What is a Poor CYP2D6 Metabolizer?

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*Background*:

I had genetic testing done as I have very unusual, extreme side effects on most medications.

As it turns out, in addition to a few other differences, I am classified as a “Poor CYP2D6 Metabolizer”
For those who are versed in pharmacology or genetics:

**CYP2D6**
*4/*41

CYP2D6*4 allele enzyme activity: None
CYP2D6*41 allele enzyme activity: Reduced

This genotype is most consistent with the **poor metabolizer phenotype**. This patient may have reduced enzyme activity as compared to individuals with the normal phenotype.

None of my providers have been overly helpful in explaining what this means exactly in terms of physiology and medication. I have tried learning about it through online lectures but I am not overly versed in chemistry.

In: 2

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The “CYP” (pronounced like sip) enzymes hang out in the liver, where they help break down and transform chemicals that arrive in the blood (chemicals like medications). There are lots of different CYP enzymes, each called “CYP-(some letters and numbers)”, and CYP2D6 is just one of them. It’s an important one for breaking down certain medications. So if you are a “poor metabolizer” of CYP2D6 it means that this particular enzyme doesn’t work great in you, so medication might not get broken down as fast as it should, so it can build up in your system if the dose is too high. You should take lower doses of those medicines, or take medicines that are metabolized through a different CYP enzyme.

When you take oral medications, the body uses enzymes to metabolize (process) those medications in order to make the active ingredients available for your body to use. Just like how your body processes say a steak you eat in your stomach and intestines to make use of the protein it is made of OR how stomach acid helps your body break that steak down to make it easier to eliminate once all the nutrients have been stashed away. This is a biomedical process with relatively simple concepts, but not all drugs are processed by the same enzyme(s)… So the details can get complex pretty quickly (considering how many drugs are out there and how many enzymes exist in the human body). To make things even more complicated, Some enzymes are a part of the preparation/use part of metabolism and some are a part of the elimination part. CYP2D6 is part of a family of enzymes that is in charge metabolizing most prescription drugs (more than half). Of that half, 2D6 is in charge of 20%. So it is actually in charge of processing a big chunk of medications. Basically if you have a reduced or no activity, that 2D6 is not going to show up to the party to do it’s job. Aka your body does not have the correct tools to make use of certain drugs OR that it has trouble eliminating them from the body. In more scientific terms, this reduced activity may decrease drug efficacy or increase drug toxicity. I would guess that you experience those unusual side effects because your body struggles to eliminate it which leads to higher risk for toxicity and adverse reactions- the drug just keeps hanging out and causes problems by overstaying its welcome. In the end, it just means that your doctor should be working very hard to research what drugs will and will not work for you based on this genetic difference. This is a task that is not outside their scope of practice, so it comes down to finding a doctor who is willing to put on that work for you. I’m sure there are specialists out there now that focus on this sort of thing. Just remember that knowing this about yourself is VERY valuable. It’s just unfortunate that what we call pharmacogenetics is not more accessible as a tool to be used by the general public. I have a pharm science degree, but I never used it after I graduated So take all this with a grain of salt! I hope it helps soothe your mind a bit! There’s nothing “wrong” with you, your body just does things differently and requires a little more help than someone who does not have reduced activity.

Edit: this link has a table that lists all the common drugs that are metabolized by this guy. [Table 2](https://www.pharmacytimes.com/view/2008-07-8624)