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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tramadol is a unique analgesic offering moderate, dose-related pain relief through its action at multiple sites. In contrast to pure opioid agonists, it has a low risk of respiratory depression, tolerance and dependence. Troublesome side-effects have been reported, but tramadol has been established as an adjunct to non-steroidal anti-inflammatory drugs in the treatment of moderate postoperative pain and to abolish shivering. It may have advantages in paediatric and day-case surgery and as an adjunct in local anaesthetic techniques. This review provides an evidence-based account of the role of tramadol in modern practice.
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PMID:Tramadol today. 1701 41

Tramadol (Ultram, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) is considered a Step 2 analgesic under the World Health Organization's guidelines for the treatment of patients with cancer pain. It is a centrally acting analgesic that has affinity for opioid receptors and influences the action of norepinephrine and serotonin at the synapse. This dual mechanism of analgesia makes it unique among Step 2 agents. It is metabolized by CYP2D6, which increases the potentialfor drug interactions. Unlike other opioids, it does not cause respiratory depression. Tramadol has been studied in cancer pain and neuropathic pain. It compares well with low-dose morphine as an analgesic. The purpose of this review is to critically examine the pharmacodynamics, pharmacology, drug interactions, and adverse effects of the drug, and, based on the data presented, discuss the drug's role in cancer care.
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PMID:Tramadol: does it have a role in cancer pain management? 1731 16

Tramadol, which inhibits the reuptake of noradrenaline and serotonin, is effective in animal models of depression. Its antidepressant-like effects may be mediated mainly by the noradrenergic system. This study investigated the role of the noradrenergic system in the antidepressant-like effects of tramadol and desipramine in the unpredictable chronic mild stress model. We assessed the involvement of beta-adrenoreceptors, particularly beta2-receptors in the activity of these drugs. In addition, we measured the level of noradrenaline and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the locus coeruleus, hypothalamus, hippocampus and cerebellum in stressed mice. Unpredictable chronic mild stress induced a degradation of coat state and decreased grooming behaviour in the splash test, which was reversed by the chronic administration of tramadol (20 mg/kg) and desipramine (10 mg/kg). The nonselective beta-adrenoreceptor antagonist propranolol (5 mg/kg, intraperitoneally) and the selective beta2-receptor antagonist ICI 118,551 (2 mg/kg, intraperitoneally) reversed the antidepressant-like effects of tramadol and desipramine. Moreover, chronic tramadol and desipramine treatment increased the level of noradrenaline (NA) and MHPG in the locus coeruleus but not in the cerebellum, whereas only MHPG level was increased in the hypothalamus. Tramadol, however, increased the levels of MHPG and NA in the hippocampus, whereas desipramine only increased NA level. These data support the view that the noradrenergic system plays an important role in the antidepressant-like action of tramadol.
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PMID:Antidepressant-like effect of tramadol in the unpredictable chronic mild stress procedure: possible involvement of the noradrenergic system. 1791 46

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.
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PMID:Unexceptional seizure potential of tramadol or its enantiomers or metabolites in mice. 1829 93

Opioids have been used for analgesia in nearly all civilizations. In paediatrics their use has become widely accepted for combating severe pain, especially postoperative pain and tumour pain. Receptors in the central nervous system are the best known sites of action of opioids, but the existence of peripheral receptors is also probable. The action depends on whether the opioid is more agonist or antagonist and on the peculiarities of physiology in childhood: in the small child a hyperdynamic blood circulation makes resorption faster, and in newborn and premature infants distribution and excretion are influenced by the different composition of the body and the immaturity of liver and kidney. The best known opioid is morphine, and it is the reference substance with which all other opioids are compared. Fentanyl has been used even for the smallest ventilated prematures in recent times, as it is easy to manage and has an early onset of action. Its depressant action on the respiratory centre is an advantage when attempts of spontaneous breathing make mechanical ventilation difficult. Obstinate constipation is the disadvantage of both morphine and fentanyl, and an exacerbation of hyperbilirubinaemia has been seen with fentanyl. Nalbuphine causes a lower degree of respiratory depression. The newer opioids alfentanil and sufentanil have already been used for the relief of paediatric postoperative pain and during mechanical ventilation, but no special advantages of their use are reported. Meperidine has been favoured especially for postoperative pain, although it appears to have no advantages over morphine. Its active metabolite normeperidine may accumulate and cause seizures; meperidine should not be used in prematures or in children with renal dysfunction. There are few publications on the use of piritramide in paediatric pain. Tramadol is widely used for emergencies, as it has the least sedative action; but it has disadvantages in causing nausea and vomiting. Codeine is widely used for its antitussive action. While the necessity of good analgesia for even the smallest infant cannot be overstated, the opioid used must be carefully selected with reference to the age of the child and the pain to be controlled.
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PMID:[Analgesia with opioids in the paediatric patient.]. 1841 33

