Pharmacogenomics

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Pharmacogenomics:

Pharmacogenomics

Pharmacogenomics:

Pharmacogenomics Pharmacology + Genomics = Pharmacogenomics Pharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms (SNP) with a drug's efficacy or toxicity. Pharmacogenomics: using genetic information to predict whether a drug will help make a patient well or ill.

Pharmacogenomics:

Pharmacogenomics studies how genes determine interindividual variability in drug response. Combines many different fields: Genetics, genomics, molecular biology, pharmacology, pharmaceutics, toxicology, population biology, statistics. For Pharmacists: It may be used to predict how a patient may respond to drug, with the help of a genetic test. Pharmacogenomics

What makes pharmacogenomics possible today?:

What makes pharmacogenomics possible today? Sequencing of the human genome reveals 2.9 billion base pairs that are constant, narrowing down variability to about 3 million base pairs, of which 100,000 capture the full human variation and <10,000 may be pharmaceutically relevant. Advances in genome sequencing technology make possible addressing those individual base pairs. Automatization and miniaturization significantly drive down cost of DNA sequencing reaction. Computer technology and computer networks facilitate handling of data. ©2009 Gus Rosania

Current Impact:

Current Impact Pharmacogenomics broadly adopted in drug discovery and development phases in the pharmaceutical industry. Pharmacogenomics research heavily invested upon by public and private companies 3. Pharmacogenomics seen as the future of medicine – so called PERSONALIZED MEDICINE. ©2009 Gus Rosania

Future Trends:

Future Trends Point-of-care (Doctor’s office/Pharmacy) genetic testing Population screening Population sequencing Personal Genomics ©2009 Gus Rosania

Factors to drug responses:

Factors to drug responses Intrinsic factors: age, gender, race/ethnicity, disease states, organ dysfunctions, and genetics. Physiological changes: pregnancy, lactation Extrinsic factors: smoking, diet, medications Polymorphisms occur in transporters, receptors, and other therapeutic targets are also associated with interindividual variability in drug response.

Pharmacogenomics:

Pharmacogenomics Genes: unit of information encoding an inherited trait. Inheritance: how traits are transmitted from parents to offspring Traits: characteristics of a person (from the color of the eyes to the response to drugs) Phenotype: The physical manifestation of genes: eye color, height, blood group, … Genotype: The actual genes we have.

Molecular Biology: How gene encode traits:

Molecular Biology: How gene encode traits Basic tenets of molecular biology: Genes are encoded in DNA. DNA is transcribed to RNA which is translated into protein. 3) Proteins and RNA are the basic building blocks of cells and tissues, and comprise the molecular machinery of life.

Pharmacogenomics:

Pharmacogenomics That variation in protein/RNA/gene structure or function determines differences in a person’s response to drug DNA is made of four “ basepairs ”:A,T,G,C Each gene is about 10,000 base pairs of DNA sequence. There are about 30,000-50,000 genes. There are 2.9 billion base pairs in the human genome, of which only 0.1% accounts for differences between individuals and 3% of which encode for genes.

Pharmacology: How drugs exert their effects on the body:

Pharmacology: How drugs exert their effects on the body That drugs act by interacting with specific proteins, blocking or enhancing the function of those proteins Studies how drugs interact with cellular molecules, and act by inhibiting or stimulating that “target” molecule Most drug targets are proteins encoded by genes Genetic variations have a predictable influence on the balance of good and bad effects (efficacy and toxicity) that a drug may have.

More business:

More business Pharmacogenomics may drive new business models based on developing preventive therapy for patients with genetic predispositions to disease. Blockbuster drugs of today probably not possible if individual genetic variation becomes integrated with drug prescription, due to reduced market sizes. Incorporation of genetic information into the diagnosis of disease and prescription of drugs will lead to new service industry. Pharmacogenomics will faster safer, less toxic drugs

Slide 13:

Cytochrome P450 Enzymes : CYP 2D6 CYP 2C19 CYP 2C9

Slide 14:

In today's world, only 30-60% of drugs work effectively to rid of a patient's illness.  However, with the application of pharmacogenomics, the success rate of drugs will increase to 100%, curing all patients.

Slide 15:

NORMAL GENE SNP VARIANT GENE TODAY’S DRUG PHARMACOGENOMIC DRUG SUCCESS FAILURE SUCCESS 60% 40% Principle of Pharmacogenomics:

Benefits of Pharmacogenomics:

Benefits of Pharmacogenomics More Powerful Medicines Better, Safer Drugs the First Time Improvements in the Drug Discovery and Approval Process Advanced Screening for Disease More Accurate Methods of Determining Appropriate Drug Dosages Decrease in the Overall Cost of Health Care

Slide 19:

Barriers to pharmacogenomics progress: Complexity of finding gene variations that affect drug response Limited drug alternatives Disincentives for drug companies to make multiple Pharmacogenomics products