Tramadol References
Fam Pract. 1999 Aug;16(4):407-13.
Diffusion of new drugs in Danish general practice.
Steffensen FH, Sorensen HT, Olesen F.
Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus.
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, 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.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10493713&dopt=Abstract Tramadol online, Ultram
Postgrad Med J. 1987;63 Suppl 3:19-28.
The antinociceptive activity of flupirtine: a structurally new analgesic.
Nickel B.
Biological Research Pharmacology, Homburg Degussa Pharma Gruppe, Frankfurt, Federal Republic of Germany.
The antinociceptive activity of flupirtine was measured in various test procedures predictive of analgesic activity. In the electrostimulated pain test in mice the oral ED50 for flupirtine was 25.7 mg/kg p.o. Thus, flupirtine was approximately 31.7 times more potent than paracetamol (ED50: 814 mg/kg p.o.) and as potent as pentazocine (ED50: 38.5 mg/kg p.o.). Morphine (ED50: 16.8 mg/kg p.o.) was 1.5 times and buprenorphine (ED50: 2.6 mg/kg p.o.) 9.9 times more potent than flupirtine. In the hot plate test (mice) flupirtine (ED50: 32 mg/kg p.o.) was approximately half as potent as morphine (ED50: 15.5 mg/kg p.o.). The oral and intravenous antinociceptive activity (ED50) of flupirtine in the electrical tooth pulp stimulation test in conscious dogs was 3.5 mg/kg p.o. and 0.7 mg/kg i.v. which was similar to that of pentazocine (ED50: 4.2 mg/kg p.o. and 0.5 mg/kg i.v.). Buprenorphine had, as expected, stronger antinociceptive activity (ED50: 1.0 mg/kg p.o. and 0.04 mg/kg i.v.). Fifteen minutes after oral administration of 40 mg/kg flupirtine, the pain threshold in the electrostimulated pain test was increased by 54%. The maximal antinociceptive effect was observed 30 minutes after dosing. The analgesia lasted at least 75 minutes. Codeine significantly elevated the pain threshold 15 minutes after dosing. Its maximal effect was also reached 30 min after application but the antinociceptive activity wore off earlier than after flupirtine. The intracerebroventricular and intrathecal administration of flupirtine also caused dose dependent antinociceptive activity in dose ranges which, when applied systematically, did not produce analgesia in rats. The antinociceptive activity of flupirtine was not abolished by naloxone whether given orally or by the intraventricular or intrathecal routes. In opiate receptor binding studies flupirtine had no affinity for mu, delta or kappa opiate receptors at the highest concentration used (10(-5) M). Whereas buprenorphine and tramadol showed a striking similarity in the pharmaco-electroencephalogram recorded from different parts of the brain (frontal cortex, thalamus, striatum and the mesencephalic reticular formation) of the freely moving rat, flupirtine was clearly different in action. It produced dose dependent increases in nearly all frequency bands but its effects were different from those of the minor tranquillizer diazepam and the anticonvulsant phenobarbitone. These findings show that the central antinociceptive activity of flupirtine is not based on an opiate mechanism and is not comparable with that of diazepam and phenobarbitone.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2833734&dopt=Abstract Tramadol online, Ultram
Postgrad Med J. 1987;63 Suppl 3:41-3.
Comparative physical dependence studies in rats with flupirtine and opiate receptor stimulating analgesics.
Nickel B, Aledter A.
Biological Research Pharmacology, Homburg Degussa Pharma Gruppe, Frankfurt, Federal Republic of Germany.
In physical dependence studies in rats the principle criterion was loss of body weight after withdrawal of the dependence producing drug. Other typical signs of withdrawal were also observed. In contrast to buprenorphine, codeine and tramadol, flupirtine caused no decrease in body weight and no other withdrawal symptoms. Flupirtine does not produce opiate type physical dependence.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2833735&dopt=Abstract Tramadol online, Ultram
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