PMID- 30549211
OWN - NLM
STAT- MEDLINE
DCOM- 20190628
LR  - 20190628
IS  - 1742-7843 (Electronic)
IS  - 1742-7835 (Linking)
VI  - 124
IP  - 4
DP  - 2019 Apr
TI  - Pharmacogenetics and prediction of adverse events in prescription opioid use 
      disorder patients.
PG  - 439-448
LID - 10.1111/bcpt.13155 [doi]
AB  - The threats involved in the long-term opioid treatment of chronic non-cancer pain 
      (CNCP) have increased notably. Strategies to identify at-risk patients are 
      important because there is no clear evidence showing which screening or 
      deprescription programmes are appropriate. Our aim was to evaluate the evidence 
      provided by pharmacogenetics applied to predict an analgesic toxicity profile in 
      prescription opioid use disorder (POUD) patients participating in an opioid 
      deprescription programme. Pharmacogenetic markers were analysed in an 
      observational, prospective deprescription programme for POUD patients (n = 88) 
      treated for CNCP. It consisted of monitoring visits (baseline, follow-up and 
      final), opioid rotation or discontinuation and the recording of adverse events 
      and suspected adverse drug reactions (ADRs). Variants in OPRM1 (A118G), ABCB1 
      (C3435T), COMT (G472A), OPRD1 (T921C) and ARRB2 (C8622T) genes were tested by 
      real-time PCR. Ethics committee approved the study. Wild-type OPRM1-AA genotype 
      carriers reported a significantly higher number of adverse events than 
      OPRM1-AG/GG (median [p25-75], 7 [5-11] vs 5 [3-9]), particularly gastrointestinal 
      system events (90% vs 63%) such as nausea (33% vs 0%). Suspected ADRs (affecting 
      17% of the patients) were three times higher in males than in females (30% vs 
      11%). The deprescription programme was effective and safe, and it achieved a 
      significant progressive reduction in the morphine equivalent daily dose, strong 
      opioids and other analgesics' use, without causing any changes in pain intensity 
      or opiate abstinence syndrome. OPRM1 gene polymorphisms could identify the risk 
      of gastrointestinal adverse events in POUD patients. Deprescription programmes 
      including pharmacogenetic analysis should be considered during the follow-up of 
      this population.
CI  - (c) 2018 Nordic Association for the Publication of BCPT (former Nordic 
      Pharmacological Society).
FAU - Muriel, Javier
AU  - Muriel J
AD  - Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical 
      Research (ISABIAL-FISABIO Foundation), Alicante, Spain.
AD  - Occupational Observatory, Miguel Hernandez University of Elche, Elche, Spain.
FAU - Margarit, Cesar
AU  - Margarit C
AD  - Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical 
      Research (ISABIAL-FISABIO Foundation), Alicante, Spain.
AD  - Pain Unit, Department of Health of Alicante-General Hospital, Alicante, Spain.
FAU - Barrachina, Jordi
AU  - Barrachina J
AD  - Occupational Observatory, Miguel Hernandez University of Elche, Elche, Spain.
FAU - Ballester, Pura
AU  - Ballester P
AD  - Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical 
      Research (ISABIAL-FISABIO Foundation), Alicante, Spain.
AD  - Occupational Observatory, Miguel Hernandez University of Elche, Elche, Spain.
FAU - Flor, Andrea
AU  - Flor A
AD  - Pain Unit, Department of Health of Alicante-General Hospital, Alicante, Spain.
FAU - Morales, Domingo
AU  - Morales D
AD  - Operations Research Centre, Miguel Hernandez University of Elche, Elche, Spain.
FAU - Horga, Jose F
AU  - Horga JF
AD  - Clinical Pharmacology Unit, Department of Health of Alicante-General Hospital, 
      Alicante, Spain.
FAU - Fernandez, Eduardo
AU  - Fernandez E
AD  - Biomedical Neuroengineering Research Group (nBio), Systems Engineering and 
      Automation Department of Miguel Hernandez University, Elche, Spain.
FAU - Peiro, Ana M
AU  - Peiro AM
AD  - Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical 
      Research (ISABIAL-FISABIO Foundation), Alicante, Spain.
AD  - Pain Unit, Department of Health of Alicante-General Hospital, Alicante, Spain.
AD  - Clinical Pharmacology Unit, Department of Health of Alicante-General Hospital, 
      Alicante, Spain.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20181213
PL  - England
TA  - Basic Clin Pharmacol Toxicol
JT  - Basic & clinical pharmacology & toxicology
JID - 101208422
RN  - 0 (Analgesics, Opioid)
RN  - 0 (OPRM1 protein, human)
RN  - 0 (Receptors, Opioid, mu)
SB  - IM
MH  - Analgesics, Opioid/*administration & dosage/adverse effects
MH  - *Deprescriptions
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Opioid-Related Disorders/*epidemiology/genetics
MH  - *Pharmacogenetics
MH  - Prospective Studies
MH  - Receptors, Opioid, mu/genetics
MH  - Sex Factors
OTO - NOTNLM
OT  - adverse events
OT  - chronic pain
OT  - opioid use disorder
OT  - pharmacogenetics
OT  - prescription opioids
EDAT- 2018/12/15 06:00
MHDA- 2019/06/30 06:00
CRDT- 2018/12/15 06:00
PHST- 2018/08/15 00:00 [received]
PHST- 2018/10/11 00:00 [accepted]
PHST- 2018/12/15 06:00 [pubmed]
PHST- 2019/06/30 06:00 [medline]
PHST- 2018/12/15 06:00 [entrez]
AID - 10.1111/bcpt.13155 [doi]
PST - ppublish
SO  - Basic Clin Pharmacol Toxicol. 2019 Apr;124(4):439-448. doi: 10.1111/bcpt.13155. 
      Epub 2018 Dec 13.