Microsoft word - prescription drug reaction q&a.doc
How has Drug Reaction DNA Testing been used up to this point? Pharmaceutical companies regularly use these tests in clinical trials, sometimes to exclude people. Medical centers around the country are also beginning to use these tests on their own patients to avoid adverse drug reactions (ADRs) and achieve more accurate prescribing. Why isn't this testing more available? ADRs don't have an organized constituency like most diseases do, no American Cancer Society or March of Dimes. Many doctors do not realize the extent of the problem and the large pharmaceutical companies and insurers may have a difficult time justifying the added costs of testing. Genelex has made this test available to the public so people can benefit now from the recent advances in pharmacogenetics. We also wish to recognize that more people want to take greater responsibility for their own healthcare. We support that decision. How are drugs processed by the body? Drugs act on target sites in body tissues to cause a therapeutic effect. They are removed from the body by being converted into an inactive form. The cytochrome P450 family of drug metabolizing enzymes inactivates most prescription drugs. The most important, best studied, and individually variable of these enzymes are CYP2D6 and CYP2C9. More than half of the population has at least one defect in these enzymes that can greatly increase the risk of an adverse drug reaction. What are adverse drug reactions? Adverse drug reactions (ADRs) are harmful side effects of medications. They depend on the type of drug or combination of drugs being taken and according to the World Health Organization definition do not include prescribing mistakes, or accidental or intentional overdoses. They have many causes and are often not well understood. Many ADRs occur because individual differences in drug metabolizing enzymes (DMEs) and other parts of the drug processing systems have not been taken into account when the drug was approved or prescribed. Three- fourths of all ADRs are dose-dependent, most occurring at recommended doses. A 1998 medical report found adverse drug reactions to be the fourth leading cause of death in the U.S., at more than 100,000 annually. What are the most useful enzymes to test genetically? • CYP2D6 (cytochrome P450 2D6) is the best studied of the DMEs (drug metabolizing enzymes) and acts on one quarter of all prescription drugs. Approximately ten percent of the population have a slow acting form of this enzyme and five percent a super-fast acting form. Drugs that interact with CYP2D6 include Prozac, Zoloft, Paxil, Effexor, Oxycontin, Hydrocodone, Amitriptyline, Claritin, Cyclobenzaprine, Haldol, Metoprolol, Rythmol, Tagamet, Tamoxifen, and the over-the-counter diphenylhydramine drugs, Allegra, Dytuss and Tusstat. •CYP2C9 (cytochrome P450 2C9) is the primary route of metabolism for Coumadin (Warfarin), Dilantin, Amaryl, Isoniazid, Sulfa and Ibuprofen. Clinical studies suggest that the use of genetic testing may be especially helpful with warfarin administration. Other drugs metaboloized by 2C9 include, Amitriptyline, Hyzaar, THC (tetrahydrocannabinol), Naproxen and Viagra. VKORC1 in conjunction with CYP2C9 (cytochrome P450 2C9) can predict your target dose for warfarin within 1.5 mg. •CYP2C19 (cytochrome P450 2C19) is associated with the metabolism of Carisoprodol, Diazepam, Dilantin, and Prevacid. •CYP1A2 (cytochrome P450 1A2) is associated with the metabolism of Amitriptyline, Olanzapine, Haloperidol, Duloxetine, Premarin, Propranolol, Theophylline, Caffeine, Diazepam, Chlordiazepoxide, Estrogens, Tamoxifen, and Cyclobenzaprine. •NAT2 is associated with metabolism of sulfa drugs, isoniazid, and occupational chemicals and carcinogens. How will my doctor or pharmacist use my personal DNA drug reaction profile? Prescription drugs on the market today have been tested and approved in a "one size fits all" manner despite the long- established knowledge that drug inactivation rates vary greatly from person to person. Now for the first time your health care providers can learn about your individual drug reaction profile and that can help them take better care of you.
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Chin Ho sp Pharm J ,2005 Aug ,Vol 25 ,No . 8Allen R , Myers A R , Frederick H , et al . The relatio nship of ser2um uric acid to risk facto rs in co ro nary heart disease [ J ] . Am JPuig J G , Mat eo s F , Bo un A , et al . Effect of Ep ro sartan andLo sartan o n uric acid met aboli sm in patient s wit h essential hyper2tensio n[J ] . Hypertens , 1999 , 17 (7) : 1033Edwareds RW , Trizna