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The Prospect of Pharmacogenetics in Pediatrics

By | Opioids, Other, Pharmacogenetic Testing, Provider | No Comments

Pharmacogenetics of Opioids as a Potential Alternative in Pediatric Pain Management

Opioid and codeine treatment in pain management for children has been a primary concern in clinical settings, specifically for surgical pain management. The concerns are the adverse reactions caused by the opioids, such as respiratory depression. Current Opinion in Anesthesiology, “Codeine and Opioid Metabolism: Implications and Alternatives for Pediatric Pain Management” (2017), reviews how important clinical factors and genetic polymorphisms affect the metabolism of opioids after surgical operations.


Adverse Side Effects of Codeine

Codeine’s efficacy has been questioned in the pain management of children. Current Opinion in Anesthesiology identifies the adverse reactions of it. The prominent ones are respiratory depression, anoxic brain injuries, and even death occurring in children. With reported doses of codeine, significant respiratory depression was found in newborns in a report by Canadian Pharmacists Journal “Pain Management in Children: A Transition from Codeine to Morphine for Moderate to Severe Pain in Children” (2012).

Opioids in Pain Management

Opioids are the cornerstone of pain and chronic pain management. “Successful pain management provides adequate analgesia without excessive adverse reactions affirms Clinical Biochemistry “Pharmacogenetics of Chronic Pain Management” (2014). Drug metabolism and responses are influenced by numerous factors, including pharmacogenetics. Genetic variations contribute to the distinct inter individual responses to pain medications.

Involvement of CYP2D6 in Codeine

Those with two nonfunctional alleles of CYP2D6 are considered poor metabolizers. Extensive metabolizers have one or two effective CYP2D6 alleles and those with duplicated CYP2D6 alleles are ultra rapid metabolizers. Canadian Pharmacists Journal indicates the functions of CYP2D6 are similar in both children and adults.

The review also acknowledges the safety concerns of CYP2D6 ultra rapid metabolizers from several studies. One study demonstrated how a breastfed newborn infant died after his mother consumed Tylenol #3 for postpartum pain. Toxicology testing found the mother had abnormally high concentration levels of morphine in her breast milk. Genotype testing found the mother was an ultra rapid metabolizer of codeine. The study concluded since the mother was an ultra rapid metabolizer, higher than normal morphine levels crossed into the breast milk and resulted in the infant dying from morphine intoxication.

Another study found a two-year-old child who also died of morphine intoxication. The child was prescribed codeine in recommended dosages after having his tonsils removed. Genotype testing revealed the child was an ultra rapid metabolizer of codeine. However, there were also other contributing factors; the child had bronchopneumonia and sleep apnea. The study concluded these factors “may have increased his risk of hypoxemia, leading to alterations in opioid receptors and increased sensitivity to morphine.”

Canadian Pharmacists Journal concludes these studies show ultra rapid metabolizers of codeine are correlated with a higher risk of morphine intoxication among children.


Alternatives to Prevent Adverse Drug Reactions

Canadian Pharmacists Journal argues morphine as a safer alternative compared to codeine. They argue morphine has “demonstrated efficacy and relative safety when used appropriately in pain management in both adults and children.” A study they analyzed found morphine treatment more effective than a placebo for children in postoperative pain.

Current Opinion in Anesthesiology also outlines the possible alternatives to prevent the risks of opioids, such as pharmacogenetics. They indicate personalized opioid therapy for pain management is “distant from reality”, but current CYP2D6 pharmacogenetic research on codeine is hopeful. The review summarizes, “pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety.”

Pharmacogenetics Emerging as a Method to Guide Medication Therapy

By | Gene Panel, Opioids, Other, Pharmacogenetic Testing, Provider | No Comments

According to a recent article published in American Family Physician “Pharmacogenetics: Using Genetic Data to Guide Drug Therapy (2015), pharmacogenetics is being more widely used by family physicians and the number of patients who are interested in acquiring genetic information is growing.


The Components of Pharmacogenetics Testing

Pharmacogenetics involves genetic variations that code for drug metabolizing enzymes. It also involves how a medication breaks down in the body and how the body responds to the medication. The most common forms of genetic variations are single nucleotide polymorphisms.

The differences in single nucleotide polymorphisms or other polymorphisms result in diverse types of genes or alleles, the American Family Physician explains. Individuals inherit these alleles that “govern expression of the gene and the cor¬responding enzyme or protein.” As a result, these genetic differences influence how the drug reacts in the body and how the body metabolizes the drug.


Genetic Variability Can Alter the Effects of Drugs

Studies have demonstrated there is a connection between genetic variations and changes in drug levels and effects.

CYP2D6 and Opioids

The enzyme activity of CYP2D6 is volatile because of single nucleotide polymorphisms and other variations of CYP2D6. American Family Physician indicates codeine metabolism occurs in 90% of patients and results in normal morphine formation. However, 1% to 2% of people are ultra rapid metabolizers of codeine signifying they have an increased risk of morphine toxicity.

