados. Caso 1: Paciente con meningioma de la convexidad parasagital izquierda en área premotora; Caso 2: Paciente con macroadenoma hipofisario, operada previamente por vía transeptoesfenoidal en otra institución con una resección parcial; Caso 3: Paciente con lesiones en pedúnculo cerebeloso medio bilateral. Se realizó la planificación prequirúrgica con el software OsiriX, fusionando y reconstruyendo en 3D las imágenes de TC e IRM, para analizar relaciones anatómicas, medir distancias, coordenadas y trayectorias, entre otras funciones. Discusión: El software OsiriX de acceso libre y gratuito permite al cirujano, mediante la fusión y reconstrucción en 3D de imágenes, analizar la anatomía individual del paciente y planificar de forma rápida, simple, segura y económica cirugías de alta complejidad. En el Caso 1 se pudo analizar las relaciones del tumor con las estructuras adyacentes para minimizar el abordaje. En el Caso 2 permitió comprender la anatomía post-operatoria previa del paciente, para determinar la trayectoria del abordaje transnasal endoscópico y la necesidad de ampliar su exposición, logrando la resección tumoral completa. En el Caso 3 permitió obtener las coordenadas estereotáxicas y trayectoria de una lesión sin representación tomográfica. Conclusión: En casos de no contar con costosos sistemas de neuronavegación o estereotáxia el software OsiriX es una alternativa a la hora de planificar la cirugía, con el objetivo de disminuir el trauma y la morbilidad operatoria. PMID:25165617

  9. [I costi farmacologici della terapia di conversione con farmaci biologici nel carcinoma del colon-retto con metastasi epatiche].

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2016-08-01

    Riassunto. Lo scopo di questo studio è quello di valutare i costi dei farmaci (con particolare riferimento alle terapie con farmaci biologici) utilizzati nella terapia di conversione in una popolazione non selezionata di pazienti affetti da carcinoma del colon-retto in stadio avanzato, al fine di ottenere una resezione epatica R0. In questa rassegna sono stati selezionati i report completi e gli aggiornamenti di tutti gli studi clinici randomizzati (di fase II e fase III) che confrontassero almeno 2 regimi di terapia con farmaci biologici in prima linea in pazienti affetti da carcinoma del colon-retto in stadio avanzato di malattia. I costi dei farmaci sono stati ricavati dalla nostra Farmacia Ospedaliera e sono espressi in euro (€). Il nostro studio inizia con la valutazione di 683 abstract. 48 tria sono stati considerati adeguati per una successiva analisi. Una valutazione più approfondita ha portato all'esclusione di 37 trial, lasciando alla valutazione finale 11 studi clinici randomizzati (3 trial di fase II, per un totale di 522 pazienti, e 8 studi di fase III, per un totale di 7191 pazienti). I costi dei farmaci utilizzati nella terapia di conversione aumentano con la sostituzione del 5-fluorouracile con la capecitabina e, in misura maggiore, con l'introduzione degli agenti biologici. In questo lavoro sono presentati due punti chiave. Primo, i costi degli agenti farmacologici utilizzati nei regimi di prima linea a base di agenti biologici più comunemente utilizzati nel trattamento del carcinoma del colon-retto in stadio avanzato sono molto variabili. Secondo, i dati di efficacia dei regimi pubblicati, in termini di tassi di resezione, dipendono dalla selezione dei pazienti, dalle caratteristiche del tumore e dal tipo di schema di terapia. PMID:27571559

  10. Paramagnetic-to-Ferromagnetic Transition in Con Under Pressure

    NASA Astrophysics Data System (ADS)

    Kasinathan, Deepa; Pickett, Warren

    2004-03-01

    Motivated by reports of synthesis of zincblende (ZB) structure CrAs in thin film form, strong interest has developed in understanding transition metal pnictides and their tendencies toward magnetic order.Literature on the experimental analysis of the structure of CoN is varied, with reports of both magnetically ordered NaCl structure CoN and non-magnetic ZB CoN. We present results of first principles analysis of electronic structure, magnetism and Murnaghan equation of state for both structures. The non-magnetic ZB structure, stable at ambient pressure transforms to a collapsed ferromagnetic NaCl phase at 10GPa (ΔV = -15%). These results will be compared to data and similarities/differences with other transition metal nitrides will be discussed.

