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side effects of opioids

Pharmacogenomic Data May Help Guide Opioid Pharmacotherapy in Patients with Cancer-related Pain

By | Cancer Treatments, Other, Pain Medications, Pharmacogenomics, Provider | No Comments

Opioids are the most potent analgesics and are used to treat severe pain, specifically pain associated with cancer – a significant factor in reducing quality of life and clinical outcomes in such patients as detailed in Cancer Control “Clinical Implications of Opioid Pharmacogenomics in Patients with Cancer” (October 2015).

 

Inter-individual Differences in Genetically Modulated Opioid Response

 
The study reviewed clinical studies involving the pharmacodynamics and pharmacokinetics of opioids. It examined the opioid agents morphine, codeine, tramadol, oxycodone, fentanyl, and hydrocodone and the relationship to single nucleotide polymorphisms (SNPs): OPRM1, COMT (specifically COMT Val Met), CYP2D6, CYP3A4/5, and ABCB1, which the study claimed are responsible for the inter-individual differences in opioid response.

 
The authors specifically found that OPRM1, COMT Val Met, and ABCB1 are most strongly correlated with morphine response. One study combined OPRM1 and ABCB1 and found that patients with both of these genetic variants were the best responders as indicated in patients’ measures of pain intensity. In another study, patients with OPRM1 and COMT Val Met needed the lowest morphine dose compared to other genotypes. All three together demonstrated no difference in morphine dose requirements.

 

CYP2D6 Variants Correlate with Drug Efficacy

 
Similarly, the presence of CYP2D6 variants correlated positively with variations in codeine and tramadol efficacy. CYP2D6 is responsible in converting the analgesic properties of codeine and tramadol. In studies investigating codeine pharmacotherapy in cancer patients, analgesic differences and adverse effects were found for CYP2D6 poor, intermediate, and extensive metabolizers.

 
The authors concluded CYP2D6 testing helps in finding which patients respond positively to codeine. Studies with tramadol focusing on non-cancer pain populations identified CYP2D6 poor metabolizers as having a decreased analgesic response compared to extensive metabolizers. However, the authors noted there has been no specific study relating to tramadol’s analgesic efficacy in cancer populations, arguing tramadol will likely have decreased clinical benefit in patients who are poor CYP2D6 metabolizers.

 

Call for Preemptive Genotyping in Clinical Practice

 
The authors assert that these findings “suggest genotyping patients for some of these genetic variants may help predict responses to pain treatments with good rates of sensitivity and specificity and with greater benefits for patients and decreased health care utilization.” Furthermore, the authors assert that utilizing pharmacogenomics data combined with a preemptive genotyping be a “key element” in guiding treatment decisions for cancer patients.

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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.

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Side Effects of Pain Medications: NSAIDs and Opioids

By | Pain Medications | No Comments

The two main types of pain medications are NSAIDs and opiates. NSAIDs stand for nonsteroidal anti-inflammatory drugs and include drugs such as aspirin, ibuprofen, and naproxen. NSAIDs are used to treat mild to moderate pain. Opiates include prescription drugs such as morphine, oxycodone, hydromorphone and various illegal drugs such as heroin and opium. Opiates provide a more profound pain relief than NSAIDs and are used to treat moderate to severe pain. Pain medication side effects vary depending on which of these pain relievers are used.

 

Pain Medication Side Effects: Opiates

 

The three main side effects of opiates are gastrointestinal system problems, addiction, and overdose. Gastrointestinal system issues are one of the most common pain medication side effects, especially for opiates. Opiates bind to receptors in the gastrointestinal tract and slow down the action of the intestines. In essence, waste is unable to move towards the anus, causing severe constipation.

 

Long-term opiate use is associated with both physical and psychological dependence. People need higher doses of the drug to achieve the same effect and they may exhibit drug-seeking behavior, putting themselves and others at risk in order obtain more of the medication. Opiate addiction is uncommon in people who use opiates for a short period, but the risk increases with long-term use or the use of powerful, illegal narcotic opiates.

