Pharmacogenomics
CYP2D6 (cytochrome P450 2D6) acts on one-fourth of all prescription drugs, including the selective serotonin reuptake inhibitors (SSRI), tricylic antidepressants (TCA), betablockers such as Inderal and the Type 1A antiarrhythmics. Approximately 10% of the population has a slow acting form of this enzyme and 7% a super-fast acting form. Thirty-five percent are carriers of a non-functional 2D6 allele, especially elevating the risk of adverse drug reactions when these individuals are taking multiple drugs.
Drugs that CYP2D6 metabolizes include:
 Prozac- Zoloft
- Paxil
- Effexor
- Hydrocodone
- Amitriptyline
- Claritin
- Cyclobenzaprine
- Haldol
- Metoprolol
- Rythmol
- Tagamet
- Tamoxifen
- The over-the-counter diphenylhydramine drugs, Allegra, Dytuss, and Tusstat.
CYP2D6 is responsible for activating the pro-drug codeine into its active form and the drug is therefore inactive in CYP2D6 slow metabolizers.
For an example of a sample report and interpretive comments, read the pfd about 2D6 poor metabolizers.
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.
For an example of a sample report and interpretive comments, read the pdf about 2C9 Extensive Metabolizers.
CYP2C19 (cytochrome P450 2C19) is associated with the metabolism of carisoprodol, diazepam, Dilantin, and Prevacid.
For an example of a sample report and interpretive comments, read the pdf about 2C19 Intermediate Metabolizers.
CYP1A2 (cytochrome P450 1A2) is associated with the metabolism of amitriptyline, olanzapine, haloperidol, duloxetine, propranolol, theophylline, caffeine, diazepam, chlordiazepoxide, estrogens, tamoxifen, and cyclobenzaprine.
 GeneMedRx is a software tool designed to help physicians predict whether or not drugs are safe and effective for patients based on genetic cytochrome P450 metabolic pathways. This prediction is based both on the potential interaction of drug combinations and the genetic ability of the patient to process drugs.
GeneMedRx software is the most extensive coverage of cytochrome P450s available and in use by physicians since 1997 that is regularly updated and algorithm processed.
View a Demo of GeneMedRx software.
Pharmacogenomics is the study of how an individual's genetic inheritance affects the body's response to drugs. Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person's own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person's response to medicines, but understanding an individual's genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.
Better, Safer Drugs the First Time Instead of the standard trial-and-error method of matching patients with the right drugs, doctors are able to analyze a patient's genetic profile and prescribe the best available drug therapy from the beginning. Not only will this take the guesswork out of finding the right drug, it will speed recovery time and increase safety as the likelihood of adverse reactions is eliminated. Pharmacogenomics has the potential to dramatically reduce the estimated 100,000 deaths and 2 million hospitalizations that occur each year in the United States as the result of adverse drug response.
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It is now clear that virtually every pathway of drug metabolism, transport and action is susceptible to genetic variation. It is estimated that 20% to 95% of individual variability is genetic based. (NEJM 348;529 & 538 2003) Within the top 200 selling prescription drugs, 59% of the 27 most frequently cited in adverse drug reaction (ADR) studies are metabolized by at least one enzyme known to have gene variants that code for reduced or non-functional proteins. This compares with 7% of a random selection from the top 200 list. (JAMA, 286,2270 2001) Many other factors such as age, physiological functioning and concomitant disease are known and can be accounted for, leaving the genotype of the patient as a major unknown factor in the prescribing of medicines.
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DNA Drug Reaction Tests from Genelex evaluate for the highly polymorphic cytochromes, CYP2D6, CYP2C9, CYP1A2, and CYP2C19. These enzymes process half of the most commonly prescribed drugs, including many with narrow therapeutic indices and frequent participation in drug-drug interactions. (Drug Interaction Principles for Medical Practice, 2nd ed. APPI, 2003) Half of your patients have genetic variations in these genes that lead to altered or absent function resulting in elevated patient susceptibility to adverse drug reactions. Genotyping to avoid adverse drug reactions is a dependable tool to improve your practice today and begins your transition to the practice of tomorrow.
Examples of Clinical Utility of Pharmacogenomic Testing are as follows:
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