Paroxetine INDEX

In contrast to anticonvulsants and alcohol, drugs such as bupropion, fluoxetine, fluvoxamine, nefazodone, quinidine, paroxetine, and some antipsychotics can inhibit specific CYP enzymes (7, 11, 36, 37, 41, 42, 43 and 44). Thus, TCAs, certain BZDs, bupropion, some steroids, and antipsychotics can all have their metabolism inhibited by drugs such as fluoxetine. For example, fluoxetine at 20 mg/day produces on average a 500% increase in the levels of coprescribed drugs which are principally dependent on CYP 2D6 for their clearance. That can lead to serious or even life-threatening toxicity if the drug has a narrow therapeutic index and the dose is not adjusted for the change in clearance caused by the coadministration of fluoxetine. 

Of the SSRIs, paroxetine is the agent most likely to cause weight gain however, in this study the authors reported no change in body mass index during the 3 months of... 

Of the SSRIs, paroxetine is the agent most likely to cause weight gain however, in this study the authors reported no change in body mass index during the 3 months of treatment, suggesting a more direct effect of paroxetine on metabolism. Further work will be needed to see if similar metabolic effects are associated with other SSRIs and in patients with other treatment indications. 

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

Antidepressant drugs A major class of psychotropic drugs with diverse chemical configurations including the monoamine oxidase inhibitors (MAOIs), the heterocyclic drugs (composed of mono-, di-, tri-, and hetero-cyclics), the serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, trazodone, and venlafaxine), and bupropion are more recent innovations. Antidepressants usually must be taken for several weeks to have the desired effect and they often have a low therapeutic index, so they must be closely monitored. 

Potentially clinically significant interactions include the tendency for fluvoxamine to increase circulating concentrations of oxidatively metabolized benzodiazepines, clozapine, theophylline, and warfarin. Sertraline and fluoxetine can increase levels of benzodiazepines, clozapine, and warfarin. Paroxetine increases levels of clozapine, theophylline, and warfarin. Fluoxetine also potentiates tricyclic antidepressants and some class 1C antiarrhythmics with a narrow therapeutic index (including encainide, flecainide, and propafenone). Nefazodone potentiates benzodiazepines other than lorazepam and oxazepam. 

A summary of these data on monoamine uptake inhibition and on inhibition of binding by rat brain synaptosomes of the selective 5-HT uptake inhibitor paroxetine and the selective NE uptake inhibitor tomoxetine taken from [53] is shown in table 5. Although the eudismic ratio (potency less active isomer/potency active isomer) of the R and S isomers of fluoxetine is fairly dose to one i.e. 1.58, the selectivity index (antilog (pl 5-HT - Pkj NE) of the S isomer is much larger than that of the R isomer. In offier words the R isomer of fluoxetine is a less selective 5-HT uptake inhibitor than the S isomer but their potendes are similar. This is also confirmed by the data on the inhibition of H-paroxetine and H-tomoxetine binding. 

The eudismic ratio of the R- and S isomer for the inhibition of %-paroxetine is one, so their potencies are the same. However, the selectivity index for the inhibition of H-paroxetine and %[-tomoxetine binding is 24 for the R isomer and 155 for the S isomer of fluoxetine indicating that the R isomer is less selective than the S isomer in regard to the afflnily of the compounds for the 5-HT tremsporter versus the NE transporter. 

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