 

Opiate overdose can be fatal. When opiate levels become higher than the body can tolerate, the drug causes a lack of awareness, altered mental status, diminished consciousness or unconsciousness, and dangerously slow breathing. If opiate overdoses not treated, breathing may stop, causing death. Opiate overdose is the most feared and serious pain medication side effects. It is not simply a problem among illegal opiate users, but it can occur with high doses of prescribed opiates.

 

NSAID Side Effects

 

The main side effects of NSAIDs are those affecting the gastrointestinal system, the kidneys, and blood. NSAIDs directly irritate the stomach and interfere with substances that help protect the lining of the stomach, such as mucus production. Thus, NSAIDs commonly cause stomach upset, pain, and can contribute to ulcers and gastrointestinal bleeding.

 

Aspirin keeps lead platelets from sticking together. This is useful when blood clots are an issue, but can increase the risk of bleeding in other circumstances. NSAIDs other than aspirin, have been shown to increase the risk of stroke and heart attack. People with chronic liver or chronic kidney disease, should not take NSAIDs because of pain medication side effects that may worsen organ function.

 

Liver Enzymes Predict Pain Medication Side Effects

 

Three cytochrome P450 enzymes are particularly important for pain medication metabolism. Most NSAIDs are metabolized via CYP2C9. On the other hand, CYP2B6 or CYP3A4 breaks down virtually all forms of opiates. People who are poor metabolizers of any of these cytochrome P450 enzymes may experience toxic accumulations of the respective pain medication. Higher-than-expected doses are responsible for various pain medication side effects.

 

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PharmGKB Recommends PGx Testing for Pediatric Codeine Therapy

By | Adverse Drug Reactions, Pain Medications, Pharmacogenetic Testing, Provider | No Comments

Last Tuesday the American Academy of Pediatrics (AAP) issued a statement that the dangers of codeine use in children outweigh the benefits, and formally recommended that codeine not be used in the pediatric population. Specifically, the AAP noted that children can be “ultra-rapid metabolizers” of codeine and thus suffer highly deleterious adverse effects to its active metabolites. The AAP interpretation was that the “majority” of the pediatric population runs such a risk.

 

In response, PharmGKB – a leading pharmacogenomics knowledge resource – argues that while it agrees that the variability in patient phenotypic response to codeine is important to consider, PharmGKB’s position is that rather than recommending such potentially highly beneficial treatment be ceased, the AAP ought to consider the enormous potential benefit of employing pharmacogenetic testing to assess whether indeed the individual patient is a rapid metabolizer of codeine.

 

Furthermore, PharmGKB characterized such measures as an “archaic” reaction that does not take into account that rapid metabolizers can be easily flagged through PGx, and expressed concern at the AAP’s disseminating such misinformation to the general population. Moreover, PharmGKB points out that codeine is in fact a potentially highly effective analgesic and an antitussive agent and the AAPs measure to recommend discontinuing it is misguided and a blunt, outdated and categorically misinformed response.

 

MD Labs agrees strongly with PharmGKB’s stance on the AAP decision. The Rxight® pharmacogenetic testing identifies patients who should be identified based on genetic profiles that would put them at risk for major contraindications from codeine and propose alternative medications for codeine based on their genetically modulated response to codeine therapy. The Rxight® test is based on SNP genotyping for hundreds of common prescription and OTC medications, including codeine and other opioids.

 

In contrast to the AAP’s “one-size-fits-all” recommendation to avoid codeine treatment entirely for all children, using Rxight® to screen children would help identify those who may have a negative metabolic reaction to codeine before they begin treatment. Rxight® would provide prescribing guidance for their physician to tailor the child’s treatment regimen accordingly, helping children either avoid codeine or enabling children for whom codeine is entirely safe to benefit from it.

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