Pharmacodynamics response variations

This volume covers topics including cultural perspectives in psychiatric diagnosis and psychopharmacotherapy, differences in pharmacokinetics and pharmacodynamics of psychotropics, pharmacogenetics of ethnic populations, ethnic variations in psychotropic responses, complementary medicines in mental disorders, attitudes towards psychotropic medications, prescribing practices in Asia-Pacific countries, pharmaco-economic implications, integrating theory and practice, and... 

Setting aside issues of compliance and administration errors, the therapeutic response experienced by each patient may be influenced by variations in pharmacokinetics (rate and extent of absorption, distribution, elimination) and pharmacodynamics (physiologic, pathologic, and genetic factors receptor interactions and tolerance). 

PB-PK modelling allows further refinement of the dose-response evaluation by partitioning the relationship into pharmacokinetic (exposure vs. tissues dose) and pharmacodynamic (tissue dose vs. toxic response) components. This allows the uncertainties associated with each component to be assessed separately and adds accuracy to the overall animal to man extrapolation. Future developments of PB-PK modelling may allow specific sub-populations such as the newborn or individuals with metabolic variations to be taken into account. However, before this can be done there will need to be considerable growth in the amounts of physiological, pharmacokinetic and pharmacodynamic information available. 

Magnitude of therapeutic response = drug pharmacodynamics + drug pharmacokinetics + individual biological variation... 

Various factors may account for the variability in response to neuroleptics. These include differences in the diagnostic criteria, concurrent administration of drugs which may affect the absorption and metabolism of the neuroleptics (e.g. tricyclic antidepressants), different times of blood sampling, and variations due to the different type of assay method used. In some cases, the failure to obtain consistent relationships between the plasma neuroleptic concentration and the clinical response may be explained by the contribution of active metabolites to the therapeutic effects. Thus chlorpromazine, thioridazine, levomepromazine (methotrime-prazine) and loxapine have active metabolites which reach peak plasma concentrations within the same range as those of the parent compounds. As these metabolites often have pharmacodynamic and pharmacokinetic activities which differ from those of the parent compound, it is essential to determine the plasma concentrations of both the parent compound and its metabolites in order to establish whether or not a relationship exists between the plasma concentration and the therapeutic outcome. 

Cultural and ethnic differences are more important than we would initially suspect Psychiatric syndromes present differently in different cultures—cultural and ethnic pathoplastic effects different attitudes toward medications and variations in pharmacokinetics and pharmacodynamics, depending on genetics and ethnic origin. Even when we examine the response to treatment in genders, the results differ. For example, women will do better than men when treated for depression with SSRIs than with TCAs. 

A relationship between pharmacokinetic data and pharmacodynamic activity is assumed. There is no interest in predicting variations in plasma concentration using a correlation if these have no measurable influence on pharmacodynamic and pharmacological activity, and therefore none on therapeutic effectiveness. In addition the moiety responsible of the therapeutic activity must be known. 

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