Side Effects of Medicines – Is it Them, or Us?

Pharmacogenetics, “how a person’s genes affect the way he or she reacts to drugs”

Medical science has always advanced. The greatest mass of advancement has occurred in the last 70 years. Despite headwinds, good science persists. Pharmacogenetics is fundamental to how we are able to diagnose and treat conditions, and in addition, how we metabolize any medication we take.

In the 1970s to 80s diagnosis and treatment of cancers was at a nascent stage. Screening exams were not mature. As a result, many patients were found at later stages of disease with little ability to stem the progression of disease. Some patients missed therapies that came to light shortly after their demise. As therapy advanced an observation was noted. Two patients with similar age, sex and general health and habits would be treated with the standard therapy for that cancer. One would do well, and one would not. Pharmacogenomic research was used to type the patient’s collective genes, and therapies were developed that aided in the survival of the patient with more tailored therapy.

Early on in these discoveries, certain laboratory tests were developed as screening markers for certain cancers. The carcinoembryonic antigen test (CEA) was initially used but it was noted that it was not a pathognomonic (specifically indicative of certain disease such as lung and colon cancer) test and now is being used to monitor the level of disease after therapy. There have been several direct to consumer attempts to test for a genetic predisposition for certain diseases but the results are poor indicators of the level of the disease or even the indication of it. This can be disturbing for an individual who tests positive for it, but extensive work up doesn’t reveal it. The statistical parameters of these tests are not those used in good medical care.

There is however, a modality to assess our genetic ability to metabolize medications, which is very specific.  It focuses on those substances in the body that do just that, our P450 cytochrome oxidases. These mitochondrial (“powerhouse of the cell”, mostly inherited from our mothers) enzymes have been categorized as the prime sources in our body that break down many of the medicines we may take. They have names like CYP2C19, CYP2D6 and CYP3A4 to name a few. Most medications have been designed for them. This is Pharmacogenetics.

 A renowned lab has a simple test for these enzymes and it is available. With data about the patient’s specific findings I am able to extrapolate it to the patient’s medication list. I then compare this information to each medication the patient is on and I am able to see if the medications are safely interacting with the patient’s health. It is not uncommon that an individual can be suffering from the effect of a medicine, despite being under excellent control of their condition. By quantifying that possibility that we may not be metabolizing the medications, it could allow choosing a different therapy if possible. Many “side effects” and “adverse reactions” are…just that.

We have never been as fortunate as we are now with the myriad of therapies available for so many conditions. We are truly in a medical renaissance in methods of controlling conditions for better quality of life.

By analysis of genetic data and the full knowledge of a drug, it can be ascertained that the specific medication is helping, not harming the patient. It also includes basic information of how long a medication stays in our body. The scientific term for that is “half life or t ½” which tells us how long it takes our body to metabolize that pill to half of the dose taken.

Some examples are:

 Valium (diazepam, little used these days): a 5 mg pill taken on Monday morning would take a normal body until Friday to breakdown 5 mg into 2.5 mg (it is metabolized by CYPs, 2C19 and 3A4). If the person taking it, has poor genetic production of either of those enzymes, it will take far longer than 96 hours to get to 2.5 mg. Simple but true.

Aricept(donepezil) for memory disorder. A typical starting dose of 10 mg (available in 5 mg as well) taken on Monday morning will take the body until Thursday morning to reduce the dose to 5 mg (it is metabolized by CYPs 2D6 and 3A4). Once again with advancing age it may take longer than 70 hours to do so.

I have observed this to be very prevalent in the patient population and when the concern arises I seek to diagnose the possibility. Simple but true. I have been offering this approach to my patients for several years and it is part of my medical care.

On A Lighter Note:

• Our heart beats about 70 beats per minute, or about 100,000 a day, since we were in the womb.
• We breathe about 14 times a minute, or over 20,000 times, daily
• Our brain’s gray matter which is where cognitive and higher thinking is, is about 1/10^th of an inch in width, and occupies about 30% of our nervous system. The rest is white matter which acts as conduction for neural messages throughout our body.
• Our Voluntary Nervous System responds to our chosen commands(reach for something)
• Our Involuntary (Autonomic) Nervous System does everything else (breathing, heart beats, digestion, filtering of toxins and repair, etc)

Thank you for reading this. I hope you have found it interesting.  If you like this, pass it on. 

Be Well,

Richard A. Levine MD FACP

Journey…Observation…Knowledge