Impact of
            <i>CYP2D6</i>
            Genotype on Amitriptyline Efficacy for the Treatment of Diabetic Peripheral Neuropathy: A Pilot Study

Chaudhry, Mamoonah; Alessandrini, Marco; Rademan, Jacobus; Dodgen, Tyren Mark; Steffens, François E.; Zyl, Danie G. Van; Gaedigk, Andrea; Pepper, Michael Sean

doi:10.2217/pgs-2016-0185

Cited by 20 publications

(21 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Again detecting these variants relies on large discovery cohorts, with sufficient statistical power. Because of this difficulty, very few pharmacogenetics studies have been conducted in NeuP to date (Brasch-Andersen et al., 2011, Chaudhry et al., 2017). Sensory phenotype stratification, together with classifying patients depending on genetic risk, has the potential to lead to personalized medicine to determine the best course for treatment.…”

Section: Main Textmentioning

confidence: 99%

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Calvo

Davies

Hébert

et al. 2019

Neuron

View full text Add to dashboard Cite

Neuropathic pain (NeuP) arises due to injury of the somatosensory nervous system and is both common and disabling, rendering an urgent need for non-addictive, effective new therapies. Given the high evolutionary conservation of pain, investigative approaches from Drosophila mutagenesis to human Mendelian genetics have aided our understanding of the maladaptive plasticity underlying NeuP. Successes include the identification of ion channel variants causing hyper-excitability and the importance of neuro-immune signaling. Recent developments encompass improved sensory phenotyping in animal models and patients, brain imaging, and electrophysiology-based pain biomarkers, the collection of large well-phenotyped population cohorts, neurons derived from patient stem cells, and high-precision CRISPR generated genetic editing. We will discuss how to harness these resources to understand the pathophysiological drivers of NeuP, define its relationship with comorbidities such as anxiety, depression, and sleep disorders, and explore how to apply these findings to the prediction, diagnosis, and treatment of NeuP in the clinic.

show abstract

Section: Main Textmentioning

confidence: 99%

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Calvo

Davies

Hébert

et al. 2019

Neuron

View full text Add to dashboard Cite

show abstract

“…It is known to inhibit the presynaptic reuptake of serotonin (5-HT) and norepinephrine (NE) and thus increase the concentrations of both neurotransmitters at the synaptic cleft (12) . Some of the side effects for amitriptyline include anticholinergic effects such as constipation, dizziness, dry mouth, blurred vision and urinary retention, besides weight gain, sexual dysfunction, orthostatic hypotension and cardiotoxicity (13) (14) .…”

Section: Introductionmentioning

confidence: 99%

Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats

Al-Obaidi¹,

Al-Shawi²

2021

IJPS

View full text Add to dashboard Cite

At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats. Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orally-treated with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks. The results showed that both drugs (Group II and Group III) induced the same extent of DNA damage, as evidenced by a significantly higher DNA fragmentation in liver and testis tissues with increased frequencies of micronuclei formation in bone marrow tissues as compared with the negative control (Group I). These findings indicates that both Fluoxetine and Amitriptyline have genotoxic potentials and can induce the same extent of cytogenetic damage in rats. Special precautions and medical supervision should be taken in consideration with their uses.

show abstract

“…Whereas CYP2C19 influences the ratio of metabolites, CYP2D6 plays a greater role in drug clearance. This may lead to raised plasma concentrations of amitriptyline and nortriptyline in CYP2D6 PMs or in patients co-administered a CYP2D6 inhibitor [ 46 ]. CPIC guidelines therefore recommend a lower starting dose when used at dosing ranges for depression [ 47 ].…”

Section: Antidepressantsmentioning

confidence: 99%

Pharmacogenomics for Primary Care: An Overview

Rollinson

Turner

Pirmohamed

2020

Genes

View full text Add to dashboard Cite

Most of the prescribing and dispensing of medicines happens in primary care. Pharmacogenomics (PGx) is the study and clinical application of the role of genetic variation on drug response. Mounting evidence suggests PGx can improve the safety and/or efficacy of several medications commonly prescribed in primary care. However, implementation of PGx has generally been limited to a relatively few academic hospital centres, with little adoption in primary care. Despite this, many primary healthcare providers are optimistic about the role of PGx in their future practice. The increasing prevalence of direct-to-consumer genetic testing and primary care PGx studies herald the plausible gradual introduction of PGx into primary care and highlight the changes needed for optimal translation. In this article, the potential utility of PGx in primary care will be explored and on-going barriers to implementation discussed. The evidence base of several drug-gene pairs relevant to primary care will be outlined with a focus on antidepressants, codeine and tramadol, statins, clopidogrel, warfarin, metoprolol and allopurinol. This review is intended to provide both a general introduction to PGx with a more in-depth overview of elements relevant to primary care.

show abstract

Impact of CYP2D6 Genotype on Amitriptyline Efficacy for the Treatment of Diabetic Peripheral Neuropathy: A Pilot Study

Abstract: Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.

Cited by 20 publications

References 28 publications

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats

Pharmacogenomics for Primary Care: An Overview

Contact Info

Product

Resources

About