Wednesday, September 07, 2011

Cytochromes

My attending on pain service right now focuses a lot on the pharmacology of pain medications, and I learned the most about cytochromes yesterday than I have in the last 3 years. We all learn about cytochromes as medical students; they are the enzymatic systems in the liver that aid breakdown of drugs. And for Step I of the Board exams, we dutifully memorize those agents that speed up or slow down each specific cytochrome. But that is usually the end of cytochromes for most physicians.

Anesthesiologists, however, have to be very familiar with the cytochromes that metabolize our drugs. For example, we are consulting on a woman who had a transplant and also has chronic pain treated with methadone. Her methadone requirements are much higher than expected, and I learned that steroids speed up the cytochrome p450 3a4 which breaks down methadone (as well as fentanyl and benzodiazepines). If eventually her immunosuppression is tapered down, her methadone should be changed in the same manner. Likewise, cytochrome p450 2d6 is responsible for metabolizing tricyclic antidepressants, a class of medications that also treat neuropathic pain, and for converting the hydrocodone in vicodin to the active metabolite hydromorphone. We have a few consults for patients on antidepressants which inhibit the action of cytochrome p450 2d6. Hence, we have to start tricyclics at a very low dose but also avoid vicodin which may never be converted to an active form.

Indeed, this week is a lot about learning the pharmacokinetics and pharmacodynamics of pain medications. We spend time discussing mechanisms of action for medications, context-sensitive half-lifes, and similar basic science applications to clinical medicine. It's fun to see these principles at work because for many of us, we feel that they are so far removed for practical medicine that we shouldn't learn them.

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