Drugs online research references
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BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) as antidepressant therapy has increased considerably since the introduction of fluoxetine in 1989. By 1999, 3 of the 4 available SSRIs were among the top 10 most frequently used drugs in the United States. In addition, SSRIs were one of the major contributors to the growth in psychotropic medication expenditures during the past 5 years. OBJECTIVE: The purpose of this article was to examine the utilization patterns of the 4 most commonly used SSRIs and their contribution to rising antidepressant medication expenditures among claimants in a publicly funded drug program. Using the results of forecasting models, we explored possible ways to control these growing expenditures. METHODS: Cross-sectional antidepressant claims and expenditure data from the Ontario Drug Benefits program for 1992 to 1998 were examined. Five scenarios were modeled in which future SSRI expenditures and claims were predicted using exponential smoothing models. RESULTS: If the historical patterns of use continued, a 20% increase in the 1998 level of expenditures was expected to occur by the year 2000. Predicted expenditures are sensitive to the composition of the SSRI claims. Exclusive use of 1 of the 4 major SSRIs (fluvoxamine, fluoxetine, paroxetine, and sertraline) could decrease projected expenditures by 30% or increase them by 11%. An "equal shares" approach, in which each of the 4 SSRIs are used in equal proportions in the population, may reduce expenditures by approximately 8%. CONCLUSIONS: The current trends in the utilization data suggest that sertraline and paroxetine are being used as first-line treatments. The results of the forecasting models suggest that growing expenditures could be curbed if these 2 antidepressants were not used in that manner. Short of limiting the drugs available on benefit formularies, there may be a way to control costs through the use of a prescribing algorithm. Although our results support the use of fluoxetine for first-line SSRI treatment as a cost-control measure, we do not definitively recommend its adoption. These findings contribute to the discussion about using fixed versus flexible formularies as a potential cost-control mechanism.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11293562&dopt=Abstract
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Drug Metab Dispos. 2001 May;29(5):656-63.
Metoprolol-paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction.
Hemeryck A, De Vriendt CA, Belpaire FM.
Heymans Institute of Pharmacology, Ghent University Medical School, 9000 Ghent, Belgium.
This study in human liver microsomes was undertaken to establish whether paroxetine stereoselectively inhibits the oxidative metabolism of metoprolol in vitro, and whether the in vivo observed magnitude of the paroxetine-metoprolol interaction was predictable from these in vitro data. Two distinct approaches were used: inhibitory effect of paroxetine on 1) the formation of alpha-hydroxymetoprolol and O-desmethylmetoprolol from the individual metoprolol enantiomers and 2) on the depletion of the enantiomers from the incubation mixture. Nonspecific binding of both metoprolol and paroxetine to human liver microsomes was also investigated. Whereas metoprolol displayed negligible binding, paroxetine was extensively bound to microsomal proteins. This was taken into account in order to obtain unbiased K(i) values and unbound concentrations of paroxetine. In the substrate depletion experiments, the intrinsic clearance (CL(int)) of (R)-metoprolol was larger than that of (S)-metoprolol. Paroxetine caused a concentration-dependent decrease in CL(int) of both enantiomers and abolished the stereoselectivity. In the metabolite formation experiments paroxetine did not stereoselectively affect alpha-hydroxylation, but preferentially inhibited the O-demethylation of the (R)-enantiomer versus the (S)-enantiomer. The use of unbound paroxetine concentrations in the two in vitro methods yielded comparable predicted increases in area under the curve (1.7-1.9 and 2.2-2.5 for (S)- and (R)-metoprolol, respectively) but underestimated the in vivo observed changes of about 7- and 10-fold, respectively. In conclusion, this study showed that paroxetine abolishes the stereoselective metabolism of metoprolol due to a stereoselective inhibition of the O-demethylation toward (R)-metoprolol. Furthermore, the extent of the in vivo metoprolol-paroxetine interaction was substantially underestimated by either one of the two in vitro approaches used when a competitive mechanism was assumed.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11302931&dopt=Abstract
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Amino Acids. 2001;20(1):35-47.
Influence of exercise on serotonergic neuromodulation in the brain.
Weicker H, Struder HK.
Department of Sports Medicine, University of Heidelberg, Federal Republic of Germany.
Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine (selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline values of Bmax of 5-HT transporters (5-HTT) and 5-HT2A receptors (5-HT(2A)R) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical efficiency improved. In contrast, after an excessive training program over four weeks, well-trained endurance athletes showed no change of Bmax of 5-HTT, but a decline of 5-HT(2A)R density and an increase in basal plasma PRL concentration. Mood was impaired and central fatigue increased. Thus, the impact of exercise on 5-HT neurotransmission may depend on training state of athletes and extent of exertion. The theoretical background of the implication of exercise and the effect of long lasting exhaustive exercise in athletes on mental and physical efficiency or central fatigue are evaluated. The significance of the primary disturbance of central neuromodulation and dysfunction of 5-HTT, 5-HT receptor subtypes and the phosphoinositol signal transduction as well as the limited modulation capacity of the 5-HT system in overstrain are also addressed.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11310929&dopt=Abstract
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