Evidence map›Paper›PMID 23748253›Full record

ArticlePain research & management

Life-threatening adverse events following therapeutic opioid administration in adults: is pharmacogenetic analysis useful?

Parvaz Madadi, Johanna Sistonen, Gregory Silverman, Rebecca Gladdy, Colin J Ross, Bruce C Carleton, Jose C Carvalho, Michael R Hayden, Gideon Koren

Open access · goldAbstract readCase Reports
In one paragraph

Article in Pain research & management. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
4.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 20 citations in OpenAlex.

  1. Observational
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 3 countries.

Parvaz MadadiClinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario. parvaz.madadi@gmail.com
Johanna Sistonen
Gregory Silverman
Rebecca Gladdy
Colin J Ross
Bruce C Carleton
Jose C Carvalho
Michael R Hayden
Gideon Koren
Child and Family Research Institute · CAHospital for Sick Children · CAMount Sinai Hospital · CAMount Sinai Hospital · USTranslational Therapeutics (United States) · USUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSystemic approaches are needed to understand how variations in the genes associated with opioid pharmacokinetics and response can be used to predict patient outcome. The application of pharmacogenetic analysis to two cases of life-threatening opioid-induced respiratory depression is presented. The usefulness of genotyping in the context of these cases is discussed.

methodsA panel of 20 functional candidate polymorphisms in genes involved in the opioid biotransformation pathway (CYP2D6, UGT2B7, ABCB1, OPRM1, COMT) were genotyped in these two patients using commercially available genotyping assays.

resultsIn case 1, the patient experienced adverse outcomes when administered codeine and morphine, but not hydromorphone. Genetic test results suggested that this differential response may be due to an inherent propensity to generate active metabolites from both codeine and morphine. These active metabolites are not generated with hydromorphone. In case 2, the patient experienced severe respiratory depression during postoperative recovery following standard doses of morphine. The patient was found to carry genetic variations that result in decreased morphine efflux transporter activity at the blood-brain barrier and increased sensitivity to opioids.

conclusionsKnowledge of the relative contribution of pharmacogenetic biomarkers and their influence on opioid response are continually evolving. Pharmacogenetic analysis, together with clinical history, has the potential to provide mechanistic insight into severe respiratory depressive events in patients who receive opioids at therapeutic doses.

Indexed as

PharmacogeneticsAdultAnalgesics, OpioidFemaleGenotypeHumansHydromorphoneMaleMiddle AgedMorphinePainPolymorphism, GeneticAnalgesics, OpioidHydromorphoneMorphine

Identifiers

PMID23748253
PMCPMC3673930
OpenAlexW69883487

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.