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Opioid Pharmacogenomics: More Than Metabolism

Published on Jul 21, 20141724 Views

Several opioids such as codeine are considered pro-drugs as they are metabolized by the highly polymorphic CYP2D6 to more potent opioids with clinical efficacy and toxicological sequelae. Many opi

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Chapter list

Opioid Pharmacogenomics: More Than Metabolism00:00
Opioid Pharmacogenomics: Overview00:09
Opioids: Wide Interpatient Variability-Response & Dosage: Morphine01:08
Role of Genomic Factors in Interindividual Variability in Response to Opioids02:08
CYP2D6: Highly Polymorphic Enzyme: EM/PM Phenotype Discovered 197602:29
Codeine Oxidation to Morphine is via CYP2D603:02
CYP2D6: The CodeineStory Clinical Evidence03:51
CYP2D6: Oxycodone Story Clinical Evidence05:21
CYP2D6 Polymorphism: Tramadol reduced effect in PMs06:25
EPOS: European Pharmacogenetic Opioid Study07:04
Transdermal Fentanyl: EPOS07:24
Fentanyl Metabolic Ratio: 6000-fold08:31
Interindividual Variability in Response to Opioids: It must be Pharmacodynamics09:36
Neuronal μ Receptor: Target09:54
OPRM1: μReceptor10:25
Alfentanil Analgesia and Respiratory Depression: OPRM1A118G10:56
PAIN11:22
Molecular Pain12:23
OPRM1A118GVariant: Increased Opioid Requirements -Postoperative Pain: Asians13:05
Morphine activates neuroinflamation in a manner parallel to endotoxin14:10
Opioid Analgesia: controlled by μ Receptor (pro) and TLR4 (con) binding14:53
Cytokines Genetics & Opioids15:44
Innate Immune Cellular Pathway Genes16:10
OPRM1+ Innate Immune Genes Contribute to Morphine Dosage: Postoperative Pain (1)17:06
OPRM1+ Innate Immune Genes Contribute to Morphine Dosage: Postoperative Pain (2)18:01
Singapore Study: Innate Immune Frequency Differences-Genetic Markers: Comparison to Caucasians19:16
Innate Immune Genetics and Opioids: Cancer Pain20:09
Where to now?20:54
Where to now? Epigenetics21:16
Can it be translated?21:42
Genetic & Non-Genetic Factors Influencing Response to Analgesics22:21
Take Home Messages23:04
Acknowledgements24:36