Tramadol ( Generic Ultram ) in rats

Tramadol ( Generic Ultram ) is an important spinal drug which produces analgesia following intrathecal injection. It is well known that fatty acids (FAs) play an important role in membrane fluidity of the blood-brain barrier (BBB) tissue, which blocks and/or controls the transportation of toxic substances into the brain. The aim of this study was to investigate the effect of a spinal drug (Tramadol ( Generic Ultram )) on the concentrations and compositions of fatty acid in BBB tissues of New Zealand male rabbits. The total cellular fatty acid profiles of the tissues in three spinal cord sections (cervical, thoracal and lumbar) and in the brain of rabbits with or without drug administration were determined by gas chromatography using Sherlock Microbial Identification System (MIS) software (Microbial ID, Newark, DE, U.S.A.) with a database of FAME profiles for eukary. The relative percentage of the fatty acid methyl ester (FAME), 24 : 1 omega9c nervonic and 17 : 1 omega8c, did not change with Tramadol ( Generic Ultram ) treatments. However, there was an increase in the concentration of the FA 16 : 0, 18 : 1 omega7c DMA, 18 : 1 omega9c, sum in future 4, sum in future 8, sum in future 9, 18 : 0, 20 : 4 omega6c, sum in future 14, 22 : 4 omega6c, in contrast to a decrease in the percentages of the following FAMEs; 20 : 0, 20 : 1 omega9c. In the brain, there was an increase in the concentration of the FA 18 : 1 omega9c, sum in future 8 and 18 : 0, in contrast to a decrease in the percentages of two FAMEs, 16 : 0, 20 : 4 omega6c and 22 : 6 omega3c. The number of fatty acids were 20 in the spinal cord sections and 8 in the brain tissues of control animals compared to 15-18 fatty acids in the spinal cord section and 7 in the brain tissues of drug administered animals. The overall changes in the concentrations and numbers of FAs suggest that the spinal drug tested in this study has a side effect of disrupting of membrane fluidity of the BBB, which may cause neurotoxicity.

Analgesia for adenotonsillectomy in children: a comparison of morphine, ketamine and Tramadol ( Generic Ultram ).Umuroglu T, Eti Z, Ciftci H, Yilmaz Gogus F.Department of Anaesthesiology and Reanimation, Medical Faculty of Marmara University, Istanbul, Turkey. BACKGROUND: Establishment of good analgesia is of major concern in the postoperative period following adenotonsillectomy. The aim of this study was to compare the effects of ketamine, morphine and Tramadol ( Generic Ultram ) on postoperative pain after adenotonsillectomy in children. METHODS: Sixty children (age 5-12 years) scheduled for adenotonsillectomy were randomized into four groups to receive intravenously (i.v.) either 0.5 mg.kg(-1) ketamine hydrochloride (K), 0.1 mg x kg(-1) morphine hydrochloride (M), 1.5 mg x kg(-1) Tramadol ( Generic Ultram ) hydrochloride (T) or normal saline (S) in a volume of 4 ml during induction. After tracheal intubation 10 microg x kg(-1).min(-1) ketamine hydrochloride in group K and 0.6 ml x kg(-1) x h(-1) saline i.v. in groups M, K and S were infused peroperatively. Postoperative analgesic requirements and side-effects were recorded. Pain was assessed by the Numeric Rating Scale (NRS) and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores. RESULTS: Heart rate increased significantly peroperatively only in group K. NRS at first and fifth minute in group M and at first minute in group T and K and CHEOPS score at first, fifth, 15th and 60th min in group M were found to be significantly lower than in the control group. The time to first analgesic requirement was significantly longer in group M compared with ketamine and the control group. Six children in group M, nine in group T, 11 in group K and 15 in group S needed additional analgesics. CONCLUSIONS: Morphine hydrochloride 0.1 mg x kg(-1) i.v. administered during induction of anaesthesia provides efficient pain relief in children undergoing adenotonsillectomy.

