Study of how an individual’s genetic inheritance affects the body’s response to drugs

1. Pharmacogeno
mics
Submitted to :
Dr Gurpreet Kaur
Department of Plant Breeding and Genetics
Submitted by :
Anusha K.R
L-2021-H-88-D
PhD 1st year
Department of Vegetable Science

2. Pharma, the Greek word i.e.
Pharmacon, related to drugs.
Genomics, related to the genome.
Pharmacogenetics is the study of the genetic
basis for variation in drug response.

3. Dose and medicine selection based on the genomic
profile
Refers to how variation in one single gene
influences the response to a single drug
Study of how an individual’s genetic
inheritance affects the body’s
response to drugs.
WhatisPharmacogenomics?

4. Deals with the influence of genetic variation on
drug response by co-relating gene expression or
polymorphism with a drug's efficacy or toxicity.
It intends to identify individuals who are either
more likely or less likely to respond to a drug and
those who require altered doses of certain drugs.
Study of the variations in a targeted gene,
or group of functionally related genes for
variability in drug response
Use of genetic information to guide
the choice of drug and dose on an
individual basis.

5. WhatistheneedofPharmacogenomics?
• To develop effective, safe medications and doses
that will be tailored to a person’s genetic
makeup.
• "One size fit all" is applicable to most drugs but
doesn’t work the same way for everyone.
• Difficult to predict who gets the benefit and
who will experience negative side effects.

6. Whydodrugsworkdifferentlyindifferentpeople?
Occupational exposures
Diet
Diseases
Age
Drug activation
Drug deactivation
Gender
Alcohol intake/ Smoking

7. FoundationofPharmacogenomics
Mutation
• The difference in the DNA code that occurs in less than 1% of the population.
• Often associated with rare diseases like Cystic fibrosis, sickle cell anemia, Huntington's disease
Polymorphism
• Difference in the DNA code that occurs in more than 1% of the population
• A single polymorphism is less likely to be the main cause of a disease
• Polymorphisms often have no visible clinical impact

8. • May result in a different amino acid or stop codon
• May result in a change in protein function
• No effect
• A Single Nucleotide Polymorphism (SNP) are DNA sequence
variation that occurs when a single nucleotide in the genome
sequence is altered.
• Occur in at least 1% of the population and makeup about 90% of
all human genetic variation

9. Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug
targets causes inter-individual differences in the efficacy and toxicity of many medications

10. GoalsofPharmacogenomics
• Maximize drug efficacy
• Minimize drug toxicity
• Predict patients who will respond to intervention
• Aid in new drug development

11. Thevalueofpharmacogenomicstothepharmaceutical
industry
The scope of clinical pharmacogenomics includes:
• the identification and characterization of candidate genes and polymorphisms
• the correlation of polymorphisms with therapy,clinical outcomes and drug effects
• the development of molecular genetic tests for prediction of drug response, or drug
selection and dosing based on genotype or gene expression.

12. Adequatetherapeuticresponse

13. Geneticpolymorphismindrugtransport
• P-Glycoprotein multidrug transporter (MDR1)
• Vincristine, vinblastine, doxorubicin, daunorubicin
• MDR1 - major cause for Low drug level in cells

14. Geneticpolymorphismsindrugmetabolism
• CYP2D6- Tricyclic antidepressants
o Poor metabolizers - high plasma
concentration-toxic effects.
o Rapid metabolizers - low plasma
concentrations - therapeutic failure
• Codeine (as analgesic)
Poor metabolizers - therapeutic failure
• CYP2C9
-Warfarin-slow metabolism-high risk of bleeding
• CYP2C19
- Clopidogrel- Loss of function alleles - decreased
activation of clopidogrel

16. Barrierstopharmacogenomicsprogress
• Complexity of finding gene variations that affect drug response
• Limited drug alternatives
• No incentives for drug companies to make multiple
Pharmacogenomics products

17. AdvantagesofPharmacogenomics
• To predict a patient's response to drugs
• To develop 'customized' prescriptions
• To minimize or eliminate adverse events
• To improve efficacy and patient compliance
• To improve rational drug development
• To improve the accuracy of determining appropriate dosages of drugs
• To screen and monitor certain diseases
• To develop more powerful, safer vaccines
• To allow improvements in drug research and development (R&D) and the approval of new drugs

18. Disadvantages
• Many genes are involved in drug action, making the drug
target very difficult
• Insufficient validation of study results
• Identification of small inter-individual variations in everyone’s
gene is very difficult
• Expensive
• Ethical issues

19. Conclusion
• There is general acceptance that the field of pharmacogenomics is
going to be one of the first areas to impact clinical care following the
completion of the human genome.
• However, although there are many opportunities, there are also
significant challenges, challenges, which will require a multidisciplinary
effort, not only within healthcare but also within the commercial
sector.
• There is a need to build upon recent successes; however, this is going
to require funding, and indeed of all the 'economics' will be the
ultimate driver.

20. Thankyou