Understanding the Essentials of Pharmacogenomics- The Potential Implications for the Future Pharmacotherapy
Correspondence Address :
P.Subish M. Pharm, Assistant Professor, Department of Hospital and Clinical Pharmacy / Pharmacology, Manipal Teaching Hospital/ Manipal College of Medical Sciences, Phulbari-11, Pokhara, Nepal. Email: email@example.com, Phone 00977-61-526420
The genetic makeup affects drug responses to a greater extend. Personalized medicine deals with the prescription of specific therapeutic agent best suited for an individual based on the pharmacogenetic and pharmacogenomic information. By understanding the genetic variations in an individual, it becomes easy for a clinician to select the appropriate drug in an adequate dose. Genetic variations can influence drug action in many ways, the common ones being the drug metabolizing enzyme (CYP450), the site of drug action (receptors), and at the drug transporter levels (p-glycoprotein). Safety and efficacy of many commonly prescribed drugs like aspirin, isoniazid, omeprazole, warfarin, hydralazine etc are affected by the genetic makeup of individuals. Similarly, the pharmacotherapy of common diseases like asthma, hypertension, depression etc is also influenced by genetic variations. Pharmacogenomics can also offer benefits like proper determination of drug dosage, and production of better vaccines and can definitely reduce the healthcare costs and helps to enable drug safety by understanding the genetic profile of an individual. Integration of pharmacogenomic information into clinical practice will also require clinical trials to assess their clinical usefulness. The usefulness of pharmacogenomic data also depends upon the affordability, ease of application, and ease of interpreting the results etc.
Aspirin resistance, Human genome, Personalized medicine, Pharmacogenetics, Pharmacogenomics
It is well recognized that different patients respond differently to the same medication. Such differences in drug toxicity or drug efficacy are often much greater across a population of patients than between monozygotic twins. Interindividual variability in drug efficacy and toxicity is related to several factors such as age, sex, race and inherited differences in the genes that control drug disposition and effects in humans.(1) Pharmacogenomics refers to the entire spectrum of genes that determine drug safety and efficacy whereas pharmacogenetics refers to monogenetic variants that affect drug response.(2) Pharmacogenomics is a science that examines inherited variations in genes that dictate drug response and express the way these variations result in good response to a drug, a bad response to a drug, or no response at all. Pharmacogenomics holds the promise that drugs might be tailor made for individuals and adapted to each personâ€™s genetic make-up which has been termed as â€˜personalized medicineâ€™. Personalized medicine means the prescription of specific therapeutic agents best suited for an individual based on pharmacogenetic and pharmacogenomic information. (3)
In this article, the authors provide an overview regarding the importance of understanding the principles of pharmacogenomics and also provide some of the clinically significant examples of variation in drug response due to the differences in the genetic make up. The authors also highlight the future benefits, barriers and ethical considerations associated with pharmacogenomics.
Pharmacogenomics principles in personalized medicine: Effective pharmacotherapy results only when the drug reaches in sufficient amount at the target site or in the systemic circulation. Many factors can influence the patientsâ€™ response to drugs including gender, dietary habits, concurrent illness, concomitant drug use etc.(2) For many medications, these interindividual differences are due in part to polymorphisms in genes encoding drug metabolizing enzymes, drug transporters, and/or drug targets (e.g., receptors, enzymes)(4).
The recognition of the complexities involved in the gene and the advance of genetics into genomics led to the broader science of pharmacogenomics. This led to the vision of "personalized medicine," that is, making drug use more effective and safer by giving drugs that fit a person's genes.5 As the initial draft of human genome has revealed, there are over 1.4 million single nucleotide polymorphisms (SNPS) in the human genome, with over 60,000 of these residing in the coding regions of human genes.(1)
Some of these SNPS have already been identified to affect metabolism or effects of drugs. For example, genes encoding cytochrome P450 enzymes, N-acetyl transferase etc. Genetic make up is thus one of the commonest factors affecting the drug response. These variations in the genetic make up of an individual can change the manner in which the patient responds to the drug. Adverse Drug Reactions (ADRs) are estimated to be one of the top ten causes of death and up to 50% of adverse reactions are possibly related to the genetic makeup of the susceptible individuals.(6) By understanding the variations in the genetic makeup of an individual, it becomes easy for a clinician to select the appropriate drug at the appropriate dose.
Genetic variations and drug response: The variations may be at the drug metabolizing enzyme (CYP450), at the site of drug action (receptors), or at the drug transporter levels (p-glycoprotein). The outcome of these variations may be lack of or decreased therapeutic efficacy or an increased risk of toxicity.
Genetic variations in genes of drug metabolizing enzymes (P450 genes): The cytochrome P450 system is a group of enzym
Many prescribed drugs either donâ€™t produce the desired therapeutic effect or have extensive undesired effects. Since pharmacogenomics is linked to drug efficacy as well as drug toxicity, it would be desirous to have genetic screening while prescribing those drugs that are affected by the human genetic makeup. Prescribing drugs to the patients based on their genetic makeup will certainly improve the quality of health care and also reduce overall cost by decreasing the number of treatment failures and adverse drug reactions. The day is not far away when a clinician changes his/her decision about a drug considered for the patient because the patientâ€™s genetic test indicate that he/she could suffer serious adverse effects to the medication. Pharmacogenomics will also transform the way the clinical trials are conducted by allowing for the selection of a more homogeneous study population, there by reducing the size and cost of clinical investigation. However, factors such as affordability, ease of application, and ease of interpreting the results play a vital role in extrapolating the pharmacogenomic data to personalized medicine.
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