AboutDr Alan Galbraith Expertise I can answer most questions on drugs, both medical and "recreational". Answers can be given in either technical or layperson terminology. My main areas of interest are psychiatric, gastrointestinal and cardiovascular drugs.
Experience I have been a university lecturer/head of department for almost thirty years, but am now retired. My research interests were alcohol, smoking and cardiovascular disease.
Organizations Institute of Biology, London.
Publications Principal author of "Fundamentals of Pharmacology" 4th Edition published in November 2003 by Pearson Education, Australia.
Expert: Dr Alan Galbraith Date: 4/14/2008 Subject: genetic polymorphism
Question using CYP2C19 as an example, explain what is meant by genetic polymorphism of drug metabolising enzymes. 10 marks
Answer Dear Mahria
As explained yesterday I am not prepared to do all your work although I do not mind helping you along. I can only send the complete paper if you supply an email address but this will give you a good idea on how to answer this question.
The paper that I can send to you is from American Journal of Health Systems Phamacy:
Identifying Drugs Needing Pharmacogenetic Monitoring in a Korean Hospital
Posted 02/23/2007
Young Mi Kim; Seung Hee Yoo; Rae Young Kang; Min Jung Kim; Yoon Young Bae; Yeon Kyung Lee; Su Jin Jeon; Kung Ju Chon; Sang Mi Shin; Sang Geon Kim; Kyoung Ho Park; In Ja Son
Abstract and Introduction
Abstract
Purpose: A decision matrix for identifying drugs for which pharmacogenetic drug monitoring (PDM) provides the greatest benefit in a Korean setting is described.
Summary: We developed a decision matrix including the ethnic frequency of clinically relevant polymorphic cytochrome P-450 (CYP) enzymes, and the metabolic profiles and adverse drug reactions of drugs. Using the developed decision matrix based on the population allele frequencies of CYP enzymes, we identified potential candidates for PDM among the most commonly used drugs at Seoul National University Hospital (SNUH). Collectively, 17 of these drugs were largely metabolized by at least one polymorphic CYP enzyme. Pharmacogenetic information was used to identify CYP2C9, CYP2C19, and CYP2D6 as the major CYP enzymes of clinical importance for pharmacologic effect and safety in Koreans. The frequencies of poor and intermediate metabolizers among Koreans were 0% and 2.3-12% for CYP2C9, 12% and 42% for CYP2C19, and 0.44% and 28% for CYP2D6, respectively. The frequency of ultrarapid metabolizers of CYP2D6 was 2.28%. The decision matrix and pharmacogenetic information were used to identify seven drugs for PDM: warfarin, glimepiride, diazepam, amitriptyline, nortriptyline, codeine, and oxycodone. This approach can be applied to other institutional hospitals or other ethnic populations and would be helpful for advancing pharmacy practice. Further work is required to assess the practical and potential clinical relevance of pharmacogenetic variations on drugs of interest before the implementation of PDM.
Conclusion: A decision matrix helped identify drugs for which PDM provides the greatest potential benefit at one Korean hospital.
Introduction
Individualized drug therapy based on patients' genetic information offers the potential to improve drug efficacy and reduce adverse drug reactions.[1] Over the past several decades, pharmacogenetic knowledge about the proteins responsible for drug disposition and effects has been rapidly increasing.[2,3] The clinical application of knowledge of the genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets will help overcome the interindividual variability in drug responses.
Pharmacogenomics aims to elucidate the genetic basis for the difference in drug responses for the purpose of optimizing drug therapy.[4-6] Current approaches to therapeutic drug monitoring (TDM) do not fully address pharmacodynamic variabilities in patients' response to drug therapy.[7] Unlike traditional TDM, pharmacogenetic drug monitoring (PDM)—TDM based on patients' pharmacogenetic information— enables clinicians to optimize dosage regimens in a noninvasive manner before drug administration. In these aspects, PDM would be complementary to the current TDM[8] and have a substantial impact on clinical pharmacy practice in the near future.[9]
PDM requires genotyping of the genes responsible for drug disposition and effects. Genotyping diagnostic kits are being developed, with a few commercial kits already available for the cytochrome P-450 (CYP) isoenzymes 2C19 and 2D6.[10] Owing to rapid advances in molecular sequencing technology, the cost of genotyping tests will probably be reduced before the optimization of drug therapy in the health care system.[6] As medication experts, pharmacists may play an important role in interpreting the results of genotyping tests and making recommendations about drug choice and dosage on the basis of a patient's genotype.[7] In this regard, appropriate and logical applications of pharmacogenomic knowledge to clinical pharmacy practice, as well as continuing education in the field of pharmacogenomics, are necessary for the advancement of hospital pharmacy.[11]
Understanding the variability of drug-metabolizing enzymes among ethnic groups is a major area addressed by pharmacogenetics. The type and frequency of variant alleles linked to alterations of drug response differ among ethnic groups.12 To our knowledge, however, there has been no systematic approach for applying ethnic pharmacogenetic information to improve pharmacy practice in an individual health system's pharmacy. CYP isoenzymes, which metabolize a large number of drugs, have been extensively studied in pharmacogenetics.[3,7,13] Given the broad information on the ethnic differences of CYP polymorphisms and their roles in drug disposition and effects, we sought to apply the information on the type and frequency of variant alleles of major CYP enzymes in Koreans to pharmacy practice. We developed a decision matrix to identify drugs for which PDM provides the greatest benefit in a hospital setting using the population's allele frequencies. With this decision matrix, we identified drugs commonly used at Seoul National University Hospital (SNUH) that might be of clinical concern because of potential alterations of metabolic profiles.