Non-steroidal antiinflammatory drugs and Tramadol ( Generic Ultram ) in the treatment of osteoarthrosis deformans in patients with arterial hypertensionThe prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can be manifested by the decreased efficiency of antihypertensive therapy. The tactics of their differential use in relation to the its effect on blood pressure (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not been developed for the most effective and safe therapy. In this connection, it is extremely urgent to study the comparative safety of used NSAIDs as to their prohypertensive effect and to work out the management of patients with AH and OA. Ninety-eight patients with second-third degree OA of the knee and hip joints concurrent with the pain syndrome and first-second grade AH were followed up. Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a control group, the analgesic Tramadol ( Generic Ultram ) was supplemented to the therapy. AH was controlled by enalapril monotherapy. In groups of patients receiving diclofenac, arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the prohypertensive effect of these drugs; this trend was most pronounced in the diclofenac and arthrotec groups. Despite its marked prohypertensive effect, nimesulide did not impair circadian BP variations. The central-acting analgesic Tramadol ( Generic Ultram ) exerted no prohypertensive effect and it did not increase BP values. The prohypertensive effect of the tested NSAIDs and Tramadol ( Generic Ultram ) increases in the following order: Tramadol ( Generic Ultram ), ketoprofen, meloxicam, nimesulide, arthrotec, diclofenac.

Analgesic efficacy and safety of Tramadol ( Generic Ultram )/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial.Peloso PM, Fortin L, Beaulieu A, Kamin M, Rosenthal N; Protocol TRP-CAN-1 Study Group.Division of Rheumatology, Roy and Lucille Carver College of Medicine, University of Iowa Health Care E330 GH, 200 Hawkins Drive, Iowa City, IA 52242, USA. OBJECTIVE: To evaluate the analgesic efficacy and safety of Tramadol ( Generic Ultram ) 37.5 mg/acetaminophen 325 mg (Tramadol ( Generic Ultram )/APAP) combination tablets for treatment of chronic low back pain (LBP). METHODS: This 91 day, multicenter, outpatient, randomized, double blind, placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months. Patients with at least moderate pain [pain visual analog scale (VAS) with scores > or = 40/100 mm] after washout were randomized to Tramadol ( Generic Ultram )/APAP or placebo. After a 10 day titration, patients received 1 or 2 tablets QID. Primary outcome measure was final pain VAS score. Secondary measures included pain relief, quality of life and physical functioning, efficacy failure, and overall medication assessments. RESULTS: In total, 336 intent-to-treat patients received Tramadol ( Generic Ultram )/APAP (n = 167) or placebo (n = 169). Mean baseline pain VAS score was 67.8. Intent-to-treat analysis showed significantly better mean final pain VAS scores (47.4 vs 62.9; p < 0.001) and mean final pain relief scores (1.8 vs 0.7; p < 0.001) for Tramadol ( Generic Ultram )/APAP than for placebo. Roland Disability Questionnaire scores and physical-related subcategories of the McGill Pain Questionnaire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for Tramadol ( Generic Ultram )/APAP patients. More patients rated Tramadol ( Generic Ultram )/APAP as "very good" or "good" than placebo (63.6 vs 25.2%; p < 0.001). Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9% (Tramadol ( Generic Ultram )/APAP) vs 54.7% (placebo; p < 0.001). The most common treatment related adverse events with Tramadol ( Generic Ultram )/APAP were nausea (12.0%), dizziness (10.8%), and constipation (10.2%). Average daily dose of Tramadol ( Generic Ultram )/APAP was 4.2 tablets (Tramadol ( Generic Ultram ) 158 mg/APAP 1369 mg). CONCLUSION: Tramadol ( Generic Ultram ) 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction, in measures of physical functioning and quality of life, and in overall medication assessments, with a tolerability profile comparable with other opioids used for the treatment of chronic LBP.

Probable ischemic colitis caused by pseudoephedrine with Tramadol ( Generic Ultram ) as a possible contributing factor.Traino AA, Buckley NA, Bassett ML.The Prince of Wales Hospital, Randwick, Sydney, Australia.OBJECTIVE: To report a case of acute self-limiting ischemic colitis in a patient who was self-medicating with a proprietary over-the-counter oral decongestant containing pseudoephedrine. CASE SUMMARY: A 46-year-old white man developed clinical, endoscopic, and histologic features of acute ischemic colitis after taking a proprietary oral decongestant containing pseudoephedrine 240 mg/day for one week. The total daily dose was at the upper limit of recommended doses for pseudoephedrine (as a single drug or in combination products). The patient was also taking Tramadol ( Generic Ultram ) 150 mg/day for chronic back pain. He made a complete recovery. There were no other explanations for the episode of ischemic colitis. DISCUSSION: An objective causality assessment based on the Naranjo probability scale revealed pseudoephedrine to be a probable cause of ischemic colitis in our patient. Pseudoephedrine occasionally causes vascular insufficiency due to intense vasoconstriction, even at standard doses. Although our patient was not taking an excessive dose of pseudoephedrine, it is possible that the concurrent use of pseudoephedrine and Tramadol ( Generic Ultram ) may have increased adrenergic vasoconstriction, predisposing to ischemic colitis. CONCLUSIONS: Prolonged or intensive use of medications containing pseudoephedrine should be avoided, and the package information should contain advice that the medication should be ceased if abdominal pain or other ischemic symptoms occur.

