Arun Kumar Dubey1 ( Department of Pharmacology )
P. Subish Palaian ( Department of Hospital and Clinical Pharmacy )
Pathiyil Ravi Shankar ( Department of Hospital and Clinical Pharmacy Manipal Teaching Hospital / Manipal College of Medical Sciences, Pokhara, Nepal. )
Madam, "One size does not fit all." This statement holds true from everyday life in case of drug therapy also. Different patients respond differently to the same dose of a drug. The inter individual 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
Genetic variations can influence drug action in many ways. Commonly it may affect the drug metabolizing enzyme (CYP450), the site of drug action (receptors), and the drug transporters (p-glycoprotein).3 The safety and efficacy of many commonly prescribed drugs like aspirin, isoniazid, omeprazole, warfarin, hydralazine etc are affected by the genetic makeup of individuals. There may be a lack of therapeutic efficacy for a drug or may predispose the individual to be more susceptible to adverse drug reactions, a major cause of morbidity and mortality with drug therapy.4 The pharmacotherapy of diseases like asthma, hypertension, depression is also influenced by genetic variations.
Personalized medicine deals with the prescription of specific therapeutic agent best suited for an individual based on the pharmacogenetic and pharmacogenomic information.5 By understanding the genetic variations in an individual, it becomes easy for a clinician to select the appropriate drug in an adequate dose best suited for the individual.
In the future, pharmacogenomics can 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.
Since, pharmacogenomics deals with the genetic information of the individual, the ethical issues gain importance. The integration of pharmacogenomic information into clinical practice will also require clinical trials to assess their clinical usefulness, affordability, ease of application, and ease of interpreting the results.
Though there are many limitations associated with the extrapolation of pharmacogenomic data to clinical practice, the day is not far away when a clinician will change his/her decision about a drug considered for the patient because the patient's genetic profile indicates that he/she could suffer serious adverse effects due to the medication.
Arun Kumar Dubey1, P. Subish Palaian2, Pathiyil Ravi Shankar3
Department of Pharmacology1, Department of Hospital and Clinical Pharmacy2,3 Manipal Teaching Hospital / Manipal College of Medical Sciences, Pokhara, Nepal.
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2. Spear BB, Health-Chiozzi, M, Huff J. Clinical application of pharmacogenetics. Trends Mol Med 2001; 7: 201-4.
3. Cavallari LH. Pharmacogenetics. In: Pharmacotherapeutics a pathophysiologic approach. Dipirio JH, Talbert RL, Yee GGC et al Editors. 6th edition. Mc-Grawhill Medical Publishing Division. New York, 2005. p 75-90.
4. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279: 1200-5
5. Jain KK. Personalized medicine. Curr Opin Mol Ther 2002; 4: 548-58