Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: a comprehensive report on seven consecutive studies.

Various monoolein-water systems containing Tramadol ( Generic Ultram ) HCl, a potent analgesic, were formulated to obtain sustained-release dosage forms which could be administered by subcutaneous, intramuscular or intrathecal injections. They were examined for their in vitro drug-release profiles and in vivo analgesic properties in rats in a 14 h period following intramuscular administration. In order to obtain a lower viscosity, we have substituted a part of monoolein by oleic acid and phospholipids. Both binary (monoolein-water) and quaternary (oleic acid-phospholipid-monoolein-water) formulations exhibited controlled drug-release profiles which were accelerated by surfactant adjunction. This surfactant action was probably due to structural changes in the lipid arrangement and was much more pronounced for the modified formulations. According to the results obtained in vitro, formulations with slower drug release (i.e. the native formulation and the modified one without surfactant) were selected for assessment of their in vivo properties. Both formulations demonstrated prolonged analgesic activities in the rat tail flick test manifested by stable pain relief during more than 10 h compared with the 3 to 4 h analgesia obtained with the commercially available Tramadol ( Generic Ultram ) HCl solution. The sustained-release capabilities were evaluated by using a modified half value duration (HVD) ratio and all sustained-released formulations exhibited a HVD ratio equal or superior to 3.9.

Opioid use by patients in an orthopedics spine clinic.Mahowald ML, Singh JA, Majeski P.Minneapolis VAMC, and the University of Minnesota, Minneapolis.OBJECTIVE: Concerns regarding the efficacy, toxicity, tolerance, dependence, and abuse of opioids have limited their use for patients with chronic spine pain. In our previous study of rheumatology clinic patients, opioid analgesics were found to be highly effective, produced only mild side effects, and had few instances of opioid abuse. The purpose of this study was to replicate our previous study in another large cohort of patients with nonmalignant pain due to well-defined spinal diseases. METHODS: Opioid use was studied in 230 orthopedics spine clinic patients by retrospective analysis of prescriptions for 3 years and cross-sectional analysis of efficacy and toxicity by patient interviews. Opioid use and stability of the daily dose over 3 years were derived from computerized pharmacy records. Medical records, operative reports, and radiographic studies were reviewed to determine the reason for dosage escalations and to detect instances of abuse or addiction behaviors. Patients were interviewed to determine the efficacy, frequency, and types of side effects and instances of obtaining opioids from sources outside the Veterans Affairs system. RESULTS: Opioids were prescribed for 152 of the 230 patients, for <3 months (short-term [STO]) in 94, >/=3 months (long-term [LTO]) in 58, and none in 72 (no opioid [NTO]). Medications prescribed were codeine, oxycodone, propoxyphene, Tramadol ( Generic Ultram ), morphine, meperidine, fentanyl, or hydroxycodone, either alone or in combination. Interviews were completed in 72 STO, 50 LTO, and 45 NTO patients. Pain severity (0-10 scale) was not different in patients with different spinal pathologies. Opioids significantly reduced the back pain severity score from 8.3 +/- 1.5 to 4.5 +/- 2.2 (mean +/- SD). Mild side effects (most commonly, constipation and sedation) were reported by 58% of the opioid-treated patients but rarely caused them to stop taking the medication. There was no significant increase from the mean +/- SD initial opioid dosage of 5.0 +/- 12.2 30-mg codeine equivalents per day (30 mg oral codeine = 5 mg oral morphine) to the mean peak dosage of 7.9 +/- 12.5 and the mean recent dosage of 4.3 +/- 6.3, suggesting that tolerance to opioid analgesia did not appear to occur in these patients. Dosage escalations of >2 30-mg codeine equivalents occurred 19 times in 17 LTO patients and was due to worsening of the underlying painful condition, complications of spine surgery, or unrelated surgical or medical problems in all but 3 of them (5%). These 3 patients also displayed other abuse behaviors. Abuse behaviors were not more frequent in those with or without a history of abuse/addiction. CONCLUSION: This study provides data on the efficacy, toxicity, tolerance, and abuse or addiction behaviors with opioid therapy in a large cohort of patients in an orthopedics spine clinic. The results provide objective data from patients with well-defined spine diagnoses to challenge the position that opioid treatment is inappropriate for chronic nonmalignant pain. This study provides clinical evidence to support and protect physicians treating patients with chronic musculoskeletal diseases, who may be reluctant to prescribe opioids because of possible sanctions from regulatory agencies. More important, it will benefit patients by permitting them to receive these effective, safe medications.

Radioelectroencephalography (Tele-Stereo-EEG) in the rat as a pharmacological model to differentiate the central action of flupirtine from that of opiates, diazepam and phenobarbital.

Chronic implantation of 4 bipolar concentric electrodes into frontal cortex, thalamus, striatum and reticular formation allowed repeated recordings of field potentials from freely moving rats. After radiotransmission the signals were quantitatively evaluated by spectral power analysis. The power in particular frequency bands changed in the presence of drugs in a characteristic manner and allowed us to describe the central action of analgesics in comparison with diazepam and phenobarbital. Analysis of the data showed that the action of diazepam was mainly confined to alpha 1 and beta 2 frequencies whereas Tramadol ( Generic Ultram ) acted predominantly on the theta and alpha range. Buprenorphine and morphine most consistently influenced the alpha 2 frequencies. Whereas buprenorphine and Tramadol ( Generic Ultram ) (2 opiate drugs) showed a striking similarity to the action of morphine in corresponding brain areas the minor tranquilizer diazepam and the anticonvulsive phenobarbital could clearly be separated from them. Flupirtine, a new analgesic not suspected of an opiate-like action profile, did not resemble any of them and thus could be confirmed to have a different mode of action.


