medizin.uni-ulm.de

INTRODUCTION: Nonsteroidal antirheumatics (NSAR; NSAID) are often used in patients with fractured bones for analgetic reasons. This animal experiment was performed to determine the influence of NSAR on the process of fracture healing. As an alternative, tramadol, the centrally acting analgetic without peripheral effects, was included in this experiment. MATERIALS AND METHODS: Wistar rats were operated on by a transverse osteotomy of the proximal tibia of the left leg. The fracture was stabilized by intramedullary nailing (healing period 21 days). All drugs were applied orally twice a day. The animals were divided into four groups with 10 rats each: Group 1 was treated with placebo (P), group 2 with tramadol (T; 20 mg/kg body weight/day), group 3 with diclofenac sodium (DS; 5 mg/kg bw/day) for 7 days followed by 14 days of placebo, group 4 with diclofenac sodium (DL; 5 mg/kgbw/day) over 21 days. On day 21 the rats were killed, and each leg was examined by X-ray, then the tibia was examined by CT scan, three-point bending, and histology. RESULTS: The results of CT and three-point bending showed that rats treated by diclofenac presented with delayed fracture healing compared with those treated by placebo or tramadol. Bone density in CT was highest in group 1 (mean 611.4+/-50.1 mg/ml), followed by group 2 (mean 542.5+/-29.5 mg/ml). Groups 3 (mean 411+/-34.0 mg/ml; p=0.006) and 4 (mean 395.2+/-15.4 mg/ml; p=0.009) were significantly lower. The stability of the bones, as measured by the breaking force ( F(max)), was highest in group 1 (mean 45.8+/-19.0 N), followed by group 2 (mean 39.0+/-7.9 N; NS); group 3 (mean 20.6+/-7.8 N; p=0.01) was significantly lower than the placebo animals, followed by group 4 (mean 26.5+/-8.3 N; p=0.03). Similar results were shown for bending stiffness: group 1 (mean 1404.6+/-611.4 Nmm/mm), group 2 (mean 1033.2+/-232.1 Nmm/mm; NS), group 3 (mean 564.2+/-457 Nmm/mm; p=0.045), and group 4 (mean 494.8+/-340.2 Nmm/mm; p=0.028). There were no significant differences between groups 1 and 2 and between groups 3 and 4, respectively. Diclofenac serum levels on day 21 in rats with long-term diclofenac application (mean 301.4+/-83.3 ng/ml) were comparable to those in humans. CONCLUSION: Oral application of diclofenac significantly delayed fracture healing in rats. This effect might be comparable to other NSAR and fracture healing in humans.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12811581&dopt=Abstract tramadol Ultram [PubMed - in process]




Anesth Analg. 2003 Jul;97(1):104-10, table of contents.
The inhibitory effects of ketamine and pentobarbital on substance p receptors expressed in Xenopus oocytes.

Okamoto T, Minami K, Uezono Y, Ogata J, Shiraishi M, Shigematsu A, Ueta Y.

Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.

Substance P receptors (SPR) modulate nociceptive transmission within the spinal cord. The effects of IV anesthetics on SPR are not clear. In this study, we investigated the effects of IV anesthetics on SPR expressed in Xenopus oocytes. We examined the effects of ketamine, pentobarbital, propofol, and tramadol on SP-induced Ca(2+)-activated Cl(-) currents mediated by SPR expressed in Xenopus oocytes using a whole-cell voltage clamp. Ketamine and pentobarbital inhibited the SPR-induced currents at pharmacologically relevant concentrations, but propofol and tramadol had little effect on the currents. We also studied the effects of ketamine and pentobarbital on [(3)H]-SP to SPR. Ketamine and pentobarbital inhibited the specific binding of [(3)H]-SP to SPR expressed in Xenopus oocytes. Scatchard analysis of [(3)H]-SP binding revealed that ketamine and pentobarbital decreased the apparent dissociation constant for binding and maximal binding, indicating noncompetitive inhibition. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ketamine and pentobarbital on SP-induced Ca(2+)-activated Cl(-) currents. The results suggest that ketamine and pentobarbital inhibit SPR function. The mechanism of their inhibition on SPR function could not be through activation of the PKC pathway and may be due to noncompetitive displacing the SP binding. IMPLICATIONS: We investigated the effects of IV anesthetics on substance P receptors (SPR) expressed in Xenopus oocytes. Ketamine and pentobarbital inhibit SPR function via noncompetitive displacing SP binding. The findings imply that the inhibition of SPR function by these compounds may play a role in the analgesic effects of these IV anesthetics.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12818951&dopt=Abstract tramadol Ultram




Prescrire Int. 2003 Jun;12(65):99-100.
Withdrawal syndrome and dependence: tramadol too.