American Family Physician analyzed a study involving the death of a breastfed infant and a mother who was an ultra rapid metabolizer of codeine. The study demonstrated the infant died of morphine intoxication. There was opioid toxicity in the breast milk, which passed onto the infant.

They recommend pharmacogenetic testing for patients who are possible poor or ultra rapid metabolizers of opioids.


CYP2C19 and Clopidrogrel

Clopidogrel is primarily metabolized in the enzyme CYP2C19. CYP2C19 is highly polymorphic and 80% of individuals metabolize clopidogrel normally. However, 18% to 45% of people have intermediate enzyme activity and 2% to 15% have poor enzyme activity.

American Family Physician presents meta-analyses of CYP2C19 poor metabolizers. Poor CYP2C19 metabolizers taking clopidogrel treatment and undergoing percutaneous coronary intervention have a higher risk of cardiovascular death, myocardial infraction, stroke, and stent thrombosis.

These results lead to the recommendation that clinicians should consider alternative treatments, such as pharmacogenetic testing of CYP2C19 to guide antiplatelet therapy.


The Benefits of Pharmacogenetics

American Family Physician examined the clinical implications of pharmacogenetic testing and the various resources available and developing to support the usage of pharmacogenetics in clinical settings. They conclude “pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects.”

The U.S. Opioid Epidemic and How Your Genetics Factor into Your Risk for Addiction

By | Opioids, Pain Medications | No Comments

Find Out Your Medication Risks with the Rxight® Genetic Test
The United States is amidst an opioid epidemic and the numbers are sobering. According to the U.S. Department of Health and Human Services, the rate of overdose deaths involving opioids, including prescription opioid pain relievers, has nearly quadrupled since 1999, and over 165,000 people have died from prescription opioid overdoses. The Rxight® Pharmacogenetics Program can help you understand how your genetics play a role in your likelihood for addiction.
On a typical day, more than 650,000 opioid prescriptions are dispensed, 3,900 people use prescription opioids, which include hydrocodone (Vicodin), codeine and tramadol (Ultram), for recreational purpose, and about 80 people die from an opioid-related overdose, according to the HHS. https://www.hhs.gov/opioids/about-the-epidemic/#us-epidemic

Tragic Reports of Opioid Overdose, Death Commonplace

Accounts of overdose and death from prescription or illicit opioids have been seen in the media with alarming frequency. For example, on Mar 17 2017, three Ohio children discovered their parents dead in bed of an apparent opioid medication overdose. In another gut-wrenching story, a panicked two-year-old from Massachusetts is seen on video attempting to revive her mother, who is unconscious on the floor in a store from an opioid overdose. The opioid epidemic has reached staggering proportions to the point where “[i]t is no longer a shock to see drug users collapse in public,” a September 2016 article in the New York Times stated.

Research Shows Certain Gene Variants May Be Linked to Addiction to Opioids

Both the ability to metabolize opioids and your susceptibility to becoming dependent on them are grounded in your genetic makeup, according to research published in Addiction Science and Clinical Practice “Pharmacogenetics: A Tool for Identifying Genetic Factors in Drug Dependence and Response to Treatment” (Dec 2010). 
Specifically, the impact of genetic variation on responses to several drugs of abuse including opioid pain medications and several variations have been implicated in likelihood for addiction and dependence. The article states that drugs including opioids activate the pathways that play an essential role in drug reward and reinforcement as well as a general sense of calm and well-being.

Your Genetics Can Indicate Your Risk for Overdose

Additionally, this study reveals how several oral opioids, such as codeine, oxycodone, and hydrocodone, are metabolized by another enzyme, which gives the users a feeling of a “high.” Some genes are highly variable, with some of these variations leading to a completely inactive enzyme. Individuals who inherit such “defective” alleles from both parents are referred to as “poor metabolizers” and thus less likely to become dependent.
Individuals proven to be poor metabolizers of these drugs are also more susceptible to toxicity and overdose at standard doses. Conversely, individuals who are “fast metabolizers” are more prone to addiction.

Pharamcogenetic Testing for Opioids with Rxight®

MD Labs’ Rxight® is the most comprehensive pharmacogenetics program available on the market, grounded in the analysis of 18 genes and their alleles. The Rxight® genotyping technology tells you how you might respond to over 200 clinically relevant prescription and over-the-counter medications, including 15 common opioid pain medications. This genetic guidance can help you determine if you could have an adverse reaction at standard doses, or conversely not respond to the medication. Rxight® specifically identifies whether you are a slow, normal or rapid metabolizer of the medications on the panel. It also flags the medications that could be of concern to you and your prescribers. Since your DNA does not change, your Rxight® test results are good for life.
Contact Rxight® by phone (888) 888-1932 or email us at info@rxight.com to get started today.