Pharmacogenomics
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Transcript of Pharmacogenomics
SK Banu, G.V.K Deepti, K Chandana, VT. Ana and B V
Krishnareddy
HOD, Department of Pharmacology, RAOS College of
Pharmacy, Nellore-524320, INDIA
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Pharmacogenomics: A revolution in
pharmaceutical R & D and personalized drug
therapy
Genomics: The study of gene organization
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.
Technical foundations of genomics
Molecular biology:
recombinant-DNA
technology
DNA sequencing
Library construction
PCR amplification
Hybridization
techniques
Log M
W
Distance
. ...
SINGLE NUCLEOTIDE
POLYMORPHISMS
Single nucleotide
polymorphisms is DNA
sequence variation
occurring when a single
nucleotide A,T,C or G in
a genome.
GENETIC POLYMORPHISM
GENETIC
POLYMORPHISMS
PHARMACOKINETIC PHARMACODYNAMIC
Transporter Metabolism Receptor Enzymes Ion
Channels
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Pharmacogenomics is the branch of pharmacologywhich deals with the influence of genetic variation ondrug response in patients by correlating geneexpression or single-nucleotide polymorphisms with adrug's efficacy or toxicity.
By Using genetic information to predict whether adrug is suitable foe individual patient or not withouttrail and error method of prescription.
Pharmacology + Genomics =Pharmacogenomics
Principle of PharmacogenomicsNORMAL
GENESNP VARIANT GENE
TODAY’S DRUG
PHARMACOGENOMIC DRUG
What makes pharmacogenomics
possible today?
Sequencing of the human genome reveals 2.9 billion base
pairs that are constant, narrowing down variability to
about 3 million base pairs, of which 100,000 capture the
full human variation and <10,000 may be
pharmaceutically relevant.
Advances in genome sequencing technology make
possible addressing those individual base pairs.
Automatization and miniaturization significantly drive
down cost of DNA sequencing reaction.
Computer technology and computer networks facilitate
handling of data.
FIG:Phenotype–genotype correlation for the CYP2D6
polymorphism. For phenotype determination, individuals
were given a probe drug, such as debrisoquine, and the
ratio of the metabolite-parent drug used to determine the
metaboliser status.
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In today's world, only 30-60% of drugs work effectively to rid of
a patient's illness. However, with the application of
pharmacogenomics, the success rate of drugs will increase to
100%, curing all patients, while decreasing the side effects
significantly.
FIG: Possible Impact of pharmacogenomics on drug
therapy
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Pharmacogenomics: drug therapies
tailored to individuals
Design therapies based on the individual’s genome
Subtle, but important, differences in genomes
Cause differences in how one responds to drugs
Identify those who will suffer harmful side effects
from particular drugs
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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
The value of pharmacogenomics to the
pharmaceutical industry
14
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; and
• the development of molecular genetic tests for
prediction of drug response, or drug selection
and dosing based on genotype or gene
expression.
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
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Conclusion: There is general acceptance that the
field of pharmacogenomics is going to be one of first
areas to impact on clinical care following the
completion of the human genome. However, although
there are many opportunities, there are also
significant 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.