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Just like “one-size-fits-all” clothing, most drugs are expected to produce the same effects in every patient. However, scientists are recognizing the need for drugs that are better tailored to individual needs. Just like in fashion, where clothing needs to fit bodies of different shapes and sizes, medication can be adapted to your unique genetic composition.
Pharmacogenomics is a new branch of science that combines pharmacology and genomics. Here, scientists study how a person’s genetic makeup determines how their body will interact with different medications. All humans share the same set of genes. However, there are small differences within those genes from person to person. This is known as polymorphism. These differences can cause different people to respond very differently to the same medication.
Keys and locks
When you take medicine, two different things happen. First, the drug does something to your body. These responses are called pharmacodynamics. But it’s important to realize that your body also does something to the drug as you digest, metabolize, and absorb it. Those responses are called pharmacokinetics.
The influence of pharmacokinetics and pharmacodynamics on the effectiveness of a drug is determined by various biological “locks”. These locks are known as metabolic enzymes. They’re made by your unique genetic information and can be opened by various “keys”. Only when the key (the medicine) fits the lock (the enzymes) can a medication carry out the chemical changes it is supposed to.
Metabolizers: the lock-key fit
In this video, Dr. Russ Altman of Stanford University discusses how different polymorphisms in the liver enzyme (CYP2D6) determine how a patient will react to the drug codeine.
Some drugs are manufactured in an active form. They don’t need to be metabolized in order for their effects to take place. Many others are produced in a more stable and inactive form known as a pro-drug. Pro-drugs (keys) must interact with the correct enzymes (locks) in order to be changed into an active metabolite. This is the active form of the drug after it has been processed by the body. However, people with certain polymorphisms may have a slightly different enzyme structure that prevents the drug molecules from fitting properly. In these cases, the drug will not work properly.
How well the drug molecules fit has a direct effect on the amount of active drug in a person’s body. If the key fits the lock especially well, the active form of the drug will be produced very quickly. In this case, the drug could have a really positive effect on the patient. This patient would be an example of an extensivemetaboliser. If the fit is really bad, very little of the active drug will be produced. As a result, the drug wouldn’t be nearly as effective as the patient would have expected it to be. This patient would be considered a poor metaboliser. Other categories used to describe how well a patient metabolises the pro-drug are “ultra-rapid” and “intermediate”.
From trial and error to personalized medicine
There is usually more than one treatment for a medical disorder. Finding the best medication with the fewest side effects for a patient can sometimes involve months of trial and error. But genetic testing could help doctors determine the best medication for a particular patient in a much shorter period of time. Personalized medicine adapted to a specific patient’s genetics could be used in a wide variety of ways. These could include treatments for mental health conditions, cancer, and infectious diseases.
For example, mental health patients sometimes require antipsychotic medication to suppress symptoms such as delusions, psychosis, and hallucination. However, within a month of starting medication, some patients suffer from side effects such as severe weight gain and muscle spasms. Pharmacogenomics can help patients avoid these unpleasant side effects.
Did you know? Scientists are studying a variety of ways to create personalized drugs based on genetics, epigenetics, proteomics, metabolomics, and even microbiomics (gut bacteria!).
Researchers have found evidence to suggest that certain polymorphisms cause greater weight gain. This means that these side effects likely involve multiple enzymes! So, the work of finding the best medication for a particular patient becomes very complex. It would involve figuring out how many enzymes contribute to the side effects and how many polymorphisms affect those enzymes.
Researchers are working to map out the genetic polymorphisms related to the enzymes that contribute to such things as weight gain. This would help them develop a strategy to help doctors determine which medication will cause the least harm to a particular patient. This would mean those long trial-and-error processes wouldn’t have to happen anymore.
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Scientists have learned a lot about the human genome (the complete set of DNA common to all humans). They have also learned a lot about the role genes play in patient reactions to drugs. Researchers are trying to develop procedures to predict how a patient will respond to medication based on their unique genetics. These procedures could eliminate the need to spend time on trial and error. Do you think this would have a significant impact on medical costs and quality of life?
This article was updated by Let's Talk Science staff on 2016-11-07 to improve readability by reducing the reading grade level.
Genomics and Drug Response (2012)
L. Wang, H. L. McLeod & Richard M. Weinshilboum, New England Journal of Medicine 364
Scientific article providing a detailed introduction to pharmacogenetics.