Pharmacogenetics of Pain
Many common pain medications require activation by CYP2D6 to become effective. Approximately half of patients have genes that alter the function of 2D6. Testing for these gene alterations allows for alteration of dosage regimens to compensate for altered metabolism and optimize the safety and efficacy of the opioid family of analgesics. Physicians who adopt pharmacogenetic testing into their practice don't know how they were ever able to get along without it. Potential for drug drug interactions (DDIs).CYP2D6 metabolizes virtually all of the anti depressants, many of which are also strong inhibitors of the enzyme. Adverse events driven by interactions between opioid analgesics and anti depressants can be greatly increased in patients with gene based decreased CYP2D6 functioning.
Screening tests to to help physicians anticipate and prevent future difficulties as more and different drugs are taken.
Individualized Patient Reports based on patient drug, herbal and diet regimens
CYP2C9 (cytochrome P450 2C9) is the primary route of metabolism for Coumadin (warfarin) and Dilantin (phenytoin). Approximately 10% of the population are carriers of at least one allele for the slow-metabolizing form of CYP2C9 and may be treatable with 50% of the dose at which normal metabolizers are treated. Other drugs metabolized by CYP2C9 include Amaryl, isoniazid, sulfa, ibuprofen, amitriptyline, Hyzaar, THC (tetrahydrocannabinol), naproxen, and Viagra. CYP2C19 (cytochrome P450 2C19) is associated with the metabolism of carisoprodol, diazepam, Dilantin, Premarin, and Prevacid. CYP1A2 (cytochrome P450 1A2) is associated with the metabolism of amitriptyline, olanzapine, haloperidol, duloxetine, propranolol, theophylline, caffeine, diazepam, chlordiazepoxide, estrogens, tamoxifen, and cyclobenzaprine. NAT2 (N-acetyltransferase 2) is a second-step DME that acts on isoniazid, procainamide, and Azulfidine. The frequency of the NAT2 "slow acetylator" in various worldwide populations ranges from 10% to more than 90%.
Now you can add another dimension to providing safer and more efficacious care to your patients by ordering DNA Drug Sensitivity Testing for them. Call (800) 523-3080 for more information or to obtain collection kits, or visit how to order for test requisition forms and sample requirements. Referenceshttp://www.medscape.com/viewarticle/508543_2 Oesterheld, Jessica, M.D. GeneMedRx Drug Metabolism Tables Foster A, Mobley E, and Wang Z. Complicated pain management in a CYP450 2D6 poor metabolizer, Pain Pract. 2007 Dec;7(4):352-6. Gan SH, Ismail R, Wan Adnan WA, Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics, Mol Diagn Ther. 2007;11(3):171-81. Kirchheiner J, Keulen JT, Bauer S, Roots I, Brockmöller J. Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol, J Clin Psychopharmacol. 2008 Feb;28(1):78-83. Stamer UM, Stüber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication, Anesth Analg. 2008 Sep;107(3):926-9. Coller JK, Christrup LL, Somogyi AA. Role of active metabolites in the use of opioids, Eur J Clin Pharmacol. 2008 Oct 29. http://www.medscape.com/viewarticle/552096 Cozza KL, Armstrong SC, Oesterheld JR (2003) Drug Interaction principles for Medical Practice. American Psychiatric Publishing Inc Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723 Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jan;369(1):23-37 Disclaimer: The content on this page is intended for healthcare professionals.
By Howard Coleman, B.S. Last Reviewed 8/20/10
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