Pharmacogenetics - introduction, history,case study,etc

1. Pharmacogenetics
Submitted To - Dr. Shaweta
Sharma
Submitted By – Pushpak
Singh Bhati

2. Overview
 Pharmacogenetics
 Historical Milestones
 Aim of pharmacogenetics
 Benefits of pharmacogenetics
 Steps in pharmacogenetics
 challenges of Pharmacogenomics
 Case Study

3. Pharmacogenetics
The word “Pharmacogenetics” comes
from the words :
 Pharmacology - The science of
drugs
Genetics - The study of genes and
their functions
Pharmacogenetics is the study of
how an individual's genetic makeup
influences their response to drugs,
guiding personalized medication
approaches.

4. Pharmacogenetics Historical
Milestones
1959
Friedrich Vogel coined the
term "pharmacogenetics" to
describe the genetic-based
differences in drug response
1968
Vesell's twin studies supported the
inference of genetic involvement in
drug metabolism, with identical twins
sharing remarkable similarities to
drug response as compared to
fraternal twins.
2003
Completion of the
Human Genome
Project (HGP).
2005
First FDA approval of a
pharmacogenetic test
(for alleles in CYP2D6
and CYP2C1).

5. Aim of Pharmacogenetics
Individualized
Treatment
Enhanced
Efficacy
Safety
Improvement
Optimized
Dosage
Reduced Trial
and Error
Advancing
Precision
Medicine

6. For example, if the same drug is given to 4 different people, the rate at which they are able to metabolize the drug will
vary.
Genetic variations in pharmacogenomics (PGx) alter how a drug moves through the body (ADME) and affects its action
by disturbing proteins in its mechanism or immune regulation.

7. Benefits of pharmacogenetics
Advancing
Precision
Medicine
Cost-Effective
Healthcare
Drug
Development
Improving
Treatment
Outcomes
Guiding Clinical
Decision-
Making
Enhancing
Drug Efficacy
Minimizing
Adverse
Reactions
Dosing
Precision
Optimizing
Drug Selection
Personalized
Treatment
Improved
Patient
Adherence

8. steps in pharmacogenetics
Patient
Assessment
Genetic Testing
Decision
Informed
Consent
Genetic Testing
Interpretation
of Results
Clinical
Decision
Support
Treatment Plan
Adjustment
Communication
with Patient
Documentation
Monitoring and
Follow-Up
Education and
Counselling
Research and
Advancements

9. Drug Genetic Test Result Effect Considerations
Warfarin
CYP2C9 and
VKORC1
Positive (Variant) Increased bleeding risk
Adjusted dosing, more frequent
monitoring
Negative (Wild
type)
Reduced therapeutic
effect
Standard dosing, regular monitoring
Clopidogrel CYP2C19 Positive (Variant)
Reduced antiplatelet
effect
Consider alternative antiplatelet
medications
Negative (Wild
type)
Normal antiplatelet
response
Standard therapy, monitored for
efficacy
Abacavir (for HIV) HLA-B57:01
Positive
(Presence)
Risk of hypersensitivity
reaction
Avoid use; alternative antiretroviral
therapy considered
Negative (Absent)
Lower risk of
hypersensitivity
Safe for use, monitored for adverse
reactions

10. Technologies and methods that used in
pharmacogenetics
Genetic Testing:
 Polymerase Chain Reaction
(PCR)
 Next-Generation Sequencing
(NGS)
 Sanger Sequencing
Genotyping Techniques:
 Microarrays
 Allele-Specific PCR
Pharmacokinetic Modelling:
 Population Pharmacokinetics
(PopPK)
Electronic Health Records
(EHR):
 Clinical Decision Support
Systems (CDSS)

11. Clinical
pharmacogenetics
resources
Clinical Pharmacogenetics
Implementation Consortium (CPIC)
Sequence2Script : online tool to translate
pharmacogenetic test results into clinically
useful recommendations.
PharmGKB: provides information about
how human genetic variation affects
response to medications.
Phenoconversion calculator : To assist
clinicians in implementing a consistent and
standardized approach for evaluating
CYP2D6 phenoconversion in clinical
practice.

