Browsing by Subject "Codeine"

Now showing 1 - 4 of 4
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    Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype
    (Wiley, 2012-02) Crews, K.R.; Gaedigk, A.; Dunnenberger, H.M.; Klein, T.E.; Shen, D.D.; Callaghan, J.T.; Kharasch, E.D.; Skaar, Todd C.
    Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine as an analgesic are governed by CYP2D6 polymorphisms. Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas the risk of morphine toxicity is higher in ultrarapid metabolizers. The purpose of this guideline (periodically updated at http://www.pharmgkb.org) is to provide information relating to the interpretation of CYP2D6 genotype test results to guide the dosing of codeine.
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    Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy
    (Wiley, 2021) Crews, Kristine R.; Monte, Andrew A.; Huddart, Rachel; Caudle, Kelly E.; Kharasch, Evan D.; Gaedigk, Andrea; Dunnenberger, Henry M.; Leeder, J. Steven; Callaghan, John T.; Samer, Caroline Flora; Klein, Teri E.; Haidar, Cyrine E.; Van Driest, Sara L.; Ruano, Gualberto; Sangkuhl, Katrin; Cavallari, Larisa H.; Müller, Daniel J.; Prows, Cynthia A.; Nagy, Mohamed; Somogyi, Andrew A.; Skaar, Todd C.; Medicine, School of Medicine
    Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes which have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1 and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone and methadone and for OPRM1 and COMT for clinical use.
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    Understanding exposure to pharmacogenetically actionable opioids in primary care
    (2016-04-21) Knisely, Mitchell R.; Carpenter, Janet S.; Draucker, Claire Burke; Broome, Marion E.; Holmes, Ann M.; Von Ah, Diane
    Pharmacogenetic testing has the potential to improve pain management through addressing wide interindividual variations in responses to pharmacogenetically actionable opioids, ultimately decreasing costly adverse drug effects and improving responses to these medications. A recent review of pharmacogenomics in the nursing literature highlighted the need for nurses to more fully embrace the burgeoning field of pharmacogenomics in nursing research, clinical practice, and education. Despite the promise of pharmacogenetic testing, significant challenges exist for evaluating outcomes related to its implementation, including oversimplification of medication exposure, the complexity of patients' clinical profiles, and the characteristics of healthcare contexts in which medications are prescribed. A better understanding of these challenges could enhance the assessment and documentation of the benefits of pharmacogenetic testing in guiding opioid therapies. This dissertation is intended to address the challenges of evaluating outcomes of pharmacogenetic testing implementation and the need for nurses to lead pharmacogenomic-related research. The dissertation purpose was to advance the sciences of nursing, pain management, and pharmacogenomics through the development of a typology of common patterns of medication exposure to known pharmacogenetically actionable opioids (codeine & tramadol). A qualitative, person-oriented approach was used to retrospectively analyze six months of electronic health record and pharmacogenotype data in 30 underserved adult patients. An overarching typology with eight groups of patients that had one of five opioid prescription patterns (singular, episodic, switching, sustained, or multiplex) and one of three types of medical emphasis of care (pain, comorbidities, or both) were identified. This typology consisted of a description of multiple common patterns that compare and contrast salient factors of exposure and the emphasis of why individuals were seeking care. Furthermore, in an aggregate descriptive analysis evaluating key clinical profile factors, these patients had complex medical histories, extensive healthcare utilization, and experienced significant polypharmacy. These findings can aid in addressing challenges related to the implementation of pharmacogenetic testing in clinical practice and point to ways in which nurses can take the lead in pharmacogenomics research. Findings also provide a foundation for future studies aimed at developing medication exposure measures to capture its dynamic nature and identifying and tailoring interventions in this population.
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    Zebrafish (Danio rerio) larvae show behavioral and embryonic development defects when exposed to opioids at embryo stage
    (Elsevier, 2021) Sales Cadena, Marilia R.; Cadena, Pabyton G.; Watson, Meredith R.; Sarmah, Swapnalee; Boehm, Stephen L.; Marrs, James A.; Psychology, School of Science
    Opioid abuse continues to plague society, and in recent years, there has been an epidemic, leading to increased addiction and death. It is poorly understood how prenatal opioid use affects the lives of children. The aim of this work was to evaluate the effect of early embryonic codeine or morphine exposure in zebrafish (Danio rerio), examining gastrulation progression (epiboly), teratogenic effects, mortality and locomotor behavior response to light/dark cycles. Zebrafish embryos were exposed to codeine or morphine (designated C or M) at 1, 5 or 10 mg/L (designated 01, 05 or 10, respectively) from 3 to 24 h postfertilization (hpf) or from 3 to 48 hpf (designated -24 or - 48 for 1 or 2 days of exposure, respectively). The C10-24, C01-48, C05-48 and C10-48 groups showed significantly smaller eyes than control larvae at 7 days postfertilization (dpf). Locomotor behavior of control larvae in light/dark cycles showed greater swimming time and distance in dark cycles. Two-day codeine exposure produced strong effects, showing no significant response due to light/dark cycles in distance moved. Morphine exposed groups showed similar effects as observed in 2-day codeine exposed groups, showing less large movement activity and also no significant difference between inactive duration in response to light/dark cycles. In conclusion, we observed low teratogenic effects and mortality effects. Animals exposed to high levels and higher exposure times of opioids were hypoactive, relative to controls, in the dark period. Future studies will be needed to understand the neural defects producing behavior changes.