INT230829

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Context Info
Confidence 0.63
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 3
Total Number 4
Disease Relevance 0.61
Pain Relevance 5.18

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mitochondrion (Cyp2d4) oxidoreductase activity (Cyp2d4) endoplasmic reticulum (Cyp2d4)
cellular_component (Cyp2d4) cytoplasm (Cyp2d4)
Cyp2d4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Duloxetine 84 99.92 Very High Very High Very High
Morphine 44 99.62 Very High Very High Very High
analgesia 18 99.58 Very High Very High Very High
Codeine 16 99.44 Very High Very High Very High
Opioid 64 99.08 Very High Very High Very High
Analgesic 68 98.08 Very High Very High Very High
tramadol 2 92.28 High High
Oxycodone 70 91.24 High High
Desipramine 3 84.96 Quite High
fluoxetine 1 74.56 Quite High
Disease Link Frequency Relevance Heat
Dizziness 7 97.72 Very High Very High Very High
Toxicity 2 79.56 Quite High
Renal Insufficiency 3 76.32 Quite High
Reprotox - General 1 25 60.72 Quite High
Arrhythmia Under Development 1 55.28 Quite High
Pain 162 50.00 Quite Low
Diabetes Mellitus 12 50.00 Quite Low
Post-operative Nausea 6 32.44 Quite Low
Fungal Infection 1 20.00 Low Low
Body Weight 1 18.56 Low Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Many other opioids, including oxycodone, codeine, dihydrocodeine, hydrocodone, and tramadol, are primarily metabolized by the cytochrome P450 (CYP) enzymes CYP2D6 or CYP3A4.46 Mutations in the CYP2D6 gene, which occur in approximately 1% to 7% of the Caucasian population, can either decrease or increase enzyme activity, leading to alterations in opioid analgesia.47 The analgesic effects of codeine are highly dependent on conversion of codeine to morphine by CYP2D6; a poor CYP2D6 metabolic phenotype can suppress codeine analgesia, and an ultra-rapid CYP2D6 metabolic phenotype can lead to increased opioid effects, such as euphoria, dizziness, and visual disturbances.47
Localization (phenotype) of CYP2D6 associated with tramadol, oxycodone, analgesic, dizziness, opioid, morphine, analgesia and codeine
1) Confidence 0.63 Published 2010 Journal Journal of pain research Section Body Doc Link PMC3004637 Disease Relevance 0.25 Pain Relevance 2.21
Drugs metabolized by CYP2D6
Localization (metabolized) of CYP2D6
2) Confidence 0.58 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2350145 Disease Relevance 0.06 Pain Relevance 0.61
Many other opioids, including oxycodone, codeine, dihydrocodeine, hydrocodone, and tramadol, are primarily metabolized by the cytochrome P450 (CYP) enzymes CYP2D6 or CYP3A4.46 Mutations in the CYP2D6 gene, which occur in approximately 1% to 7% of the Caucasian population, can either decrease or increase enzyme activity, leading to alterations in opioid analgesia.47 The analgesic effects of codeine are highly dependent on conversion of codeine to morphine by CYP2D6; a poor CYP2D6 metabolic phenotype can suppress codeine analgesia, and an ultra-rapid CYP2D6 metabolic phenotype can lead to increased opioid effects, such as euphoria, dizziness, and visual disturbances.47
Localization (phenotype) of CYP2D6 associated with tramadol, oxycodone, analgesic, dizziness, opioid, morphine, analgesia and codeine
3) Confidence 0.55 Published 2010 Journal Journal of pain research Section Body Doc Link PMC3004637 Disease Relevance 0.25 Pain Relevance 2.33
The pharmacokinetics of lasofoxifene are linear over a wide dose-range (0.01 to 100 mg)57 and are not significantly affected by age, ethnicity, weight, moderately impaired hepatic or renal function, or medications such as warfarin, ketoconazole, and digoxin.60–63 In a study of lasofoxifene disposition in healthy male subjects, it was eliminated by phase I oxidative metabolism (largely mediated by CYP2D6 and CYP3A4) and phase II conjugation.64

Preclinical studies

Localization (mediated) of CYP2D6
4) Confidence 0.30 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2773750 Disease Relevance 0.06 Pain Relevance 0.03

General Comments

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