Treatment

What You Need to Know About Drug Metabolism

The difference between success and failure in your meds treatment may be your liver.

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," according to an article in the British Medical Journal.

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 Prozac, Paxil, Effexor, the tricyclic antidepressants, Haldol, and Risperdal - in the liver. According to the BMJ, 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 hypotension 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 . For example, Tegretol induces CYP3A, requiring higher levels of Depakote and Lamictal, antipsychotics, and the benzodiazepines, and makes birth control problematic.

(Drugs metabolized through CYP3A include Elavil, Tofranil, Serzone, Zoloft, Effexor, and the benzodiazepines.)

Modern DNA testing requires only a small tissue sample - blood from a finger prick, cells from a mouth wash, or hair follicle cells - to provide a rapid and reliable patient genotype.

Pharmacogenetic testing is done at a number of teaching hospitals. It is most widely used in Scandinavia, and is most common for CYP2D6 genotyping to aid in the dose selection of drugs used to treat mental illness. In June 2003, Roche entered the US market with an Amplichip CYP450 test.

In the meantime, most of the information your doctor needs is right at his or her fingertips. Details of more than 20 drugs known to be broken down by CYP2D6 are provided in the Physicians Desk Reference. According to the American Family Physician:

"A physician can often anticipate drug interactions in a patient by knowing which medications inhibit or induce P450 enzymes."

And in the words of the BMJ:

"This may allow the choice and doses of specific drugs, particularly those for treating psychiatric disorders, to be used more appropriately."

Hopefully, your psychiatrist will be able to satisfy you in full over what "more appropriately" means for you.

Updated Jan 1, 2003, reviewed Feb 10, 2008

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