Transcript Pharmacogenomics

Pharmacogenomics: Improving the
Dynamic of Care in Medication
Management
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Main Topics
• Current Issues in Medication Management
and Pharmacogenomics
• Brief Biology & Pharmacogenomics
Overview
• Drug Metabolism
• Clinical Implementation and physician
adoption of Pharmacogenomics
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Current Issues in LTC
• New CMS Five Star Ratings
• Antipsychotic drugs - 693,000 residents
revealed that 32.2% lacked appropriate
indications for use 28.5% of the doses
received were excessive
• Adverse Drug Reactions (ADR’s): Over
350,000/yr in nursing homes alone
• Unnecessary Medications - 27% of residents
take 9 or more medications
Institute of Medicine, National Academy Press, 2000;
Lazarou J et al. JAMA 1998;279(15):1200–1205:
Gurwitz JH et al. Am J Med 2000;109(2):87–94
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Issues
Elderly Populations
• Drug treatments may be unpleasant,
painful, and life-threatening
Drug Metabolism
• A patient may need twice the
standard dose to be effective
• A drug works for one patient but not
another
• One patient has side-effects and
another doesn’t
Drugs
• Ineffective drugs cost $billions/year
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Medication-related Problems
• Falls, dizziness, impaired coordination
• GI bleeding
• Headaches, muscle pain, generalized
aching/pain
• Rash, pruritus
• Seizure activity
• Spontaneous or unexplained bleeding, bruising
• Unexplained decline in functional status
• Urinary retention or incontinence
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High Cost of Adverse Drug Reactions
(ADRs)
• ADR’s are 4th leading cause of in death in the US
• 5th leading cause of illness
2.2 million hospitalizations per year
• 28% of hospitalized patients have ADRs
• Cost of drug related morbidity & mortality =
$177 billion
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Cost of ADR’s in Long Term Care
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Average hospital cost: $1,939 to $2,595 per ADR
Total additional hospital cost: $3 - $4 billion
Nursing facilities cost due to ADRs: $7.6 billion
Medicare spends $3.5 billion on ADR’s in hospital
setting and they account for 2-8% of
readmissions
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Quick Tour of You and Your DNA
46 Chromosomes
3 billion base
pairs
100,000 genes
capture full
human variant
Less than 10,000
may be
pharmacologically
relevant
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Genes
• Over 20,000 genes (which encode proteins)
• 99.9% shared by humans, only 0.1% different
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SNP’s (“SNIPS”) and DNA Variation
• SNP’s are a variation in
the DNA sequence when
a single nucleotide (A, T,
C, or G) differs in
individuals
• These DNA variations
can affect how humans
develop diseases and
how they respond to
medications
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Past Approach to
Medication Management
“Adults: take 2 aspirin”
What if Wilt is a poor
metabolizer and Bill is an
ultrarapid metabolizer of
another pain med?
Pharmacogenomics is a
stronger determinant of
efficacy than dosing
factors such as age,
weight and gender
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New Definition of Medication
Management using Pharmacogenomics
“Products and Services that leverage
genomics (directly or indirectly) to
enable individualized approaches to care,
and to choose the right medication at
the right dose at the right time”
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Personalized Medication Management
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Pharmacogenomics: “The study of
how Genes affect a person’s
response to medication”
• Pharmacogenomics seeks to predict what
response an individual will have to a drug
• Human drug metabolism is largely an
inherited trait
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Genes and Drug Metabolism
• Variations in genes that code for proteins can
lead to poor response and ADR’s
• Cytochrome P450 genes encode enzymes that
influence the metabolism of 70-80% of current
prescription drugs
• Common examples are pain meds and
antipsychotics, (CYP2D6), Warfarin (CYP2C9 &
VKORC1), and Plavix (CYP2C19)
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Examples of known medication issues
• Plavix – 19% of Americans are poor
metabolizers. The FDA has added warning to
Plavix label and recommends genetic testing
• Warfarin – very narrow therapeutic range; 20% of
patients are hospitalized for bleeding within 6
months of starting. Research shows roughly
60% of patients should be prescribed a nonstandard dose.
• Oncology: several drugs have known lethal
toxicities and Pharmacogenomic testing is
required before administering
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Interpreting Reports - Genotype and
Phenotype
• Genotypes are the
letters of the DNA, or
the Genes inside you.
You cannot SEE
Genotype.
• Phenotypes are the
physical characteristics
that you have - you can
SEE Phenotype.
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Drug Response by Phenotype
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Example: Codeine Metabolism & 2D6
2D6 Phenotype Frequency in population:
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Codeine Metabolism and Response
- Active Drug
(Warfarin) takes
effect immediately
-Prodrug (Codeine)
becomes active after
metabolism
-Poor Metabolizers
of Codeine get little
or no response
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Majority of Drugs are Ineffective
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Individualized Medication Management
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Pharmacogenomics (PGx)
Guided Treatment
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Variables involved in Personalized
Medication Management
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Physician attitudes towards adoption of PGx
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Reading a Pharmacogenomics Test Report
PGx Test Result Interpretation - Example
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Current Medications and “Guidance Levels”
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Current Meds and Guidance Levels (cont)
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Potentially Impacted Medications and
Drug Appendix
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PGx Case Study Follow-up
In response to PGx test results for this resident ,
action (in the form of medication changes) was
taken in which outcomes improved
Physician Report on quality of life improvement:
Resident discontinued Risperidone. Zyprexa initiated 2.5mg.
Remeron was increased to 15mg. “Behaviors improved and
not as many listless days”
PGx changes = “red flag” antipsychotic with possible toxic
side effects stopped; new antipsychotic (Zyprexa) added;
dosage of antidepressant with no warnings increased
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Benefits of Pharmacogenomics
• End to Trial and Error - Enables doctors to prescribe the
“right dose of the right medicine at the right time”
• Increase the effectiveness of patient’s medication
• Reduce or eliminate drug toxicity or treatment failures
• Decrease adverse drug events (ADR’s)
• Decrease the total number of drugs taken by an
individual
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