[No authors listed]

(1) Tramadol carries a risk of dependence and abuse, even in patients with no history of drug abuse. (2) Abrupt withdrawal of treatment with tramadol, even at the recommended dose, can induce withdrawal symptoms. (3) In practice, patients must be advised to stop their treatment gradually, especially after lengthy treatment periods. Prescription renewals are a good opportunity to re-assess the need for tramadol. Use of this opioid analgesic should not be trivialised.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12825576&dopt=Abstract tramadol Ultram




Radiol Med (Torino). 2003 Apr;105(4):350-5.
Chemoembolization for hepatocellular carcinoma: effect of intraarterial lidocaine in peri- and post-procedural pain and hospitalization.

[Article in English, Italian]

Romano M, Giojelli A, Tamburrini O, Salvatore M.

Dipartimento Assistenziale di Radiologia e Radioterapia, Universita Federico II, Naples, Italy.

PURPOSE: To assess the efficacy of intraarterial lidocaine on peri- and post-procedural pain and on length of hospital stay in hepatocellular carcinoma (HCC) patients undergoing chemoembolization. MATERIALS AND METHODS: Twenty-eight patients (19M, 9F, age range 49-76) who underwent hepatic chemoembolization at our Institution between March 2000 and February 2002 were included in the study. Group A consisted of 14 patients who received intraarterial lidocaine immediately before and during chemoembolization, while in the 14 patients of group B lidocaine was substituted with saline solution. The doses of centrally acting narcotics (tramadol) administered periprocedurally and in the three days following the procedure were compared, as were the hospitalization times. Subjective pain was measured using the visual analogue scale. Chemoembolizations were performed with an emulsion of lipiodol, cisplatin and epirubicin followed by embolizing material (gelfoam of Contour particles) in order to achieve complete blood flow stop in the proper hepatic artery. RESULTS: No side effects were noted that could be due to systemic administration of lidocaine. All patients experienced some degree of post-embolization syndrome. Periprocedural, day 1 and day 2 post chemoembolization dosages of tramadol were significantly lower in group A with respect to group B patients. No group A patient required analgesia on day 3. No statistical difference was observed in time persistence of nausea and vomiting, fever and hospitalization time between the two patient groups. CONCLUSIONS: Intraarterial administration of lidocaine before and during chemoembolization is a safe and effective method for preventing or reducing peri- and post-procedural pain and dosage of narcotic analgesics in patients with HCC. Hospitalization times did not differ significantly between the two groups, probably because of the other components of post-embolization syndrome, such as fever, nausea and vomiting.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12835628&dopt=Abstract tramadol Ultram




Drugs Today (Barc). 2000 Jan;36(1):55-76.
Lornoxicam, a new potent NSAID with an improved tolerability profile.

Radhofer-Welte S, Rabasseda X.

Pharma Consulting, Linz, Austria.

Lornoxicam is a member of the oxicam group of nonsteroidal antiinflammatory drugs (NSAIDs). Oxicams have potent antiinflammatory and analgesic effects, but their use is associated with a high risk of gastrointestinal adverse effects. Lornoxicam has been shown to be at least as effective as comparative NSAIDs and more effective than 10 mg morphine when used at doses > or = 8 mg to control pain after oral surgery. In addition, oral doses of lornoxicam of 16-24 mg daily have been more effective than tramadol 300 mg daily in pain following knee surgery. Lornoxicam combines the high therapeutic potency of oxicams with an improved gastrointestinal toxicity profile as compared to naproxen, for example. This is probably due to the short half-life of lornoxicam as compared to the other oxicams. The clinical trials published so far, mostly comparative, clearly do- cument the efficacy of lornoxicam as a potent analgesic with excellent antiinflammatory properties in a range of painful and/or inflammatory conditions, including postoperative pain and rheumatoid arthritis.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12879104&dopt=Abstract tramadol Ultram