Non-selective and cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) have been the mainstay of treatment for musculoskeletal pain of moderate intensity. However, in addition to gastrointestinal and renal toxicity, an increased cardiovascular risk may be a class effect for all NSAIDs. Despite these safety risks and the acknowledged ceiling effect of NSAIDs, many doctors still use them to treat moderate, mostly musculoskeletal pain. Recent guidelines for treating osteoarthritis and low back pain, issued by numerous professional medical societies, recommend NSAIDs and COX-2 inhibitors only in strictly defined circumstances, at the lowest effective dose and for the shortest possible period of time. These recent guidelines bring more focus to the usage of paracetamol and opioids. But opioids still remain under-utilized, although they are effective with minimal organ toxicity. In this setting, the atypical, centrally acting analgesic tramadol offers important benefits. Its multi-modal effect results from a dual mode of action, ie, opioid and monoaminergic mechanisms, with efficacy in both nociceptive and neuropathic pain. Moreover, fewer instances of side effects such as constipation, respiratory depression, and sedation occur than with traditional opioids, and tramadol has been prescribed for 30 years for a broad range of indications. Tramadol is now regarded as the first-line analgesic for many musculoskeletal indications. In conclusion, it is recommended to better implement the more recent guidelines focusing on pain management and consider the role of tramadol in musculoskeletal pain treatment strategies.
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PMID:The role of tramadol in current treatment strategies for musculoskeletal pain. 1847 96

The patient was a 44-yr-old man with end-stage renal disease who had developed chorea as a result of hypoglycemic injury to the basal ganglia and thalamus and who was subsequently diagnosed with depression and restless legs syndrome (RLS). For proper management, the presence of a complex medical condition including two contrasting diseases, chorea and RLS, had to be considered. Tramadol improved the pain and dysesthetic restlessness in his feet and legs, and this was gradually followed by improvements in his depressed mood, insomnia, lethargy, and feelings of hopelessness. This case suggests that the dopaminergic system participates intricately with the opioid, serotoninergic, and noradrenergic systems in the pathophysiology of RLS and pain and indirectly of depression and insomnia.
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PMID:A case of a patient with both chorea and restless legs syndrome. 1858 95

Tramadol as a centrally acting analgesic is extensively used in the management of moderate to severe pain. It slightly affects opioid receptors and inhibits the reuptake of norepinephrin and serotonin in the CNS. There are reports about toxicity and abuse of tramadol. The objective of the present study was to evaluate epidemiology of intentional tramadol intoxications. All poisoning cases that admitted to Loghman-Hakim Hospital Poison Center from April to May 2007 were studied. A total of 114 cases (82 men and 32 women) of intentional tramadol intoxications with the median age of 23.66 +/- 6.87 years (range 16-54 years) were identified. Other illicit drugs were found to be used in combination with tramadol in some of the cases, which among them benzodiazepines were the most common. Tramadol overdose has been one of the most frequent causes of drug poisoning in the country in the recent years, especially in male young adults with history of substance abuse and mental disorders. Nausea, vomiting, Central Nervous System (CNS) depression, tachycardia, and seizure are the most common findings in this kind of poisoning. Cardiopulmonary arrest was found as the cause of death in cases who had ingested more than 5000 mg tramadol.
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PMID:Tramadol intoxication: a review of 114 cases. 1865 Feb 51

The purpose of this study was to determine the pharmacokinetics of tramadol and the active metabolite mono-O-desmethyltramadol (M1) in 6 healthy male mixed breed dogs following intravenous injection of tramadol at 3 different dose levels. Verification of the metabolism to the active metabolite M1, to which most of the analgesic activity of this agent is attributed to, was a primary goal. Quantification of the parent compound and the M1 metabolite was performed using gas chromatography. Pharmacodynamic evaluations were performed at the time of patient sampling and included assessment of sedation, and evaluation for depression of heart and respiratory rates. This study confirmed that while these dogs were able to produce the active M1 metabolite following intravenous administration of tramadol, the M1 concentrations were lower than previously reported in research beagles. Adverse effects were minimal, with mild dose-related sedation in all dogs and nausea in 1 dog. Analgesia was not documented with the method of assessment used in this study. Tramadol may be useful in canine patients, but additional studies in the canine population are required to more accurately determine the effective clinical use of the drug in dogs and quantification of M1 concentrations in a wider population of patients.
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PMID:Pharmacokinetics of intravenous tramadol in dogs. 1878 21

Tramadol hydrochloride is a widely prescribed, centrally acting analgesic marketed in over 90 countries. Before being released in the U.S. in 1995, the drug had been available in Europe for almost two decades. Thus, the pharmacokinetic and pharmacodynamic properties of tramadol have been extensively investigated. However, additional information about the drug continues to be discovered. Tramadol exists as a racemic mixture with the (+)-enantiomer and the (-)-enantiomer, and at least some of their metabolites, having different effects. Tramadol has dual mechanisms of action by which analgesia may be achieved: micro-opioid receptor activation and enhancement of serotonin and norepinephrine transmission. Serotonin syndrome may occur in patients taking combinations of tramadol and other agents that increase serotonin activity. The relative degree of contribution of each mechanism toward pain control is not fully understood. By increasing serotonin and norepinephrine neurotransmission, tramadol may conceivably also exert a degree of antidepressant effect. Therefore, tramadol may be of particular value in patients with chronic pain who also suffer from depression. This drug has been shown to be beneficial in the treatment of a wide range of acute and chronic pain syndromes, including neuropathic pain. While abuse of tramadol may occur, several large studies have demonstrated that the incidence of abuse is rather low, about one case per 100,000 patients.
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PMID:Tramadol: basic pharmacology and emerging concepts. 1918 Feb 60


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