This document provides an overview of pharmacogenomics. It defines pharmacogenomics as the study of how genetic variations influence individual drug responses. It discusses how single nucleotide polymorphisms (SNPs) can alter drug metabolism and response. Examples are provided of genes like G6PD, TPMT, CYP2D6 and CYP2C9 that influence drug toxicity and efficacy. Benefits of pharmacogenomics include more powerful and safer drugs through personalized treatment based on an individual's genetic profile. Ethical concerns around privacy, discrimination, and drug availability are also discussed.

1. By,
Shabnam Relhan
M.Pharm(Biotech.)
AIP

2. OVERVIEW
 Pharmacogenomics
 Single nucleotide polymorphism
 Importance of pharmacogenomics
 Examples of altered drug reponse
 Benefits of pharmacogenomics
 Pharmacogenomic drugs
 Ethical concerns
 Challenges to the growth and expansion

3. PHARMACOGENOMICS
 Pharmacology + Genomics = pharmacogenomics

4. PHARMACOGENOMICS
 IT IS THE BRANCH OF PHARMACOLOGY WHICH
DEALS WITH THE INFLUENCE OF GENETIC
VARIATION ON DRUG RESPONSE BY CO-
RELATING GENE EXPRESSION OR SINGLE
NUCLEOTIDE POLYMORPHISM WITH A DRUG’S
EFFICACY OR TOXICITY.
 It is an approach to PERSONALIZED MEDICINE.

5. SINGLE NUCLEOTIDE
POLYMORPHISMS (SNPs)
 A Single Nucleotide Polymorphism (SNP) are DNA
sequence variation that occurs when a single
nucleotide in the genome sequence is altered.
 …CTAGATACGAACTGCATC…
 …CTAGATACGGACTGCATC…
 Occur in atleast 1% of the population and make up
about 90% of all human genetic variation
 •Frequency: 1: 300 to 500 Nucleotides

6. Personalized Medicine
 It refers to an approach of clinical practice
where a particular treatment is not chosen
based on the ‘average pateint’ but on
characteristic of an individual pateint.

7. Simple Definition

8. Corelation
Pharmacogenetics:- The study of
inherited differences or variations in
drug metabolism and response.
Pharmacogenomics:- The study of the
role of inheritance in individual
variation in drug response.

9. IMPORTANCE OF
PHARMACOGENOMICS
 “ONE SIZE FITS ALL” Only work for
about60 percent of the population at the
best. And the other 40 percent of the
population increase their risks of adverse
drug reaction because their genes do not do
what is intended of them

10. ONE SIZE DOES NOT FIT ALL
 A 1998 study of hospitalized patients
published in the Journal of the American
Medical Association reported that in 1994,
adverse drug reactions accounted for more
than 2.2 million serious cases and over
100,000 deaths, making adverse drug
reactions (ADRs) one of the leading causes
of hospitalization and death in the United
States.

11. EXAMPLES OF ALTERED DRUG RESPONSE
ENZYME/DISEASES GENE
GLUCOSE -6 -PHOSPHATE G6PD
DEHYDROGENASE DEFICIENCY
THIOPURINE S-METHYL TRANSFERASE TPMT
CYTOCHROME P450 ENJYME AND - CYP2D6
DRUG METABOLISM
WARFARIN AND COAGULATION
CYP2C9 VKORC1

12. GLUCOSE 6-PHOSPHATE
DEHYDROGENASE
 It is a cytosolic enzyme.
 Enjyme in Hexose Monophosphate Shunt
 It is a principal source of NADPH generation.
 NADPH is required to reduce the thiol groups on the
glutathione and other proteins.
 Glutathione prevents the Red blood cells damage.

14. GLUCOSE 6- PHOHPHATE
DEHYDROGENASE DEFICIENCY
 GSH deficiency in Red blood cells results in
 Membrane Fragility Haemolysis Hemolytic
Anaemia
SYMPTOMS:-
Prolonged neonatal jaundice
Hemolytic Anaemia.