  11. Detail of conning tower atop the submarine. Note the wire ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of conning tower atop the submarine. Note the wire rope wrapped around the base of the tower, which may have been used in an attempt to pull the submarine offshore. - Sub Marine Explorer, Located along the beach of Isla San Telmo, Pearl Islands, Isla San Telmo, Former Panama Canal Zone, CZ

  12. Inclusion: The Pros and Cons--A Critical Review

    ERIC Educational Resources Information Center

    Savich, Carl

    2008-01-01

    The purpose of this paper was to review, analyze, and critique the pros and cons, the advantages and disadvantages, of inclusion. The methodology consisted in analyzing and comparing research findings on the benefits and costs of inclusion. Federal legislation and regulations on inclusion were examined, analyzed, and discussed. The results showed…

  13. Teaching after Retirement: The Pros and the Cons

    ERIC Educational Resources Information Center

    Sommer, Robert

    2014-01-01

    Having enjoyed teaching during my active career, I continued to teach summer school following retirement. Self-observed sensory and cognitive impairments, although not mentioned by students in their evaluations, induced me to consider the pros and cons of continuing to teach. My hope is that this list of benefits and problems will be of assistance…

  14. The Academic Con-Men. Advice to Young College Professors.

    ERIC Educational Resources Information Center

    Kerins, Francis J.

    1979-01-01

    The academic con-man is defined as one who, despite a lack of striking originality or tremendous learning, becomes extraordinary, well-known, and revered in the world of higher education. Advice is offered to young college professors on how they can achieve such status. (Article originally published in 1961.) (AF)

  15. LunGradCon: The Lunar Graduate Conference

    NASA Astrophysics Data System (ADS)

    Dove, A.; Poppe, A.; Neish, C.; Fagan, A.; Fuqua, H.; Kramer, G. Y.; Horanyi, M.

    2011-12-01

    Members of the Colorado Center for Lunar Dust and Atmospheric Studies (CCLDAS) initiated the Lunar Graduate Conference (LunGradCon), modeled after the highly successful Astrobiology Graduate Conference (AbGradCon). The purpose of this conference is to enhance the professional development of graduate students and early postdoctoral researchers by providing an opportunity to present and discuss scientific research in an environment of their peers. For the first two years, LunGradCon has been held as a one-day conference in conjunction with the NASA Lunar Science Institue's (NLSI) Lunar Science Forum at the NASA Ames Research Center. Activities include an invited overview talk on each of the NASA Lunar Science Institute's three main research areas (OF the Moon, ON the Moon, and FROM the Moon), submitted oral presentations from graduate students and postdoctoral researchers, and networking opportunities with established member of the lunar science community and the NLSI. In each of the first two years of LunGradCon, there have been 20-25 attendees, with about 15 of those presenting submitted talks. Each speaker received feedback forms from the other participants in order to improve on their presentation techniques. Participants also provided feedback on the conference as a whole in order to evaluate the content and provide suggestions for improvement in following years. Overall, the feedback has been extremely positive. This talk will summarize the achievements of past LunGradCons and plans for expansion of the conference to ensure a long-term positive impact on the early careers of future lunar, planetary and space science researchers.

  16. Runtime Verification for Generic Classes with ConGu 2

    NASA Astrophysics Data System (ADS)

    Crispim, Pedro; Lopes, Antónia; Vasconcelos, Vasco T.

    Even though generics became quite popular in mainstream object-oriented (OO) languages, approaches for checking at runtime the conformance of such programs against formal specifications still lack appropriate support. In order to overcome this limitation within ConGu, a tool-based approach we have been developing to support runtime conformance checking of Java programs against algebraic specifications, we recently proposed a notion of refinement mapping that allows to define correspondences between parametric specifications and generic classes. Based on such mappings, we also put forward a notion of conformance between the two concepts. In this paper we present how the new notion of conformance is supported by version 2 of the ConGu tool.

  17. ConStrains identifies microbial strains in metagenomic datasets

    PubMed Central

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-01-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived data sets provides insights into microbial community dynamics. PMID:26344404

  18. ConStrains identifies microbial strains in metagenomic datasets.

    PubMed

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-10-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics. PMID:26344404

  19. Apoyo a Estudios Geodinamicos con GPS en Guatemala

    NASA Astrophysics Data System (ADS)

    Robles, V. R.

