Pharmacogenetics

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