Personalized prescribing
The actual efficacy of most drugs is about 20-30% and in 60-70% of cases, the drugs are either ineffective or toxic. This is particularly important when treating individuals with autism, autism spectrum disorders or dementia who are likely to have compromised communication skills. Antidepressants, antipsychotics or mood stabilizers are commonly prescribed to these patients, which infrequently leads to medication-induced side effects and toxicity. However, because of the compromised communication skills, many patients with autism or autism spectrum disorders as well as memory disorders are oftentimes unable to convey their discomfort to a prescriber.
Genomic Medicine enables physicians and other prescribers to rely on pharmacogenomic (PGx) data to implement personalized prescribing adapted to the patient’s genetic profile. Unlike the “Blockbuster” or “one-size-fits-all” prescribing model, PGx enables prescribers to optimize medication use, which assures improved efficacy and reduced toxicity for most patients.
PGx – based prescribing: How does it work?
Illustrations below compare the ‘Blockbuster’ or ‘one-size-fits-all’ drug prescribing model with PGx – based prescribing. The Blockbuster approach ignores individual differences in a patient responses to medications. The PGx approach highlights the individual variability, which shortens time to the positive treatment outcome and reduces the incidence of side effects.
PGx – based prescribing: The technical part
Drug target effects
The relationship between a drug dose and its effectiveness can be separated into pharmacodynamic and pharmacokinetic components. Genetic variants associated with the pharmacodynamic component are usually associated with a drug target. Thus, a drug target for opiates is opiate mu-receptor. If a person is a carrier of a variant known as 118A>G (rs1799971) within the opiate receptor OPMR1 gene, that person will likely require 2-4 times more of an analgesic drug to achieve a comparable degree of analgesia as non-carriers.
Drug metabolism: Poor, Intermediate, Extensive and Ultra-rapid metabolizer types
Drug effectiveness and side effects also depend on pharmacokinetic processes: absorption, distribution, and elimination. Cytochrome P450 (CYP) system is responsible for elimination of 60 – 80% of all drugs and its activity depends on what genetic variants are present. Depending on the CYP gene variants present, a person can be either Extensive, Poor, Intermediate or Ultra-rapid metabolizer for different drugs. The most important CYP genes that code for corresponding metabolizer enzymes are CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2C19 and CYP3A4.
Extensive metabolizers (two functional alleles)
No dose adjustment is required.
Poor metabolizers (two non-functional alleles)
These individuals are most prone to medication side effects. If a poor metabolizer (or PM) is prescribed a regular dose of a medication that is metabolized by the affected enzyme, significant side effects may ensue. The US Food and Drug Administration (FDA) recommends drug dose adjustment in such cases.
Intermediate metabolizers (one functional and one non-functional allele)
These individuals are most prone for developing side effects when a new medication is added. If an intermediate metabolizer (or IM) is prescribed a medication that is an inhibitor of the affected enzyme, that person becomes a poor metabolizer, a phenomenon called phenoconversion. This may result in a sudden appearance of side effects associated with a drug that a patient had been taking without problems.
Ultra-rapid metabolizers (duplication of a functional allele or a greater potency variant)
These individuals are most prone to a poor response to a medication. If a person is an Ultra-rapid metabolizers (or UM) and is taking a medication that is metabolized by the affected CYP enzyme the drug may be ineffective if give at a regular dose. FDA recommends dose adjustment for UMs.
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