Transcript Pharmacogenomics: Using a Patient*s Genetic Blueprint to

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Lotricia Guerrier, ARNP/CNS, CCNS, FNP-BC, CCRN
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The learner will be able to:
o Define pharmacogenomics
o Define pharmacogenetics
o Discuss potential use of pharmacogenomics with prescribing and
medication management.
o Identify resources for interpreting results of genetic drug testing.
o Discuss implications of pharmacogenomics for future healthcare
research.
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No conflicts of interest have been disclosed by the
presenters or planning committee of this activity
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“One size fits all” and “trial and error”
Difficult to determine who will respond and how
Adverse drug reactions and allergies are a significant cause
of hospitalization and death in the US
Personalized Medicine
Providers base the majority of their drug prescriptions on
clinical factors, such as a patient’s age, weight, sex, and
liver and kidney function.
For a small subset of drugs, researchers have identified
genetic variations that influence how people respond.
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Genetic factors may account for 20-95% of the observed
variation in drug response
Five Stages of Pharmacokineticso Absorption into the body
o Distribution to the their site of action in the body
o Target interaction-binding to cellular receptors
o Metabolic processing -using the drug and giving off byproduct
o Excretion from the body-getting rid of the byproduct
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Gender
Age
Body Mass
Diet
Other medications
Exposure to certain
chemicals/toxins (ie
cigarette smoking)
Particular disease states.
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PharmacoGENETICs- the study of genetic influences on an
individual’s response to drugs.
o Analysis of a specific gene or group of genes
o Use to predict responses to a specific drug or class of drugs
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PharmocoGENOMICs-refers collectively to all the genes that
influence a drugs response
o Examines the entire genome
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New field that combines pharmacology (the science of drugs)
with genomics (the study of genes and their functions)
Genetic differences will be used to predict whether a medication
will be effective for a particular person and to help prevent
adverse drug reactions.
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Pharmocokinetico Impacts drug metabolizing enzymes and drug transporters
o How the drug is handled by the body
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Pharmacodynamico Impacts drug targets such as enzymes, receptors, ion channels, and
their associated pathways.
o How the body is effected by the drug.
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In the future, pharmacogenomics will allow the
development of tailored drugs to treat a wide range of
health problems, including cardiovascular disease,
depression, Alzheimer’s, cancer, HIV/AIDS, and asthma.
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Efficacy-maximum benefit or therapeutic response that a
drug can produce
Toxicity-the extent to which a drug induces unwanted or
harmful health effects.
High Efficacy + Low toxicity= most ideal drug regimen
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CYP2D6 gene -This enzyme acts on a quarter of all prescription
drugs, including the painkiller codeine, which it converts into the
drug’s active form, morphine.
Some people have hundreds or even thousands of copies of the
CYP2D6 gene (typically, people have two copies of each gene).
Those with extra copies of this gene manufacture an
overabundance of CYP2D6 enzyme molecules and metabolize
the drug very rapidly.
As a result, codeine may be converted to morphine so quickly and
completely that a standard dose of the drug can be an overdose.
On the other end of the spectrum, some variants of CYP2D6
result in a nonfunctional enzyme. People with these variants
metabolize codeine slowly, if at all, so they might not experience
much pain relief.
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HIV-Before prescribing Abacavir an antiviral drug, routine
testing of the genetic variant that increases likelihood of
adverse reaction
Breast Cancer- Trastuzumab - this drug only works for
women whose tumors have a particular genetic profile that
leads to the overproduction of a protein called HER2
Acute Lymphoblastic Leukemia (ALL)- MercaptopurineGenetic variant interferes with ability to process the drug,
causing severe side effects and increased risk of infection
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The Food and Drug Administration, which monitors the
safety of all drugs in the United States, has included
pharmacogenomic information on the labels of more than
150 medications.
This information—which can cover dosage guidance,
possible side effects or differences in effectiveness for
people with certain genomic variations—can help providers
tailor their drug prescriptions for individual patients.
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Pharmaceutical companies are beginning to use
pharmacogenomic knowledge to develop and market drugs for
people with specific genetic profiles.
Studying a drug only in those likely to benefit from it could speed
up and streamline its development and maximize its therapeutic
benefit.
Additionally, if scientists can identify the genetic basis for certain
serious side effects, drugs could be prescribed only to people
who are not at risk for them.
As a result, potentially lifesaving medications, which otherwise
might be taken off the market because they pose a risk for some
people, could still be available to those who could benefit from
them.
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Pharmacogenetic testing should only be performed based
upon medical necessity.
o Patients taking a large number of medications with the potential for
serious adverse effects.
o Patients taking medications with a high risk of drug interactions.
o When patients do not respond to drug treatment and options are
limited.
o Patients with an unexpected pattern of side effects to medications.
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Reduced number of clinic visits to titrate medications or
select new medications.
Reduced total medication cost because fewer pills are
“wasted” because they are not effective.
