1. Introduction to Pharmacogenetics
Jamaluddin Shaikh, Ph.D.
Associate Professor
School of Pharmacy, University of Nizwa
Lecture 2
February 14, 2012

2. Pharmacogenomics
Pharmacogenomics is the study of the relationship between the interindividual variability of a candidate's genes and the influence of this variation on drug disposition and effects.

3. Drug Response Factors
Drugs may be administered in various ways: Orally, Sublingually, Intravenously, Intramuscularly, Subcutaneously, Transdermally, Intranasally, or via Inhalation. In general, there is a direct relationship between the dose of a drug that is administered and intensity of pharmacologic response.
Individuals vary in their response to standard doses of prescription and non-prescription drugs due to:
1. Drug specific factors.
2. Patient specific factors.
3. Regimen specific factors.

4. Drug Response Factors Drug specific factors: Disposition of the drug
Drug receptor interaction
Site of Biological Effect
Patient specific factors:
Environmental/Diet Exposures
Mental/Psychological Status
Genetic Constitution
Organ Function
Enzyme Activity
Age/Sex
Drug Interactions

5. Drug Response Factors Regimen specific factors: Dosage Form
Dosage Interval
Route
Dose Amount
Genetic constitution affects both:
Drug disposition (pharmacokinetics)
Receptor-mediated cellular responses (pharmacodynamics).

6. Pharmacokinetics and Pharmacodynamics
Pharmacokinetics (PK) : Effects of body on the drugs
Absorption
Distribution
Metabolism
Excretion
Pharmacodynamics (PD): Effects of the drugs on body

7. Inherited variability in drug disposition and response
For major classes of drugs, a large proportion of patients do not show enough response, or may experience adverse drug reactions in response to recommended doses. Inherited variations in drug response are common and some tests that incorporate pharmacogenomics into clinical practice are now available. So, we can use these pharmacogenomic tests to assist in individualizing therapy of patients.
For inherited variations in drug response, the genotype underlies all of the changes in drug disposition and response
(phenotype), and ultimately results in a clinical outcome.

8. Inherited variability in drug disposition and response
The genotype shows candidate gene's influence
on drug disposition and effects

9. Allele
Allele: is a different form of a gene. There may be numerous alleles for any gene.
The diploid cells contain two copies of each of the 22 non sex chromosomes. The 'normal' or more common allele is called the wild type. Modified or altered alleles may be called mutant allele.
If the allele is copied and one copy is inherited from the mother and the other from the father:
Similar alleles mean the individual is homozygous for that
genetic variation.
Different alleles mean the individual is heterozygous. There
may be many mutant alleles to a particular gene.

10. Allele

11. Genotype Vs Phenotype
Genotype is the genetic composition, or the actual alleles present in an individual, whereas, a phenotype is the way that the genotype or alleles physically manifest themselves.

12. Polymorphism
The major pharmacogenomic effects on drug response are due to polymorphic expression of gene products relating to drug metabolism, drug transporters, and drug receptors. 
Polymorphism occurs when two or more clearly different phenotypes exist in the same population of a species

13. Clinical value of a pharmacogenetic testing
Certain types of drug therapy may not benefit from pharmacogenetic testing, either:
1. Because therapy has a wide therapeutic and safety range.
2. Because of good clinical ability to monitor and predict response.
However, other types of drug therapy may benefit from pharmacogenetic testing, either:
1. Because diseases have a poor response to therapy.
2. Because of poor clinical ability to monitor and predict response.

14. Human Genome
Pharmacogenomics is not just a concept about how information from the Human genome Project can be used in health care. 
Nowadays, targeted drugs and pharmacogenomic testing is applicable in several areas of therapeutics. 
We are however at the beginning of a long process of understanding the human genome and how it influences disease processes and their response to drug therapy.