PGx in clinical pratice

1. Discuss the benefits and challenges associated
with translation of pharmacogenomics in Clinical
practice

2. Human genome sequencing and the mapping of genetic variations between people are
two recent developments in DNA research. These interindividual genetic variants have
been linked to potential disease, treatment response, and adverse reaction risk in
recent years and have been employed to this end. Findings from pharmacogenetic
research have been used to varied degrees in a number of therapeutic sectors and are
anticipated to help a further move toward a more individualized, less empirical
approach to healthcare.
Molecular diagnostics and targeted medicines will have an impact on patient care,
clinical outcomes, and cost-effectiveness, but we are just starting to grasp how. The
application of pharmacogenomic research findings to clinical practice is hampered
despite major advancements by numerous scientific, financial, educational, legal, and
commercial impediments.

3. The study of genetically influenced variations in drug response, or
"pharmacogenomics," has also involved DNA sequencing. Pharmacogenomics is "the
study of differences in DNA and RNA properties as related to drug response," according
to the FDA.
BENEFITS
- Genetic biomarkers may support a shift in focus from population-based, empirical
treatment approaches toward ones that are stratified based on improved patient
results, ending the "trial-and-error" method of therapy as genomic medicine
develops. Only 50% of patients are thought to benefit from their drugs. As a result, if
a treatment is ineffective, half of the patient population may not receive the right
dosage or may face therapeutic delays.

4. - Since adverse drug reactions (ADRs) are a major cause of death in the United States, this
unpredictability poses a significant safety risk.5,7 Finding the genetic factors that may
predispose a patient to an ADR would be extremely helpful in preventing such reactions.
Genetic testing may also be useful for predicting drug interactions. Between 20% and 25% of
medications are thought to be at least partially metabolized by the cytochrome P450 (CYP)
isoenzyme 2D6 (CYP2D6).3 Patients who have multiple copies of the CYP2D6 gene may be
quick metabolizers of these medications and may not achieve therapeutic plasma levels at
the usual drug dose. On the other hand, people with few functional CYP2D6 genes may have
slow metabolisms, resulting in pharmacological levels that are higher than what is considered
to be therapeutic.

5. - Additionally, it is anticipated that molecular screening tests may be able to detect a
variety of diseases at an earlier stage, when they may still be treatable, preventative, or
even curable. Given that genetic information is available far before many disease
processes begin, early DNA testing may play a crucial role in disease preventive
measures. For instance, a laboratory test that finds increased cholesterol levels may
portend a future risk of heart disease. But before cholesterol levels rise, a genetic test
might spot a variation in the LDLR gene. Given that this DNA mutation can be found long
before cholesterol levels start to rise, genetic testing may therefore be more effective
than conventional phenotypic examinations.

6. CHALLENGES
- Personalised medicine will require more tests than normal to be
done
- High quality trial evidence of clinical utility in large population in
instances where drug response is influenced by complex
multifunctional traits
- Proving that these test add to the present best practice and
improves the outcomes remains a challenge due to issues such as
outdated information sources.
- Personal implication and potential change of way of living as
personalised medicine may provide much more information about
the health of an individual.

7. 1. COORDINATION- PGx requires stakeholders through the health ecosystem to
work together, but there may be challenges of cooperation or not being used
to work together.
2. RESOURCES- right staff, technology and funding is needed in order to sustain
the program of PGx. Once all resources are available the program of PGX will
succeed
3. KNOWLEDGE THAT PHYSICIANS CONCERNING PGx- tends out that physicians
has limited knowledge in PGx area and also how to implement implement
pharmacogenomics in their daily life. Educating physicians is the way to go.

8. 4. DRUG INTERACTIONS- Additionally, medication interactions can affect drug
responsiveness and frequently account for why a drug metabolism phenotype does
not precisely reflect a genotype. The interaction between heredity and environment
and how it affects pharmaceutical response is still partially understood. These
complicated considerations underscore the need for personalized prescriptions that
take phenotypic, environmental, and genetic information into account in order to
drastically lower therapeutic failures and adverse drug reactions.
5. PROLONGED RESEARCH- The prolonged and thorough research needed to
clinically confirm genetic risk factors that are thought to have an impact on
medication pharmacokinetics and pharmacodynamics is another complicating
element. There are not many pharmacogenetic applications that have evidence-
based guidelines because only 3% of published clinical data in this area focuses on
phase 2 trials and beyond.

9. 6. ENVIRONMENTAL FACTORS- Only 10% to 15% of genetic indicators, according
to estimates, are directly related to treatment response. Instead, a complex
interplay between environmental, genetic, and gene-environment interactions is
more frequently responsible for influencing drug response characteristics. For
instance, it's well documented that tumor-associated inflammatory responses
can inhibit CYP3A-mediated medication metabolism, which increases the
variability of docetaxel (Taxotere, Sanofi-aventis; Docefrez, Sun) drug clearance
and toxicity in cancer patients.