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What is pharmacogenetics?

Updated: Jun 14, 2023

By Noa Nordenberg


Pharmacogenetics is the interdisciplinary study combining genetics and pharmacology. It applies the knowledge of genetics to help develop and administer drugs in a safe manner. Genes and related single nucleotide polymorphisms (SNPS) are studied to find which SNPs are correlated to which drug response. This knowledge is extremely important as it helps doctors and pharmacists prescribe medicine that will effectively and efficiently target the problem and prevents them from prescribing medicine that can cause adverse drug reactions. Essentially, pharmacogenetics helps medication a more personalized experience.


There are two key aspects that affect the process of a drug response. The first, pharmacokinetics, is how much of the drug is needed so it reaches its target. Pharmacokinetics encompasses four major aspects that affect the drug quantity needed: absorption, distribution, metabolism, and excretion. Absorption and distribution explain the travel of the drug, into the bloodstream and after respectively. Metabolism refers to the process of the drug being degraded, and excretion is the process of removing the resulting waste products. The second aspect, pharmacodynamics, describes all the possible processes and elements a target cell could have to recognize the drug and respond. Some components are ion channels, cell surface targets like receptors, immune system parts, and various enzymes and proteins which would be considered intracellular targets.


Cytochrome P4502D6 (CYP2D6) is a drug metabolizing enzyme with numerous pharmaceutical substrates, whose gene (on chromosome 22) has many polymorphisms which heavily impact the pharmacokinetics and pharmacodynamics components of a drug reaction. A pharmacokinetic study on antiarrhythmic sparteine in 1972 at the University of Bonn helped discover the impact of CYP2D6 SNPs. One individual they treated excreted almost an entire dose of sparteine in contrast to a group where the majority excreted the components of sparteine. What the study found was that that individual inherited an autosomal recessive trait of poor metabolism caused by a CYP2D6 SNP. Other metabolism phenotypes include: intermediate metabolizer, extensive metabolizer, and ultra rapid metabolizer. The alleles that cause these traits range from complete deletion to many copies, with multiple causing one phenotype.


CYP2D6 gene’s polymorphisms impact the metabolism component of pharmacokinetics. Depending on the metabolism of the individual the clearance of the broken down components varies. So depending on the genotype of the CYP2D6 genes, the enzymatic activity of the enzyme changes and with that the oxidation rate of the drugs varies, which is recorded when excreted from the body.


Now the pharmacodynamic impact of the CYP2D6 gene variations are a lot more complex. Essentially, the definite impact cannot be overarching and instead has to be described for each and every drug. Enzyme activity will impact how large the dosage must be to be effective because of the change in metabolism. For example, for the antidepressant nortriptyline, people with a slow metabolism only require 10 mg while people with the ultra rapid metabolism require 500mg. Furthermore, the 500mg dosage is far above the suggested maximum for patients suggesting that these patients are commonly at the risk of being treated with an extremely low dosage that would be ineffective. Another issue arises when the drug has to undergo metabolic activation by the enzyme. For example, analgesic codeine has to be metabolically activated by the CYP2D6 to become morphine. For individuals with a poor metabolism a very small amount of morphine formed so there was little analgesic activity, an indication that the drug will be unable to effectively perform its task when the patient has this SNP. The complexity of the pharmacodynamic effects emphasize how important it is to make note of important SNPs before administering the drugs so the doctor can alter the prescription to make it more effective and prevent adverse drug reactions.


Through the help of the Human Genome Project and the developing study of pharmacogenetics, prevention of adverse drug effects continues to strengthen. FDA posts on drug labels biomarkers, genetic variants or abnormalities, essentially listing which genotypes make the drug dangerous to take. Pharmacogenetic testing has also been developed which, using saliva or blood, tells an individual which drugs would be the best and worst for them by examining genes and SNPs. As the field of pharmacogenetics continues to strengthen, it is clear medicating will become a safer and more efficient process, so personalized it is based on your individual genetic makeup.


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