    2013-05-01

    El Instituto Geografico Nacional de Guatemala implemento 17 estaciones GNSS en el año 2009, como un proyecto de credito mixto de donacion de equipamiento del Gobierno de Suiza, el cual, este equipamiento de estaciones CORS GNSS es un sistema de recepción y transmisión de datos crudos GPS RInex que utiliza la tecnologia Spider Web de Leica, asi mismo este sistema esta sirviendo para el espablecimiento de un marco geodesico nacional de coordenadas geodesicas oficiales, el cual se calculan u obtienen las velocidades en tiempos temporales programados de las 17 Estaciones CORS. La infraestructura del marco geodesico de Guatemala esta sirviendo de base para las aplicaciones de estudios geodinamicos como el monitoreo de del desplazamiento de las placas tectonicas por medio de un estudio que se inicio en el año de 1999, llamado medicion con GPS el sistema de Fallas de los rios Polochic Motagua de Guatemala, tambien para un estudio que se implemento para deformación de corteza terrestre local en un Volcan Activo de Guatemala llamado Pacaya. Para el estudio de medicion con GPS en el sistema de falla de los Rios del polochic Motagua se implementaron 16 puntos para medir con GPS de dos frecuencias en el año de 1999, el cual, tres puntos son estaciones geodesicas CORS IGS llamados GUAT, ELEN y HUEH, despues en el año de 2003 se hizo otra medicion en un total de 20 puntos, que permitió calcular las velocidades de desplazamieinto de los puntos en mención, usando como referencia el modelo NUVEL 1A de DeMets de la placa de Norteamerica. Este estudio fue en cooperación internacional por la universidad de Nice de Francia y el IGNde Francia. Para el estudio del monitoreo con GPS del volcan activo de Guatemala, se implementaron cuatro puntos al rededor del volcan, el cual, se realizan cuatro mediciones al año, que permiten determinar axialmente la distancias entre los puntos, y rebisar estadisticamente cual es el comportamiento de las distancias en funcion del tiempo, si

  20. Topical Oxygen for Chronic Wounds: A PRO/CON Debate

    PubMed Central

    Mutluoglu, Mesut; Cakkalkurt, Aslican; Uzun, Gunalp; Aktas, Samil

    2014-01-01

    The role of oxygen in wound healing is universally accepted and does not require any further evidence; however the controversy as to whether oxygen delivery systems have the potential to improve wound healing remains to be concluded. Topical oxygen treatment (TOT) involves the delivery of 100% oxygen for a mean of 90 min, once a day at an atmospheric pressure slightly above 1 atm abs. The use of TOT gained increasing interest recently. The current manuscript will summarize the pros and cons of TOT in the view of the available literature. PMID:26199891

  1. [Modern tribology in total hip arthroplasty: pros and cons].

    PubMed

    Gómez-García, F

    2014-01-01

    The wear products and adverse reactions that occur on bearing surfaces represent one of the greatest challenges in prosthetic replacements, as the latter experience increasing demands due to the large number of young and older adult patients that have a long life expectancy and remarkable activity. The purpose of this review is to analyze the pros and cons of the new advances in the bearing components of the articular surfaces of current total hip arthroplasties. We also discuss the strategies used historically, their problems, results and the surgeon's role in prescribing the tribologic couple that best fits each patient's needs. We conclude with practical recommendations for the prescription and management of the latest articular couples for total hip arthroplasty. PMID:26021098

  2. RoboCon: Operator interface for robotic applications

    SciTech Connect

    Schempf, H.; Warwick, J.; Fung, M.; Chemel, B.; Blackwell, M.

    1996-12-31

    Carnegie Mellon U. and ORNL`s Robotics and Process Systems Division are developing a state-of-the-art robot operator control station (RoboCon) with standardized hardware and software control interfaces to be adaptable to a variety of remote and robotic equipment currently funded by DOE`s Office of Science & Technology Robotics Technology Development Program. The human operation and telerobotic and supervisory control of sophisticated and remote and robotic systems is a complex, tiring, and non-intuitive activity. Since decontamination & decommissioning, selective equipment removal, mixed waste operations, and in-tank cleanup are going to be a major future activity in DOE environmental restoration and waste management cleanup agenda, it seems necessary to utilize an operator control station and interface which maximizes operator comfort and productivity.

  3. Gradient Optimization for Analytic conTrols - GOAT

    NASA Astrophysics Data System (ADS)

    Assémat, Elie; Machnes, Shai; Tannor, David; Wilhelm-Mauch, Frank

    Quantum optimal control becomes a necessary step in a number of studies in the quantum realm. Recent experimental advances showed that superconducting qubits can be controlled with an impressive accuracy. However, most of the standard optimal control algorithms are not designed to manage such high accuracy. To tackle this issue, a novel quantum optimal control algorithm have been introduced: the Gradient Optimization for Analytic conTrols (GOAT). It avoids the piecewise constant approximation of the control pulse used by standard algorithms. This allows an efficient implementation of very high accuracy optimization. It also includes a novel method to compute the gradient that provides many advantages, e.g. the absence of backpropagation or the natural route to optimize the robustness of the control pulses. This talk will present the GOAT algorithm and a few applications to transmons systems.

