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
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Ethnic and racial bias
Perception of stigma
Expensive
Impact on equity and access to the drugs