Betty Chaffee/ August 17, 2018/ Medication Management, Personalized Medicine, Pharmacogenetics, Precision Medicine/ 0 comments


Personalized medicine is here to stay. It gives us all an opportunity – more than that, a responsibility – to make sure our health concerns are dealt with in a way that fits us as individuals. We talked in general terms about personalized (or precision) medicine in the first article of this series, and then discussed the importance of communication between patients and their healthcare providers in the second. Now we get to the fun part!


What part do genetics play in medication effectiveness and safety?

Our DNA makes us unique; different in so many ways from everyone else. Eye and hair color, height, gender, ability to run fast or eat lots of food without gaining weight. All of these things are determined, at least in part, by our genetic makeup. We look different from each other and respond to our environment in different ways. Why did anyone ever think that medications would work identically in every individual?

With the mapping of the human genome, it became possible to identify genetic differences that make us more likely to respond to a particular medication or more likely to have severe side effects with another. This field of study is called pharmacogenetics  — “the study of how genetics affects a person’s response to drugs“.  You may also see the term pharmcogenomics –it’s often used linterchangeably, but technically encompasses some broader aspects of drug effects. For our purposes, we’ll use the term pharmacogenetics, which focuses specifically on drug metabolism and transport.

 Let’s start at the beginning.

Medications are typically metabolized by enzymes the body produces. Metabolism may be required for the drug to have its intended effect, or metabolism may occur later so the drug can be eliminated from the body. Over the years we’ve learned that there are a handful of enzymes that are responsible for the metabolism of lots of commonly-prescribed drugs. And the enzymes we’re talking about are encoded by the genes we inherited.

There are also enzymes that transport drugs across membranes within the body. As with metabolism, sometimes the drugs need to be transported in order to have their intended effect, and other times they need to be transported so they can be eliminated. These enzymes also are encoded by our genes.

You’ve likely heard of genetic testing to determine ancestry. That became feasible after the human genome was completely mapped in the early 2000’s. The tests are relatively affordable for many people, and provide interesting information that was previously unavailable. Well, that same kind of testing can be used to determine the genetic coding of enzymes that metabolize and transport drugs. And it turns out that the efficiency of the enzymes can vary widely from one individual to another.

Our genetic makeup may cause our metabolizing enzymes to work extra hard, metabolizing certain drugs very quickly. Or they may be sluggish and metabolize slowly. Same with the transport enzymes – some people have variations that cause these enzymes to be extremely efficient getting drugs from one place to another; others have lower-than-average efficiency. All of that to say that by testing genetic makeup, we can predict with much more accuracy than ever before how an individual might respond to certain drugs.

Here are a few examples of the ways genetics can affect drug response.

Plavix is a medication that works to keep blood from clotting quickly. It’s used commonly after a heart attack, or after a procedure to prevent an imminent heart attack. It’s one of those drugs that has to be metabolized in order to work. But we’ve learned that the enzyme responsible for its metabolism works much more slowly in people with a certain genetic makeup. If they are given Plavix, they’re much more likely to have another heart attack than those with normally functioning enzymes. If that genetic difference is known ahead of time, the doctor can prescribe a different medication that’s more likely to work.

The treatment of mental health disorders is often dependent on medications that are overwhelmingly metabolized by the enzymes we’ve been talking about. Certain individuals may eliminate drugs so quickly they are essentially useless; other individuals may have a higher sensitivity, be more likely to suffer from side effects and stop using them. Either way, the person is at risk of not getting benefit from the medication. To be fair, the treatment of mental health problems is quite complex, and success or failure of a treatment plan isn’t only about the medications. But still, medications are a mainstay of treatment for lots of people, and knowing the likelihood of response may shorten the time to treatment success.

Omeprazole (Prilosec) is commonly-used medication for heartburn and other intestinal problems. It has to be metabolized in order to be eliminated from the body. Some individuals have enzymes that metabolize omeprazole so rapidly that they don’t get the intended effect from it. Knowing that ahead of time would allow for substitution of a similar drug that doesn’t share the same metabolic pathway.

Then there are the “statins” – drugs that reduce cholesterol and work to prevent heart attack and stroke in certain individuals. The elimination of these drugs from the body is dependent on one of those transporter enzymes we talked about. Certain individuals have a transporter enzyme that works more slowly than average, which allows certain statins to stay in the body much longer and often results in more adverse effects. If genetic information is available, the right drug can be chosen the first time.

So what can you do to make your healthcare more personal?

Pharmacogenetic testing is available now with a simple procedure. In the next article in this series we’ll explore where the test can be obtained, how it’s done, how results are documented and interpreted, and what your role is in making sure your genetic makeup is taken into account by your healthcare providers. Healthcare can be personal!




Betty Chaffee, PharmD, is owner and sole proprietor of BetterMyMeds, a Medication Management service devoted to helping people get the maximum benefit from their medications.
Share this Post

Leave a Comment

Your email address will not be published. Required fields are marked *