  4. Caffe con Troll: Shallow Ideas to Speed Up Deep Learning

    PubMed Central

    Hadjis, Stefan; Abuzaid, Firas; Zhang, Ce; Ré, Christopher

    2016-01-01

    We present Caffe con Troll (CcT), a fully compatible end-to-end version of the popular framework Caffe with rebuilt internals. We built CcT to examine the performance characteristics of training and deploying general-purpose convolutional neural networks across different hardware architectures. We find that, by employing standard batching optimizations for CPU training, we achieve a 4.5× throughput improvement over Caffe on popular networks like CaffeNet. Moreover, with these improvements, the end-to-end training time for CNNs is directly proportional to the FLOPS delivered by the CPU, which enables us to efficiently train hybrid CPU-GPU systems for CNNs. PMID:27314106

  5. Molecular classification of myeloproliferative neoplasms-pros and cons.

    PubMed

    Qureshi, Moosa; Harrison, Claire

    2013-12-01

    Dameshek first postulated a common myeloproliferative heritage for the myeloproliferative disorders, now termed neoplasms. This prescient observation was validated by the description of a common mutation in exon 14 of JAK2 for patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis. In recent years, our knowledge of the molecular abnormalities underpinning these disorders has expanded significantly. At the same time, we have continued to use a classification based largely upon the first clinical descriptions of these entities, which sometimes proves problematic in differentiating between these conditions and normal reactive processes, myelodysplasia and between the myeloproliferative neoplasm entities themselves. Here, we discuss the pros and cons of a molecular classification and its potential utility in diagnosis, prognosis, and therapeutics. PMID:24091831

  6. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J. ); Do Van Luu; Lee, E.K.; Hong, S.S. )

    1996-01-01

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  7. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J.; Do Van Luu; Lee, E.K.; Hong, S.S.

    1996-12-31

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  8. Tramadol hydro­chloride–benzoic acid (1/1)

    PubMed Central

    Siddaraju, B. P.; Jasinski, Jerry P.; Golen, James A.; Yathirajan, H. S.; Raju, C. R.

    2011-01-01

    In the cation of the title co-crystal salt {systematic name: [2-hydroxy-2-(3-meth­oxy­phen­yl)cyclo­hexyl­meth­yl]dimethyl­aza­nium chloride–benzoic acid (1/1)}, C16H31NO2 +·Cl−·C7H6O2, the N atom is protonated and the six-membered cyclo­hexane ring adopts a slightly distorted chair conformation. The dihedral angle between the mean planes of the benzene rings in the cation and the benzoic acid mol­ecule is 75.5 (9)°. The crystal packing is stabilized by weak inter­molecular O—H⋯Cl, N—H⋯Cl and C—H⋯π inter­actions, forming a two-dimensional chain network along the b axis. The benzoic acid mol­ecule is not involved in the usual head-to-tail dimer bonding, but instead is linked to the ammonium cation through mutual hydrogen-bonding inter­actions with the chloride anion. PMID:22058967

  9. Opciones de cirugía para mujeres con CDIS o con cáncer de seno- página de publicaciones

    Cancer.gov

    Contiene información sobre los tipos de cirugía de seno, como la operación para conservar el seno y la mastectomía, y ayuda a las mujeres diagnosticadas con CDIS o con cáncer de seno a decidir cuál cirugía es la más conveniente para ellas.

  10. Investigation on the conA binding properties of Klebsiella pneumoniae.

    PubMed

    Anuar, A S S; Tay, S T

    2014-12-01

    Klebsiella pneumoniae is a healthcare-associated bacterial pathogen which causes severe diseases in immunocompromised individuals. Concanavalin A (conA), a lectin which recognizes proteins with mannose or glucose residues, has been reported to agglutinate K. pneumoniae and hence, is postulated to have therapeutical potential for K. pneumoniae-induced liver infection. This study investigated the conA binding properties of a large collection of clinical isolates of K. pneumoniae. ConA agglutination reaction was demonstrated by 94 (51.4%) of 183 K. pneumoniae isolates using a microtiter plate assay. The conA agglutination reactions were inhibited in the presence of 2.5 mg/ml D-mannose and 2.5 mg/ml glucose, and following pretreatment of the bacterial suspension with protease and heating at 80ºC. Majority of the positive isolates originated from respiratory specimens. Isolation of conA-binding proteins from K. pneumoniae ATCC 700603 strain was performed using conA affinity column and the conA binding property of the eluted proteins was confirmed by western blotting analysis using conA-HRP conjugates. Proteins with molecular weights ranging from 35 to 60 kDa were eluted from the conA affinity column, of which four were identified as outer membrane protein precursor A (37 kDa), outer membrane protein precursor C (40 kDa), enolase (45 kDa) and chaperonin (60 kDa) using mass spectrometry analysis. Several conA binding proteins (including 45 and 60 kDa) were found to be immunogenic when reacted with rabbit anti-Klebsiella antibody. The function and interplay of the conA binding proteins in bacterium-host cell relationship merits further investigation. PMID:25776607

  11. Control del dolor: Apoyo para las personas con cáncer

    Cancer.gov

    Contiene información sobre las medicinas contra el dolor para pacientes con cáncer, los planes para controlarlo, cómo hablar con su equipo de atención médica sobre el dolor que usted siente y qué hacer para controlar los efectos físicos y emocionales del

