Background and Description of Cytochrome P450 Enzyme SystemĬytochrome P450 hepatic enzymes, primarily found in the mitochondrial inner-membrane or endoplasmic reticulum in cells are encoded by protein-coding genes located throughout the genome with over 50 in number 7. For several years, it was known that certain anesthetic agents and doses would be altered depending on the individual’s response, signs and symptoms during surgical procedures when anesthesia was administered indicating variable responses from person to person possibly related to differences in their genetic patterns. The conceptualization of drug interaction and potential relationship to an individual’s ability to break down drugs or metabolism influenced by genetics was raised by Motulsky in 1957 15,16 and later supported by genetic-based pharmacokinetics research. Relevant gene polymorphisms with different racial distributions are identified sources of variability in drug responses by the modulation of drug-metabolizing cytochrome P450 enzymes discussed in this report. Inter-individual variability in drug response is now recognized as a major clinical problem in westernized societies where polymedication is common. The Federal Drug Administration (FDA) and National Institutes of Health (NIH) have identified pharmacogenetics and pharmacogenomics as important key tools in development and testing of new drugs and their impact in treating individuals with human disease 10,13,14. Hence, pharmacogenetics deals with single genes and their structure while pharmacogenomics relates to gene function influenced by the environment, both can play a role in human disease including drug metabolism. Pharmacogenomics is the study of DNA and RNA characteristics impacting gene function but can change or be influenced by factors (e.g., environment) 10-12. The response to medications depends on each individual’s ability to metabolize drugs with most drugs broken down by this enzyme system dependent on the genetic makeup of each person. Pharmacogenetics is most often based on the cytochrome P450 enzyme system, primarily found in the liver and involves genes coding for the production of cytochrome P450 enzymes 6-9. DNA remains stable and does not change with time or age. Pharmacogenetics is the study of DNA structural variations and impact on drug metabolism, efficacy and tolerability. Personalized or precision medicine is emerging in the treatment of human diseases and management based on each individual’s genetic pattern and response to drugs categorized into two areas: 1) pharmacogenetics and 2) pharmacogenomics 1-5. Pharmacogenetics and Psychiatric Care: A Review and Commentaryĭepartments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA
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