&
Personalized Medicine
Personalized Medicine
Medicine is personal:
We are all different.
Some of our differences translate into how we react to drugs as individuals.
This is why personalized medicine is important to everyone.
R!
Same symptoms,
Same findings,
Same disease?
Different patients
Same drug
Same dose
Differential drug
efficacy
At a recommended prescribed dosage
Different Effects
Lack of efficacy
Unexpected side-effects
Genotyping
Toxic responders
Non-responders
Responders
Same symptoms,
Same findings,
Same disease?
Different patients
Same drug
Same dose
SNP
Different Effects
Ethnicity
Age
Pregnancy
Genetic factors
Disease
Drug
interactions
Possible Reasons:
Individual variation
By chance
R!
AAGCTTAC
to ATGCTTAC
Insertion/Deletion Polymorphisms
Insertion/Deletion (INDEL) polymorphisms are quite
common and widely distributed throughout the human
genome.
Personalized drugs
Pharmacogenetics
Study of interindividual variation in DNA sequence related
to drug absorption and disposition (Pharmacokinetics) and/or
drug action (Pharmacodynamics) including polymorphic
variation in genes that encode the functions of transporters,
metabolizing enzymes, receptors and other proteins.
The study of how people respond differently to medicines
due to their genetic inheritance is called pharmacogenetics.
Pharmacogenetics VS.
Pharmacogenomics
Pharmacogenetics: Study of variability in
drug response determined by single
genes.
Pharmacogenomics: Study of variability in
drug response determined by multiple
genes within the genome.
Pharmacogenetics
Genetic Polymorphism:
SNPs; INDEL; VNTRs
dose administered
Pharmacokinetics
ABSORPTION
concentration in
systemic circulation
DISTRIBUTION
drug in tissues
of distribution
ELIMINATION
concentration at
site of action
Pharmacodynamic factors
- Target proteins
- Downstream messengers
Clinical response
Efficacy
- Absorption
- Distribution
- Metabolism
- Elimination
Pharmacologic effect
Toxicity
Pharmacokinetic factors
Pharmacodynamics
Purine Analogs:
A Case Study in Pharmacogenetics
6-mercaptopurine, 6-thioguanine, azathioprine
Used to treat lymphoblastic leukemia, autoimmune disease,
inflammatory bowel disease, after transplant
Interferes with nucleic acid synthesis
Therapeutic index limited by myelosuppression
6-mercaptopurine
6-thioguanine
azathioprine
Metabolism of 6-MP
Percentage of non-responders
Any questions?
Thank you