  12. Gestational surrogacy: could be a way to be a way to reproduction? Pros and cons.

    PubMed

    Clementina, Peris

    2011-06-01

    The aim of this article was to address pros and cons of gestational surrogacy, the social and psychological issues involved in surrogate motherhood triads. Pros and cons of surrogacy, the possible insurgence of a hematologic disease in the fetus, hemolytic disease of the newborn, naturally acquired microchimerism in surrogacy cases, ethical, medical, psychologic, legal and religious issues of a problem are discussed. PMID:21778533

  13. Pruebas de BRCA en pacientes jóvenes con cáncer

    Cancer.gov

    Pruebas de mutaciones genéticas fuertemente asociadas con un mayor riesgo de cáncer de seno han aumentado dramáticamente entre mujeres menores de 40 años diagnosticadas con la enfermedad, según un nuevo estudio.

  14. ConSearch: An Electronic Document Research and Retrieval Utility for Windows from Management Information Technologies.

    ERIC Educational Resources Information Center

    Combs, Joseph, Jr.

    1995-01-01

    Reviews ConSearch 3.0, a product that provides flexible searching of electronic files, allowing the location of related meanings as well as exact matches. ConSearch 3.0 differs from other file retrieval approaches by relating words in search phrases of questions to the "meaning" of the words, which are stored in a "conceptual database," or lexicon…

  15. Meeting Report: Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    EPA Science Inventory

    The Pittsburgh Conference and Exposition, or "PittCon" (www.pittcon.org/), is one of the largest international conferences for analytical chemistry and instrumentation typically attracting about 25,000 attendees and 1,000 commercial exhibitors. PittCon began in 1950 as a small sp...

  16. Pros and Cons of Medical Management of Ulcerative Colitis

    PubMed Central

    Navaneethan, Udayakumar; Shen, Bo

    2010-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffuse mucosal inflammation limited to the colon and rectum. Although a complete medical cure may not be possible, UC can be treated with medications that induce and maintain remission. The medical management of this disease continues to evolve with a goal to avoid colectomy and ultimately alter the natural history of UC. Emergence of antitumor necrosis factor-α (TNF-α) agents has expanded the medical armamentarium. 5-Aminosalicylates continue to be used in mild to moderate UC and corticosteroids are mainly used for induction of remission with immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as steroid-sparing agents for maintenance therapy. Infliximab has been approved by the U.S. Food and Drug Administration and used in the treatment of moderate to severe UC; nevertheless, its use may be associated with significant adverse effects and have a negative impact on the postoperative course should the patients undergo restorative proctocolectomy. In addition, there is always a concern about patients' compliance to medical therapy, cost of medications, and risk for UC-associated dysplasia. The authors discuss the pros and cons of medications used in the treatment of UC. PMID:22131893

  17. Pros, Cons, and Alternatives to Weight Based Cost Estimating

    NASA Technical Reports Server (NTRS)

    Joyner, Claude R.; Lauriem, Jonathan R.; Levack, Daniel H.; Zapata, Edgar

    2011-01-01

    Many cost estimating tools use weight as a major parameter in projecting the cost. This is often combined with modifying factors such as complexity, technical maturity of design, environment of operation, etc. to increase the fidelity of the estimate. For a set of conceptual designs, all meeting the same requirements, increased weight can be a major driver in increased cost. However, once a design is fixed, increased weight generally decreases cost, while decreased weight generally increases cost - and the relationship is not linear. Alternative approaches to estimating cost without using weight (except perhaps for materials costs) have been attempted to try to produce a tool usable throughout the design process - from concept studies through development. This paper will address the pros and cons of using weight based models for cost estimating, using liquid rocket engines as the example. It will then examine approaches that minimize the impct of weight based cost estimating. The Rocket Engine- Cost Model (RECM) is an attribute based model developed internally by Pratt & Whitney Rocketdyne for NASA. RECM will be presented primarily to show a successful method to use design and programmatic parameters instead of weight to estimate both design and development costs and production costs. An operations model developed by KSC, the Launch and Landing Effects Ground Operations model (LLEGO), will also be discussed.

  18. Surgical animal models of neuropathic pain: Pros and Cons.

    PubMed

    Challa, Siva Reddy

    2015-03-01

    One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain. PMID:24831263

  19. Determination of composition in stoichiometric Co-N ultrathin films by nitrogen plasma sputtering

    NASA Astrophysics Data System (ADS)

    Su, C. W.; Huang, M. S.; Chang, Y. C.; Tsai, T. H.; Lee, Y. H.; Lee, J. C.

