Ethnic differences pharmacodynamics

With respect to other ethnic groups, African Americans may have a differential sensitivity to weight gain on clozapine (de Leon etal, 2007). They may also require lower doses than Caucasians (Kelly et al, 2006) and inter-individual as well as ethnic responsiveness maybe partly explained by differences in dopamine receptor polymorphisms (Hwang et al, 2005). It is conceivable that side effects may also be differentially expressed based on pharmacodynamic differences resulting from polymorphisms in other receptor types (histaminergic, muscarinic, etc.). This area remains largely unexplored with respect to ethnic differences in antipsychotic side effects. 

There is little published information that directly examines ethnic differences in olanzapine pharmacokinetics or pharmacodynamics. Indirectly, examining stable... 

As amisulpride has no hepatic metabolism, low protein binding, and is directly excreted in urine, there is little reason to suspect pharmacokinetic ethnic differences. Of course body mass and pharmacodynamic differences might occur, but to date have received little investigative attention. 

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. 

An example of ethnic differences in pharmacodynamics is response to propranolol, a beta-blocker drug used to control high blood pressure, or hypertension. Studies have shown that African Americans are least responsive (blood pressure, heart rate) to propranolol, Asians are most responsive, and Causians are midway between the two other groups. 

The most studied ethnic differences in transcultural psychopharmacology have been those between Caucasian and Asian populations. In this chapter, we review pharmacokinetics, pharmacodynamics, and sociocultural influences on drug response in Asians, focusing on the major classes of psychotropic medications. 

Some ethnic differences in therapeutic doses and side effects of various psychotropic medications, including neuroleptics, lithium, and TCAs, have also been explained by pharmacodynamic factors such as tissue or receptor sensitivity (Kalow 1989 Lin et al. 1995 Pi 1998). 

As mentioned in two critical reviews on transcultural psychopharmacology of the TCAs (Pi et al. 1993a Sramek and Pi 1999), the concept of differences between Asian and non-Asian populations in the pharmacokinetics and pharmacodynamics of TCAs has gained support from clinical reports and controlled studies. Whether these differences are due to ethnicity, pharmacokinetics, pharmacodynamics, environmental factors, or shortcomings of study design (such as small sample size) is not definitely known. Although recent studies of CYP polymorphism support the possibility of genetic differences, future studies will need to address these issues. 

Although research efforts in the field of ethnopharmacology have been limited, it is increasingly clear that medication dosing may be significantly affected by ethnic differences related to the pharmacodynamics, pharmacokinetics, and pharmacogenetics of certain medications. Fortunately, the literature on this subject is steadily proliferating. 

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... 

Zhang-Wong, J. et al. (1998). An investigation of ethnic and gender differences in the pharmacodynamics ofhaloperidol. Psychiatry Res., 81, 333-9. 

It is widely held that differences exist in the usage and dosage of antipsychotics among ethnic minority groups. A number of factors are felt to account for these differences and include sociocultural variables (racial bias, cultural divide between patient and physician, language), as well as biological variables (pharmacogenetic, pharmacokinetic, and pharmacodynamic). 

What are the variations in pharmacokinetics and pharmacodynamics of new generation psychotropics in different ethnic and cultural groups Are clinical drug trial data from specific population subgroups required before new drug approval is given ... 

Up to this point in our discussion of pharmacokinetics and pharmacodynamics, our discussion has emphasized the body s neurochemical changes in response to Its ingestion of chemical compounds we call drugs. This emphasis is consistent with the content and long history of the research that has been done on pharmacokinetics and pharmacodynamics. However, a more recently developed and much smaller area of research is concerned with possible ethnic and cultural differences in pharmacokinetics and pharmacodynamics (Lin Poland, 1995). 

The mechanisms underlying ethnic/cultural differences in pharmacokinetics and pharmacodynamics are not always clear and warrant considerably more study. Such group differences do remind us, however, that nonpharmacological factors may influence the drug experience at any point along the steps" listed in Table 4.1. 

Pharmacodynamics is concerned with the effect of a drug on the body, including tissue sensitivity or receptor binding. Pharmacokinetic differences between ethnic groups have received the most study, but pharmacodynamic differences have also been demonstrated. 

In conclusion, because metabolism of these drugs may vary by ethnic group (in addition to varyingbecause of pharmacodynamic differences), understanding similarities and differences in cultures can play an important role in ensuring that patients receive optimum therapy and appropriate care. Until it is possible to predict which patients will be most sensitive to the effects of a given medication, the standard of practice should be applied for all ethnic groups—namely, prescription of the lowest dose needed to maximize therapeutic effects and minimize side effects. 

Differences seen across regions and nations, both in reports of efficacy and incidence of adverse reactions, are much greater than can be accounted for by ethnic variations of pharmacokinetics and pharmacodynamics. Other objective differences are now discussed. 

Ethnic Background. It is known that Chinese subjects are more responsive than white subjects to the same dose or plasma concentrations of racemic propranolol. A study [65] investigated whether this could be attributed to higher (—) (-I-) AUC ratios in Chinese subjects, compared with the ratio in the white population. Although the plasma concentrations of both enantiomers were substantially lower in Chinese volunteers, the ratio was the same in both populations [65], suggesting a pharmacodynamic difference in these two populations with regard to the beta-blockade effect. 

In contrast to the Chinese, the black population responds less to the same dose of propranolol, than the white population. Sowinski et al. [45] showed that both the systemic and oral clearances of both enantiomers of propranolol are substantially higher in blacks than in whites. This difference was mostly attributed to a higher intrinsic clearance of propranolol enantiomers, in association with a slightly lower (9%) hepatic blood flow in blacks. The limited available information on the effects of ethnicity on the pharmacokinetics of propranolol suggest that the racial differences in the effects of this drug cannot be attributed to the stereoselectivity in the pharmacokinetics of the drug. Rather, these differences may be due to pharmacodynamic differences among ethnic populations. 

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