Pharmacogenomics explores how genetic factors influence drug metabolism and impact individual responses to medications. Precision medicine allows healthcare providers to personalize treatment plans based on a patient’s genes, environment, and lifestyle. By identifying the optimal medication choice, patients will likely experience fewer side effects and their health condition can be managed more effectively. The most common conditions that may elicit pharmacogenetic testing from your healthcare provider include the treatment of HIV, certain cancers, depression, and heart disease.
The prevalence of Adverse Drug Reactions (ADR) shows the significance of understanding an individual’s genetics and environmental factors contributing to how they metabolize and respond to medications. In 2022, there were 1.25 million serious adverse reactions to drugs and 175,000 associated deaths. The causes of these adverse reactions are not fully understood, so by using the field of pharmacogenomics, healthcare professionals can have another resource to help make informed decisions when prescribing medications. The complexity of drug metabolism is further showing us that it is not a one-size-fits-all solution. We are unique individuals who require personalized medical care.
Drug Metabolism
The four main steps of drug metabolism are absorption, distribution, metabolism, and excretion. Absorption is the movement of the drug to the bloodstream and can be affected by how the drug is administered, the chemical properties of the drug, and drug interactions. Once the drug is absorbed, it gets distributed across the body to start exerting its effects. The drug must be metabolized by enzymes and subsequently excreted from the body. Within these steps of drug metabolism, there are a variety of factors that cause people to metabolize drugs differently. The most common are age, genetics, diet, lifestyle, and the presence of other medical conditions.
Enzymes At Work
Enzymes are essential molecules that help speed up biochemical reactions in the body. Without them, many of these necessary reactions would not occur. Our genetic material provides the code for producing the enzymes needed to facilitate these biochemical reactions. Cytochrome P450 enzymes facilitate the biochemical reactions involved in the metabolism of approximately 75% of commonly prescribed drugs. The importance of this enzyme in drug metabolism makes it one of the most studied enzymes in pharmacogenomics. CYP2D6, a type of cytochrome P450 enzyme, is highly polymorphic, meaning the DNA sequence varies between individuals. These variations can be small but have large impacts on enzyme production and the subsequent breakdown of medications. Genetic variations in the gene influence individual differences in drug metabolism, including adverse effects and drug efficacy.
Clinical Significance
Nephrologists have identified the potential benefits of pharmacogenetic research in clinical practice. Nephrologists are physicians who commonly treat patients with kidney disease. To manage many associated medical conditions, nephrologists commonly prescribe medications including anticoagulants, antiplatelets, statins, and transplant medications. The metabolism of these widely prescribed drugs is influenced by genetics, and research has indicated population differences between poor metabolizers (PMs), intermediate metabolizers (IMs), normal metabolizers (NMs), rapid metabolizers (RMs), and ultrapid metabolizers (UMs). In a clinical setting, a patient characterized as a rapid metabolizer may need a higher dosage of the drug than a patient who is a poor metabolizer. By understanding this important distinction, patients can be given the correct medication dosage, and physicians may know which medication will be the most effective.
Current Limitations
While the implementation of pharmacogenomics into clinical practice seems promising, some limitations need to be considered. A genetic test may give only some of the information about how an individual will respond to a medication. There are many enzymes responsible for the metabolism of drugs that may be overlooked, and there are other factors unrelated to genetics that also affect drug metabolism such as the use of other medications. In addition, healthcare professionals may need more training to feel confident in using genetic information to inform their clinical decisions. Increasing education, training, and communication among physicians, nurses, geneticists, and pharmacists may help close this gap and lead to better outcomes with precision medicine. Lastly, the availability of genetic testing is a barrier for patients, driven by high costs and insurance coverage.
References:
Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine - PMC
A Review of the Important Role of CYP2D6 in Pharmacogenomics - PMC
Interindividual Variability in Cytochrome P450–Mediated Drug Metabolism - PMC
Pharmacogenomics in Patient Care - Center for Individualized Medicine - Mayo Clinic Research
Genetics may help predict the right blood pressure drug for you | American Heart Association
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