Preoperative intravenous Tramadol ( Generic Ultram ) versus ketorolac for preventing postoperative pain after third molar surgery.Ong KS, Tan JM.Department of Oral & Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore. The objective of this study was to compare the analgesic efficacy of a single-dose of preoperative intravenous Tramadol ( Generic Ultram ) versus ketorolac in preventing pain after third molar surgery. Sixty-four patients undergoing elective third molar surgery were randomly assigned into one of the two groups (32 in each group): Group I received Tramadol ( Generic Ultram ) 50 mg, and Group 2 received ketorolac 30 mg intravenously preoperatively before the surgery. After injection of the study drugs, a standard intravenous sedation technique was administered and the impacted third molars were removed under local anaesthetic. The difference in postoperative pain was assessed by four primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 h, median time to rescue analgesic, postoperative acetaminophen consumption, and patient's global assessment. Throughout the 12-h investigation period, patients reported significantly lower pain intensity scores in the ketorolac versus Tramadol ( Generic Ultram ) group (P = 0.05, Mann-Whitney U-test). Patients also reported significantly longer median time to rescue analgesic (9.0 h versus 7.0 h, P = 0.007, log rank test), lesser postoperative acetaminophen consumption (P = 0.02, Mann-Whitney U-test) and better global assessment (P = 0.01, chi2 test) for the ketorolac versus Tramadol ( Generic Ultram ) group. Preoperative intravenous ketorolac 30 mg is more effective than Tramadol ( Generic Ultram ) 50 mg in the prevention of postoperative dental pain.

Synthesis and analgesic activity of some condensed analogs of anpirtoline.

AIM: To investigate the transportation of the enantiomers of trans Tramadol ( Generic Ultram ) (trans T) and its active metabolite, O-demethylTramadol ( Generic Ultram ) (M1) across blood-brain barrier. METHODS: Rats were sacrificed by femoral artery bleeding 1 h after i.p. administration of trans T hydrochloride, 16.7 mg.kg-1 or 50.0 mg.kg-1. Blood, cerebrospinal fluid and cerebral cortex were taken out. The enantiomers of trans T and M1 were analyzed by high performance capillary electrophoresis (HPCE). RESULTS: Among the three tissues, the concentration of each enantiomer of trans T and M1 was the highest in the cerebral cortex, and the lowest in the cerebrospinal fluid. In the serum, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of the enantiomers of M1 were similar. In the cerebrospinal fluid and cerebral cortex, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of (+)-M1 was lower than that of (-)-M1. CONCLUSION: The transportation across blood-brain barrier of the enantiomers of trans T and M1 was stereoselective. In the brain tissues, the concentrations of (+)-trans T and (-)-M1 were higher than those of their enantiomers.

Nonsteroidal antirheumatics (NSAR; NSAID) are often used in patients with fractured bones for analgetic reasons. This animal experiment was performed to determine the influence of NSAR on the process of fracture healing. As an alternative, Tramadol ( Generic Ultram ), the centrally acting analgetic without peripheral effects, was included in this experiment. MATERIALS AND METHODS: Wistar rats were operated on by a transverse osteotomy of the proximal tibia of the left leg. The fracture was stabilized by intramedullary nailing (healing period 21 days). All drugs were applied orally twice a day. The animals were divided into four groups with 10 rats each: Group 1 was treated with placebo (P), group 2 with Tramadol ( Generic Ultram ) (T; 20 mg/kg body weight/day), group 3 with diclofenac sodium (DS; 5 mg/kg bw/day) for 7 days followed by 14 days of placebo, group 4 with diclofenac sodium (DL; 5 mg/kgbw/day) over 21 days. On day 21 the rats were killed, and each leg was examined by X-ray, then the tibia was examined by CT scan, three-point bending, and histology. RESULTS: The results of CT and three-point bending showed that rats treated by diclofenac presented with delayed fracture healing compared with those treated by placebo or Tramadol ( Generic Ultram ). Bone density in CT was highest in group 1 (mean 611.4+/-50.1 mg/ml), followed by group 2 (mean 542.5+/-29.5 mg/ml). Groups 3 (mean 411+/-34.0 mg/ml; p=0.006) and 4 (mean 395.2+/-15.4 mg/ml; p=0.009) were significantly lower. The stability of the bones, as measured by the breaking force ( F(max)), was highest in group 1 (mean 45.8+/-19.0 N), followed by group 2 (mean 39.0+/-7.9 N; NS); group 3 (mean 20.6+/-7.8 N; p=0.01) was significantly lower than the placebo animals, followed by group 4 (mean 26.5+/-8.3 N; p=0.03). Similar results were shown for bending stiffness: group 1 (mean 1404.6+/-611.4 Nmm/mm), group 2 (mean 1033.2+/-232.1 Nmm/mm; NS), group 3 (mean 564.2+/-457 Nmm/mm; p=0.045), and group 4 (mean 494.8+/-340.2 Nmm/mm; p=0.028). There were no significant differences between groups 1 and 2 and between groups 3 and 4, respectively. Diclofenac serum levels on day 21 in rats with long-term diclofenac application (mean 301.4+/-83.3 ng/ml) were comparable to those in humans. CONCLUSION: Oral application of diclofenac significantly delayed fracture healing in rats. This effect might be comparable to other NSAR and fracture healing in humans.