Withdrawal characteristics following frequent intravenous administration of several opioids in rats

Characteristics of withdrawal signs of several opioids were compared in rats after short-term frequent intravenous infusions. Male Sprague-Dawley rats with catheters implanted in the jugular veins were infused with a fixed dose of a drug hourly for 72 hrs. Thirty min after the final infusion, naloxone 4 mg/kg, s.c. was administered and withdrawal signs were observed for 1 hr and the severity of the withdrawal signs was scored, classified into a behavioral sign score, autonomic sign score, and body weight loss score. As a result, total withdrawal scores of morphine, methadone, d-propoxyphene, loperamide, Tramadol ( Generic Ultram ), and pentazocine were significantly higher than that of saline, with the highest score being observed for 4 mg/kg or more of morphine. The total score of ethylketocyclazocine was slightly but significantly higher than that of saline. Buprenorphine and thebaine produced no observable withdrawal signs. The behavioral sign score tended to be higher than the other 2 scores in the drugs showing relatively low but significant total scores such as Tramadol ( Generic Ultram ), pentazocine, and ethylketocyclazocine, while the score of autonomic signs or the body weight loss tended to be higher in drugs showing high total scores. Thus, in the case of opioids, it is considered that the severity of withdrawal signs was mainly derived from the autonomic signs including diarrhea which may result in body weight loss.


Population pharmacokinetic modelling of Tramadol ( Generic Ultram ) with application of the NPEM algorithms.Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Jelliffe RW.Department of Pharmacology, School of Medical Science, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. BACKGROUND AND OBJECTIVE: Although the kinetic behaviour of Tramadol ( Generic Ultram ) has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of Tramadol ( Generic Ultram ) hydrochloride. METHODS: The parametric Iterative Two-stage Bayesian Population Model (IT2B) program followed by the Non-parametric Expectation Maximization Population Model (NPEM2) program was used to determine population pharmacokinetic parameter values of Tramadol ( Generic Ultram ) in 138 postoperative orthopaedic Malaysian patients. All patients had received a 100 mg intravenous dose of Tramadol ( Generic Ultram ), infused over 2-3 min, as their first postoperative analgesic. Blood was sampled at 0 min and subsequently at 15, 30 min, 1, 2, 4, 8, 16, 20 and 24 h for serum Tramadol ( Generic Ultram ) high-performance liquid chromatography analysis. RESULTS AND DISCUSSION: The one-compartmental model pharmacokinetic parameters--volume of distribution (Vd), elimination rate constant (kel) and the total clearance rates (ClT)--found were: mean Vd = 167.6 +/- 63.84 L; median Vd = 161.48 L; mean kel = 0.1241 +/- 0.056 h(-1); median kel = 0.1138 h(-1); ClT = 19.57 +/- 9.51 L/h; median ClT =18.12 L/h. The interindividual coefficient of variation of ClT (48.56%) was higher than that of Vd (38.09%), indicating the presence of other possible influencing factors on Tramadol ( Generic Ultram )'s ClT such as CYP2D6 polymorphism, gender and age. Overall, NPEM2 suggested more diversity in the population than did IT2B.

Gas chromatographic method using nitrogen-phosphorus detection for the measurement of Tramadol ( Generic Ultram ) and its O-desmethyl metabolite in plasma and brain tissue of mice and rats.

The objectives of this study were first to investigate the compatibility and physical stability of drug admixtures destined for s.c. administration through elastomeric infusion pumps to terminally ill cancer patients followed up at home by staff of the Palliative Care Unit (AECC), "La Paz" Hospital, Madrid and secondly, to evaluate the local side-effects related to the infusion of some of the drug mixtures to a population of 50 patients. The drug mixtures prepared included combinations of two, three, four and five of the following drugs: morphine hydrochloride, 60 mg/day; midazolam hydrochloride, 15 mg/day; haloperidol lactate, 7.5 mg/day; hyoscine-N-butyl-bromide, 60 mg/day; dexamethasone sodium phosphate, 16 mg/day; metoclopramide hydrochloride, 40 mg/day, and Tramadol ( Generic Ultram ), 400 mg/day. Out of 86 mixtures evaluated in vitro, 52 were found to be physically compatible. Precipitation was always obtained when dexamethasone sodium phosphate at the concentrations assayed was combined with haloperidol lactate and/or midazolam hydrochloride. However, no precipitation occurred when morphine hydrochloride, the opioid most frequently used in patients of this type, and dexamethasone sodium phosphate were combined. Of the drug mixtures that were physically compatible, 18 were administered to the patient population evaluated. Very good symptom control was obtained with all of them, and especially with the mixture of morphine + midazolam + haloperidol + hyoscine, which is the one most frequently administered to cancer patients for palliative care in the final stages of life in our Unit.


