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I Dream of Genie

© John McManamy

"Several million people are at risk of compromised metabolism or adverse drug reactions."

Pharmacogenetics - practice saying it until it rolls off the tongue. While you're at it, try this on for size: "Cytochrome P450 enzymes," first real slowly, then with marbles in your mouth.

The bright new dawn of tailor-made medications to match our individual genes may be some time away, but there is another phase of pharmacogenetics that is applicable today, with the current drugs, and those lucky enough to get themselves to the right facility may be able to spare themselves some of the pain and sorrow we take for granted as part of our present-day practice of hit-or-miss pharmacy.

All this is laid out in two eye-opening articles.

To start, according to an article in the British Medical Journal, variations in certain genes affect how we process our medications. Enter the cytochrome P450s, "a multigene family of enzymes found predominantly in the liver that are responsible for the elimination of most of the drugs currently used in medicine."

It seems not everyone has the same cytochrome P450s, which explains why different people react so differently to the same drug. Of particular interest is the cytochrome P450 CYP2D6, which breaks down a large number of psychotropic drugs, including both tricyclic and SSRI antidepressants, in the liver. According to the article, this enzyme is "highly polymorphic" (ie prone to mutation) and is inactive in 6 percent of white people.

In the words of the BMJ: "In Britain several million people are thus at risk of compromised metabolism or adverse drug reactions" when unwittingly prescribed such drugs.

A person whose enzymes metabolize poorly might require only 10-20 mg of Aventyl (nortriptyline), for example, while an ultra-rapid metabolizer could need as much as 500 mg a day. Poor metabolizers are at risk for drug accumulation and toxicity. Those taking antipsychotic drugs risk exacerbated side effects such postural hyptension and oversedation.

Then there are complications from drug interactions. According to an article in American Family Physician, enzyme INHIBITION involves competition with another drug for the enzyme binding site. For example, Serzone, Luvox, Zoloft, Paxil, and Prozac can interfere with P450 enzymes responsible for the metabolism of a patient's other medications. But these are fairly weak compared to the cardiac drug quinidine.

Enzyme INDUCTION drugs, on the other hand, enhance the enzyme's metabolizing capacity on other drugs, which is an opportune moment to introduce yet another P450 enzyme, this time CYP3A. The mood stabilizer Tegretol, for example, can exaggerate the effects of a patient's other medications.

According to the BMJ article, pharmacogenetic testing is done at a limited

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