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Strong Analgesic (strong + analgesic)
Selected AbstractsThe importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Dr Nobuko Futaki Abstract Objectives Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effecls of lornoxicam in relatioin to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. Methods A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01,1 mg/kg), celecoxib (0.3,30 mg/kg) or loxoprofen (0.3,30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall,Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzme-immunoassay. Key findings In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornnoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen siginificantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Conclusions Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus. [source] Hospitalizations for opioid poisoning: a nation-wide population-based study in Denmark, 1998,2004ADDICTION, Issue 1 2009Anne-Mette Bay Bjørn ABSTRACT Aims To assess hospitalization rates (HR) for poisoning with heroin, methadone or strong analgesics and relate them to quantities of prescribed methadone and strong analgesics in Denmark between 1998 and 2004. Design Population-based ecological study. Settings We extracted data on all emergency department visits and hospital admissions registered in the Danish National Patient Registry with a diagnosis of poisoning with heroin (n = 1688), methadone (n = 173) or strong analgesics (n = 384). To ascertain sale of prescribed medications we used data from the Danish Medicines Agency. Measurements Age- and gender-standardized HR and defined daily doses (DDD) per 1000 people per day. Findings HR for heroin poisoning was 4.4 [95% confidence interval (CI): 3.8,4.9] per 100 000 person-years (p-y) in 1998 and 4.6 (CI: 4.0,5.2) per 100 000 p-y in 2004. HR for methadone poisoning increased from 0.1 (CI: 0.0,0.2) per 100 000 p-y in 1998 to 1.1 (CI: 0.8,1.4) per 100 000 p-y in 2004. HR for poisoning with strong analgesics increased from 0.6 (CI: 0.4,0.9) per 100 000 p-y in 1998 to 2.1 (CI: 1.8,2.6) per 100 000 p-y in 2004. The sale of prescribed strong analgesics (5.0 DDD per 1000 people per day in 1998 to 5.9 DDD in 2004) and methadone (3.0 DDD per 1000 people per day in 1998 to 3.4 DDD in 2004) increased slightly between 1998 and 2004. Conclusion Increasing sale of prescribed methadone and strong analgesics coincided with increasing HRs of poisoning with these drugs, whereas HR of heroin poisoning varied. Further longitudinal studies are important for the guidance of future policy making. [source] Postmortem Blood Concentrations of R - and S -Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein GenotypeJOURNAL OF FORENSIC SCIENCES, Issue 2 2010Anders Buchard M.Sc. Abstract:, We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R - and S -methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R -enantiomer concentrations significantly exceeded that of the S -enantiomers (Wilcoxon's test, p < 0.001). The samples were divided into four groups according to other drugs detected (methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R -methadone/total methadone ratios among the four groups. The median R/S ratio was 1.38, which tends to be higher than that reported for the plasma of living subjects. In addition, we investigated whether small nucleotide polymorphisms in the MDR1 gene that encode the drug transporter P-glycoprotein were associated with the concentrations of R - and S -methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. No significant association was detected. [source] | ||||||||||