Non-steroidal anti-inflammatory drugs antagonise the constipating effects of tramadol.

Puig MM.

Department of Pharmacology, Barcelona University School of Odontology, Barcelona, Spain.

We report an antagonistic interaction between tramadol and non-steroidal anti-inflammatory drugs (NSAIDs), on gastrointestinal transit in rats. Transit was evaluated with charcoal and results are expressed as %inhibition. Tramadol and morphine had ED(50)s of 120.70+/-9.54 and 3.20+/-0.26 mg/kg, respectively, while metamizol (85 mg/kg), paracetamol (100 mg/kg) or ibuprofen (50 mg/kg) had no effect. All combinations of tramadol plus an NSAID, resulted in a rightward, non-parallel shift of the curves, which showed (two-way analysis of variance, ANOVA) significant differences from tramadol alone for the dose (P<0.0001), the drug (P<0.0001) and their interaction (P<0.0001), demonstrating antagonism. No interaction was present for morphine plus NSAIDs. The results demonstrate that NSAIDs antagonise the constipating effects of tramadol in rats, a fact that could have clinical relevance when combinations of these drugs are used in pain management in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14660026&dopt=Abstract tramadol



Analysis of the analgesic interactions between ketorolac and tramadol during arthritic nociception in rat.

Deciga-Campos M.

Laboratorio No. 7, Dolor y Analgesia del Departamento de Farmacobiologia, CINVESTAV-IPN, Calzada de los Tenorios No. 235, Col. Granjas Coapa, Deleg. Tlalpan, Mexico, DF, CP 14330 Mexico. flopezm prodigy.net.mx

The potential advantage of using combination therapy is that analgesia can be maximized while minimizing the incidence of adverse effects. In order to assess a possible synergistic antinociceptive interactions, the antinociceptive effects of ketorolac tromethamine, p.o., a nonsteroidal anti-inflammatory drug (NSAID), and tramadol hydrochloride, p.o., an atypical opioid analgesic, administered either separately or in combination, were determined using a rat model of arthritic pain. The data were interpreted using the surface of synergistic interaction (SSI) analysis and an isobolographic analysis to establish the nature of the interaction. The surface of synergistic interaction was calculated from the total antinociceptive effect produced by the combination after subtraction of the antinociceptive effect produced by each individual drug. Female rats received orally ketorolac alone (0.18, 0.32, 0.56, 1.0, 1.78, 3.16, and 5.62 mg/kg), tramadol alone (3.16, 5.62, 10.0, 17.78, 31.62, 56.23, and 100.0 mg/kg), or 24 different combinations of ketorolac plus tramadol. Ten combinations exhibited various degrees of potentiation of antinociceptive effects (17.78 mg/kg tramadol with either 0.18, 0.32, or 0.56 mg/kg ketorolac; 10.0 mg/kg tramadol with either 0.18, 0.32, 0.56, or 1.8 mg/kg ketorolac; 5.6 mg/kg tramadol with either 0.32 or 0.56 mg/kg ketorolac; and 3.16 mg/kg tramadol with 0.32 mg/kg ketorolac), whereas the other 14 combinations showed additive antinociceptive effects. Three combinations of ketorolac+tramadol (1.0+17.78, 1.78+10, and 1.78+17.78, mg/kg respectively) produced the maximum antinociceptive effects, and two combinations (0.32+10.0 and 0.56+10.0 mg/kg, respectively) presented effects of high potentiation (P<0.001). This combination caused gastric injuries less severe than those observed with indomethacin. The synergistic antinociceptive effects of ketorolac and tramadol were important and suggest that combinations with these drugs may have clinical utility in pain therapy.

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Effects of tramadol on behavioural indicators of colic pain in a rat model of ureteral calculosis.

Vecchiet L.

Pathophysiology of Pain Laboratory, Department of Medicine and Science of Aging, G. D'Annunzio University of Chieti, Italy.

This study investigated the effect of prolonged administration of tramadol vs. placebo on behavioural indicators of ureteral pain and referred lumbar muscle hyperalgesia in a rat model of artificial ureteral calculosis. Four groups of 10 rats each (female, Sprague-Dawley) were treated twice a day, for 4 days, with i.p. injections of tramadol 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg or saline, respectively. The first injection was delivered 45 min before laparotomy (under pentobarbital anaesthesia) for formation of the stone in the upper left ureter via injection of dental cement. All rats were video-taped 24 h non-stop from the immediate postoperative period until the 4th day for recording of behavioural ureteral crises indicative of colic pain. Lumbar muscle sensitivity was tested daily over the same period by verifying presence or absence of vocalization upon pinching of the parietal layers at L1 level, bilaterally, at a constant predefined pressure value with calibrated forceps. Tramadol significantly reduced number and global duration (ANOVA, P < 0.008 and P < 0.004) of ureteral crises with respect to saline and the effect was dose-dependent (linear regression analysis between doses and parameters of crises, P < 0.003 and P < 0.002). The drug also significantly reduced the incidence of referred muscle hyperalgesia (ANOVA, P < 0.0001). It is concluded that tramadol is highly effective in controlling pain phenomena from urinary stones and can represent a valid therapeutic approach in patients with urinary colics.

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Paracetamol + tramadol: new preparation. No advance.

.

(1) First-line treatment for both acute and chronic pain is paracetamol or, if necessary, ibuprofen, a nonsteroidal antiinflammatory drug. If relief is inadequate, the best option is a combination of paracetamol with codeine (a weak opiate). (2) A fixed-dose combination of paracetamol (325 mg) and tramadol (37.5 mg), a weak opiate, arrived on the French market in May 2003. (3) In the acute setting, three trials in a total of 1197 patients showed that a single dose of the paracetamol 650 mg + tramadol 75 mg combination after dental surgery was no more effective than ibuprofen 400 mg. Compared with each drug used alone, the paracetamol + tramadol combination prolongs the analgesic effect but does not increase its intensity. (4) A trial after gynaecological surgery and another trial after orthopaedic surgery showed that a single dose of paracetamol 975 mg + tramadol 112.5 mg had similar efficacy to tramadol alone at 112.5 mg. (5) In the chronic setting, we found no trials comparing the paracetamol + tramadol combination with each drug used alone. A comparative double-blind trial in 462 patients with low back pain or osteoarthritic pain showed no difference in efficacy between paracetamol 325 mg + tramadol 37.5 mg and paracetamol 300 mg + codeine 30 mg. (6) The main adverse effects of the paracetamol + tramadol combination are the same as other weak opiates: nausea, vomiting, dizziness, headache, drowsiness and constipation. Tramadol carries a higher risk of drug interactions than codeine. (7) In practice, the paracetamol + tramadol combination offers patients no advantages relative to standard analgesics.

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Bladder dysfunction during the use of tramadol.

van Puijenbroek EP.

Netherlands Pharmacovigilance Foundation LAREB, MH's-Hertogenbosch, The Netherlands.

The Netherlands Pharmacovigilance Foundation LAREB received five case reports concerning transient impairment of micturition or urinary retention, suspected to be induced by tramadol. In all patients--three women and two men--the symptoms occurred in temporal association with the use of tramadol and promptly recovered after stopping of the drug. Tramadol was taken orally in doses within the recommended therapeutic range (150 mg or less daily). Disturbance of micturition is not mentioned as a side-effect in the summary of product characteristics of Tramal 50 and 100. Tramadol is an opioid agonist, however, and morphine is known to increase the tonus of the bladder sphincter and to cause urinary retention. Copyright 1999 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15073888&dopt=Abstract tramadol