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Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice.

Abstract The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title clinical chemistry
Publication Year Start




PMID- 28637770
OWN - NLM
STAT- MEDLINE
DA  - 20170622
DCOM- 20170710
LR  - 20170713
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Linking)
VI  - 63
IP  - 7
DP  - 2017 Jul
TI  - Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in
      Clinical Practice.
PG  - 1204-1213
LID - 10.1373/clinchem.2016.264986 [doi]
AB  - BACKGROUND: The use of opioids to alleviate pain is complicated by the risk of
      severe adverse events and the large variability in dose requirements.
      Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on 
      an individual's genetic background. Many potential genetic markers have been
      described, and the importance of genetic predisposition in opioid efficacy and
      toxicity has been demonstrated in knockout mouse models and human twin studies.
      Such predictors are especially of value for neonates and young children, in whom 
      the assessment of efficacy or side effects is complicated by the inability of the
      patient to communicate this properly. The current problem is determining which of
      the many potential candidates to focus on for clinical implementation. CONTENT:
      We systematically searched publications on PGx for opioids in 5 databases, aiming
      to identify PGx markers with sufficient robust data and high enough occurrence
      for potential clinical application. The initial search yielded 4257 unique
      citations, eventually resulting in 852 relevant articles covering 24 genes. From 
      these genes, we evaluated the evidence and selected the most promising 10
      markers: cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 
      family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 3 subfamily A
      member 5 (CYP3A5), UDP glucuronosyltransferase family 2 member B7 (UGT2B7), ATP
      binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C
      member 3 (ABCC3), solute carrier family 22 member 1 (SLC22A1), opioid receptor
      kappa 1 (OPRM1), catechol-O-methyltransferase (COMT), and potassium voltage-gated
      channel subfamily J member 6 (KCNJ6). Treatment guidelines based on genotype are 
      already available only for CYP2D6. SUMMARY: The application of PGx in the
      management of pain with opioids has the potential to improve therapy. We provide 
      a shortlist of 10 genes that are the most promising markers for clinical use in
      this context.
CI  - (c) 2016 American Association for Clinical Chemistry.
FAU - Matic, Maja
AU  - Matic M
AD  - Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam,
      the Netherlands.
AD  - Intensive Care and Department of Pediatric Surgery, Erasmus University Medical
      Center-Sophia Children Hospital, Rotterdam, the Netherlands.
FAU - de Wildt, Saskia N
AU  - de Wildt SN
AD  - Intensive Care and Department of Pediatric Surgery, Erasmus University Medical
      Center-Sophia Children Hospital, Rotterdam, the Netherlands.
AD  - Department of Pharmacology and Toxicology, Radboud University Medical Center,
      Nijmegen, the Netherlands.
FAU - Tibboel, Dick
AU  - Tibboel D
AD  - Intensive Care and Department of Pediatric Surgery, Erasmus University Medical
      Center-Sophia Children Hospital, Rotterdam, the Netherlands.
FAU - van Schaik, Ron H N
AU  - van Schaik RHN
AD  - Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam,
      the Netherlands; [email protected]
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (Analgesics, Opioid)
RN  - 0 (P-Glycoprotein)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.4.1.17 (UGT2A1 protein, human)
SB  - IM
MH  - Analgesics, Opioid/pharmacology/*therapeutic use
MH  - Genetic Variation
MH  - Glucuronosyltransferase/genetics
MH  - Humans
MH  - P-Glycoprotein/genetics
MH  - Pain/*drug therapy
MH  - Pain Management
MH  - Pharmacogenetics/standards/*trends
EDAT- 2017/06/24 06:00
MHDA- 2017/07/14 06:00
CRDT- 2017/06/23 06:00
PHST- 2016/08/22 [received]
PHST- 2016/12/28 [accepted]
AID - clinchem.2016.264986 [pii]
AID - 10.1373/clinchem.2016.264986 [doi]
PST - ppublish
SO  - Clin Chem. 2017 Jul;63(7):1204-1213. doi: 10.1373/clinchem.2016.264986.