This Presentation is about Pharmacogenomics and Pharmacogenetics , its Working , application, History. It also contain a little bit info related to polypharmacy and its effects. You can also see information regarding Drug Metabolism Phase, and drug Metabolizing Enzymes like CYPs, VKORC1, TPMT

1. PRESENTATION
ON
“PHARMACOGENOMIC”
Submitted to
Rajasthan University of Health Sciences, Jaipur
in partial fulfillment of requirement for award of degree of
Bachelor of Pharmacy
(Batch 2017-2021)
Supervised by:
Dr. Gaurav Bhaduka
(Associate Professor)
Submitted by:
Prakhar Gupta
Enrollment no. (2017/0685)
MAHATMA GANDHI COLLEGE OF PHARMACEUTICAL SCIENCES
ISI 15 (A) RIICO Institutional Area, Sitapura, Tonk Road, Jaipur-302022

2. CONTENTS
Introduction
History
Working of Pharmacogenomic
Application of Pharmacogenomic
Polypharmacy
Benefits
Reference
Conclusion

3.  Pharmacogenetics and Pharmacogenomics terms sometimes used
interchangeably.
 Pharmacogenetics: defined how variation in one single gene
influences response to a single drug.
 Pharmacogenomics:
Usually broader term than pharmacogenetics
How all of the genes in the genome can have effect in response
to drugs.

4. INTRODUCTION
• Pharmacogenomic = “Pharmaco +
Genomics”
• Pharmacogenomics is the study of the
role of the genome in drug response.
• It’s aim to develop rational means to
optimize drug therapy, with respect to
the patients genotype, to ensure
maximum efficiency with minimal
adverse effects.

5.  Drug metabolism phase
Phase I
• Functionalization reaction.
• Converts the parent drug to more polar metabolite by introducing or unmasking
a functional group (-OH, -NH2, -SH)
Phase II
• Conjunction reaction.
• Subsequent reaction in which a covalent linkage is formed between a functional
group on the parent compound or phase I metabolite and an endogenous
substrate such as glucuronic acid, sulfate, acetate, or an amino acid.

6.  Drug-metabolizing Enzymes
• There are several known enzymes which are largely responsible for the variances in drug metabolism and
response.
• The focus of this presentation will remain on the enzymes that are more widely accepted that are :-
i. Cytochrome P450s (CYP)
ii. VKORC1 (Vitamin K epoxide reductase complex subunit 1)
iii. TPMT ( Thiopurine methyltransferase)

7. (i). Cytochrome P450 (CYP)
• These are the most prevalent drug-metabolizing enzymes (DME). These enzymes introduce reactive or polar groups into
xenobiotics such as drugs. The human CYP family consists of 57 genes, with 18 families and 44 subfamilies.
• CYP proteins are conveniently arranged into these families and subfamilies on the basis of similarities identified between
the amino acid sequences.
• Enzymes that share 35-40% identity are assigned to the same family by an Arabic numeral, and those that share 55-70%
make up a particular subfamily with a designated letter. For example, CYP2D6 refers to family 2, subfamily D, and gene
number 6.
• The most commonly tested CYPs are:-
a) CYP2C9 :- Tolbutamide, ibuprofen, mefenamic acid
b) CYP2D6 :- Metoprolol, Propranolol
c) CYP2C19 :- Omeprazole
d) CYP3A4 and 5 :- Erythromycin, Nifedipine

8. (ii). VKORC1
• Vitamin K epoxide reductase complex subunit-1 (VKORC1) is responsible for the pharmacodynamics of warfarin.
• VKORC1 along with CYP2C9 are useful for identifying the risk of bleeding during warfarin administration.
(iii) TMPT
• Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurines, thereby regulating the balance between
cytotoxic thioguanine nucleotide and inactive metabolites in hematopoietic cells.
• TPMT is highly involved in 6-MP metabolism i.e. Mercaptopurine.
• Codeine, clopidogrel, tamoxifen are few examples of medications that follow
the above metabolic pathways.