15. GLUCOSE 6- PHOHPHATE
DEHYDROGENASE DEFICIENCY

16. SOME AGENTS THAT CAUSE HEMOLYSIS IN
G-6-P D DEFICIENT INDIVIDUALS
 Primaquine
 Nitrofurantoin
 Sulfacetamide
 Sulfanilamide
 Sulfapyridine

17. EXAMPLES OF ALTERED DRUG RESPONSE

18. Thiopurine methyl transferase
 It is an enjyme that methylates thiopurine compounds.
 The methyl donor is S- adenosyl-L- methionine which
is converted to S-adenosyl-L-homocysteine.
 TPMT is best known for the role in the metabolism of
thiopurine drugs such as :-
 Azathioprine
 6- Mercaptopurine
 6- thioguanine

19. THIOPURINE METHYL
TRANSFERASE DEFICIENCY
 Decreased methylation Decreased
inactivation of 6 MP
Bone marrow toxicity
Anaemia, Bleeding tendency,
and infection.

20. EXAMPLES OF ALTERED DRUG RESPONSE

21. CYTOCHROME P450
CYP:- It is a host of enzyme that use iron
to oxidize things.
Found in liver and small intestine.
There are thousand different cytochromes
Although the no. in man is only about 50

22. CYP ISOFORMS
CYP3A4
CYP2D6
CYP2C9
CYP2C19

23. CYTOCHROME P2D6
 There is high expression of CYP2D6 in many persons
of Ethiopian and Saudi Arabian origin.
 2D6 is not inducible, so these people have developed a
different strategy to cope with the high load of toxic
alkaloids in their diet .
 These CYPs therefore chew up a variety of drugs,
making them ineffective - many antidepressants and
neuroleptics

24. CYTOCHROME P2D6 Deficiency
 Many individuals lack functional 2D6.
 These subjects will be predisposed to drug toxicity
caused by antidepressants or neuroleptics
 Other drugs include:
 Dexfenfluramine
 Perhexiline (withdrawn from the market due to
neuropathy)

25. EXAMPLES OF ALTERED DRUG RESPONSE

26. WARFARIN
 •The Most Commonly Prescribed Anticoagulant
 •Patients Maybe: Resistant - Need Higher Dose to
Prevent Strokes
 Sensitive - Need Lower Dose to Prevent CNS Bleeds
 • Warfarin Is Metabolised by the Cytochrome P450,
Cyp2c9
 • Warfarin Metabolism Involves Vitamin K Epoxide Reductase
(VKORC1).

30. BENEFITS OF
PHARMACOGENOMICS
 More Powerful Medicines
 Safer Drugs The First Time
 More Accurate Methods Of
Determining The Dosages.
 Better Vaccines.

32. PHARMACOGENOMIC DRUGS
HERCEPTIN
GLEEVAC

33. ETHICAL CONCERNS
 Many fear the implications pharmacogenomics can bring to their
lives:
1. Through the development of individual pharmacogenomic
profiles, an individual's privacy and confidentiality are at risk
2. Certain individuals (such as Health Insurance Companies or
Employers) can obtain the profiles of others and use the "weak
points" in their genes to discriminate
(The U.S. Senate and the U.S. House of Representatives are
attempting to pass the Genetic Information Nondiscrimination
Act of 2007 in hopes of protecting individuals from genetic
discrimination in terms of health insurance and employment).

34. ETHICAL CONCERNS

3. Since the drugs are more focused, the test
groups become smaller, which can lead to rare
and more fatal Adverse Drug Reactions
4. Developing drugs beneficial to one group but
dangerous to another

5. Should physicians inform patients that due to
their genetic makeup, they have a high chance of
developing a disease that currently has no effective
treatment?

35. ETHICAL CONCERNS

6. How will the FDA regulate the development and
distribution of genetic tests and associated
medicines?
7. It will become challenging to fully inform
patients on possible risks.
8. Will these "personalized medicines" be
available only to those who can afford it?


36. Challenges to the growth and
Expansion
 Education of various healthcare providers regarding
pharmacogenomics.
 Potentially smaller and more specialized drug markets.
 Resistance to genetic testing.
 Ethical & Legal issues.
 Expense.

37. REFERENCE
 One size does not fit all: The promise of
pharmacogenomics A pharmacogenomics primer for
the national centre for Biotecnology
information(NCBI)
 Zdanowicz Martin M” Concept in
Pharmacogenomics” page no-61-66
 Ingelman-Sundberg et al.
Polymorphic cytochrome P450 enzymes: an
opportunity for individualized drug treatment
Trends in Pharm Sci Aug 1999 342-9

38. Reference
 Eichelbaum M, Ingelman-Sundberg M, Evans WE.
“Pharmcogenomics and individualized drug
therapy”. Annu Rev Med. 2006.57:119-137.
 Dr D.P katare “Basics in Biotechnology”page no. 267-
269

39. THANK YOU