2C9, Drug Detoxification, and Drug Side-Effects, Toenail Fungus Ads

2C9 - Your Power Enzyme
Rant 'O the Month - Television Ads and Toenail Fungus
Monroe Street Clinic News - Doctor Talk

2C9 - Your Power Enzyme

Grandpa's Miracle Cure

A few years back, while substituting for a vacationing physician in Ilwaco, WA, I was called to the nursing home to see a dying patient. The family was gathered in the room. Grandfather had been going downhill for some time, they explained. He didn't want any heroic measures. He had stopped eating and could hardly drink. He lay in the bed barely conscious. He was having difficulty swallowing, but the nurses were having him to choke down his medications, about 10 of them every day. The family asked me tell the nurses to stop the meds.

Grandpa, in his nineties, had a dozen different diseases. It seemed there was nothing else I could do to help. I told the nurses to obey the family's wishes and just be sure we kept him comfortable. The next day when I stopped in to see him, there was the unexpected: grandpa, sitting on the side of his bed, much more alert. He was surrounded by his proud family, eying me, the medical professional, with some well-deserved humor.

So, how could withdrawing his meds make such a difference? I suspect it had something to do with cytochrome 2C9.

What the Heck is Cytochrome 2C9?

Cytochrome 2C9 is an enzyme produced by the liver, part of a system of enzymes that cleans your system of drugs and other foreign substances. You've got a number of such systems and many different cytochromes. Let me introduce you to 2C9; she is a typical cytochrome. She doesn't have a real catchy name, but cytochrome 2C9 deserves your respect. Mother nature developed 2C9 and her sisters to neutralize toxins in our food and to eliminate metabolic poisons from our systems. There are different types of cytochromes, but I'm going to focus in on the cytochrome P450 system, a family that includes several cytochromes, including your new friend, cytochrome 2C9.

In our June 2004 newsletter, I said that a pharmaceutical drug may cause side effects in one person and be well tolerated by another. It depends on their metabolic makeup, and that's where 2C9 comes in. Her activities can alter what a drug does in your system.

Here's an example: Say you take some ibuprofen for a sore muscle. The package says to take it three times a day. Why not once a day as with some other drugs? The reason is that 2C9 continually purifies the blood of foreign material, including anti-inflammatory drugs. In eight hours, she will have reduced the levels enough that ibuprofen loses most of its effect.

Drug Interactions

Again, 2C9 has a lot of brothers and sisters, but let's talk just about her (her favorite subject!) Now, 2C9 is a hard worker, but she is sensitive. Give her some fluoxetine (Prozac) or paroxetine (Paxil) and she gets too mellow and can't get anything done. In biochemical terms we say that her activity is inhibited by fluoxetine and paroxetine. So, if you take ibuprofen and fluoxetine together, the ibuprofen will not be cleared from your body as quickly as normal, and will build up to higher levels. This may raise those ibuprofen levels high enough that your stomach starts to complain or you get some other side effect.

Our friend 2C9 doesn't always do what you'd expect. If you take phenobarbital, it may sedate you, but she responds by working harder. If you take phenobarbital and ibuprofen together, 2C9 will work faster, clear out the ibuprofen more quickly, and you'll experience less anti-inflammatory effect.

The chances are slim, but you may be that one person in a hundred has no 2C9 at all in your system. Cytochrome 2C9 hates to tell you that she told you so, but you will miss her when she is gone. With no 2C9, you will be much more likely to suffer side effects from ibuprofen and the other substances she detoxifies for you. The pharmaceuticals she clears from your system include celecoxib [Celebrex], naproxen [Naprosyn], warfarin [Coumadin], and numerous others. Slow down 2C9's good labors with ibuprofen, metronidazole (Flagyl), and other drugs she is sensitive to, and a normal coumadin dose bids fair to anticoagulate you to death.

No Two People Alike

Cytochrome makeup varies a great deal from person to person, not just for our new friend 2C9, but for all her siblings. This is why two people can take the same drug, and one can get an upset stomach and the other will have no unpleasant side effects.

We inherit our cytochrome make-up from our parents, in the same way we do eye color. Our cytochrome make-up determines how we are going to respond to drugs and to combinations of drugs. Tests to determine our cytochrome pattern are just becoming available, but the cost is still in the hundreds-of-dollars range. Once those costs come down, we will routinely determine your cytochrome profile. Once in your lifetime is all you will need, for these are as constant as blood type and eye color. With the cytochrome profile, we'll be better able to predict an effective dose without all the trial and error, and we'll be better able to avoid side effects.

Natural Remedies and Cytochromes

Cytochromes are influenced not only by pharmaceuticals, but also by natural substances. St John's Wort (Hypericum perforatum) affects a couple of cytochrome 2C9's sisters. It increases the activity of cytochrome 3A4 and decreases the activity of cytochrome 2D6. As a result, St John's Wort interacts with many cardiac, antidepressant, and other drugs, either reducing their effect or increasing the risk of side effects. For more information on St. John's Wort's effect click here.

St John's Wort is not the only natural substance to influence the cytochrome system. Grapefruit is another. We have to be concerned about not only pharmaceuticals but herbs and foods as well. In that light, it seems clear that once the cost of determining our individual cytochrome make-up falls into a practical range, we should start using these cytochrome profiles to find out how the drug will affect us, rather than using ourselves as a human test-tube. And where better to keep that information than on your driver's license, the one piece of paper that is likely to make it into the emergency room if you find yourself in trouble? Then the physician who cares for you there will be better able to choose drug doses for you based upon your unique capacity to deal with them.

How to Avoid Drug Interactions

Until then, follow this guideline. Always get your prescriptions at the same pharmacy. The pharmacy computers are all programmed these days to keep track of all your medications and alert the pharmacist to potential interactions.

Rant O' the Month - Television Ads and Toenail fungus

Although I do not have broadcast or cable television in my home (for reasons of health and equanimity), whenever I stay in a hotel, I like to cruise the tube to study the culture. One thing I recently noted is that they are flogging terbinafine (Lamisil) pretty hard these days for toenail fungus.

So, TV viewers, here's full story on terbinafine, including the part the ads leave out. Terbinafine is one of the most cost-effective drugs for toenail fungus. That much is true. The cost of treatment, including the drug, lab monitoring, and physician visits, averaged about $800 in 1999. The cure rate is about 77 percent, so the cost per person cured was $1040. The average length of time until the fungal infection recurs is about 963 days (you say they didn't mention that in the ad, Bunky?), so the cost per symptom-free day was about $1.10 back in 1999. In addition, terbinafine can harm your liver, though the liver disorders are only "rarely fatal" according to the package insert.

Terbinafine is not an evil drug. Usually it minds its manners and causes no harm. We use it topically (and sometimes for a couple of weeks orally) as part of our toenail fungus treatment.

But the ads, oh those ads, with an animated foot and the promise of a problem-free, permanent cure. No, no, no, it ain't so.

12/15/06