INT230829

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

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 Morphine 44 99.62 analgesia 18 99.58 Codeine 16 99.44 Opioid 64 99.08 Analgesic 68 98.08 tramadol 2 92.28 Oxycodone 70 91.24 Desipramine 3 84.96 fluoxetine 1 74.56

Disease Link Frequency Relevance Heat Dizziness 7 97.72 Toxicity 2 79.56 Renal Insufficiency 3 76.32 Reprotox - General 1 25 60.72 Arrhythmia Under Development 1 55.28 Pain 162 50.00 Diabetes Mellitus 12 50.00 Post-operative Nausea 6 32.44 Fungal Infection 1 20.00 Body Weight 1 18.56

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

This test has worked.