knowledge of pharmacogenomics and in ayurveda their importance.

1. Knowledge
of
Pharmacogenomics
Presentedby
Vd. Dharmendrakumarpandey
Guided by
Vd. S. B. Singh
Ex. Associate professor
Dravyaguna
GACH, PATNA

2. People having
same diseases
and same
medication
Severe adverse
effect
No effect
Partial response
Full response
Variation in drug response
Response with side
effect

3. INTRODUCTION
• Why does this drugs for you but not for me ?
• Why does someone need twice the standard
dose to be effective ?
• Why do have side-effect and you don’t?
• Why do some people get cancer and other
don’t?

4. Limitation of conventional allopathic
medicine
• Genetic variation not considered in drug
development.
• Reductionist approach rather than holistic
approach.
• ADR due to lack of selectivity in some case.

5. Pharmacogenetic :-
The study of variation in drug responses which
are under hereditary control.
Or
Study of difference in inherited genetic material
which effect the individual response to drugs.
Or
The study of variations in DNA sequence as
related to drug response.

6. Definition:-
• Pharmacogenomics combination of two
words pharmaco + genome , reflects its
combining of pharmacology and genomics.
• Study of how genetics affects response to
medication/drugs.
• Study of variation of DNA and RNA
characteristics as related to drug response.

7. Conti….
• Normally, you have two copies of each gene.
• You inherit one copy from each parent.
• At any single point in your DNA sequence,
you have two letters.
• Genotype- combination of DNA letters at a
certain point( e.g. A T ,C G).
• Phenotype- A physical characteristics which is
influenced by your genotype.

8. History
• Pharmacogenomics was first recognised by
Pythogoras around 510 BC.
• Pharmacogenetic term was first coined in 1959
by FRIEDRICH VOGEL of Heidelberg.
• Pharmacogenomics first began appearing
around the 1990s.
• The first FDA approval of a pharcogenetic test
was in 2005 ( for alleles in CYP2D6 and
CYP2C19)

9. Factor affecting drugs response
Gender
Environmental agents
Age
Body mass
Co-medication
Diet
Genetic factor
Disease

10. Genetic factor

11. DNA sequence variation that occurs when a single nucleotide in
genome sequence is altered.

12. • DNA contains instruction called genes.
• Genes tell the cell how to make proteins.
• Changes in DNA sequence causes in proteins.
Gene
Protein

13. Principle of pharmacogenomics
A T
Today’s drug
Pharcogenomic drug
Normal variant
Protin (drug target)
SNP variant
Protein (drug target)

14. Pharmacokinetcs example- clopidogrel
• Blood thinner used to prevent
cardiac problems like strokes or
heart attacks.
• Broken down to an active
metabolite in the liver.
• Active metabolite goes into the
blood and stops platelets from
sticking together.
• Clopidogrel is converted to the
active metabolite by the
enzyme CYP2C19.
clopidogrel
intermediate
Active
metabolite
CYP2C19
CYP3A4
CYP2C19 CYP2B4
CYP3A4
CYP1A2

15. Pharmacodynamics example-
aminoglycoside antibiotics
aminoglycoside
aminoglycoside aminoglycoside
12Sr RNA
MT-RNR1
16s r RNA
Gram negative
bacterial cell
TRANSLATION
CELL DEATH
MITOCHONDRION
TRANSLATION
CELL DEATH
HEARING
LOSS
•Aminoglycosides bind bacterial 16srRNA molecules- stops protein production and kills
bacteral cell.
•MT-RNR1 encodes 12s Rrna molecule found in humans- some variants change 12sr
RNA structure to more closely resembles the 16s rRNA subunit.
•Aminoglycosides bind variant 12sr RNA molecules- kills innerear cells-hearing loss.

16. CYP enzymes
• Group of enzymes which break down >90% of drugs.
• Name of each group member begins with ‘CYP’.
• Series of numbers and letters distinguishes between
different group members(e.g. CYP2D6, CYP3A4,
CYP2C19).
• CHANGES IN CYP enzymes can make them:
More active than normal.
Less active than normal
Completely inactive.
• Changes in CYPs are defined using ‘star alleles’
• People typically have two star alleles for each CYP gene.

