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

Opioid analgesics represent one of the most important tools in a sequential pharmacological approach to oncological pain relief. They are recommended by the WHO when nonsteroidal anti-inflammatory drugs (NSAIDs) no longer provide adequate analgesia. However, the use of opioids is limited because of their numerous and often severe adverse effects. This aspect of opioids has motivated continuous research projects aimed at discovering drugs that can provide maximum pain relief but with improved tolerability. Tramadol is a new, centrally acting analgesic with a dual mechanism of action. It shows a selective interaction with mu receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release. From a pharmacokinetic standpoint, tramadol offers high bioavailability, with similar patterns after oral or parenteral administration (half-life 5 to 7 hours, time to peak plasma concentration 3.1 hours, and approximately 20% plasma protein binding). Although the efficacy of tramadol is comparable to that of other drugs with similar modes of action, the incidence of side effects such as constipation and respiratory depression is lower. The frequency of euphoria and dysphoria is negligible, resulting in little risk of abuse or dependence. It therefore seemed appropriate to further investigate the efficacy and tolerability of tramadol, defined as having only weak potency, in comparison with a widely used opioid, in oncological pain. Buprenorphine was selected as an opioid with a potency equivalent to half that of morphine, but with tolerability that is partially limited by the fact that it frequently gives rise to adverse reactions considered typical of stronger opioids. To compare the analgesic effect and tolerability of tramadol and buprenorphine, 60 patients (44 men, 16 women; average age 61.4 years), all presenting with advanced tumours, were treated orally in a controlled crossover trial with randomised sequences. Patients took both drugs, each for a week, with a 24-hour washout period between treatments. Tramadol was prescribed at the daily dose of 300mg, orally, and buprenorphine at 0.6 mg/day, as a sublingual preparation. Assessments were made of Karnofsky performance status and severity of pain before and during the 4 hours after taking the 2 drugs. Each patient also completed a daily diary recording the severity of pain 1 hour after the dose, the evolution of pain during the day and its severity compared with that on the previous day. They also assessed the duration and quality of sleep. The Karnofsky index changed little with either treatment, but all other variables showed worthwhile improvement, indicating the significant analgesic effect of both drugs. Buprenorphine and tramadol had a similar analgesic effect, although the improvement with the test drug was significant within 1 hour of administration (p < 0.05 compared with baseline) and more marked (p < 0.05 on day 2 compared with buprenorpine). At the end of tramadol treatment, sleep had also improved, both quantitatively and qualitatively (both p < 0.05). The final assessment was significantly in favour of tramadol as regards efficacy (p < 0.05) and patient acceptability (p < 0.01). Thus, tramadol was better tolerated than buprenorphine, and caused fewer and milder adverse reactions. Only 1 patient discontinued tramadol, compared with 18 using reference therapy. Tramadol, although theoretically less potent, nevertheless brought about as much pain relief as the comparator opioid. In conclusion, for this class of drug, tramadol provides an excellent balance between efficacy and tolerability, confirming preliminary studies.
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PMID:[Effectiveness and tolerance of tramadol in cancer pain. A comparative study with respect to buprenorphine]. 919 Mar 24

Tramadol is a centrally acting opioid with a low affinity for mu-opioid receptors, which has been claimed not to depress respiration as do the classic opioids. The respiratory effects of intravenous (i.v.) pethidine (0.6 mg kg-1) and tramadol (0.6 mg kg-1) were compared in 36 ASA Grade I-II patients in a placebo-controlled double-blind study. After induction of anaesthesia with propofol followed by suxamethonium-facilitated endotracheal intubation, the patients spontaneously breathed halothane in 70% nitrous oxide and oxygen via a non-rebreathing valve. Inspiratory and expiratory oxygen, and end-tidal carbon dioxide concentrations (PETCO2), tidal volume (VT), minute volume of ventilation (MV) and respiratory rate were monitored by a side-stream spirometry at an end-tidal halothane of 0.3%. The recordings were collected before surgery. Pethidine caused significant respiratory depression seen as an increase in fractional inspiratory-expiratory oxygen difference and PETCO2 and as a decrease in MV and respiratory rate. However, the effects of tramadol were similar to those of a placebo. Tidal volume was not affected by any study drug. In conclusion, tramadol 0.6 mg kg-1 was shown not to be associated with respiratory depression, unlike equipotent dose of pethidine in this setting.
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PMID:Comparison of respiratory effects of tramadol and pethidine. 952 44