12. Challenges of Pharmacogenetics
Data Interpretation and Standardization
Patient and Provider Education
Complex Regulatory Landscape
Dynamic Nature of Genetic Information
Cost and Accessibility
Limited Clinical Evidence
Ethical and Privacy Concerns
Diversity in Genetic Testing Platforms:
Psychosocial Impact

13. Recent Updates
In 2022, the Clinical Pharmacogenetics
Implementation Consortium (CPIC)
published new guidelines for warfarin
dosing that incorporate
pharmacogenetic information. These
guidelines are expected to help improve
the safety and efficacy of warfarin
therapy.
FDA approval of the first
pharmacogenetic test for clopidogrel in
2021, the FDA approved the first
pharmacogenetic test for clopidogrel, a
blood thinner used to prevent heart
attacks and strokes. The test, called the
CYP2C19 genotyping test, can identify
patients who are at risk of poor response
to clopidogrel.

14. Case Study
Background and
Introduction:
• The aging population is
increasingly using
multiple medications,
leading to a higher risk of
drug-related issues.
• Pharmacogenomics (PGx)
is discussed as a tool to
optimize medication
regimens by identifying
genomic variants
affecting drug disposition
and response.
Case Description:
• A 59-year-old patient
with MDD, GAD, and
chronic pain experienced
a fall due to excessive
sedation caused by a
prescribing cascade of
fluoxetine, bupropion,
and doxepin.
• The patient was also
taking hydrocodone for
chronic pain.
• Pharmacogenomics (PGx)
testing was eventually
performed to understand
the genetic factors
influencing drug
metabolism and
response.
Pharmacist
Recommendations:
• A pharmacist-led fall
consult recommended
tapering off doxepin due
to its high sedative
burden and suggested
PGx testing to inform
antidepressant and
opioid therapy.
• PGx results revealed
genetic variants
influencing drug
metabolism.
• Pharmacist
recommendations
included adjusting
antidepressant therapy
and considering
alternative opioids based
on the PGx results.
Discussion:
• Drug-induced
phenoconversion is
common in older adults
with polypharmacy,
especially in the
treatment of MDD and
pain.
• PGx-guided prescribing
for antidepressants and
opioids is discussed as a
way to improve response
rates and reduce adverse
drug reactions.
• The case highlights the
importance of
considering drug–gene
interactions (DGIs) and
drug–drug–gene
interactions (DDGIs) in
medication management.

15.  Enhanced Medication Precision: Pharmacogenetics allows for a personalized approach,
optimizing drug selection and dosing based on individual genetic factors, potentially improving
treatment outcomes.
Reduced Adverse Events: By identifying genetic variants impacting drug metabolism,
pharmacogenetics helps minimize the risk of adverse drug reactions, promoting safer
medication regimens.
Streamlined Treatment Optimization: Integrating pharmacogenomics in clinical decision-
making can streamline the trial-and-error process, leading to more effective antidepressant
and pain management strategies.
Preventive Medication Safety: Proactive pharmacogenetic testing, when applied pre-
emptively, holds promise in preventing medication-related issues, offering a proactive
approach to patient care.

16. conclusion
• Pharmacogenetics presents a transformative
frontier in healthcare, promising personalized
treatment strategies based on individual genetic
profiles. Despite challenges in genetic variability,
ethical considerations, and integration,
advancements in technology, AI, and collaborative
research are propelling its future.
• For instance, the implementation of
pharmacogenetic data in routine clinical practice,
enhanced by standardized testing methods and
global cooperation, can optimize drug selection and
dosing. This evolution toward patient-centric,
genetically informed medicine reflects a promising
paradigm shift with the potential to revolutionize
therapeutic approaches and ultimately improve
patient outcomes.

17. •Thank You