17. Decreasing function
• Star alleles can be used to predict a person’s
metabolized phenotype:
Ultrarapid metabolizer
Rapid metabolizer
Normal metabolizer
Poor metabolizer

18. Aim
• Select the right drug at the right dose for the
right patient.
• Used interchangeably with pharmacogenetics.

19. One fits all medication Personalized medication
Without personalized medicine:
Some benefit, some do not, some ADR
With personalized medicine:
Each patient receives the right medicine for
them
patients
therapy
Benefits
patients
Biomarker
diagonostics
Therapy
Each patient benefits from
individualized treatment
ADR effect
No benefits

20. Advantages of pharmacogenomics :-
• To predict a patient’s response to drugs
• To develop ‘customized’ prescriptions.
• To minimize or eliminate adverse events.
• To improve efficacy and patients compliance.
• To improve rational drug development.
• To screen and monitor certain diseases.
• To deveelop more powerful, safer vaccines.
• To allow improvements in drug research and
development(R&D)and the approval of new
drugs.

21. Barriers of pharmacogenomics:-
1. complexity of finding gene variations that affect
drug response.
 Millions of SNPs must be identified and analyzed to
determine their involvement ( if any ) in drug
response.
Many genes are likely to influence response.
Limited knowledge of which genes are involved with
each drug response.
Confidentiality, privacy and the use and storages of
genetic information.

22. Barriers of pharmacogenomics
2. Educating healthcare providers & patients
Complicates the process of prescribing and
dispensing drugs.
Physicians must execute an extra diagnostic step
to determine which drug is best suited to each
patient.
Need for a better understanding of genetics by all
physicians.

23. Barriers of pharmacogenomics
3. Disincentives for drug companies to make
multiple pharmacogenomic.
 Most pharmaceutical companies have been
successful with their “one size fits all” approach
to drug development.
 For small market- pharmaceutical companies has
to spend hundreds of millions of $ on
pharmacogenomics based drug development

24. &

25. Doshas are restrained within normal limits in
health
 perturbation in doshic proportions beyond
threshold leads to disease.
 The proportion of vata, pitta, kapha invariant
in an individual
Vata
Pitta Kapha
सर्वशरीरचरास्तु र्ातपित्तश्लेष्माणः सर्वस्मिञ्छरीरे क
ु पिताक
ु पिताः शुभाशुभापि क
ु र्वस्मि-
प्रक
ृ पतभूताः शुभान्युिचयबलर्णवप्रसादादीपि, अशुभापि िुिपर्वक
ृ पतमािन्ना पर्कारसञ्ज्ञकापि||च०सु०
20/9
Vata, pitta, & kapha pervade the entire body and thus produces good or bad consequences in the entire
body when non aggravated or aggravated. In the state of normalcy good consequences like
development, strength, complexion, cheerfulness etc. while in that abnormality they cause bad
consequences known as disorders
Tridoshas: latent variables that determine prakriti

26. AYURVEDA
• हिताहितं सुखं दुुःखमायुस्तस्य हिताहितम|
मानं च तच्च यत्रोक्तमायुर्वेदुः स उच्यते||
च०सू०1/41

27. त्रयस्तु िुरुषा भर्न्त्यातुराः, ते त्विातुरास्तन्त्रािरीयाणा पभषजाम्|
तद्यथार्ातलः, पित्तलः, श्लेष्मलश्चेपत|
तेषापमद पर्शेषपर्ञािर्ातलस्य र्ातपिपमत्ताः, पित्तलस्य पित्तपिपमत्ताः,
श्लेष्मलस्य श्लेष्मपिपमत्ता व्याधयः प्रायेण बलर्िश्च भर्स्मि|| च०पर्०
6/15
Normal phenotypic variation as “prakriti” concept described in ayurveda 1500 bc
Ayurveda classifies individuals into seven prakriti types.
सप्त प्रक
ृ तयो भर्स्मि- दोषः िृथक
् , पिशः, समस्तश्च ||६२||sushuta sharira 4/62
Three most contrasting prakriti : vata , pitta & kapha are most vulnerable.

28. Prakriti: Outcome of Genes &
Environment
• शुक्रशोपणतसयोगे यो भर्ेद्दोष उत्कटः |
प्रक
ृ पतजावयते तेि तस्या मे लक्षण शृणु || (सु शा ४/६३)
• Prakriti is a consequence of relative
proportion of three physiological entities
(tridoshas )vata, pittaand kapha which is not
only genetically determined.
• But also influenced by-
तत्र प्रक
ृ पतजावपतप्रसक्ता च, क
ु लप्रसक्ता च, देशािुिापतिी च,
कालािुिापतिी च र्योऽिुिापतिी च, प्रत्यात्मपियता चेपत|
जापतक
ु लदेशकालर्यःप्रत्यात्मपियता पि तेषा तेषा िुरुषाणा
ते ते भार्पर्शेषा भर्स्मि || च०इ०1/5