Improved efficiency and time savings in managing patients.
Reduced risk of drug interactions and adverse events.
Increased medication adherence.
Studies show that 38% of Americans do not metabolize
antidepressants properly and 50% of Americans are poor
metabolizers of arthritis medications.
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Average costs range from $250-$500
FDA approved list is generally reimbursed by most
insurance companies.
Most insurance companies consider the vast majority of
these test “experimental” because of lack of high quality
research results with each one.
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Some laboratories are offering a larger number of gene tests
Some laboratories are only offering tests that are “reimbursed”
by insurance and they are ignoring the value of broader gene
testing.
The changing reimbursement landscapes by Medicare and other
payers is making it difficult for laboratories to provide “all
inclusive” testing that is not based on medical necessity.
Reports are getting better, and easier to interpret and implement.
Improved reports are less intimidating to providers and helps
them embrace pharmacogenetic testing faster
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The test is a simple specimen collection via a buccal (q-tip)
swab. It is non-invasive and the provider receives the results
generally within 48 hours.
It is a ONE TIME test with a lifetime impact.
Repeat testing is not needed unless additional genes are
available in the future.
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Genetic Test Registry (GTR)
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Find tests for a condition or drug response
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Query for a test by clicking on the Tests tab on the home page or by selecting 'Tests' from the pull-down menu to
the left of the Search button on any other page,
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Start typing the name of the condition or drug.
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If you see the name of the disorder in which you are interested appear under the query bar, click on it, otherwise
click on Search
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If you used Search, the result page will probably list multiple disorders in the left column. Click on the one you
want
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If there are multiple tests listed for the condition in which you are interested, you can focus on those of most
interest to you by selecting from filter options in the left column, such as method used in the test, certifications of
the offerer, and location of the laboratory.
Find tests using words in the test name
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Query for tests with one or more words in the test name within the Tests tab.
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Use double quotation marks around the word(s) and an asterisk after the last word, e.g.
"mitochondrial*"[testname]" or "respiratory chain*"[testname]. Click Search.
Find a laboratory
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Query for a laboratory by clicking on the Labs tab on the home page or by selecting 'Labs' from the pull-down
menu to the left of the Search button on any other page
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You can query on any of the following: name of tests, conditions, genes, proteins, laboratories, staff, or services.
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Start typing your query
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If you see the value in which you are interested appear under the query bar, click on it, otherwise click on Search.
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If there are multiple laboratories listed in the result set, you can focus on those of most interest to you by
selecting from filter options in the left column, such as certifications, special services, and location of the
laboratory.
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Clinical Pharmacogenetics Implementation Consortium
(CPIC) Dosing Guidelines
FDA- drug labeling
Lab
Pharmacist
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Drug labeling may contain information on genomic
biomarkers and can describe:
o Drug exposure and clinical response variability
o Risk for adverse events
o Genotype-specific dosing
o Mechanisms of drug action
o Polymorphic drug target and disposition genes
Amitriptyline
 Aripiprazole
 Atomexetine
 Carvedilol
 Celecoxib
 Citalopram
 Clopidogrel
 Codeine
 Diazepam
 Phenytoin
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Exomeprazole
 Imipramine
 Metoprolol
 Pantoprazole
 Risperidone
 Tolterodine
 Tramadol
 Warfarin
 Nitrofurantoin
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More research
o Various medications
o When used a tool, not exclusively, will it truly impact overall
outcomes.
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The National Institute of General Medical Sciences offers a list of Frequently Asked Questions about Pharmacogenomics. .
http://www.nigms.nih.gov/education/Pages/factsheet-pharmacogenomics.aspx
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Additional information about pharmacogenetics is available from the Centre for Genetics Education
http://www.genetics.edu.au/Publications-and-Resources/Genetics-Fact-Sheets/FactSheet25
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GTR: Genetic Test Registry-is a single location to learn more about genetic tests, including those used for pharmacogenomics.
http://www.ncbi.nlm.nih.gov/gtr/
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The Smithsonian National Museum of Natural History’s exhibit ‘Genome: Unlocking Life’s Code’ discusses the utility of
pharmacogenomics http://unlockinglifescode.org/explore/genomic-medicine/pharmacogenomics.
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The Genetic Science Learning Center at the University of Utah offers an interactive introduction to pharmacogenomics.
http://learn.genetics.utah.edu/content/pharma/
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The American Medical Association explains what pharmacogenomics is and provides a list of practical applications.
http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/currenttopics/pharmacogenomics.page
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The National Genetics and Genomics Education Centre of the National Health Service (UK) provides information about predicting
the effects of drugs. http://www.geneticseducation.nhs.uk/genomics-in-health/predict-drug-effects
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PharmGKB is a pharmacogenomics resource sponsored by the National Institutes of Health that collects information on human
genetic variation and drug responses also includes CPIC Guidelines. https://www.pharmgkb.org/
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Questions/Comments?