Diffusion of new drugs in Danish general practice.

OBJECTIVES: There is a large variation in implementing research findings in clinical practice. We examined whether the concept of early or late adopters is universal for the diffusion of all new drugs, and whether it is associated with non-scientific factors in general practice. METHODS: We identified all prescriptions for five new drugs from the population-based prescription database in North Jutland County, Denmark (490000 inhabitants) from 1993 to 1996, and calculated the period from release of the drugs to the issuing of the first prescription by each GP. Logistic regression was performed to predict early or late prescribing from physician characteristics, practice activity and the number of prescriptions, adjusted for age and sex. RESULTS: The distributions of the diffusion time of the drugs by 95 solo practitioners were asymmetrical, with a long upper tail representing the late prescribers. The shape and slope of the diffusion curve were highly drug dependent. There was poor agreement of the three adopter categories (early, intermediate and late prescribers) between the five drugs (kappa < 0.35), but being a late prescriber was the most consistent condition. Late prescribing of Tramadol ( Generic Ultram ), compared with intermediate prescribing, was associated with female physicians (odds ratio (OR) 5.7; 95% CI 1.5-21.3), smaller list size (OR 0.1; 95% CI 0.0-0.8), a strong general restrictive attitude to pharmacotherapy (OR 0.07; 95% CI 0.01-0.68) and a tendency to lower diagnostic activity per patient (OR 0.4; 95% CI 0.1-1.9). CONCLUSIONS: The slope and shape of the diffusion curve are both dependent on physician and drug characteristics, but late prescribers share some common characteristics.


Ketoprofen (ketonal): a drug for preventing and treating postoperative pain

An inert matrix to control the release of Tramadol ( Generic Ultram ) HCl was prepared using glyceryl behenate as a matrix-forming agent. The matrices were prepared by either direct compression of a physical mixture of the drug and the matrix-forming agent or by compression of granules prepared by hot fusion of the drug and the matrix-forming agent. The hot fusion method was found to be more effective than compression of physical mixtures in retarding the release of the drug from the matrix. Drug release was adjusted by using release enhancers, such as microcrystalline cellulose and lactose, and the results showed that higher release rates were obtained using lactose. However, the release of the drug was independent of the compression force and the pH of the dissolution medium. This study showed that glyceryl behenate is an appropriate waxy material that can be used as a matrix-forming agent to control the release of a water-soluble drug such as Tramadol ( Generic Ultram ) HCl.

To investigate the analgesic efficacy and safety of epidural infusion of clonidine in children undergoing major abdominal surgery. DESIGN: Randomized open-label study. SETTING: Postoperative anesthetic unit and pediatric ward of a metropolitan hospital. PATIENTS: Forty children aged 0 to 3 years undergoing major abdominal surgery. INTERVENTIONS: Children were randomly allocated to receive a 24-hour epidural infusion of clonidine 1 microg.mL(-1) at rate of 0.2 mL.kg -1.h -1 preceded by a bolus of 2 microg.kg -1 (CLON group) or a mixture of clonidine 1 microg.mL -1 and ropivacaine 0.1% at rate of 0.2 mL.kg -1.h -1. Both groups received intravenous (IV) ketoprofen 2 mg.kg -1 every 8 hours. Breakthrough pain was treated with IV Tramadol ( Generic Ultram ) 1 mg.kg(-1). MEASUREMENTS: Tramadol ( Generic Ultram ) requirement, sedation and respiratory and hemodynamic changes were measured. MAIN RESULTS: Approximately 77% and 59.3% of the CLON and CLON+ROPIV groups, respectively, required no Tramadol ( Generic Ultram ) or only one dose over a 24-hour period. Except for those patients who exhibited frequent coughing during the night (4 and 5 patients in the CLON and CLON+ROPIV groups, respectively), no study patients required an analgesic and all had good sleep quality during the first night. Sedation and decreased systolic blood pressure were observed after the clonidine bolus was given. CONCLUSION: For children undergoing major abdominal surgery, the addition of epidural infusion of clonidine or clonidine plus ropivacaine to IV ketoprofen provided good analgesia quality for postoperative rest pain.
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Persistent non-malignant pain is common, often neglected and under-treated among older persons. Some older adults do not complain because they consider chronic pain to be a characteristic of normal aging. Physicians have concerns regarding adverse effects of pharmacological treatment. The model of the World Health Organization for treatment of cancer pain is generally accepted and also recommended for persistent non-cancer pain. Furthermore, non-pharmacological treatment should complement drug treatment whenever possible. An initial assessment and possible treatment of underlying causes of pain are pertinent. Modern pharmacological pain management is based on non-opioid and opioid analgesics. NSAIDs are among the most widely prescribed class of drugs in the world. The new cyclo-oxygenase-2 inhibitors such as celecoxib and rofecoxib offer an alternative for the treatment of mild-to-moderate pain in patients with a history of gastric ulcers or bleeding. Paracetamol (acetaminophen) is being used widely for the management of mild pain across all age groups as it has moderate adverse effects at therapeutic dosages. For moderate pain, a combination of non-opioid analgesics and opioid analgesics with moderate pain relief properties (e.g. oxycodone, codeine, Tramadol ( Generic Ultram ) and tilidine/naloxone) is recommended. For severe pain, a combination of non-opioid analgesics and opioid analgesics with strong pain relief properties (e.g. morphine, codeine) is recommended. The least toxic means of achieving systemic pain relief should be used. For continuous pain, sustained-release analgesic preparations are recommended. Drugs should be given on a fixed time schedule, and possible adverse effects and interactions should be carefully monitored. Adjuvant drugs, such as antidepressants or anticonvulsants, can be very effective especially in the treatment of certain types of pain, such as in diabetic neuropathy. Effective pain management should result in decreased pain, increased function and improvement in mood and sleep.


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.

Evidence of self-synergism in the antinociceptive effect of Tramadol ( Generic Ultram ) in rats.de Pozos-Guillen AJ, Aguirre-Banuelos P, Arellano-Guerrero A, Hoyo-Vadillo C, Perez-Urizar J.Facultad de Estomatologia, Universidad Autonoma de San Luis Potosi, Zona Universitaria CP 78290 San Luis Potosi SLP.Tramadol ( Generic Ultram ) is an atypical opioid with a complex mechanism of action including the synergistic interaction between the parent drug and an active metabolite. However, the local action of the parent drug is poorly documented. This study was designed to evaluate the site-site interaction of the antinociception produced by Tramadol ( Generic Ultram ) given by two different routes. The effects of individual and fixed-ratio combinations of locally (subcutaneous) and systemically (intraperitoneal) dosed Tramadol ( Generic Ultram ) were evaluated using the formalin test in rats. Isobolographic analysis was employed to identify the synergy produced by combinations. In the second phase of the formalin test, Tramadol ( Generic Ultram ) was active not only by the systemic (ED50 7.15+/-0.46 mg/kg i.p.) but also by the local route (ED50 134.6+/-25.1 microg/paw). The isobolographic analysis evidenced a "self-synergism" in the antinociceptive effect between the two routes of administration since the experimental ED50 (30.8+/-0.1 "dose units") of the combination was significantly lower than the theoretical ED50 (70.9+/-12.6 "dose units"). The mechanism underlying this self-synergism appears to be partially opioid since naloxone reversed the potentiation. The observed site-site interaction in the antinociceptive action of Tramadol ( Generic Ultram ) provides insights for alternatives in the management of pain.

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 ( Generic Ultram ), 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 ( Generic Ultram ) (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 ( Generic Ultram ). 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.