Such variations have remained mostly obscure, however, because many of the reports were published in nonclinical journals. More recently, studies aimed at identifying genetic determinants of disease susceptibility, temperament, and behavioral traits have led to the discovery of genetic variations that affect psychotropic responses. The gene that encodes the serotonin 5-HT transporter and the enzyme catechol- O -methyltransferase serve as the most prominent examples.
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Since almost all of the alleles that affect the activity of such genes are unevenly distributed across ethnic groups, subsequent human genomic studies have been compelled to take ethnicity and race into serious consideration. Genetic variations fundamentally affect both of these processes and are responsible for cross-ethnic and interindividual differences in drug response. Cytochrome P 2D6 CYP2D6 may represent the best clinically significant example of ethnic variations at the genetic level.
The result is a remarkable divergence in therapeutic responses and propensity for adverse effects. CYP2D6 has more than 50 distinct variant alleles that lead to the production of enzymes with divergent activities and that effectively divide patients into 4 groups:. As is true with the majority of the genes that have been studied, these CYP2D6 genotype groups are highly unevenly distributed across ethnic and racial groups. The regulation of the expression of CYP3A4 provides an illuminating example of how environmental factors exert significant influences on this and other enzymes that contribute significantly to drug metabolism.
Grapefruit juice and red wines have long been known to inhibit the activity of the enzyme, which can lead to potentially lethal toxicity with immunosuppressants and antivirals and to oversedation with benzodiazepines and nefazodone Drug information on nefazodone. The result may be reduced effectiveness and symptomatic relapse. The mechanism for such induction involves the steroid and xenobiotics receptor SXR involved in the regulation of the metabolism of steroids and phytochemicals.
As the name implies, the SXR is activated by a wide range of foreign substances, including manufactured drugs, medicinal herbs, nutrients, and environmental toxins. Dietary practices and the use of medicinal herbs vary widely across cultural groups, which represents another major reason for variations in drug responses across ethnic and cultural populations.
East Asians and Asian Americans metabolize these agents more slowly than do their white counterparts, probably a result of environmental rather than genetic factors. Dietary differences and the use of medicinal herbs also vary significantly in different regions of the world and across different ethnic and cultural groups. Many medicinal herbs are potent inhibitors or inducers of CYP enzymes, which may also contribute to observed cross-ethnic and cross-cultural variations in drug metabolism.
This article aims to provide a glimpse of recent developments that are relevant to cultural and ethnic influences on psychopharmacological responses.petdonate.ru/components/ms/contactos-mujeres-marina-alta.php
Drug Metabolism and Personalized Therapy
Instead of considering these influences as just factors of peripheral significance, they should be regarded as central in determining the success of treatment interventions. These factors crucially influence the symbolic as well as the instrumental dimensions of pharmacological effects. Neglect of these issues can lead to miscommunication, distrust, medication nonadherence, diminished placebo response, and treatment failure. Both of these processes are genetically and environmentally determined. While pharmacogenomics as a field is starting to show great promise in enabling us to predict both cross-ethnic and interindividual variations in treatment responses, the goal of individualized or personalized pharmacotherapy may be a number of years off.
Nevertheless, the awareness of such variations will go a long way toward optimizing pharmacotherapeutic gains. Tools such as DSM-IV-TR cultural formulation guidelines should prove extremely useful in providing the foundation for such benefits to take place. As shown in Figure 2 , simultaneous attention to the cultural and biological aspects of pharmacotherapeutic responses as well as to their interactions is crucial and indispensable.
New York: Raven Press; Psychopharmacotherapy in the context of culture and ethnicity. In: Ruiz P, ed.
Psychopharmacology and Psychobiology of Ethnicity | JAMA | JAMA Network
Ethnicity and Psychopharmacology. Psychopharmacology and Psychobiology of Ethnicity. Kalow W. Pharmacogenetics of Drug Metabolism. New York: Pergamon Press; Haloperidol and prolactin concentrations in Asians and Caucasians.
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J Clin Psychopharmacol. London: British Medical Journal Books; Medication adherence: a review of the literature and implications for clinical practice. J Psychiatr Pract. Kleinman A.
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Pharmacogenetics of cytochrome P and its applications in drug therapy: the past, present, and future. Trends Pharmacol Sci. Clin Pharmacol Ther. Luo H, Wan Y. At all times medical advice should be obtained by professional doctors. Read more World map: interethnic differences in drug metabolism: CYP2D6. World map: interethnic differences in drug metabolism: CYP2C9 coming soon. World map: interethnic differences in drug metabolism: CYP2C19 coming soon. World map: interethnic differences in drug metabolism: CYP3A5 coming soon. Welcome About Contact Special topics References.