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Pain Physician 2015Individual response to opioid analgesics varies among patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individual response to opioid analgesics varies among patients.
OBJECTIVE
This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain.
STUDY DESIGN
A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain.
SETTING
This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain.
METHODS
A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases.
RESULTS
Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms.
LIMITATIONS
Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information.
CONCLUSION
The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management.
Topics: Analgesics, Opioid; Female; Genetic Variation; Humans; Male; Middle Aged; Pain Management; Pain, Postoperative; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Receptors, Opioid, mu
PubMed: 25794200
DOI: No ID Found -
Revista de Neurologia Jan 2015We conduct a systematic review of the preclinical studies published to date involving the use of latrepirdine (Dimebon ®). Latrepirdine is capable of modulating... (Review)
Review
We conduct a systematic review of the preclinical studies published to date involving the use of latrepirdine (Dimebon ®). Latrepirdine is capable of modulating different targets, such as those related with mitochondria, acetylcholinesterase activity or intraneuronal calcium levels, perhaps thanks to its action upon the N-methyl-D-aspartate-type receptor, which belongs to the glutamate family. The findings published on the possible effect of latrepirdine in protein aggregation processes in disorders such as Alzheimer's disease and Parkinson's disease are quite controversial. Likewise, the possible neuroprotective effect of latrepirdine has been evaluated in animal models of neurodegenerative diseases, again with heterogeneous results. Consequently, it can be concluded that no preclinical scientific evidence has been found to justify carrying out clinical trials.
Topics: Animals; Biological Availability; Calcium Signaling; Cholinesterase Inhibitors; Disease Models, Animal; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists; Humans; Indoles; Mice; Mitochondria; Molecular Structure; Motor Neurons; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Parkinsonian Disorders; Protein Aggregation, Pathological; Rabbits; Rats; Receptors, N-Methyl-D-Aspartate; Tissue Distribution
PubMed: 25522862
DOI: No ID Found