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10% of Caucasians are “non metabolizers”. This means that they cannot metabolize more than 50% of today’s drugs such as adderall, and other SSRIS. It is suspected that the heinous trend of school shootings and suicides are caused by non metabolizers who are given psychiatric drugs without first being tested for their ability to metabolize them. Because this test is not standard of care hospitals and doctors who destroy lives by giving counter indicated medication can not be successfully sued. There is a movement to make this test standard of care but it is being thwarted by the invested pharmacuetical companies who would stand to lose billions of dollars if the public knew.
The cytochrome p450 (CYP450) family is involved in the metabolism of a significant proportion of currently administered drugs, and genetic variants in cytochrome p450 are associated with altered metabolism of many drugs. It is proposed that genetic testing for cytochrome p450 variants may assist in selecting and dosing drugs that are impacted by these genetic variants.
Drug efficacy and toxicity vary substantially between individuals. Because drugs and doses are typically adjusted to meet individual requirements as needed by using trial and error, clinical consequences may include a prolonged time to optimal therapy and serious adverse events.
Various factors may influence the variability of drug effects, including age, liver function, concomitant diseases, nutrition, smoking, and drug-drug interactions. Inherited (germline) DNA sequence variation (polymorphisms) in genes coding for drug metabolizing enzymes, drug receptors, drug transporters, and molecules involved signal transduction pathways also may have major effects on the activity of those molecules and also on the efficacy and toxicity of the drug.
Pharmacogenomics is the study of how an individual’s genetic inheritance affects the body’s response to drugs. It may be possible to predict therapeutic failures or severe adverse drug reactions in individual patients by testing for important DNA polymorphisms (genotyping) in genes related to the metabolic pathway (pharmacokinetics) or single transduction pathway (pharmacodynamics) of the drug. Potentially, test results could be used to optimize drug choice and/or dose for more effective therapy, avoid serious adverse effects and decrease medical costs.
Some CYP450 enzyme genes are highly polymorphic, resulting in some enzyme variants that have variable metabolic capacities among individuals, and some with little to no impact on activity.
Individuals with a lack of function activity in these enzymes (CYP2C19, CYP2D6, CYP2C9, etc.) can be classified according to how fast they metabolize medications:
- Poor metabolizers (PMs): lack active enzyme gene alleles, they will process a certain drug more slowly than normal because of the missing enzyme(s), the medication can build up in their system which can increase the likelihood that it will cause side effects. The individual might still be able to benefit from the medication, but at lower dosages.
- Intermediate metabolizers (IMs): have one active and one inactive enzyme gene allele, these individuals have a reduced enzyme function in processing drugs, they may not process some medications as well as a normal metabolizer would. This can increase risk of side effects and drug interactions.
- Normal metabolizers (extensive metabolizers Ems): these individuals have 2 copies (alleles) of the most common (wild type) DNA sequence of a particular CYP450 enzyme gene resulting in an active molecule and are termed extensive metabolizers. Medications are processed normally, these individuals are more likely to benefit from treatment and have fewer side effects than people who don’t process the same medication(s) as well.
- Ultra-rapid metabolizers (UMs): individuals with more than 2 alleles of an active enzyme gene, which cause the medications to leave the body too quickly and often before they have had a chance to work properly. These individuals will likely need a higher than usual dose of medications.