My recovery continues . On Sunday I walked two-and-a-half miles. That’s not a big deal for someone who used to run marathons, but for four weeks out from bypass surgery it’s not bad.

I left the hospital with prescriptions for all sorts of medicines. So many, in fact, that to keep things straight I got one of those plastic boxes with individual slots for each day of the week. Now, one thing to remember about all these medications—medicines for blood pressure, for cholesterol, for heart rhythms, and my favorite, for pain—is that they are really powerful chemicals. The have effects and they have side effects.

Some of the effects are predictable. The blood pressure medicine, atenolol, makes me a bit light-headed when I stand up. Other effects are not predictable. Is it medicine that’s making me have a runny nose? Is it a medicine that’s making me have weird dreams? I’m not sure, but I’ll bet some of the strangeness I’m experiencing is because of the pharmacological stew that’s coursing through my veins.

Today I got to discontinue one of the medicines—amiodarone—that was stared in the hospital when I had a brief run of atrial fibrillation. Now, the experience of having a heart bypass operation is probably sufficient to engender weird dreams, but I’m holding out for the possibility that it might be the amiodarone. One thing my patients have taught me over the years that I’ve been in practice is that not every side effect is listed on the package insert. If a patient tells me that he or she is having a funny reaction to a medicine, I’m inclined to believe it. These are, after all, very powerful substances.

It’s probably not utopian to think that in a few more years our knowledge of pharmacogenetics will have expanded to the point that we will have reasonably priced tests that will screen for hundreds of genetically mediated drug effects and side effects. Already some researchers are talking about a chip that can help determine an entire human genome and do it for $1000 or less.

The shadows are getting long. It’s time to turn on the porch light and get ready for the trick-or-treaters. I’ll let you know how my dreams go.

Technorati Tags: side effects, bypass, pharmacogenetics

The FDA advisory committee that met yesterday has recommended that Tamoxifen prescribing information now include mention of the possibility that the drug may be ineffectual for post-menopausal breast cancer survivors who carry the “poor metabolizer” CYP2D6 genotype. Here’s the story from the Chicago Sun Times.

Technorati Tags: breast cancer, tamoxifen, FDA, CYP2D6, poor metabolizer

This Wednesday, October 18, 2006, an advisory committee of the US FDA will meet to discuss possible changes in the package insert recommendations for tamoxifen. Currently more than 500,000 post-menopausal women with estrogen receptor positive breast cancer take tamoxifen. Recent pharmacogenetic discoveries suggest that a significant proportion of these women may not be getting the full benefit of tamoxifen either because of their genetic constitution, because of drug interactions, or because of both.

Tamoxifen is a prodrug, meaning that it must be metabolized to an active form—endoxifen—before it can exert its full influence as an estrogen receptor blocker. The enzyme mostly responsible for this metabolic transformation is the 2D6 form of cytochrome P450 (CYP2D6). Perhaps as many as ten-percent of women who take tamoxifen have a form of CYP2D6 that cannot metabolize tamoxifen to endoxifen.

Further, some of the popular selective serotonin uptake inhibitor (SSRI) antidepressants, including Paxil and Prozac, can inhibit the metabolism of tamoxifen by blocking the action of the CYP2D6 enzyme. Many women take both tamoxifen and SSRIs.

If the FDA committee concludes these findings have significant implications for the treatment of breast cancer, the language of the tamoxifen package insert will likely be changed. One consequence will be the more widespread use of genetic testing for forms of the CYP2D6 enzyme. Such tests are already available, though not always covered by health insurance.

Technorati Tags: tamoxifen, CYP2D6, breast cancer, FDA

I may never have the chance to travel to outer space, but I recently had the opportunity to experience first hand another marvel of the Twentieth Century.  I just had open heart surgery with a three-vessel bypass.  That’s the reason why I have not been able to tend to this blog for the last three weeks.

In the days to follow, I’ll try to keep you all abreast of developments in pharmacogenetics with maybe in the short term a little extra coverage of the pharmacogentics of cardiovascular medications.

My own heart disease was self-diagnosed.  I’m 62 years old, a non-smoker (I quit many years ago), and a fitness devotee.  Three weeks ago I set out on my customary 4-mile run when, about half a mile into the run, I experienced a very mild burning sensation along the right side of my breast bone.  Whatever this was—I thought—it sure didn’t suggest any sort of heart problem.  The sensation went away and I continued my run.

The next day I did the same run and experienced the same sensation at the same point.  Again this was a sensation and not really anything I’d call pain.  Nevertheless, recalling the lesson of the late James Fixx, a runner and best selling author who died of heart disease while running, I went to see a cardiologist and had a treadmill stress test.

Ten minutes into the stress test, dripping with sweat with a pulse of 140, I saw the nurse’s eyes get a little wider as she looked at my EKG strip.  Positive!  The next day I took the same test with a concurrent echocardiogram.  Again positive.  So I was admitted to the hospital. The next morning I had a cardiac catheterization.  Although heavily sedated,  I do recall the cardiologist who did the cath showing me the images and saying “surgical…bummer.”

So here I am, two weeks post-op.  My only real complaint is that I’m very tired, a common post-operative symptom no matter what the operation.  The doctors tell me that I should be back to most activities in three months.  I didn’t have a heart attack and there’s no permanent damage.  Every morning I look in the mirror and ask myself “can this really be happening to me?”

Enough for now.  I’m tired.   More to follow.