    2009-02-01

    This work utilizes low-energy sputtering to incorporate the generated nitrogen plasma into an epitaxial 1.4nm Co film on the surface of a ZnO(002) substrate. In this method, ultrathin Co-N amorphous films were formed. Interestingly, Co is key to the formation of Co-N films. Without the deposition of Co on the ZnO(002), nitride films cannot be formed. Observations of the surface composition of the Co-N films after the firing of a N+ ion beam onto it demonstrated that the surface concentration of Co reduced at the same rate as the reduction in the concentration of N upon successive sputtering. Theoretical calculations based on the Auger peak-to-peak amplitudes established that the composition of the amorphous Co-N thin films may be Co3N2.

  20. The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM)

    Cancer.gov

    The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM) was formed to promote international, multidisciplinary collaborations to advance our understanding of the etiology and outcomes of kidney cancer.

  1. CONspiracies to crush competition. Hospitals using CON laws to thwart rival's projects.

    PubMed

    Burda, D

    1991-07-01

    In their eagerness to protect their market share and check advances by rivals, hospitals are trying to use state certificate-of-need laws to their advantage. Some hospitals are clinging to CON laws, which require state approval of new construction and renovation, because they protect them from competitors who threaten their market. A look into CON wars in five states uncovers some competitive tactics. PMID:10111448

  2. Evaluation of the ACT*DE*CON{sup SM} process for treating gunite tank sludge

    SciTech Connect

    Spencer, B.B.; Chase, C.W.; Egan, B.Z.

    1996-05-01

    A test was conducted to evaluate this process for selectively removing actinides from Gunite tank sludge. Mixed waste sludge from Gunite tank W-6 was subjected to the ACT*DE*CON selective leaching process. (Nearly all the TRU content was attributed to Pu.) The sludge sample was first washed with 0.01M NaOH to remove excess sodium and nitrate in the interstitial liquid supernatant. The washed wet solids were treated with the ACT*DE*CON solvent (aqueous carbonate solution containing a chelating agent and an oxidant), using a ratio of 20 ml solvent per gram wet solids. Sludge and solvent were separated by centrifugation, and the ACT*DE*CON treatment was repeated twice. Analyses showed that 71% of the solids in the sludge were dissolved while 80% of the TRU-waste components dissolved. Low separation of the TRU-waste components from other components of the sludge mixture is indicated. Almost all the U and Ca were removed from the sludge. For sludges where most of the TRU content is Pu, the ACT*DE*CON process as tested is not effective in rendering the sludge a non-TRU waste. It is recommended that ACT*DE*CON be optimized for this specific application and that other processes using different chelating and oxidizing agents be tested. Also, the ACT*DE*CON process should be tested on TRU mixed waste in which most of the TRU elements are not Pu.

  3. SLUDGE PARTICLE SEPAPATION EFFICIENCIES DURING SETTLER TANK RETRIEVAL INTO SCS-CON-230

    SciTech Connect

    DEARING JI; EPSTEIN M; PLYS MG

    2009-07-16

    The purpose of this document is to release, into the Hanford Document Control System, FA1/0991, Sludge Particle Separation Efficiencies for the Rectangular SCS-CON-230 Container, by M. Epstein and M. G. Plys, Fauske & Associates, LLC, June 2009. The Sludge Treatment Project (STP) will retrieve sludge from the 105-K West Integrated Water Treatment System (IWTS) Settler Tanks and transfer it to container SCS-CON-230 using the Settler Tank Retrieval System (STRS). The sludge will enter the container through two distributors. The container will have a filtration system that is designed to minimize the overflow of sludge fines from the container to the basin. FAI/09-91 was performed to quantify the effect of the STRS on sludge distribution inside of and overflow out of SCS-CON-230. Selected results of the analysis and a system description are discussed. The principal result of the analysis is that the STRS filtration system reduces the overflow of sludge from SCS-CON-230 to the basin by roughly a factor of 10. Some turbidity can be expected in the center bay where the container is located. The exact amount of overflow and subsequent turbidity is dependent on the density of the sludge (which will vary with location in the Settler Tanks) and the thermal gradient between the SCS-CON-230 and the basin. Attachment A presents the full analytical results. These results are applicable specifically to SCS-CON-230 and the STRS filtration system's expected operating duty cycles.

  4. Virulence, Speciation and Antibiotic Susceptibility of Ocular Coagualase Negative Staphylococci (CoNS)

    PubMed Central

    Priya, Ravindran; Mythili, Arumugam; Singh, Yendremban Randhir Babu; Sreekumar, Haridas; Manikandan, Palanisamy; Panneerselvam, Kanesan