Diabetic neuropathy: an intensive review.

PURPOSE: The epidemiology, classification, pathology, and treatment of diabetic neuropathy are reviewed. SUMMARY: Diabetic peripheral neuropathy is a common complication of diabetes that can cause significant morbidity and mortality. Some 30% of hospitalized and 20% of community-dwelling diabetes patients have peripheral neuropathy; the annual incidence rate is approximately 2%. The primary risk factor is hyperglycemia. Sensorimotor neuropathy is marked by pain, paresthesia, and sensory loss. Cardiac autonomic neuropathy (CAN) may contribute to myocardial infarction, malignant arrhythmia, and sudden death. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy. Genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder. The pathology of diabetic neuropathy involves oxidative stress, advanced glycation end products, polyol pathway flux, and protein kinase C activation; all contribute to microvascular disease and nerve dysfunction. For symptom management current evidence from clinical trials supports the use of desipramine, amitriptyline, capsaicin, Tramadol ( Generic Ultram ), gabapentin, bupropion, and venlafaxine as preferred medications. Citalopram, nonsteroidal antiinflammatory drugs, and opioid analgesics may be used as adjuvant agents. Lamotrigine, oxcarbazepine, paroxetine, levodopa, and alpha-lipoic acid are alternative considerations. Evidence supporting the use of zonisamide, fluoxetine, mexiletine, dextromethorphan, and phenytoin is considered equivocal. Complementary therapies have also shown efficacy. The symptoms of CAN may be ameliorated with fludrocortisone, clonidine, midodrine, dihydroergotamine or caffeine, octreotide, and beta-blockers. Gastroparesis may be treated with metoclopramide or erythromycin. The most promising disease-modifying therapy is ruboxistaurin, which is in Phase III trials. Glycemic control remains the foundation of prevention and the prerequisite of adequate treatment. CONCLUSION: Diabetic neuropathy is a many-faceted complication of diabetes that can be managed symptomatically with an array of drugs.


Antidepressant-like effects of Tramadol ( Generic Ultram ) and other central analgesics with activity on monoamines reuptake, in helpless rats.

Affective states are regulated mainly by serotonin and noradrenaline. However the opioid system has been also related to antidepressant-induced mood improvement, and the mu-opioid receptor has been involved in affective responses to a sustained painful stimulus. Similarly, antidepressant drugs induce an antinociceptive effect via both the monoaminergic and opioid systems, probably involving sensorial and affective dimensions of pain. The aim of this study was to test three opiate analgesics, which also inhibit monoamine reuptake, in the learned helplessness model of depression in rats. Helpless rats receiving (+/-)Tramadol ( Generic Ultram ) (10, 20 mg/Kg) or (-)methadone (2, 4 mg/Kg) showed a decreased number of failures to avoid or escape aversive stimulus (shock) in both the second and the third daily sessions, compared with controls. Rats receiving levorphanol (0.5, 1 mg/Kg) showed a decreased number of such failures in the third session. The number of crossings in the intertrial interval (ITI) was not significantly modified by (+/-)Tramadol ( Generic Ultram ) or (-)methadone. Levorphanol enhanced ITI crosses at 1 mg/Kg. These results, together with other clinical and experimental data, suggest that analgesics with monoaminergic properties improve mood and that this effect may account for their analgesic effect in regulating the affective dimension of pain. From this, it seems probable that the analgesic effect of opiates could be induced by adding together the attenuation produced of both the sensorial and the affective dimensions of pain.