Seventy patients (40 male, 30 female), mean (SD) age 60.8 +/- 13.7 years were treated with parenteral morphine (10 mg/1 ml ampul) or tramadol (100 mg/2 ml ampul) to verify their analgesic effects in pain following abdominal surgery. The multicenter trial followed an open, controlled experimental design between patients, randomized within the centers. The drugs were given by intramuscular injection, as requested by patients, starting in the postoperative period when pain was more than 70 mm, assessed on a visual analog scale. Patients were allowed up to six ampuls of tramadol or morphine in the 24-h trial but in the first 4 h, if they asked for supplementary analgesic, only diclofenac (75 mg in a 3-ml ampul) was allowed. Both test drugs gave rapid and constant pain relief. After the first dose, pain intensity was reduced 36.2% with tramadol, and 51% with morphine; the pain-free interval was similar for both treatments. The quality of sleep and the number of hours of sleep the night after surgery were similar for both groups. Tramadol was tolerated better, giving rise to no untoward reactions; with morphine there was one case of mild respiratory depression. In abdominal surgery, therefore, tramadol given by intramuscular injection has postoperative analgesic activity similar to morphine, but is better tolerated.
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PMID:Multicenter trial comparing tramadol and morphine for pain after abdominal surgery. 960 44

Tramadol may cause awareness and EEG activation during anaesthesia. We compared tramadol with morphine, administered during wound-closure, surmising that tramadol may cause earlier awakening, more rapid recovery, less respiratory depression and equivalent pain relief. Forty patients received nitrous oxide-enflurane for abdominal surgery. At wound closure, patients received tramadol 3 mg kg-1 or morphine 0.2 mg kg-1 and end-tidal enflurane concentrations were maintained at 0.5 kPa until skin closure, whereupon anaesthesia was discontinued. Times to spontaneous respiration, awakening and orientation were similar in the two groups, as were blood-gas tensions, ventilatory frequency, pain scores and incidence of nausea. Half of each group required supplementary analgesia during their 90-min stay in the recovery room. P-deletion counts improved more rapidly in the tramadol group. This study confirms previous reports that tramadol did not antagonize the hypnotic effects of volatile anaesthetics. Tramadol, administered during operation, was as effective as morphine in providing postoperative analgesia while permitting more rapid psychomotor recovery.
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PMID:Tramadol or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy. 1019 86

Tramadol is a widely-used analgesic for pre- and post-operative pain which has a different pharmacological profile to that of classical opioids, since it does not induce respiratory depression, constipation, sedation, tolerance or dependence. However, tramadol frequently produces nausea and vomiting as side-effects. In the present study, the interactions between tramadol and several adrenergic and serotonergic compounds with antinociceptive activity were studied by isobolographic analysis. Antinociceptive activity was evaluated using the acetic acid writhing test in mice. Dose-response curves for the antinociceptive effect of tramadol, prazosin, clonidine, xylamine, clomipramine and cyproheptadine were obtained, and ED(50)s were calculated for isobolographic analysis, which was performed by administration of fixed-ratios of tramadol with each of these drugs, given both systemically and intrathecally. The isobolograms of all combinations tested, either systemically or intrathecally showed superadditivity. The synergies observed with these combinations suggest a complex modulation of the descending noradrenergic and serotonergic systems that exert inhibitory influences on the transmission of nociceptive information, probably in addition to effects on receptors in the primary neurons of the spinal cord. The co-administration of analgesic drugs that produce superadditive effects constitutes a significant new avenue for the treatment of pain, since a similar level of antinociception can be obtained with considerable reductions in the dose of each analgesic. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.
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PMID:Interactions in the antinociceptive effect of tramadol in mice: an isobolographic analysis. 1070 Mar 29

Tramadol, a weak opioid mu-receptor agonist, may have a favourable potency and side effect profile for intravenous patient-controlled analgesia (PCA). In a prospective, double-blind, randomized study involving 54 patients, tramadol was compared with oxycodone in PCA after maxillofacial surgery. All the patients were given diclofenac sodium 1 mg kg-1 intramuscularly and dexamethasone 8 mg twice a day. Post-operatively patients received tramadol or oxycodone by a PCA apparatus (lockout 5 min, tramadol 0.3 mg kg-1 bolus, oxycodone 0.03 mg kg-1 bolus). During the immediate recovery period, opioid was administered i.v. in a double-blind fashion, either tramadol 10 mg or oxycodone 1 mg increments until the pain control was judged to be satisfactory by the patient. Pain was assessed at rest and during activity (mouth opening) before and after loading, at 2 h after commencing the PCA, as well as at 21.00 and at 09.00 hours on the following morning. Side effects were recorded. The potency ratio of tramadol to oxycodone was found to be approximately 8:1. There was no significant difference between the groups in the VAS scores for pain. No respiratory depression was identified. Tramadol was found to provide adequate analgesia after maxillofacial surgery without risk of respiratory depression. However, the incidence of nausea was slightly greater in the tramadol group than in the oxycodone group (44% vs. 28%, NS).
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PMID:Efficacy and side effects of tramadol versus oxycodone for patient-controlled analgesia after maxillofacial surgery. 1074 12

