Pharmacogenomics.ppt

Disclaimers Grant funding from NIMH, NIGMS, NCI. Private foundations: Bakk Mental Illness Research Fund, Piscopo and Ruan Family Foundations. Consultant to Johns Hopkins for OMIM and NASA. Financial relationship from AssureRx for a patented treatment algorithm related to pharmacogenomic work. $0.00 to date. What is Psychiatric Pharmacogenomics? The use of genotypic screening to make clinical decisions about choice of psychotropic medication Most psychotropic medications are metabolized by the p450 enzymes True of selective serotonin reuptake inhibitors True of tricyclic antidepressants True of some benzodiazepines and antipsychotics There are at least ten key p450 enzymes Each is coded for by a specific gene. There is extensive variability in allele distribution of some of these genes. There is considerable variability in the distribution of these polymorphisms across different ethnic groups. Key polymorphisms of these genes are associated with variability in the effectiveness of metabolism Poor Metabolizers (PM) Intermediate Metabolizers (IM) Extensive Metabolizers (EM) Ultrarapid Metabolizers (URM) Poor Metabolizers Poor Metabolizer (PM) range in severity and can result in a serious inability to clear medications that can result in serious side effects. Intermediate Metabolizers Intermediate Metabolizers (IM) actually represent a wide range of levels of enzyme activity. Some intermediate metabolizers have fairly adequate capacity to produce sufficient enzymes while others are more vulnerable. Inhibition by other medications is intermediate metabolizers is a more serious concern. Extensive Metabolizers Extensive Metabolizers (EM) are “normal”. Molecular biologists refer to them as “wild types”. In most Caucasian populations they are in fact the most common genotype. Current dosing schedules assume that the patient is an extensive metabolizer. Ultrarapid Metabolizers Ultrarapid Metabolizers (URM) rapidly clear medications and can minimize or eliminate the th