9. History:-
YEAR INDIVIDUAL(s) LANDMARKS
510 B.C Pythagoras Recognition of the dangers of ingesting fava beans, later
characterized to be due to deficiency of G6PD.
1866 Mendel Establishment of the rules of heredity
1956 Carson et al. Discovery of glucose-6-phosphate dehydrogenase
deficiency.
1957 Kalow & Genest Characterization of serum cholinesterase deficiency
1957 Vogel Coined the term pharmacogenetics
1988 Gonalez Characterization of the genetic defect in debrisoquine
hydroxylase, later termed CYP2D6.
2000 Public Private partnership Completion of the first draft of the human genome

10. Working of pharmacogenomic:-
• Drugs interact with your body in numerous ways, depending both on how you take the drug and where the drug acts in
your body.
(i) Drug Receptors
Some drugs need to attach to proteins on the surface of cells called receptors in order to work properly.
Example: Breast Cancer and T-DM1

11. (ii) Drug Uptake
• Some drugs need to be actively taken into the tissues and cells in which they act. Your DNA can affect uptake of certain
drugs. Decreased uptake can mean that the drug does not work as well and can cause it to build up in other parts of your
body, which can cause problems.
Example : Statins and Muscle problem

12. (iii) Drug Breakdown
• Your DNA can affect how quickly your body breaks down a drug. If you break the drug down more quickly than most
people, your body gets rid of the drug faster and you might need more of the drug or a different drug. If your body breaks the
drug down more slowly, you might need less of the drug.
Example:- Depression and amitriptyline

13. APPLICATIONS OF PHARMACOGENOMIC :-
The list below provides a few commonly known applications of pharmacogenomic :
• Improve drug safety, reduce its ADRs;
• Tailor treatment to meet patients’ unique genetic pre- disposition, identify optimal dosing
• Improve drug discovery targeted to human diseases;
• Improve proof of principle for efficacy trails
Pharmacogenomics may be applied to several areas of medicine, including pain management, cardiology,
oncology, and psychiatry. A place may also exist in forensic pathology, in which pharmacogenomic can be used in
determine the causes of deaths where no findings emerge using autopsy.

14. Polypharmacy:
• Polypharmacy is often defined as a prescription of five or more drugs taken each day. This common since many
elderly patients , suffer from more than three medical diseases.
• Pharmacogenomics may play a potential role to reduce the occurrence of polypharmacy. It is theorized that
with tailored drug treatments, patients will not have the need to take several medications that are intended to
treat the same condition.
• They could potentially minimize the occurrence of ADRs, have improved treatment outcomes, and can save
costs by avoiding purchasing extraneous medications.

16. Conclusion:-
So pharmacogenetics and pharmacogenomics are the terms
sometimes used interchangeably. Its major aim is to develop
rational mean to optimize drug therapy, according to
patients genotypes, to ensure maximum efficacy and
minimal adverse effects or no adverse effects and also to
improve drug discovery targeted to human diseases.
This study also help to reduce the polypharmacy so that
elderly patients won’t need to take many medicines for
different diseases and to overcome the ADR.

17. Reference:-
1. Arias, E. (2010). United States life tables, 2006. National Vital Statistics Reports, 58(21). Retrieved from
http://www.cdc.gov/nchs/data/ nvsr/nvsr58/ nvsr58_21.pdf
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3. Jump up to: Johnson JA (November 2003). "Pharmacogenetics: potential for individualized drug therapy through
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4. "overview of pharmacogenomics". Up-to-Date. May 16, 2014. Retrieved 2014-06-25.
5. "Center for Pharmacogenomics and Individualized Therapy". Unc Eshelman School of Pharmacy. Retrieved 2014-06-
25.
6. Shin J, Kayser SR, Langaee TY (April 2009). "Pharmacogenetics: from discovery to patient care". American Journal
of Health-System Pharmacy. 66 (7): 625– 37. doi:10.2146/ajhp080170. PMID 19299369.
7. Nebert DW. Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist? Clin Genet.
1999; 56:345–347.
8. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;
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AND MORE…….