29. शरीरार्यर्ास्तु िरमाणुभेदेिािररसङ्ख् येया भर्स्मि,
अपतबहुत्वादपतसौक्ष्म्यादतीस्मियत्वाच्च|
तेषा सयोगपर्भागे िरमाणूिा कारण र्ायुः कमवस्वभार्श्च || च ०शा ०7/17
Body components according to division in smallest units are innumerable due to over
abundance, over minuteness and trancending perception. The causative agent in conjunction
and disjunction of cell is vata and alo nature of activties.
Vata regulates all activity body co-ordination with PITTA and KAPHA at
equilibrium stage
समदोषः समापिश्च समधातुमलपक्रयः |
प्रसन्नात्मेस्मियमिाः स्वस्थ इत्यपभधीयते ||४१|| su . Sutra 15

31. Ayurgenomics
Ayurgenomics combine of two words i.e.
Ayur+ genomics
ayurveda genomes
Study of ayurveda (basic concepts and prakriti)
and their correlation with human genome with
help of modern technology as termed as
ayurgenomics

32. Genetic basis of prakriti
• Early studies in 2005 evaluated76 subject both for theirprakriti
and human leucocyteantigen HLA DRB1 type.
– Corelation between HLA type prakriti
• HLADRB1*02 absent in vata prakriti
• HLADRB1*13 absent in kapha type
• HLA DRB1*10 had higherallele frequency in kapha type compared pitta
&vata.
• Study in 2010 high altitude adaptation and prakriti (in table)
Prakriti type Gene expression Disease
Kapha/vata EGLN1 higher High altitude pulmonary
edema
Pitta EGLN1 lower More adaptive for higher
altitudes

33. Modern medicine and ayurgenomics
• Modern medicine uses a highly redutionist system to
describe the fundamental basis of our physiology and
health, using term like genome, gene expression and
epigenetic.
• Ayurveda an entirely different holistic system includes
dosha and prakriti.
• Ayurgenomics offers a new bridge between traditional
and modern medicine by providing a rigorous scientific
understanding of basic concepts and at the same time
incorporating the practical preventative approaches of
ayurveda into modern medicine.

34. • तद्यथा
शुक्रशोपणतप्रक
ृ पत, कालगभावशयप्रक
ृ पत, आतुरािारपर्िारप्रक
ृ पत, मिाभूतपर्कारप्रक
ृ पत च गभवशरीर
मिेक्षते|
एतापि पि येि येि दोषेणापधक
े िक
े िािेक
े ि र्ा समिुबध्यिे, तेि तेि दोषेण गभोऽिुबध्यते; ततः
सा सा दोषप्रक
ृ पतरुच्यते मिुष्याणा गभावपदप्रर्ृत्तातिाच्छ्लेष्मलाः प्रक
ृ त्या क
े पचत्, पित्तलाः क
े पचत्,
र्ातलाः क
े पचत्, ससृष्ाः क
े पचत्, समधातर्ः क
े पचद्भर्स्मि| तेषा पि लक्षणापि व्यायास्यामः||९५||
charak vi. 8
• श्लेष्मा पि पिग्धश्लक्ष्म्णमृदुमधुरसारसािमन्दस्मस्तपमतगुरुशीतपर्ज्जलाच्छः|
तस्य िेिाच्छ्लेष्मलाः पिग्धाङ्ाः, श्लक्ष्म्णत्वाच्छ्लक्ष्म्णाङ्ाः, मृदुत्वाद् ृपष्सुखसुक
ु मारार्दातगात्राः, मा
धुयावत् प्रभूतशुक्रव्यर्ायाित्याः, सारत्वात् सारसितस्मस्थरशरीराः, साित्वादुिपचतिररिूणवसर्ावङ्ाः, म
न्दत्वान्मन्दचेष्ािारव्यािाराः, स्तपमत्यादशीघ्रारम्भक्षोभपर्काराः, गुरुत्वात् सारापधपितार्स्मस्थतगतयः,
शत्यादल्पक्षुत्तृष्णासिािस्वेददोषाः, पर्ज्जलत्वात् सुस्मश्लष्सारसस्मधिबबधिबिाः, तथाऽच्छत्वात् प्रसन्नदशव
िाििाः प्रसन्नपिग्धर्णवस्वराश्च भर्स्मि|
त एर्ङ्ख् गुणयोगाच्छ्लेष्मला बलर्िो र्सुमिो पर्द्यार्ि ओजस्मस्विः शािा आयुष्मिश्च भर्स्मि||९
६||charak vi. 8