Isobolographic analysis of interaction between cyclooxygenase inhibitors and Tramadol ( Generic Ultram ) in acetic acid-induced writhing in mice.Satyanarayana PS, Jain NK, Singh A, Kulkarni SK.Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used analgesics in the management of acute and chronic pain. Combined use of NSAIDs and opioids has been indicated for achieving better analgesia with reduced side effects. The present study was aimed at evaluating the combination of different NSAIDs, which inhibit cyclooxygenase (COX) enzymes and Tramadol ( Generic Ultram ) against acetic acid-induced writhing in mice. The expected beneficial effect of combination regimen was analyzed by isobolographic analysis. The oral and intrathecally administered Tramadol ( Generic Ultram ), a mu-opioid and naproxen, a nonselective COX inhibitor produced dose-dependent antinociception, however, rofecoxib, a selective COX-2 inhibitor lacked analgesic efficacy in writhing test. Isobolographic analysis showed synergistic or supra-additive interactions for the combinations of naproxen and Tramadol ( Generic Ultram ) after oral and intrathecal administration. However, similar interaction was not observed when Tramadol ( Generic Ultram ) was combined with rofecoxib. Pretreatment with naloxone partially reversed the antinociceptive effect of Tramadol ( Generic Ultram ) per se and its combination with naproxen without modifying the per se effect of NSAID. The results demonstrated marked synergistic interaction between naproxen and Tramadol ( Generic Ultram ) and such interaction involved opioid as well as non-opioid mechanisms of Tramadol ( Generic Ultram ) and inhibition of COX-1 but not COX-2 by naproxen.

The effect of concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic polymers (hydrogenated castor oil [HCO], ethylcellulose) on the release rate of Tramadol ( Generic Ultram ). Hydrophilic matrix tablets were prepared by wet granulation technique, while hydrophobic (wax) matrix tablets were prepared by melt granulation technique and in vitro dissolution studies were performed using United States Pharmacopeia (USP) apparatus type II. Hydrophobic matrix tablets resulted in sustained in vitro drug release (>20 hours) as compared with hydrophilic matrix tablets (<14 hours). The presence of ethylcellulose in either of the matrix systems prolonged the release rate of the drug. Tablets prepared by combination of hydrophilic and hydrophobic polymers failed to prolong the drug release beyond 12 hours. The effect of ethylcellulose coating (Surelease) and the presence of lactose and HPMC in the coating composition on the drug release was also investigated. Hydrophobic matrix tablets prepared using HCO were found to be best suited for modulating the delivery of the highly water-soluble drug, Tramadol ( Generic Ultram ) hydrochloride.
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AIM: To compare the pharmacokinetics of the enantiomers of trans-Tramadol ( Generic Ultram ) (trans-T) and its active metabolite, trans-O-demethylTramadol ( Generic Ultram ) (M1), in male and female rats. METHODS: Following a single oral dose of 10 mg/kg trans-T hydrochloride to rats, (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 in plasma were determined by a high performance capillary electrophoresis method. RESULTS: The females showed higher plasma concentrations of (+)-trans-T, (-)-trans-T, and (+)-M1 than the males. The enantiomers of trans-T were absorbed and eliminated more slowly in the females than in the males. (+)-M1 was eliminated more slowly in the females than in the males. All pharmacokinetic parameters but Tmax of the two enantiomers of trans-T were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of the pharmacokinetic parameters for trans-T in the males were similar to those in the females. The values of Cmax, AUC(0-infinity) of the two enantiomers of M1 were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of Cmax, AUC(0-infinity) for M1 were lower than 1 in the males, larger than 1 in the females. CONCLUSIONS: Systemic exposure of (+)-trans-T, (-)-trans-T, and (+)-M1 was higher in female rats than in male rats. The stereoselectivity in pharmacokinetics of trans-T was similar, and that of M1 was different in male and female rats.

Switching opioids to transdermal fentanyl in a clinical setting

INTRODUCTION: The use of transdermal fentanyl is gaining in importance in the management of cancer pain. We describe the reasons for switching opioid medication to transdermal fentanyl in a pain management unit. METHODS: Case records of patients treated with transdermal fentanyl in our pain clinic were evaluated retrospectively. Conversion ratios were calculated from the opioid dosage before and after conversion. Pain intensities were assessed on a numeric rating scale (NRS 0: no pain, 10: worst pain imaginable). RESULTS: From October 1995 to December 1997 101 patients received transdermal fentanyl. Thirty-six patients had been treated with transdermal fentanyl before admission to our pain clinic, and relevant information was missing for one patient, so 64 patients were evaluated. Opioid therapy was switched to transdermal fentanyl during in-patient treatment for 53 patients and during out-patient treatment for 11 patients. Before conversion patients were treated with slow-release morphine (48%), immediate-release morphine (17%), buprenorphine (11%), Tramadol ( Generic Ultram ) (11%), levomethadone (5%), tilidine/naloxone (5%) and piritramid (3%). Reasons for opioid rotation were inadequate pain relief ( 33%), the patients' wish to reduce oral medication (20%), gastrointestinal side effects such as nausea (31%), vomiting (13%) and constipation (19%), dysphagia (27%) or others.