Pharmacogenomics is the study of how an individual’s genetic inheritance affects the body’s response to drugs. The term comes from the words pharmacology and genomics and is thus the intersection of pharmaceuticals and genetics. Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person’s own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person’s response to medicines, but understanding an individual’s genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.
Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genes, proteins, and single nucleotide polymorphisms. BENEFITS OF PHARMACOGENOMICS 1- More Powerful Medicines Pharmaceutical companies will be able to create drugs based on the proteins, enzymes, and RNA molecules associated with genes and diseases. This will facilitate drug discovery and allow drug makers to produce a therapy more targeted to specific diseases. This accuracy not only will maximize therapeutic effects but also decrease damage to nearby healthy cells. 2- Better, Safer Drugs the First Time
Instead of the standard trial-and-error method of matching patients with the right drugs, doctors will be able to analyze a patient’s genetic profile and prescribe the best available drug therapy from the beginning. Not only will this take the guesswork out of finding the right drug, it will speed recovery time and increase safety as the likelihood of adverse reactions is eliminated. Pharmacogenomics has the potential to dramatically reduce the the estimated 100,000 deaths and 2 million hospitalizations that occur each year in the United States as the result of adverse drug response (1). – More Accurate Methods of Determining Appropriate Drug Dosages Current methods of basing dosages on weight and age will be replaced with dosages based on a person’s genetics –how well the body processes the medicine and the time it takes to metabolize it. This will maximize the therapy’s value and decrease the likelihood of overdose. 4- Advanced Screening for Disease Knowing one’s genetic code will allow a person to make adequate lifestyle and environmental changes at an early age so as to avoid or lessen the severity of a genetic disease.
Likewise, advance knowledge of a particular disease susceptibility will allow careful monitoring, and treatments can be introduced at the most appropriate stage to maximize their therapy. 5- Better Vaccines Vaccines made of genetic material, either DNA or RNA, promise all the benefits of existing vaccines without all the risks. They will activate the immune system but will be unable to cause infections. They will be inexpensive, stable, easy to store, and capable of being engineered to carry several strains of a pathogen at once.
Improvements in the Drug Discovery and Approval Process Pharmaceutical companies will be able to discover potential therapies more easily using genome targets. Previously failed drug candidates may be revived as they are matched with the niche population they serve. The drug approval process should be facilitated as trials are targeted for specific genetic population groups –providing greater degrees of success. The cost and risk of clinical trials will be reduced by targeting only those persons capable of responding to a drug. 6- Decrease in the Overall Cost of Health Care
Decreases in the number of adverse drug reactions, the number of failed drug trials, the time it takes to get a drug approved, the length of time patients are on medication, the number of medications patients must take to find an effective therapy, the effects of a disease on the body (through early detection), and an increase in the range of possible drug targets will promote a net decrease in the cost of health care. ESSENCE OF PHARMACOGENOMICS Pharmacogenomics is the study of the effect of polymorphisms on drug metabolism and toxic side effects of pharmaceutical agents.
Oligonucleotide arrays can be used to identify presence of specific alleles in individuals, or to quantify allele ratios in populations e. g. Affymetrix CYP chip (18 known mutations defining 10 alleles of CYP2D6 and 2 alleles of CYP2C19). Microelectronic arrays can improve sensitivity/accuracy in detecting single nucleotide differences. pharmacogenetics is the intersection of the fields of pharmacology and genetics. Simply stated, pharmacogenetics is the study of how genetic variations affect the ways in which people respond to drugs.
These variations can manifest themselves as differences in the drug targets or as differences in the enzymes that metabolize drugs. A difference in the target will usually lead to differences in how well the drug works, whereas differences in metabolizing enzymes can result in differences in either efficacy or toxicity. It’s also possible that genes not directly involved in a particular pathway could end up being predictive of clinical outcomes. Although pharmacogenomics has the potential to radically change the way health care is provided, it is only in its infancy.
In the future, pharmacogenomics could find uses along the entire drug discovery and development timeline, all the way from target discovery and validation to late-stage clinical trials. Beyond that, pharmacogenomic tests could find their way into the doctor’s office as a means to get the right medicine to the right patient at the right time. While genetics and genomics are often used synonymously, pharmacogenetics is more focused in scope than and is viewed as a subset of pharmacogenomics, which encompasses factors beyond those that are inherited.
Some people believe that pharmacogenomics will lead to the stratification of diseases into genetically defined categories. George Orphanides and Ian Kimber, 2004, in a review article titled Review: Toxicogenetics: Applications and Opportunities’, indicated that the response to drugs and environmental chemicals varies with genotype. Some patients react well to drugs, while others may not benefit, or may even respond adversely. Individuals also experience different reactions to environmental agents, such as allergens.
The sequencing of the human genome and the large-scale identification of genome polymorphisms have provided opportunities for understanding the genetic basis for individual differences in response to potential toxicants: an area of study that has come to be known as toxicogenetics. The author concluded that hazard identification, and risk assessment, understanding of the health consequences of the interaction of xenobiotics with biological systems would all be potential results of pharmacogenomics.
The author added that potential benefits include (a) accelerated discovery of gene polymorphisms associated with idiosyncratic toxicity, (b) the identification of genetic markers for the prediction of adverse reactions to drugs, (c) the definition of genetic markers for drug efficacy, and (d) characterization, at the molecular level, of inter-individual differences in susceptibility to xenobiotic-induced adverse health effects that can be used as the basis for development of more differentiated and more accurate assessments of human risk.