    2014-01-01

    Background: Coagulase negative Staphylococci (CoNS) are common inhabitants of human skin and mucous membranes. With the emergence of these organisms as prominent pathogens in patients with ocular infections, investigation has intensified in an effort to identify important virulence factors and to inform new approaches to treatment and prevention. Aim: To isolate CoNS from ocular specimens; to study the possible virulence factors; speciation of coagulase negative staphylococci (CoNS) which were isolated from ocular complications; antibiotic susceptibility testing of ocular CoNS. Materials and Methods: The specimens were collected from the target patients who attended the Microbiology Laboratory of a tertiary care eye hospital in Coimbatore, Tamilnadu state, India. The isolates were subjected to tube and slide coagulase tests for the identification of CoNS. All the isolates were subjected to screening for lipase and protease activities. Screening for other virulence factors viz., slime production on Congo red agar medium and haemagglutination assay with use of 96-well microtitre plates. These isolates were identified upto species level by performing biochemical tests such as phosphatase test, arginine test, maltose and trehalose fermentation tests and novobiocin sensitivity test. The isolates were subjected to antibiotic susceptibility studies, based on the revised standards of Clinical and Laboratory Standards Institutes (CLSI). Results: During the one year of study, among the total 260 individuals who were screened, 100 isolates of CoNS were obtained. Lipolytic activity was seen in all the isolates, whereas 38 isolates showed a positive result for protease. A total of 63 isolates showed slime production. Of 100 isolates, 30 isolates were analyzed for haemagglutination, where 4 isolates showed the capacity to agglutinate the erythrocytes. The results of the biochemical analysis revealed that of the 100 isolates of CoNS, 43% were Staphylococcus epidermidis. The other

  5. conSSert: Consensus SVM Model for Accurate Prediction of Ordered Secondary Structure.

    PubMed

    Kieslich, Chris A; Smadbeck, James; Khoury, George A; Floudas, Christodoulos A

    2016-03-28

    Accurate prediction of protein secondary structure remains a crucial step in most approaches to the protein-folding problem, yet the prediction of ordered secondary structure, specifically beta-strands, remains a challenge. We developed a consensus secondary structure prediction method, conSSert, which is based on support vector machines (SVM) and provides exceptional accuracy for the prediction of beta-strands with QE accuracy of over 0.82 and a Q2-EH of 0.86. conSSert uses as input probabilities for the three types of secondary structure (helix, strand, and coil) that are predicted by four top performing methods: PSSpred, PSIPRED, SPINE-X, and RAPTOR. conSSert was trained/tested using 4261 protein chains from PDBSelect25, and 8632 chains from PISCES. Further validation was performed using targets from CASP9, CASP10, and CASP11. Our data suggest that poor performance in strand prediction is likely a result of training bias and not solely due to the nonlocal nature of beta-sheet contacts. conSSert is freely available for noncommercial use as a webservice: http://ares.tamu.edu/conSSert/ . PMID:26928531

  6. ConA-based glucose sensing using the long-lifetime azadioxatriangulenium fluorophore

    NASA Astrophysics Data System (ADS)

    Cummins, Brian; Simpson, Jonathan; Gryczynski, Zygmunt; Sørensen, Thomas Just; Laursen, Bo W.; Graham, Duncan; Birch, David; Coté, Gerard

    2014-02-01

    Fluorescent glucose sensing technologies have been identified as possible alternatives to current continuous glucose monitoring approaches. We have recently introduced a new, smart fluorescent ligand to overcome the traditional problems of ConA-based glucose sensors. For this assay to be translated into a continuous glucose monitoring device where both components are free in solution, the molecular weight of the smart fluorescent ligand must be increased. We have identified ovalbumin as a naturally-occurring glycoprotein that could serve as the core-component of a 2nd generation smart fluorescent ligand. It has a single asparagine residue that is capable of displaying an N-linked glycan and a similar isoelectric point to ConA. Thus, binding between ConA and ovalbumin can potentially be monovalent and sugar specific. This work is the preliminary implementation of fluorescently-labeled ovalbumin in the ConA-based assay. We conjugate the red-emitting, long-lifetime azadioxatriangulenium (ADOTA+) dye to ovalbumin, as ADOTA have many advantageous properties to track the equilibrium binding of the assay. The ADOTA-labeled ovalbumin is paired with Alexa Fluor 647-labeled ConA to create a Förster Resonance Energy Transfer (FRET) assay that is glucose dependent. The assay responds across the physiologically relevant glucose range (0-500 mg/dL) with increasing intensity from the ADOTA-ovalbumin, showing that the strategy may allow for the translation of the smart fluorescent ligand concept into a continuous glucose monitoring device.

