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Stain Drugs and Drug Metaabolism

Statin Drugs: Dr. Peter Rice

Why is it that uncommon drug responses, such as Statin Drugs often run in families?


When we last visited, I told of a woman who experienced the same unusual drug response with her sister. We noted that many disease states can be passed along from parents to children.

Why is it that uncommon drug responses often track within a family like statin drugs?

My mom is 90 years old and fairly healthy, but she has had high cholesterol for many years. A number of physicians had started her on one of the common statin drugs, but each time she feels so miserable while taking the statin that she stops it after a brief time.

I too have high cholesterol. Some years ago, my doc put me on simvastatin. I have never felt so old in my life. My muscles were weak and sore; I remember crouching down to get a book off my bottom shelf and not being sure if I could get up again. Eventually, I asked about how bad I had to feel while taking the medication, and when the nurse suggested that I take it until I die, I decided not to press my luck. I stopped taking my statin.

That allowed me to feel well enough to start exercising regularly. Exercise is also good for you.

Statin Drugs and Drug Metabolism

Statin Drugs and Drug Metabolism

It’s intriguing that my mom and I have the same uncommon response to statin drugs, but it is not surprising.

One of the hot areas in pharmacology is called pharmacogenomics, the study of how genetics affects the action and metabolism of drugs. As we look at responses to drugs, we find that responses are often associated with genetics, from ethnic groups to family.

For example, drugs are metabolized by liver enzymes that are given names like CYP (pronounced ‘sip’, like having a drink) 3A4 and 2D6. These CYP enzymes can be more active or less active depending on fine details in their protein building blocks; these fine details are often ‘mutations’ which are passed along from parents to children.

CYP 3A4 and the related enzyme 3A5 are involved in the metabolism of many statin drugs. High activity of these enzymes limits the times the statins remain in the body and decrease their effectiveness. Low activity, either because of genetics or drug interactions, makes the drugs more effective but also much more likely to produce adverse effects. It may be that my mom has low activity CYP 3A4/3A5 enzymes and that I share that trait.

CYP enzyme differences can also account for inactivity of drugs that require drug metabolism for activity. The drugs hydrocodone and tramadol require metabolism by the enzyme CYP 2D6 to become active pain relievers. Around 7% of the US population lack this enzyme activity and find the drugs to be ineffective. But there are large differences depending on ethnicity; Caucasians are more likely to have low CYP 2D6 activity, while individuals of Ethiopian or Spanish descent are more likely to have very high activity.

It can be quite complex. At some time in the future, we can expect that it will become common to test patients for their unique patterns of metabolizing drugs and to use that information to optimize drug therapy like statin drugs.

In the meantime, when you talk with your pharmacist about your medications, they may be able to use the information you provide to suggest drugs which are more or less likely to be good choices for you. Your community pharmacist is there for you. Talk about your meds and take good care of yourself.





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Dr. Peter J. Rice

Dr. Peter J. Rice is a professor of Pharmacology emeritus at the East Tennessee State University Quillen College of Medicine and Professor of Clinical Pharmacy at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences. He received his BS in pharmacy from Northeastern University, PhD in pharmacology from the Ohio State University and PharmD from the University of Kentucky. He is a Board Certified Pharmacotherapy Specialist and practices in the ambulatory care and community pharmacy settings. Professor Rice is the author of Understanding Drug Action: An introduction to pharmacology (APhA, 2014) and is a fellow of the American Pharmacists Association.




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