Post on 09-Apr-2018
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Mirza Ahmed Hammad
Changing the world to
individual Drugs managementsystem
Ph a rm acoG e n o m ics
:Roll No 1255 -Session 2007 2011
D
e p a r t m e n t
O f
-
B i o
I n f o r m a t
i c s
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Pharmacogenomics
The study of genome-derived data to predicta bodys response to a drug or susceptibility to adisease:
Human genetic variation in DNA Single nucleotide polymorphisms (SNPs) Copy number differences Insertions Deletions
Duplications Rearrangements
RNA and protein expression differences
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D rugs costs are
! e sca la tin g
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..Drug efficacy is questioned
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UK ADRs Study
6.5% of new hospital admissions to internalmedicine wards are directly related to ADRs!(1,225 admissions out
of 18,820 during sixmonths)
4% of bed occupancy - directly due to ADRs
Annual UK cost: EUR 706 million(direct hospitalization costs - actual costs muchhigher!)
Women: 59% of ADRs (while only 52% of admissions)
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:Treat Responders and Patients
Not Predisposed to Toxicity
l l pat ients with same diagnosis
:Remove( ) -1 non responders( )2 toxic responders
Which is more urgent?
What should our prioritiesbe?
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Improving drug efficacy Difficulties with ensuring better Drug
Efficacy:
Tailoring the most effective drug anddosage for the individual patient isextremely complex.(exception: in oncology some success)
Hundreds of polymorphic gene alleles areinvolved
Many non-genetic factors participate indrug efficacy:
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Are we Ready for Personalized Medicine?
Better Drug Efficacy? Not Yet!We are not yet ready, with few exceptions:
- Oncology (Herceptin, anti-EGFR)- Depression (5-HTT genotyping)
- High blood pressure Bidil (FDAapproved June 2005)(ethnic considerations in drug prescription asan interim phase ACE inhibitors ineffectivein African-Americans, preference for NOdonors & calcium channel inhibitors)
In most medical disciplines, we are not likelyto be ready for Personalized Medicine in the
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Medicine If we focus first on better drug
safety Consideration #1: Society almost ready..- Growing public awareness on costs of
drug toxicity(both economic costs and human suffering)
- Growing awareness of genetic factorsaffecting health
for complex diseases (not just forgenetic disorders)
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(Almost) Ready for Personalized Medicine
Consideration #2: Government almost read
Drug regulatory agencies are (almost) ready:USA: In March 2005, the FDA has issued the
Guidance forIndustry: Pharmacogenomic Data
Submissionshttp://www.fda.gov/cber/gdlns/pharmdtasub.h
Europe: In February 2005, WHO/CIOMSWorking Group onPharmacogenetics has issued the report,
Pharmacogenetics
Towards improving treatment with medicines(Council for International Organizations of Medical
http://www.fda.gov/cber/gdlns/pharmdtasub.htmhttp://www.fda.gov/cber/gdlns/pharmdtasub.htm8/7/2019 Current PharmacoGenomics
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Medicine If we focus first on better drug
safety Consideration #3: Pharmaceutical Industry Pharma, which traditionally objected to PGx a
a threat
to market size and profits, begin to see theadvantages:
- Lower costs for clinical trials (lessparticipants)
- New orphaned markets- Can charge more for safer drugs
- Marketing a diagnostic test along withthe drug
can bring added revenues
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Medicine If we focus first on better drug
safety Consideration #4: Diagnostic Tools Diagnostic tools focusing on better drug
safety have been approved by the FDAand the EC and are entering the market:
Roche Diagnostics AmpliChip P450:- approved by the EC in September
2004, and by the FDAin December 2004
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AmpliChip CYP450: CYP2D6 &CYP2C19
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urren rac ce: r a anError
- What about Safety?
Toxicity No Effect
!Oops!Oops Too Much Too Little
Decrease dose Increase dose
No effect
Increase dose or change drug
Toxicity
Decrease dose or change drug
Favorable Effect
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Drug Pharmacokinetics
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Depression The most prevalent affective
disorder:10%-20% of the population
(lifetime)
Decreased raphe serotonin
Excessive activity of the serotonin
transporter??
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Health, Genes, & Society:Where do we go from here?
Should we oblige industry to do'something' for people who do not
have the right genotype for theirdrug? What should it include?
How can society ensure betterequality in healthcare, along withindividualization of
pharmacotherapy?
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: Personalized Medicine
, : Not if rather when?
Opinion : (~ )This sort of card would initially 2025? include mostly information related to drug metabolizing enzymes
~Around 2050 it might include an entire individual genome( , ..)or at least few millions SNPs
In your wallet by2025?
Or maybe by 2050?
N
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... NewYorker]
Are we ready?! :Not quite yet We need
Comprehensive data Affordable genotyping
tools
Professional Education !Solving ethical issues
,Meanwhile we should focus on improving drugsafely :
!This is almost at hand
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REFERENCES & Conclusion
Although it is expected to take another decade forPharmacoGenomics to be an accepted andintegral part of mainstream healthcare, butwith the help of other Biological groupsattached with the Genomes could catapult theindustry into the public consciousness. Drugsbased on individual testing can be moreeffective giving required or near to requiredresults. For this there is a need of developing
new Biomarkers, Cell responses, Biotechnologytools and Bio-Informatics tools, so thatdiagnosis and screening of a disease couldeasily be done.