  7. ConSole: using modularity of Contact maps to locate Solenoid domains in protein structures

    PubMed Central

    2014-01-01

    Background Periodic proteins, characterized by the presence of multiple repeats of short motifs, form an interesting and seldom-studied group. Due to often extreme divergence in sequence, detection and analysis of such motifs is performed more reliably on the structural level. Yet, few algorithms have been developed for the detection and analysis of structures of periodic proteins. Results ConSole recognizes modularity in protein contact maps, allowing for precise identification of repeats in solenoid protein structures, an important subgroup of periodic proteins. Tests on benchmarks show that ConSole has higher recognition accuracy as compared to Raphael, the only other publicly available solenoid structure detection tool. As a next step of ConSole analysis, we show how detection of solenoid repeats in structures can be used to improve sequence recognition of these motifs and to detect subtle irregularities of repeat lengths in three solenoid protein families. Conclusions The ConSole algorithm provides a fast and accurate tool to recognize solenoid protein structures as a whole and to identify individual solenoid repeat units from a structure. ConSole is available as a web-based, interactive server and is available for download at http://console.sanfordburnham.org. PMID:24766872

  8. Structural basis of ConM binding with resveratrol, an anti-inflammatory and antioxidant polyphenol.

    PubMed

    Rocha, Bruno A M; Teixeira, Claudener S; Silva-Filho, José C; Nóbrega, Raphael B; Alencar, Daniel B; Nascimento, Kyria S; Freire, Valder N; Gottfried, Carmem J S; Nagano, Celso S; Sampaio, Alexandre H; Saker-Sampaio, Silvana; Cavada, Benildo S; Delatorre, Plínio

    2015-01-01

    Resveratrol can also inhibit the activation of proinflammatory mediators and cytokines at the early gene expression stage. It is well known that lectins are sugar-binding proteins that act as both pro- and anti-inflammatory molecules. Thus, the objective of this work was to verify the binding of a polyphenol compound with a lectin of Canavalia maritima (ConM) based on their ability to inhibit pro-inflammatory processes. To accomplish this, ConM was purified and crystallized, and resveratrol was soaked at 5mM for 2h of incubation. The crystal belongs to the monoclinic space group C2, the final refinement resulted in an Rfactor of 16.0% and an Rfree of 25.5%. Resveratrol binds in the rigid β-sheet through H-bonds and hydrophobic interaction with amino acids that compose the fifth and sixth β-strands of the rigid β-sheet of ConM. The ConM and resveratrol inhibited DPPH oxidation, showing synergic activity with the most effective ratio of 2:3 and carbohydrate binding site is not directly related to antioxidant activity. It is the interaction between ConM and resveratrol that indicates the synergism of these two molecules in acting as free radicals scavengers and in reducing the inflammatory process through the inhibition of many pro-inflammatory events. PMID:25192853

  9. Orbit and spin resolved magnetic properties of size selected [ConRh]⁺ and [ConAu]⁺ nanoalloy clusters.

    PubMed

    Dieleman, Dennis; Tombers, Matthias; Peters, Lars; Meyer, Jennifer; Peredkov, Sergey; Jalink, Jeroen; Neeb, Matthias; Eberhardt, Wolfgang; Rasing, Theo; Niedner-Schatteburg, Gereon; Kirilyuk, Andrei

    2015-11-14

    Bi-metallic nanoalloys of mixed 3d-4d or 3d-5d elements are promising candidates for technological applications. The large magnetic moment of the 3d materials in combination with a high spin-orbit coupling of the 4d or 5d materials give rise to a material with a large magnetic moment and a strong magnetic anisotropy, making them ideally suitable in for example magnetic storage devices. Especially for clusters, which already have a higher magnetic moment compared to the bulk, these alloys can profit from the cooperative role of alloying and size reduction in order to obtain magnetically stable materials with a large magnetic moment. Here, the influence of doping of small cobalt clusters on the spin and orbital magnetic moment has been studied for the cations [Co(8-14)Au](+) and [Co(10-14)Rh](+). Compared to the undoped pure cobalt [Co(N)](+) clusters we find a significant increase in the spin moment for specific Co(N-1)Au(+) clusters and a very strong increase in the orbital moment for some Co(N-1)Rh(+) clusters, with more than doubling for Co12Rh(+). This result shows that substitutional doping of a 3d metal with even just one atom of a 4d or 5d metal can lead to dramatic changes in both spin and orbital moment, opening up the route to novel applications. PMID:26104269

  10. Pros and cons of quitting, self-efficacy, and the stages of change in smoking cessation.

    PubMed

    Dijkstra, A; de Vries, H; Bakker, M

    1996-08-01

    In The Netherlands, 34% of the population smoke, and 70% of these smokers are not planning to quit. The lower percentages in the U.S. population seem to reflect a difference in smoking culture. This study analyzes the pros and cons of quitting and self-efficacy expectation in the 5 stages of change in the Dutch population. The results are compared with the pattern of the pros and cons of smoking and self-efficacy expectations found in U.S. samples. The data show the hypothesized pattern: In the first 2 stages, the expected positive outcomes of quitting discriminated better between the stages than self-efficacy, whereas for later stages, self-efficacy was the better discriminator. This study shows that the stage typology is applicable to the Dutch population and that the pattern of the pros, cons, and self-efficacy is very similar to the pattern found in the U.S. populations. PMID:8803366