At CytoVive, we understand that chronic pain is one of the most debilitating conditions that an individual can be faced with. Suffering from severe pain can take the joy out of life and steal a person's ability to live the way that they choose. Successful pain management hinges on personalized medication plans that achieve a balance between providing sufficient analgesic effects while minimizing side effects and adverse drug reactions. We are proud to offer industry leading diagnostic tools and reporting services that assure your patients receive the best medication plan possible giving them the freedom to break the grips of pain while maintaining the clarity necessary to live and enjoy life again!
Pharmacological and Legal Need for Toxicology Assurance
The incorporation of toxicology assurance programs as part of the care plan for pain management patients is both a medically and legally necessary component of the overall care plan. It is the standard of care. This type of urinalysis provides data regarding the presence or absence of corresponding medication metabolites and allows physicians to monitor and adjust the dose of prescribed medications on an individualized basis in order to ensure the best physiological outcome for each patient!
When a patient's body is not producing the proper active drug metabolites from their medication it alludes to one of several possibilities:
One: The patient is likely a variant metabolizer for that medication and could be at an elevated risk for an adverse drug reaction. A dosage adjustment or alternative medication may be recommended.
Two: The patient could be (knowingly or unknowingly) consuming a substance that either induces or inhibits a metabolic pathway necessary for their medication to be properly metabolized.
Three: The patient is not actively taking and potentially diverting their medication.
Qualitative toxicology assurance can protect physicians from malpractice claims and is highly valuable in determining which patients qualify as prime candidates for pharmacogenetic testing. This screening is the first line of defense against potentially fatal adverse drug reactions, and serves as a responsible control that helps pain management practices guard against patient addiction and abuse, as well as ensure prescription narcotics with a "high street value" are not getting into the wrong hands (5,7).
Opioid Risk Rates by CYP2D6 Phenotype
"Ultra Rapid Metabolizers"
Copyright PGXL Laboratories 2016
Leading pain management drugs are metabolized by the Cytochrome P450 superfamily of enzymes, and the CYP2D6 enzyme is a key player in opioid metabolism. The high prevalence of CYP2D6 variant metabolizers in our population dictates a tremendous need for the toxicological urinalysis of all pain management patients and the pharmacogenetic analysis of prime candidate patients. Many pain patients often take high levels of medication/multiple medications to help manage their pain. Operating at those high thresholds, toxicity and overdose are very serious potential risks, therefore physicians must know precisely how much of each drug the patient is actually metabolizing (8). This is why reporting drug-gene interactions, drug-drug interactions, as well as contraindicated pathway inducers and inhibitors is so important. That information can literally be the difference between life and death.
Chronic Pain and Depression
Patients who are dealing with chronic pain are at a much higher risk of depression than members of the general population. According to the American Pain Foundation, about 32 million people in the U.S. report pain lasting longer than one year and more than half of patients who complain about pain to their doctor show signs of depression (6). This high prevalence of comorbid behavioral health conditions in pain management patients increases the number of patients who receive coadministered anti-depression medications and greatly increases the risk of adverse drug reactions in this population.
Common Pain Management Medication Metabolism Pathways
Copyright PGXL Laboratories 2016
"Normal Metabolizers": How Normal Is Normal?
Copyright PGXL Laboratories 2016
Pain Management Relevant Genes In The PRIMER Panel
Gene - Gene Product Description
CYP2D6 – Metabolizes more than 25% of all drugs, including tamoxifen, many antidepressants, antipsychotics, beta-blockers, and opioids. Detecting variants of the CYP2D6 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP2D6 substrates. Medications which require activation or inactivation by CYP2D6 should be used with caution in patients with CYP2D6 variants.
CYP2C19 – Metabolizes approximately 10-15% of all drugs, including clopidogrel, citalopram, diazepam, and many of the proton pump inhibitors. Detecting variants of the CYP2C19 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP2C19 substrates.
CYP2C9 – Metabolizes approximately 10% of all drugs, including warfarin, phenytoin, non-steroidal anti-inflammatory drugs (NSAIDs), and antihyperglycemic sulphonylureas. Detecting variants of the CYP2C9 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP2C9 substrates.
CYP3A4 - A liver enzyme that, in concert with CYP3A5, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A4 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A4 substrates. Roughly 4-10% of the general population possesses inherited differences in 3A4 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A4.
CYP3A5 – A liver enzyme that, in concert with CYP3A4, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A5 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A5 substrates. More than half of the general population (60-80%) possesses inherited differences in 3A5 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A5.
CYP1A2 – Metabolizes many medications, including theophylline, diazepam, caffeine, and amitriptyline. CYP1A2 can be induced by several medications, substrates, and constituents of tobacco smoke. CYP1A2 can also be inhibited by several medications. Basal metabolic capacity remains relatively consistent among the different genotypes in the absence of an inducer. Detecting variants of the CYP1A2 gene that cause altered enzymatic induction in the presence of an inducer can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP1A2 substrates.
OPRM1 – Opioid agonists, such as morphine, hydromorphone, and oxymorphone, exert their analgesic properties via stimulation of the mu-1 opioid receptor. Analgesic efficacy of mu-acting drugs has been linked to the 118A>G single nucleotide polymorphism (SNP) of OPRM1, the gene encoding the mu-1 receptor. The frequency of the variant G allele varies from 10% to 48% depending on the population studied. Studies show that patients carrying the GG (homozygous variant) genotype require much higher opioid doses to achieve pain relief. Additionally, patients with the AA genotype display higher relapse rates with respect to naltrexone treatment for alcohol dependence.
1) Menu of Tests [Internet]Louisville, KY: PGXL Laboratories; c2016 [cited 2016 11/20]. Available from: http://www.pgxlab.com/test-menu/.
2) Opioid Overdoses Driving Increase in Drug Overdoses Overall [Internet]United States: Center for Disease Control and Prevention; c2014 [cited 2016 10/10]. Available from: www.cdc.gov/drugoverdose.
3) Pathways for Common Medications. Louisville, KY: PGXL Laboratories; 2016:PGXL Primer. Personalized Medicine. Results For Life.
4) Reynolds et al Pers Med 2007; Zhu et al Clin Chem 2006; Linder et al J Thrombosis Thrombolysis 2002.
5) Rifat MD. Pharmacological and Legal Need for Quantitative Drug Analysis. San Diego, CA: Alcala Testing and Analysis; 2016.
6) Saber-Tehrani A, Bruce RD, Altice FL. Pharmacokinetic drug interactions and adverse consequences between psychotropic medications and pharmacotherapy for the treatment of opioid dependence. American Journal of Drug & Alcohol Abuse 2011 01;37(1):1-11.
7) What is Toxicology? [Internet]: News Medical Life Sciences; c2016 [cited 2016 10/10]. Available from: http://www.news-medical.net/health/What-is-Toxicology.aspx.
8) Yiannakopoulou E. Pharmacogenomics and opioid analgesics: Clinical implications. International Journal of Genomics 2015 05/14;2015:1-8.