Pharmacogenetics: P harmacogenetics PowerPoint Presentation: The term pharmacogenetics often is used interchangeably with the term pharmacogenomics . However, pharmacogenetics generally refers to monogenetic variants that affect drug response, whereas pharmacogenomics refers to the entire spectrum of genes that interact to determine drug efficacy and safety. PowerPoint Presentation: For example, a pharmacogenetic study would examine the influence of the β1-adrenergic receptor gene on blood pressure response to carvedilol . A pharmacogenomic study might examine the interaction between CYP2D6 and β1-, β2-, and α1- adrenergic receptor genes on carvedilol effects. PowerPoint Presentation: To date, most studies of gene–drug responses are pharmacogenetic in nature. However, given that multiple proteins are involved in determining the ultimate response to most drugs, many investigators are taking a more pharmacogenomic approach to elucidating genetic contributions to drug response . For simplicity, this treats pharmacogenetics and pharmacogenomics as synonymous. PowerPoint Presentation: Pharmacogenetics is the study of the impact of genetic polymorphisms on drug response . GOAL: GOAL The goals of pharmacogenetics are to optimize drug efficacy limit drug toxicity based on an individual’s DNA . The goals of pharmacogenetics are to optimize drug therapy and limit drug toxicity based on an individual’s genetic profile. PowerPoint Presentation: Thus, pharmacogenetics aims to use genetic information to choose a drug, drug dose, and treatment duration that will have the greatest likelihood of achieving therapeutic outcomes with the least potential for harm in a given patient. PowerPoint Presentation: The results of pharmacogenetic research ultimately will provide opportunities for clinicians to use genetic tests to predict individual responses to drug treatments, specifically to select medications for patients based on DNA profiles and to develop novel strategies for disease treatment and prevention based on an understanding of genetic control of cellular functions. PowerPoint Presentation: Genetic variations occur as either rare defects or polymorphisms. Polymorphisms are defined as variations that occur at a frequency of at least 1% in the human population. For example, the genes encoding the CYP450 enzymes CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 are polymorphic, with functional mutations of >1% occurring in different ethnic groups . In contrast, rare mutations occur in<1 % of the population and cause inherited diseases such as cystic fibrosis, hemophilia, and Huntington’s disease. POLYMORPHISMS IN GENES FOR DRUG-METABOLIZING ENZYMES: POLYMORPHISMS IN GENES FOR DRUG-METABOLIZING ENZYMES Polymorphisms in the drug-metabolizing enzymes represent the first recognized and the most documented examples of genetic variants with consequences in drug response and toxicity . The major phase I enzymes are the CYP450 superfamily of isoenzymes . CYTOCHROME P450 ENZYMES: CYTOCHROME P450 ENZYMES Currently, 57 different CYP450 isoenzymes have been documented to be present in humans, with 42 involved in the metabolism of exogenous xenobiotics and endogenous substances such as steroids and prostaglandins. PowerPoint Presentation: Functional genetic polymorphism has been discovered for CYP2A6, CYP2C9, CYP2C19, CYP2D6 example of prodrugs dependent on CYP2D6- mediated conversion to active forms are codeine. Codeine converted by CYP2D6 to morphine. CYP2C9: CYP2C9 Warfarin , phenytoin , and tolbutamide are examples of drugs with a narrow therapeutic index that are metabolized by CYP2C9. Genetic Polymorphisms in Drug Targets and Response to Drug Therapy: Genetic Polymorphisms in Drug Targets and Response to Drug Therapy Genetic polymorphisms occur commonly for drug target proteins,including receptors, enzymes, ion channels, and intracellulaR signaling proteins. Drug target genes may work in concert with genes that affect pharmacokinetic properties to contribute to overall drug response. PowerPoint Presentation: RECEPTOR GENOTYPES AND DRUG RESPONSE ENZYME GENES AND DRUG RESPONSE GENES FOR INTRACELLULAR SIGNALINGPROTEINS , ION CHANNELS, AND DRUG RESPONSE. DISEASE-ASSOCIATED GENES PowerPoint Presentation: Traditionally, genetic testing refers to screening human genetic material to identify genotypes associated with disease susceptibility or carrier status for inherited diseases, such as Huntington’s disease, Alzheimer’s disease, and breast cancer. PowerPoint Presentation: This kind of testing can have profound legal, ethical, and social implications . For example, knowledge that a patient is at risk for developing a genetic disorder could result in discrimination by employers or insurance companies. GENE THERAPY: GENE THERAPY Many of the ethical concerns with gene therapy center on transgenic manipulation of somatic versus germ-line cells . Somatic gene therapy only affects the recipient, that is, genetic alterations introduced by gene therapy are not passed on to future generations/ Gene therapy aims to cure disease caused by genetic defects by changing gene expression. . ROLE OF PHARMACISTS : ROLE OF PHARMACISTS Pharmacists are broadly trained in a number of medicationrelated areas , including pharmacology, pharmacokinetics, and pharmacodynamics . This training places pharmacists in a unique position to deal with the complexities of the drug-decision process in the age of pharmacogenetics . PowerPoint Presentation: Pharmacists will be in key positions to interpret the results of genetic tests, determine the ultimate effects of multiple genetic variations on drug response, and choose the most appropriate drug for a given patient based on the individual’s DNA.