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Sex Bias and Genotype Influence on Opioid Safety Profile in Chronic Low Back Pain


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Title:
Sex Bias and Genotype Influence on Opioid Safety Profile in Chronic Low Back Pain
Authors:
Margarit, César
Roca, Reyes
Inda, María del Mar
Muriel, Javier  
Ballester, Purificación
Flor, Andrea  
Morales, Domingo  
Peiró, Ana  
Editor:
Wolkers Kuwer
Department:
Departamentos de la UMH::Farmacología, Pediatría y Química Orgánica
Issue Date:
2020-07
URI:
https://hdl.handle.net/11000/32324
Abstract:
Objectives: The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Among potential modulators are the individual’s genetic background and being female. Our aim was to evaluate sex bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), the most frequent chronic noncancer pain. Methods: A 3-year prospective study was developed in opioid-naive CLBP patients. Data were self-reported by patients (pain [Visual Analogy Scale], adverse events [AEs], and health care resource utilization) and physicians (analgesic prescription, morphine equivalent daily dose, and suspected adverse drug reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without (control) together with patients’ sex and genotype. Gene variants in OPRM1 (rs1799971), COMT (rs4680), ABCB1 (rs1045642), UGT2B7 (rs12233719 and rs7438135), KCNJ6 (rs2070995 and rs6517442), and CYP3A5*3 (rs776746) were assessed. The hospital ethics committee approved the study, and statistical analyses were performed with R, v.3.2.4. Results: A total of 179 patients were included (64% female, mean pain intensity 73±16mm), and 90% of them presented at least 1 AE (median of 3 (1 to 6) AEs/patient) with a rate of 5 AEs: 1 ADR without differences due to sex. However, there is a significant delay in referral of female patients (a mean of 6 years) to the Pain Unit, being significantly 3 to 5 times more likely to present sleep or psychiatric disorders. Meanwhile male individuals showed more sexual and reproductive system disorders. Genotypes influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related problems. Conclusions: Sex bias affects female patients resulting in a CLBP diagnostic delay and a different analgesic safety profile. Moreover, the individual’s genetic background might be useful to predict certain AEs in opioid-naive patients under an opioid titration procedure. Addressing sex in necessary to resolve inequalities in health care access.
Keywords/Subjects:
pharmacogenetics
sex
chronic low back pain
opioids
COMT
ABCB1
Type of document:
application/pdf
Access rights:
info:eu-repo/semantics/closedAccess
DOI:
https://doi.org/10.1097/AJP.0000000000000824
Appears in Collections:
Artículos Farmacología, Pediatría y Química Orgánica



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