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

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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.