Pharmacogenetics of Chronic Pain and Its Treatment

Světlík, Svatopluk; Hronová, Karolína; Bakhouche, Hana; Matousková, O; Slanař, Ondřej

doi:10.1155/2013/864319

Cited by 23 publications

(16 citation statements)

References 219 publications

(166 reference statements)

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“…This article will describe CYP2D6 (cytochrome p450 2D6) and OPRM1 (μ1 opioid receptor), the most important gene coding, respectively, for a metabolizing enzyme and receptor for opioids (5)(6)(7)(8)(9)(10)(11). Integration of their variability in each patient allows for building a rational and scientific basis for personalized pain management ( Fig.…”

mentioning

confidence: 99%

Fundamental Considerations for GeneticallyGuided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms

Ruaño

2018

Pain Phys

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Background: A major challenge for effective pharmacotherapy in pain management is to provide the drug best suited to the patient’s innate characteristics. Objective: The article illustrates pharmacogenetic principles to optimize treatments for patients and increase the likelihood of pain relief without dependence. Genetic variances are particularly relevant to opioid drugs used in pain control, and can now be harvested for predictive clinical decision support. Study Design: Clinically actionable polymorphisms in CYP2D6 (cytochrome p450 2D6) and OPRM1 (μ1 opioid receptor), the most important gene coding, respectively, for a metabolizing enzyme and receptor for opioids are reviewed, and functional effects described. Methods: Risk of dysfunction is calculated from the frequency of the alleles with null function for CYP2D6, and from the low function polymorphism for OPRM1. Integration of genetic variability was performed for 9 combinatorial scenarios for CYP2D6 and OPRM1. Each combination was quantified in frequency and classified for clinical impact. A rational and pharmacological basis for personalized pain management based on pharmacokinetic and pharmacodynamic modeling is extracted from the frequency of the combinations. Results: Patients can be classified in 3 broad risk categories for opioid side effects and dependence. Patients at high-risk with dysfunctional CYP2D6 or OPRM1 account for ~14% of the population and are best managed with non-opioids. Patients at medium risk with subnormal CYP2D6 or OPRM1 account for ~48% of the population and can be managed with dose monitoring. Patients at low risk with functional CYP2D6 and OPRM1 account for ~38% of the population and should be availed to opioid therapy. Limitations: Heuristic clinical decision support considerations are not validated yet by deployment in large clinical practices. Environmental modifiers such as other drugs and dietary supplements interact with innate characteristics to modify the genetic predictions. Conclusion: Through clinical decision support interpreting the genotyping data, drug choices and doses can then be tailored to provide safe and effective therapy for individual patients. This precision affords personalized medicine to be practiced in pain treatment. Genetic factors could help determine why some patients seem more vulnerable than others to opioid side effects and dependence. Key words: Pain management, opioids, CYP2D6, OPRM1, clinical decision support, pharmacokinetics, pharmacodynamics, pharmacogenetics, combinatorial genotypes

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confidence: 99%

Fundamental Considerations for GeneticallyGuided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms

Ruaño

2018

Pain Phys

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“…Medical literature provides several studies which have revealed that the polymorphism of inflammatory cytokine genes influences pain perception and analgesics dose. Furthermore, the altered levels of fatigue, depression and response to analgesics in pancreatic, lung or breast cancer have been described [15,[36][37][38][39][40][41][42][43]. These types of studies, however, have not been conducted for patients with multiple myeloma, though during the formation of bone destructions, anti-inflammatory cytokines are emitted by plasma cells and bone marrow stroma cells.…”

Section: Palliation For Painmentioning

confidence: 99%

The Role of Radiology and Radiotherapy for Multiple Myeloma

Rudžianskienė¹,

Rudžianskas²,

Dambrauskienė³

et al. 2019

Update on Multiple Myeloma

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Skeletal-related events occur in 80% of patients with multiple myeloma (MM). Osteoporosis, osteoclastic destructions, pathological fractures of the bone, spinal cord and compression can impair patients' quality of life and reduce survival. Many imaging techniques can be used for the detection of MM bone lesions. Many clinical studies suggest modern imaging techniques for their greater sensitivity. Radiotherapy is a treatment of choice for solitary plasmacytoma of the bone and extramedullary plasmacytomas. However, radiation treatment of MM can be used as a palliative approach for uncontrolled pain, impending pathological fractures and in the cases of spinal cord compression. Radiotherapy induces analgesic effect in 75-100% of patients and promotes a recalcification in 40-60%. In patients with spinal cord compression, radiation therapy is given along with dexamethasone, and up to half of patients may experience improvement. It is well known that pain perception, response to analgesics and pain relief effect of radiotherapy are quite different for multiple myeloma patients. Clinical, laboratory and genetic factors may influence the pain perception and analgesic effect of radiotherapy. Side effects of radiation are generally mild, are limited to the radiotherapy site and can be predicted.

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“…Гены CYP3A4/CYP3A5 кодируют изофермент CYP3A4/5 цитохрома P450 печени, обеспечивающий метаболизм 50 % всех наркотических анальгетиков, включая фентанил. Вышеуказанные гены локализованы на хромосоме 7q22.1 и обеспечивают 3085 % вариабельности активности изофермента 3A4 [15]. Распределение известных одиночных нуклеотидных полиморфизмов (ОНП) гена CYP3A4 по скорости метаболических превращений представлено в табл.…”

Section: фармакогенетические аспектыunclassified

Pharmacokinetic and Pharmacogenetic Aspects of Personalized Analgetic Therapy With Fentanil TTS in Clinical Oncology

Боброва¹,

Дыхно²,

Шнайдер³

et al. 2018

Sib. onkol. ž.

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The aim of the study was the pharmacokinetic and pharmacogenetic analysis of analgetic efficacy and safety of transdermal fentanyl for cancer patients.Material and methods. A comprehensive search for journal articlespublished between 2012 and 2017 was carried out using PubMed, Scopus, Web of Science, and E-library databases.Results. The analysis of the data showed that pharmacokinetic and pharmacogenetic factors can influence the interindividual variability of analgesic therapy with fentanyl TTC for cancer patients, predetermining phenotypic differences in the efficacy and safety of analgesia. Enforced polypharmacotherapy with the use of inducers or inhibitors of the CYP3A4 isoenzyme activity can significantly change the effectiveness of analgesic therapy and result in undesirable side effects of strong opioids. Contradictory data on the effect of some single nucleotide polymorphisms of metabolic genes, transport genes and mu-opioid receptor genes dictate the necessity of further studies in this field.Conclusion. To date, there is no single explanation for interindividual variability of analgesic therapy with fentanyl TTS. A comprehensive assessment of the pharmacokinetic and pharmacogenetic factors affecting the efficacy and safety of analgesic therapy with potent opioids is a tool of a personalized approach for anesthesia in clinical oncology.

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Pharmacogenetics of Chronic Pain and Its Treatment

Cited by 23 publications

References 219 publications

Fundamental Considerations for GeneticallyGuided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms

Fundamental Considerations for GeneticallyGuided Pain Management with Opioids Based on CYP2D6 and OPRM1 Polymorphisms

The Role of Radiology and Radiotherapy for Multiple Myeloma

Pharmacokinetic and Pharmacogenetic Aspects of Personalized Analgetic Therapy With Fentanil TTS in Clinical Oncology

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