Pain Management: Is It Time To Start Looking At The Patient's Genes?

Genomics.

Now that is a word that has some real catchiness to it, a virtual aphrodisiac for even the most adroit etymologist. I just like to say "genomics.” It conjures up the great line ("Plastics?") Dustin Hoffman repeated in The Graduate.

“Mrs. Robinson (another reference from The Graduate), we’re into ‘genomics’ now and we need to take a look at your genomes so I can provide you with the best perioperative care for your upcoming reconstructive foot surgery.”

“Really?” she replies. “Is there a test for that and will it hurt?”

“No, there is nothing to it. We just need to take a little swab from the inside of your mouth.” Amazing what these white coat cerebral bench scientists are able to discover from a little buccal mucosa now days. I usually just fish out a raspberry seed or something else unidentifiable, trying to recall the last mastication.

“Doctor, can you give me something other than Vicodin? It does not work well for me.”

Most of you are now drawing the same conclusion that I used to draw. “Dammit, I am the doctor and you are a drug seeker. You just want the ‘percs,' better known as Percocet (Endo Laboratories)." Naturally, you say this internally in order not to offend the patient or, even worse, suffer the ignominy and hassle of a board complaint. Maybe you even scream it like the thunder of an internal Tourette’s syndrome but now we know that Mrs. Robinson may really be on to something because of the results of her simple DNA test.

As I touched on in last month’s blog (http://tinyurl.com/cpppu5v ), the last thing we really want to have happen is the acute pain of our surgery becoming a difficult and life changing (for the worse) chronic pain. Like we talked about last month, say the patient does not have the cytochrome P-450 2D6 enzyme and it is estimated that 7 percent of the U.S. population does not (it’s even higher in psychiatric patients). Giving her a prescription for hydrocodone in the form of Vicodin or Vicoprofen (both Abbott Laboratories) is going to be as effective of a remedy as asking her to rub the aloe vera extract on her newly shaped hallux.1

We know that hydrocodone is a prodrug that needs that little hepatic martini (CYP450 2D6 and 3A4) to convert into the active drug of hydromorphone.2 If we had that information, we could simply prescribe hydromorphone. Voilà!

Now here is a really cool thing. Morphine has very little need for these enzymes so you could also give morphine to patients. You see Mrs. Robinson’s face light up when you reassure her that you completely understand now because you have implemented DNA testing. You subsequently say: “You are right. I know you want Percocet but what if we give you morphine instead?”

“Morphine. That is really powerful, isn’t it?” she says, trying to hold back the smirk of victory.

“Yes and I want you to have the best pain management possible. Do you want to know something else?” While pausing to turn back to your computer to complete the electronic medical record, you can see her react to this pharmacologic discussion, squirming on the exam table. (She thought you would not give her or at least hesitate to give her the desired “percs” and now you are telling her you’re going to prescribe her morphine.) Dude, you’re the candy man! Well, not really.

You just know your pharmacology and genomics. You know Mrs. Robinson is a genetically impaired metabolizer of some opioids and you have proven that with state-of-the-art DNA analysis. (I know that there are some anti-DNA analysis activists out there.) Then you give her the really cool — no the ultra cool — pharma fact closing: “Percocet requires the same enzymes to be effective that you do not have so what we are giving you is specifically tailored to you. Is there any better medicine than that?” The song starts playing in your noggin.

So here’s to you Mrs. Robinson
DNA analysis loves you more than you will know
God bless you please, DNA analysis lab
Pain relief holds a place for those who have docs who know
Hey, hey, hey, DNA …

She is now so impressed by your empathy, pharmacologic prowess and overall clinical acumen that she invites you for a cocktail after clinic hours. (I know you can’t do that as it violates professional ethics but I have to have a story here, so give me a little latitude). She suggests you share her favorite drink: a grapefruit juice martini. Whoa!

You are thinking another bullet dodged as you are passing off the newly signed morphine script to her outstretched hand. Grapefruit juice, as you all know, is a potent inhibitor of the cytochrome P450 2D6 and 3A4 enzymes. So even if she had the hepatic juice, her “percs” would not work as well. Can you imagine how awkward it would be after telling her “no percs” and now have to tell her face to face that no, “I’m sorry I cannot have a cocktail with you as much as I would like to and, by the way, we would have to cut out your favorite drink, the grapefruit juice martini, if we gave you Percocet.” You are now a real hero.

Genomics. It is the future.

If you are interested in this type of testing, you can check out GeneSightRx Analgesic by AssureRx Health at www.assurexhealth.com . I have no financial interest or relationship to this company.

References

1. De Leon J, Barnhill J, Rogers T, Boyle J, Chou WH, Wedlund PJ. Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital. Am J Psychiatry. 1998; 155(9):1278-1280.

2. Pergolizzi J, Raffa, RB. Common opioid-drug interactions: what clinicians need to know. In: Tollison CD, Satterthwaite Jr, Tollison JW (eds): Practical Pain Management, Lippincott Williams and Wilkins, Philadelphia, 2012.



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