Mar. 31, 2010: Lecture- Introduction to Pharmacogenomics
After this lecture, you should be able to answer the following:1. What is the difference between pharmacogenetics and pharmacogenomics?
2. Describe the clinical implications for poor metabolizers of substrates for N-acetyltransferase (NAT2). What adverse effect of isoniazid is observed in NAT2 poor metabolizers?
3. With respect to CYP2D6, what types of metabolic phenotypes have been observed? Which ethnicities have high percentages of poor metabolizers? Use the metabolic clearance of nortriptyline as an example of interindividual variability in drug clearance. How many alleles of CYP2D6 have been observed in the population?
4. What is thiopurine methyl transferase (TPMT)? What are the common TPMT alleles in the human genome? Describe the interindividual variability among children taking these drugs for leukemia? How can one assay the function of TPMT activity in vitro? What other type of method can be used to test for polymorphisms? With respect to the dose of thiopurine drug, what should be done in patients that are poor-metabolizers?
5. Why are people with glucose 6-phospho dehydrogenase deficiencies prone to severe hemolysis when exposed to oxidant drugs such as antimalarials such as primaquine or chloroquine? What is malignant hyperthermia? Discuss this disorder from a pharmacogenomic point of view.
6. What are SNPs? Are SNPs common or uncommon?
7. What are ABC transporters?
8. What is the MDR1 transporter? What is its physiological role? Its pathophysiological role?
9. You have identified a new SNP in the CYP3A4 enzyme. Design both in vitro and in vivo experiments to determine whether or not that SNP affects the function of the 3A4 enzyme.
10. How is it possible that a life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia? Provide a possible explanation.
11. Describe abacavir hypersensitivity in term of pharmacogenomics. What is abacavir normally used for?
The following web-site contains some more information on pharmacogenomics. It is maintained by the U.S. Department of Energy and also has some interesting links relating to pharmacogenomics:
http://ornl.gov/sci/techresources/human_genome/medicine/pharma.shtml
The following web-site contains information on toxicogenomics. Toxicogenomics is the science interested in understanding the effects of toxicants on the genome. Type in your favorite toxicant, and see what comes out of the database!!
http://ctd.mdibl.org/
The following web-site contains information on SNPs.
http://www.aacr.org/home/public--media/patients--family/fact-sheets/cancer-concepts/snps.aspx/
Good Luck!
posted by Blase Billack, Ph.D. @ 2:45 PM
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