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Pharmacogenetics

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  • 1. Pharmacogenetics Dr. Gyanendra Raj Joshi PharmD, RPh
  • 2. Pharmacogenetics • Definition: – Pharmacology – Genetics • Study of genetic factors that influence how a drug works. • Pharmacogenomics – Use of genetic information for choice of drug
  • 3. Genetic determinants of drug response • Transporters • Metabolizing enzymes • Receptors
  • 4. Genetic polymorphism • Genotype • Phenotype • Monogenic traits • Polygenic traits • Single nucleotide polymorphisms (SNPs)
  • 5. • G-6-P-D deficiency • Over expression of P-gp resulting to tumor resistance • N-acetyl transferase 2 (NAT2 ) gene polymorphism • Malignant hyperthermia
  • 6. • CYP polymorphism – CYP2C9 : slow warfarin metabolism – CYP2D6: antidepressants , antipsychotic toxicity • Thiopurine methyl transferase (TPMT) deficiency : bone marrow toxicity • Succinylcholine apnoea
  • 7. Current use of pharmacogenetics • Personalised medicine • Determine drug responses in the treatment of cardiac , respiratory and psychiatric conditions. • Develop drug targets in the treatment of cancers • Classify patients as slow and fast metabolisers of drugs • Gene therapy
  • 8. • Drug Response : – ACE inhibitors better in Europeans – Some people lacking response to salbutamol • Drug targets: – Haloperidol and its ability to bind with D2 receptors – HER2 gene and drug Herceptin (trastuzumab) • Drug metabolism – Cytochrome P450 enzyme system
  • 9. Benefits of pharmacogenetics • More powerful medicines • Safer drugs the first time • More accurate methods of determining the dosages • Better vaccines
  • 10. Limitations of pharmacogenetics • Complex targeting due to multiple gene involvement • Difficult and time consuming to identify small variations in genes • Interaction with other drugs and environment to be determined
  • 11. Ethical issues • • • • Ethnic and racial bias Perception of stigma Expensive Impact on equity and access to the drugs