35. Pitta prakriti
• पित्तमुष्ण तीक्ष्म्ण द्रर् पर्स्रमम्ल कटुकञ्च|
तस्यौष्ण्यात् पित्तला भर्न्त्युष्णासिा, उष्णमुखाः, सुक
ु मारार्दा
तगात्राः [१] , प्रभूतपर्प्लुव्यङ्पतलपिडकाः, क्षुस्मििासार्िः, पक्ष
प्रर्लीिपलतखापलत्यदोषाः, प्रायोमृिल्पकपिलश्मश्रुलोमक
े शाश्च
; तक्ष्म्यात्तीक्ष्म्णिराक्रमाः, तीक्ष्म्णाियः, प्रभूताशििािाः, क्लेशा
सपिष्णर्ो, दन्दशूकाः; द्रर्त्वास्मच्छपथलमृदुसस्मधिबमासाः, प्रभूतसृ
ष्स्वेदमूत्रिुरीषाश्च; पर्स्रत्वात् प्रभूतिूपतकक्षास्यपशरःशरीरग
धिबाः; कट्वम्लत्वादल्पशुक्रव्यर्ायाित्याः; त एर्ङ्ख
् गुणयोगात् पि
त्तला मध्यबला मध्यायुषो मध्यञािपर्ञािपर्त्तोिकरणर्िश्च भ
र्स्मि || च०पर्०8/97
•

36. Vata prakriti and sansargat prakriti
• र्ातस्तु रूक्षलघुचलबहुशीघ्रशीतिरुषपर्शदः|
तस्य रौक्ष्यािातला रूक्षािपचताल्पशरीराः प्रततरूक्षक्षामसन्नसक्तजजवरस्वरा
जागरूकाश्च भर्स्मि, लघुत्वाल्लघुचिलगपतचेष्ािारव्यािाराः, चलत्वादिर्
स्मस्थतसन्ध्यपक्षभ्रूिन्वोिपजह्वापशरःस्कधिबिापणिादाः, बहुत्वाद्बहुप्रलािकण्डरा
पसराप्रतािाः, शीघ्रत्वाच्छ
र ीघ्रसमारम्भक्षोभपर्काराः शीघ्रत्रासरागपर्रागाः श्रुत
ग्रापिणोऽल्पिृतयश्च, शत्याच्छीतासपिष्णर्ः प्रततशीतकोिेिकस्तम्भाः, िारु
ष्यात् िरुषक
े शश्मश्रुरोमिखदशिर्दििापणिादाः, र्शद्यात् स्फ
ु पटताङ्ार्य
र्ाः सततसस्मधिबशब्दगापमिश्च भर्स्मि; त एर्ङ्ख
् गुणयोगािातलाः प्रायेणाल्पबला
श्चाल्पायुषश्चाल्पाित्याश्चाल्पसाधिाश्चाल्पधिाश्च भर्स्मि||९८|| च०पर्०8/98
•
ससगावत् ससृष्लक्षणाः||९९|| च०पर्० 8/99

38. P4 medicine
• Over the last ten years, a new field has arisen in modern
medicine, which known as P4 medicine.
• Four Ps :-
• Predictive
• Preventive
• Personalized
• Participatory
• P4 medicine attempts to switch the emphasis from a
disease oriented system to wellness oriented system
centered around the patient.
• Ayurveda have been patient oriented and predictive,
preventive, personalized and participatory for many
thousands of years.

39. • Bharat since ancient times has been practising
predictive & personalised medicine.
• िेतुपलङ्ौषधञाि स्वस्थातुरिरायणम्|
पत्रसूत्र शाश्वत िुय बुबुधे य पितामिः||२४|| च०सु० 1
• It also had an advanced way of dealing with
health and diseases management through
personalized recommendations.
• The good news is that this is contemporary and
can propel discoveries with modern sciences.

40. P4 medicine -
• Genetic polymorphism causes variation in body
and mind.
• Genotypic and phenotypic variation called
prakriti
• Responses to drug & susceptibiltiy to a disease
depands on prakriti
• Classical ayurvedic text says-
– योगमासा तु यो पर्द्याद्देशकालोििापदतम्|
िुरुष िुरुष र्ीक्ष्य स ञेयो पभषगुत्तमः|| च०सू०1/123
Best physician who know how to administer the medicine in
accordance with their region , time and prakriti only after
examining each patient individually.

41. Normal
Pre-disease
Disease onset
Progress
Complications
&side effects
screening
& Prevention
Prediction &
prognosis
Customization of therapy drugs, diet &life
style
Maintain health
Maintain quality of life
management
Personalized medicine
प्रयोजि चास्य स्वस्थस्य स्वास्थ्यरक्षणमातुरस्य पर्कारप्रशमि च||२६|| charak
sutra 30