Pharmacogenomics

Pharmacogenomics

1. PHARMACOGENOMICS
-Jayati Shrivastava

2. Pharmacogenomics
•The term pharmacogenomics comes from the combination of
two words: "pharmacology" and"genomics".
•Pharmacology is the study of how drugs work in the body and
genetics is the study of how characteristics that result from the
action of a single gene or of several genes acting together are
inherited and how they work in the cells of the body.
•Therefore, pharmacogenomics is the study of genetic factors that
influence how a drugworks.
•Factors that influence how an individual responds to medication
include their external andinternal environments and overall
health, as well as their genetic make-up

3. Pharmacogenomics
The study of how genetics affects response to
medication/drugs
Select the right drug at the right dose for the right
patient
Used interchangeably with pharmacogenetics and
often shortened to PGx

5. Goal of Pharmacogenomics
•The goal of pharmacogenomics is to understand
the role that an individual's genetic make-up plays
in how well a medicine works, as well as what side
effects are likely to occur in the individual's body.
Understanding this can help tailor drugs for a
particular individual (personalised medicine) or
group of people.

6. Principle of Pharmacogenomics
Normal gene.
Today's Drug
SNP Varient
.
Pharmacogenomics Drug.

7. Genomic
•DNA is made of four "basepairs":A,T,G,C
•. Each gene is about 10,000
•base pairs of DNA sequence.
•. There are about 30,000-50,000
•genes. There are 2.9 billion base pairs in the human
genome, of which only 0.1% accounts for
differences between individuals and 3% of which
encode for genes.

8. SINGLE NUCLEOTIDE POLYMORPHISMS
•Single
nucleotide
polymorphism
s is DNA
sequence
variation
occurring
when a single
nucleotide
A,T,C or G in a
genome.

9. Pharmacogenomics can affect a drug.
•Pharmacokinetics (PK)-what the body does to the
drug (e.g. metabolism
• or
•Pharmacodynamics (PD)-what the drug does to
the body (e.g. drug target)

10. CYP Enzyme
•Group of enzymes which break down >90% of drugs.
•Name of each group member begins with 'CYP'.
•Series of numbers and letters distinguishes between different
group. members (e.g. CYP2D6, CYP3A4, CYP2C19).
•Changes in CYP enzymes can make them:
•More active than normal
•Less active than normal
•. Completely inactive
•Changes in CYPs are defined using 'star alleles' (e.g. *2, *17).
•People typically have two star alleles for each CYP gene (e.g.
*1/*2).

12. Using Pharmacogenomics to predict
effective ness.

13. Blood thinner used to prevent cardiac problems like
strokes or heart attacks.
Broken down to an active metabolite in the liver.
Active metabolite goes into the blood and stops
platelets from sticking together.
Clopidogrel is converted to the active metabolite by the
enzyme CYP2C19.
Pharmacokinetics example: Clopidogrel.

15. •CYP2C19 poor metabolizers don't make enough active
metabolite. Increased risk of cardiac problems.
•Guideline from Clinical Pharmacogenetics
Implementation Consortium (CPIC)

16. Pharmacodynamics example: aminoglycoside
antibody.
•Aminoglycosides bind bacterial 16S rRNA
molecules→ stops protein production and
•kills bacterial cell.
•MT-RNR1 encodes 12S rRNA molecule found in
humans. Some variants change 125 rRNA structure
to more closely resemble the 16S rRNA subunit
•Aminoglycosides bind variant 12S rRNA
molecules→→ kills inner ear cells → hearing loss

18. Benefits of pharmacogenomics:
•More rationale Medicines and therapy can be emerged
•Better, Safer profile of new Drugs the
•Improvements in the Drug Discovery and Approval
•Process
•>More Accurate Methods of Determining Appropriate
•Drug Dosages and individualization of therapy >
Decrease in the Overall Cost of Health Care

19. Barriers to pharmacogenomics progress:
•Complexity of finding gene variations that affect
drug response
•Limited drug alternatives No incentives for drug
companies to make multiple
•Pharmacogenomics products