NAME= MIRZA OMER - BBT193033

HEALTH BIOTECH SEC 2

A1 Pharmacogenomics
Date 4/7/2021

What is pharmacogenomics?
Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively
new field combines pharmacology (the science of drugs) and genomics (the study of genes and
their functions) to develop effective, safe medications and doses that will be tailored to a person’s
genetic makeup.
Many drugs that are currently available are “one size fits all,” but they don't work the same way
for everyone. It can be difficult to predict who will benefit from a medication, who will not respond
at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug
reactions are a significant cause of hospitalizations and deaths in the United States. With the
knowledge gained from the Human Genome Project, researchers are learning how inherited
differences in genes affect the body’s response to medications. These genetic differences will be
used to predict whether a medication will be effective for a particular person and to help prevent
adverse drug reactions
In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range
of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and
asthma.

Working Principal
For the same dose of a drug, two people might experience different effects because different
amounts of the drug reach the receptor sites; in other words they differ in drug
pharmacokinetics. People also differ in pharmacodynamics, for example the number of drug
receptors they have or their physiological response to a particular concentration of drug at the
site of action. Some of these differences are inherited and relate to the genetics of drug
metabolizing enzymes or receptor types and some are acquired as a person ages or suffers from
a disease.

How pharmacogenomics differs from genetic testing

Standard genetic testing is a type of testing that searches for specific genes. For example, a test
may look for BRCA1 and BRCA2 genes, which are linked with a higher risk of breast and ovarian
cancer. The results from standard genetic test may prompt preventive or risk reduction steps.
These include:

• More frequent cancer screening

• Lifestyle changes
• Preventive treatment
Pharmacogenomics is a type of genetic testing. It looks for small variations within genes. These
variations may affect whether genes activate or deactivate specific drugs. Test results help the
doctor choose the safest and most effective drug and dose. Pharmacogenomics is constantly
changing. Researchers continue to identify gene variations that affect how a drug works. As
personalized medicine grows, testing for gene variations may become more common.

Why drugs work differently in different people

Drug activation. Many drugs that treat cancer need to be "turned on" to work. This process is
called activation. Proteins called enzymes speed up chemical reactions in the body. This activates
a drug so that it can do its job.
Each person inherits variations in enzymes. The variations affect how fast a drug changes into its
active form. For example, some bodies break down drugs slowly. This means standard doses of
treatment may not work as well.

Drug deactivation. Drugs also need to be "turned off" to limit the drug’s exposure to healthy
tissues. This process is called
deactivation.
Some people may have slower
enzymes. As a result, high levels of the
drug may remain in their bodies for a
long time. This means that they may
have more side effects from the drug.
Besides pharmacogenomics, other
factors may influence a person’s
reaction to a drug:
 • Age and gender
• The cancer’s stage
• Lifestyle habits, such as smoking and drinking alcohol
• Other diseases
• Medications taken for other conditions

CYP2D6
CYP2D6- make a protein responsible for breaking many different
medications including the painkiller Codeine When CYP2D6 breakdown
codeine ,it converts into another biological molecule morphine
Some people have variant in the CYP2D6 gene that causes it to be Figure 1: Cytochrome P450 2D6 (CYP2D6) is an
enzyme involved in the metabolism of many drugs
less effective. When these people known as poor metabolizers, active in the central nervous system, such as
take Codeine, it doesn't get converted to Morphine as efficiently antidepressants, antipsychotics and central opioids.
This enzyme is coded by a polymorphic gene, with
this means the medication may be less effective at relieving pain. 7% of the Caucasian p
Other people has a variant in CYP2D6 that causes them to convert
Codeine to morphine too quickly. In these people known as
Rapid or Ultra Rapid metabolizer even normal doses of
Codeine can cause too much Morphine to build up in the
body. This means they Might be at an increased risk of side
effects one of the aim of pharmacogenomics is to
understand whether people are poor or Rapid metabolizes
for certain medications

Challenges to pharmacogenomics
Here are some challenges in the development and practical
use of pharmacogenomics:

• It is expensive, particularly if insurance does not cover the costs.

• Access to certain tests may be limited in some places.
• Privacy issues remain, despite federal anti-discrimination laws. These laws prohibit
discrimination based on genetic information.

Pharmacogenomic testing in practice

Here are some examples of pharmacogenomic testing in cancer care:

1. Colorectal cancer. Irinotecan (Camptosar) is a type of chemotherapy. Doctors

commonly use it to treat colon cancer. In some people, genetic variations cause a
shortage of the UGT1A1 enzyme. This enzyme is responsible for metabolizing
 irinotecan. Metabolism is the chemical reaction that helps the body process the
drug. With a UGT1A1 shortage, higher levels of irinotecan remain in the body.
This may lead to severe and potentially life-threatening side effects. The risk is
greater with higher doses of the drug.

UGT1A1 test
Doctors may use a pharmacogenomic test called the UGT1A1 test. It shows which people
have this genetic variation. Then, the doctor may prescribe a lower dose of irinotecan.
Often, the lower dose is just as effective for these people.

2. Acute lymphoblastic leukemia (ALL). Doctors use pharmacogenomic

testing for children with ALL. About 10% of people have genetic variations in
an enzyme called thiopurine methyltransferase (TPMT). TPMT is responsible
for metabolizing chemotherapy for ALL. Children with lower TPMT levels
receive lower chemotherapy doses. This helps prevent severe side effects.

3. Other cancer types.

Fluorouracil (5-FU) is a type of chemotherapy. It is used to treat several types of cancer
including colorectal, breast, stomach, and pancreatic cancers.
A genetic variation in some people causes lower levels of the enzyme called
dihydropyrimidine dehydrogenase (DPD). DPD helps the body metabolize fluorouracil.
Doctors may use a pharmacogenomic test to find this variation. If found, a lower
fluorouracil dose helps prevent serious side effects.

References:
https://www.ashp.org/-/media/assets/pharmacy-practice/resource-
centers/emerging-sciences/pharmacogenomics-principles-and-
concepts.ashx?la=en&hash=16C84DADBCC18588776025726E3D49B3E82D36B5

https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-
and-targeted-therapies/understanding-pharmacogenomics