The pupillary effects of intravenous morphine, codeine, and Tramadol ( Generic Ultram ) in volunteers.Knaggs RD, Crighton IM, Cobby TF, Fletcher AJ, Hobbs GJ.University Department of Anaesthesia, Queen's Medical Centre, University Hospital, Nottingham, UK.Opioid analgesics have pharmacological effects in many organ systems, including the eye. Because the metabolites of morphine and codeine contribute to their overall pharmacological effect pupil diameter measurements were made over a 6-h period. We studied the pupillary effects of IV morphine (0.125 mg/kg), codeine (1 mg/kg), Tramadol ( Generic Ultram ) (1.25 mg/kg), or placebo (10 mL 0.9% w/v sodium chloride) in 10 healthy volunteers. Pupil diameter was measured every 30 min using a pupil densitometer. Comparisons of the change in pupil diameter for each drug were made using analysis of variance with repeated measures. No significant change in pupil diameter was observed after placebo. After IV morphine and codeine administration there was a 26% decrease in pupil diameter (P < 0.001). Over the course of the study period, pupil diameter gradually returned to baseline values. After administration of Tramadol ( Generic Ultram ) there were no significant changes in pupil diameter until 150 min after administration, after which there was a significant reduction for the remainder of the study period (P < 0.01). The changes in pupil diameter may be explained in part by the pharmacokinetic profiles of the opioids studied. Measurement of pupil diameter may have a place in monitoring the central effect of opioids.

Changes in the pattern of opioid analgesic consumption in Spain

BACKGROUND: Data from different sources have proved an infrautilization of opioid analgesics in Spain. A descriptive study has been conducted in order to know the utilization of these drugs and changes in the pattern of use in the last few years. MATERIAL AND METHOD: To know the consume of narcotic analgesic drugs, N02A group of the Anatomic Therapeutic Classification, a search was developed in the ECOM database from the Spanish Ministry of Health. This database contains information of drug preparations prescribed throughout the National Health Care System. RESULTS: The consumption of opioid analgesics in Spain has been multiplied by 5.2 during this period. It has increased from 94.7 defined daily dose per 1,000,000 inhabitants in 1985 to 489.4 in 1994. The most consumed drug in 1994 was dihydrocodeine, followed by Tramadol ( Generic Ultram ). The number of defined daily dose per inhabitant and day of parenteral administration have decreased during the last years. CONCLUSIONS: Availability of new analgesic opioid drugs with better pharmacokinetic profiles has contributed to an increase of their consume in Spain.

The antinociceptive effect of Tramadol ( Generic Ultram ) on a model of neuropathic pain in rats.

BACKGROUND: The introduction of the laparoscopic approach to bariatric surgery has brought similar advantages as those seen in general surgery. There have been no trials assessing postoperative pain after laparoscopic adjustable silicone gastric banding (LASGB). We compared prospectively postoperative pain and outcome in LASGB and laparoscopic cholecystectomy (LC), to determine if morbidly obese patients can expect the same benefits from a laparoscopic approach in gastric banding as those which are known for LC in non-obese and obese patients. METHODS: In a prospectively collected database of 80 patients undergoing LASGB, information including a survey assessing the postoperative pain, the amount of analgetic drugs used, operative reports, laboratory data, and follow-up data was collected. This was compared to an equal number of patients undergoing LC. Postoperatively, all patients received standardized pain medication of 150 mg Tramadol ( Generic Ultram ) per day. Pain was assessed twice on postoperative days 1-3 using a patient questionnaire. RESULTS: Patient characteristics and duration of hospital stay were similar in the two groups. Although there was no significant difference in type and intensity of pain experienced by the patients in either group, the gastric banding patients reported less postoperative pain overall than those in the LC group. CONCLUSION: The analyzed data show that LASGB offers the same advantages as other laparoscopic operations, in that it induces less pain and enables the patient to return quickly to normal activity and work. The advantage over the compared LC group may be due to higher patient motivation, but was not statistically significant.