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曲马多与酒精同时滥用时CYP24A1和CYP3A4水平、肾脏和肝脏变化以及氧化应激发生率

CYP24A1 and CYP3A4 Levels, Renal, Hepatic Changes, and Incidence of Oxidative Stress in Tramadol-Alcohol Concomitant Misuse.

作者信息

Dic-Ijiewere Ebenezer O, Osadolor Humphrey B

机构信息

Medical Laboratory Science, University of Benin, Benin, NGA.

出版信息

Cureus. 2023 Mar 29;15(3):e36877. doi: 10.7759/cureus.36877. eCollection 2023 Mar.

DOI:10.7759/cureus.36877
PMID:37123794
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10147408/
Abstract

Introduction Long-term population-based research has demonstrated a link between heavy drinking and the prevalence of kidney disorders; similarly, alcohol abuse has long been recognized as one of the main causes of liver diseases. A recent trend of concomitant use of the opioid analgesic Tramadol and alcohol among young males in sub-Saharan Africa has emerged. Aim and objectives This study's primary aim was to evaluate the incidence of concomitant use of alcohol and Tramadol among adult males, and observe the role of cytochrome p450 3A4 and CYP24A1 proteins and some oxidative stress indicators such as Malondialdehyde, lactate dehydrogenase, among study participants. The secondary aim was to evaluate the effect of alcohol and Tramadol concomitant use on Liver and kidney indices. Methods Our study population was male subjects with a history of Alcohol and Tramadol concomitant use. Liver enzymes, renal indices, oxidative stress markers, and CYP3A4 and CYP24A1 were determined from the serum of test and control participants. IBM Statistical Package for Social Sciences (SPSS) Statistics (version 21.0) was used to analyze the data obtained. Result One hundred and forty-two male subjects were included in this study. Eighty two (82) were males who admitted to abuse of Alcohol and Tramadol concomitantly for at least a year. The dose of Tramadol commonly used by Test subjects was 200 mg (43.9% of the test population), Tramadol users in the study population were largely Undergraduates (75.6% of Test participants). Gamma-glutamyl transferase and lactate dehydrogenase were significantly higher in Test subjects consuming Tramadol and alcohol combination (43.13±1.02 and 117.29±2.45, respectively) versus control (24.87±0.82; p=0.00 and 101.93±1.25; p=0.00). There was a significant decrease in serum bicarbonate levels of Test subjects (16.19±0.53) versus control (22.60±0.68; p=0.000). Cytochrome P450 24A1, was significantly lower in Test subjects (subjects consuming Tramadol and alcohol combination) (0.90±0.06; p=0.01), and significantly threefold higher in subjects with acute myeloid leukemia (AML) (5.16±0.5; p=0.00), when compared with values of non-drug/alcohol users that served as normal control (1.27±0.07). Conclusion The menace of Tramadol and alcohol concomitant abuse has taken a worrisome dimension in sub-Saharan Africa. In this study 77.4% of participants reported euphoria as reason for combining Alcohol and Tramadol, 6.5% claimed it was for faster pain relief and enhanced sexual performance or prolong penile erection was the response of 58.1% of the test participants. Findings of reduced CYP3A4 with Alcohol and Tramadol concomitant use could be associated with delayed drug inactivation and increased drug euphoric action.

摘要

引言 长期基于人群的研究表明,大量饮酒与肾脏疾病的患病率之间存在关联;同样,酗酒长期以来一直被认为是肝脏疾病的主要原因之一。最近,撒哈拉以南非洲的年轻男性中出现了同时使用阿片类镇痛药曲马多和酒精的趋势。

目的 本研究的主要目的是评估成年男性中同时使用酒精和曲马多的发生率,并观察细胞色素p450 3A4和CYP24A1蛋白以及一些氧化应激指标(如丙二醛、乳酸脱氢酶)在研究参与者中的作用。次要目的是评估同时使用酒精和曲马多对肝脏和肾脏指标的影响。

方法 我们的研究人群是有同时使用酒精和曲马多病史的男性受试者。从试验组和对照组参与者的血清中测定肝酶、肾指标、氧化应激标志物以及CYP3A4和CYP24A1。使用IBM社会科学统计软件包(SPSS)统计(版本21.0)分析获得的数据。

结果 本研究纳入了142名男性受试者。其中82名男性承认同时滥用酒精和曲马多至少一年。试验组受试者常用的曲马多剂量为200毫克(占试验人群的43.9%),研究人群中的曲马多使用者大多是本科生(占试验参与者的75.6%)。与对照组相比,同时服用曲马多和酒精的试验组受试者的γ-谷氨酰转移酶和乳酸脱氢酶显著更高(分别为43.13±1.02和117.29±2.45)(对照组分别为24.87±0.82;p=0.00和101.93±1.25;p=0.00)。试验组受试者的血清碳酸氢盐水平显著低于对照组(16.19±0.53)(对照组为22.60±0.68;p=0.000)。与作为正常对照的非药物/酒精使用者的值(1.27±0.07)相比,细胞色素P450 24A1在试验组受试者(同时服用曲马多和酒精的受试者)中显著更低(0.90±0.06;p=0.01),而在急性髓系白血病(AML)患者中显著高出三倍(5.16±0.5;p=0.00)。

结论 在撒哈拉以南非洲,曲马多和酒精同时滥用的威胁已达到令人担忧的程度。在本研究中,77.4%的参与者报告称欣快感是同时使用酒精和曲马多的原因,6.5%声称是为了更快缓解疼痛,58.1%的试验参与者表示是为了增强性功能或延长阴茎勃起时间。同时使用酒精和曲马多导致CYP3A4降低的结果可能与药物失活延迟和药物欣快作用增强有关。

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