Respiratory depression following change of medication from tramadol to morphine is described in two patients. Tramadol is metabolized by cytochromoxidase CYP2D6 to O-desmethyl-tramadol with opioid agonist activity. Of the western population 7% have a mutation of the gene responsible for CYP2D6, resulting in low enzyme activity. These persons will have little effect of tramadol. When tailoring analgesia, the lack of response to tramadol may be interpreted as a need for opioid dose increase. In such cases, excessive opioid doses may be prescribed resulting in opioid side effects.
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PMID:[Respiratory depression following medication change from tramadol to morphine]. 1077 58

The atypical opioid, tramadol, has recently been introduced into Australia and New Zealand. Tramadol's efficacy in a wide range of acute and chronic pain states, its multi-formulation availability, and its low serious side-effect potential at high doses and in prolonged therapy, combine to bestow on it a user-friendly profile, for short- and long-term use in hospitals and communities. This paper reviews the following: its formulation and routes of administration; its unique enantiomeric biochemistry and metabolism; its triple mechanisms of action; its pharmacokinetics and pharmacodynamics; its analgesic efficacy compared with other opioids; the indications for its clinical use in a variety of acute and chronic (including cancer) painful states; its specific use in the elderly, in paediatric and in obstetric patients; its adverse event (including drug interaction) and safety profile; its advantages in terms of its relative lack of respiratory depression, major organ toxicity and histamine release, and dependence and abuse potential. The review looks at new uses for this drug and what can be expected in this area in the future.
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PMID:Tramadol--present and future. 1096 62

1. The centrally acting analgesic tramadol has recently been reported to cause seizures at re-commended dosages in patients, whereas animal experiments had indicated that seizures only occur in high, toxic doses. Tramadol has a dual mechanism of action that includes weak agonistic effects at the mu-opioid receptor as well as inhibition of monoamine (serotonin, norepinephrine) re-uptake. Its major (M1) metabolite mono-O:-desmethyltramadol, which is rapidly formed in vivo, has a markedly higher affinity for mu receptors and may thus contribute to the effects of the parent compound. Furthermore, the pharmacological effects of tramadol appear to be related to the different, but complementary and interactive pharmacologies of its enantiomers. In the present study, we evaluated (+/-)-tramadol, its enantiomers, and its M1 metabolite ((+)-enantiomer) in the amygdala kindling model of epilepsy in rats. Adverse effects determined in kindled rats were compared to those in nonkindled rats. 2. At doses within the analgesic range, (+/-)-tramadol and its enantiomers induced anticonvulsant effects in kindled rats. However, at only slightly higher doses seizures occurred. With (+/-)-tramadol, generalized seizures were observed at 30 mg kg(-1) in most kindled but not in nonkindled rats. The (-)-enantiomer induced myoclonic seizures at 30 mg kg(-1) in most kindled but not in nonkindled rats, although myoclonic seizure activity was observed in some nonkindled rats at 10 or 20 mg kg(-1). Seizures were also observed after the (+)-enantiomer and the (+)-enantiomer of the M1 metabolite, but experiments with higher doses of these compounds were limited by marked respiratory depression. 3. The data demonstrate that kindling enhances the susceptibility of rats to convulsant adverse effects of tramadol and its enantiomers, indicating that a preexisting lowered seizure threshold increases the risk of tramadol-induced seizures.
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PMID:Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. 1099 12

Tramadol acts through multiple mechanisms and has a low risk of post operative respiratory depression. We compared the efficacy of epidural tramadol with that of morphine for postoperative analgesia in these patients. The demographic data and the summed pain intensity difference scores (SPID) were similar in both the groups. The time to first supplementary dose was significantly shorter in the tramadol group compared to the morphine group (p<0.05). No patient in either group suffered respiratory depression.
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PMID:Comparison of efficacy and side effects of epidural tramadol and morphine in patients undergoing laminectomy: a repeated dose study. 1114 13


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