Drugs online research references
J Pain Symptom Manage. 1998 Aug;16(2):121-4.
Paroxetine for pruritus in advanced cancer.
Zylicz Z, Smits C, Krajnik M.
Hospice Rozenheuvel, Rozendaal, The Netherlands.
Pruritus associated with malignancy may be one of the most bothersome symptoms in advanced cancer. Its control is still difficult to achieve and is a challenge to palliative medicine specialists. We describe five patients suffering from pruritus of different etiologies who responded rapidly to administration of paroxetine, a serotonin reuptake inhibitor, in a dose-dependent manner. Two patients experienced transient but severe nausea and vomiting. We suggest that paroxetine's antipruritic effect may be explained by rapid downregulation of the 5-HTs receptors, which may have an important role in the generation of pruritus and pain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9737103&dopt=Abstract
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Clin Ther. 1998 Jul-Aug;20(4):780-96.
Economic consequences of selective serotonin reuptake inhibitor use with drugs also metabolized by the cytochrome P-450 system.
Ozminkowski RJ, Hylan TR, Melfi CA, Meneades LM, Crown WH, Croghan TW, Robinson RL.
The MEDSTAT Group, Inc., Ann Arbor, Michigan, USA.
Administration of selective serotonin reuptake inhibitors (SSRIs) may increase plasma concentrations of concomitant medications that are also metabolized by the cytochrome P-450 system (CYP-450), in particular by the 2D6 and 3A4 isoenzymes. This may lead to side effects or other clinical events that might be expected to incur higher health-care expenditures. The purpose of this study was to assess whether there was a difference in expenditures during the first 90 days of SSRI therapy with paroxetine or sertraline versus fluoxetine in patients who were also receiving a stable dosage of a nonpsychiatric drug also metabolized by the CYP-450 2D6 or 3A4 isoenzyme systems. A sample of 2445 patients who initiated therapy with an SSRI while receiving a stable dosage of a nonpsychiatric drug was obtained from a private insurance claims database. Multivariate regression techniques were used to estimate total health-care expenditures in the first 90 days after receiving a prescription for an SSRI. After adjusting for nonrandom SSRI prescription patterns and controlling for observable and unobservable characteristics that might correlate with SSRI selection, total health-care expenditures were 95% higher for patients initiating SSRI therapy with sertraline or paroxetine compared with fluoxetine. Results suggest that there are cost differences between SSRIs during concomitant therapy with drugs also metabolized by the CYP-450 system. To determine whether there are additional differences in expenditures across SSRIs, future research should focus on (1) simultaneous initiation of SSRI therapy and a nonpsychiatric drug also metabolized by the CYP-450 enzyme system, and (2) addition of nonpsychiatric drug therapy to stable SSRI therapy. Relationships between additional expenditures, drug interactions, and clinical outcomes should also be assessed directly using medical records and patient interview data that are not available in claims-based files.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9737837&dopt=Abstract
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Brain Res Bull. 1998 Aug;46(6):547-54.
Selective serotonin reuptake inhibitors reduce the spontaneous activity of dopaminergic neurons in the ventral tegmental area.
Di Mascio M, Di Giovanni G, Di Matteo V, Prisco S, Esposito E.
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Electrophysiological techniques were used to study the effects of paroxetine, sertraline, and fluvoxamine on the basal activity of dopaminergic neurons in the ventral tegmental area (VTA) of rats. Acute i.v. administrations of paroxetine (20-1280 microg/kg), sertraline (20-1280 microg/kg), and fluvoxamine (20-1280 microg/ kg) caused a slight but significant reduction in the firing rate of the VTA dopaminergic cells studied. Paroxetine produced a maximal inhibitory effect of 10 +/- 11% at the cumulative dose of 160 microg/kg. Sertraline induced a dose-related inhibition of VTA dopaminergic neurons, which reached its maximum (10 +/- 7%) at the cumulative dose of 1280 microg/kg. The effect of fluvoxamine on the basal firing rate of VTA dopaminergic neurons was more pronounced as compared to that of paroxetine and sertraline, in that it produced a maximal inhibition of 17 +/- 12% at the cumulative dose of 1280 microg/kg. Acute i.v. injections of paroxetine (20-1280 microg/kg), sertraline (20-1280 microg/kg), and fluvoxamine (20-5120 microg/kg) caused a dose-dependent decrease in the basal firing rate of serotonergic neurons in the dorsal raphe nucleus (DRN). Paroxetine and sertraline stopped the spontaneous firing of serotonergic neurons at the cumulative dose of 1280 microg/kg, whereas fluvoxamine reached the same effect only at the cumulative dose of 5120 microg/kg. Pretreatment with the 5-HTA1A receptor antagonist tertatolol (1 mg/kg, i.v.) reduced the inhibitory effects of paroxetine, fluvoxamine, and sertraline on the basal activity of serotonergic neurons in the DRN. Administration of tertatolol induced a 15-fold increase in the ED50 for fluvoxamine. The antagonistic effect of tertatolol was much less evident in blocking the inhibitory action exerted by paroxetine and sertraline on the activity of serotonergic neurons. Pretreatment with tertatolol (1 mg/kg, i.v.) potentiated the inhibitory effect of fluvoxamine on the basal activity of VTA dopaminergic neurons. Tertatolol did not affect the inhibitory action exerted by paroxetine and sertraline on these neurons. It is concluded that inhibition of the basal firing rate of dopaminergic neurons in the VTA is a common characteristic of selective serotonin reuptake inhibitors (SSRIs). The effects of SSRIs on VTA dopaminergic cell activity might be relevant for their therapeutic action and may explain the origin of the reported cases of akathisia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9744293&dopt=Abstract
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