According to the CDC, adverse drug events are a serious public health problem. An estimated 82% of American adults take at least one medication, and 29% take five or more. Each year, adverse drug events result in 700,000 emergency department visits and 120,000 hospitalizations.
Three and a half billion USD is spent on unnecessary medical costs due to adverse drug events annually, with at least 40% of these costs outside hospitals being preventable.
Often, an effective drug response is found in only a few treated cases, while most patients benefit little or not at all. Significant improvements could be made if we could predict the optimal medication for each individual before treatment begins.
Researchers are learning how inherited differences in genes affect the body's response to drugs. These genetic differences will be used to predict whether a drug will be effective for a particular person and help prevent adverse drug responses.
Just as a patient's age, lifestyle, comorbidities, and other medications affect the selection of a drug, genetic predisposition can also be a critical clinical factor that healthcare providers now consider.
Case Study
There are four main isoforms or families of mixed-function oxidases known as cytochrome P450 (CYP450) involved in drug metabolism. One of these enzymes, CYP2C19, metabolizes some commonly prescribed medications.
Metabolism by CYP2C19 can either activate or alter the activity of a drug. For example, Clopidogrel (a platelet inhibitor) is activated by CYP2C19.
Amitriptyline (used for various psychiatric indications) is metabolized by CYP2C19 to a less active form. Genetic variations in the CYP2C19 gene may lead to changes in the enzyme's metabolic activity (increased or reduced function).
What are a person's odds of having reduced CYP2C19 function?
Approximately 40% of the population has reduced function, though the exact percentage varies by race.
What can we expect with low CYP2C19 activity?
Low CYP2C19 activity is associated with a reduced antiplatelet response to Clopidogrel, leading to a higher risk of another heart attack or stroke.
Actions: Alternate Therapy
Amitriptyline, when metabolized by a person with low CYP2C19 activity, would be associated with a higher prevalence of adverse events and toxicity. Starting with a lower dose or considering an alternative therapy is recommended.
Understanding the activity of various genes will lead to more predictable patient outcomes when assessed alongside environmental exposures, medical history, family background, and other factors.
Many community resources are available to assist with medication therapy. You can consult a healthcare professional to help choose the right drug and dosage, increasing the likelihood of achieving the desired therapeutic effect and reducing the risk of unintended adverse drug responses.
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