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慢性恰加斯病患者使用苯硝唑治疗的不良反应和生化变化的因果关系和严重程度。

Causality and Severity of Adverse Reactions and Biochemical Changes to Benznidazole Treatment in Patients with Chronic Chagas Disease.

机构信息

Universidade Federal do Ceará, Fortaleza, CE - Brasil.

出版信息

Arq Bras Cardiol. 2024 Aug;121(8):e20230787. doi: 10.36660/abc.20230787.

DOI:10.36660/abc.20230787
PMID:39292117
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11495806/
Abstract

BACKGROUND

Chagas disease (CD) is a serious public health problem in Latin America. Benznidazole (BNZ) is used for the treatment of CD and, despite its wide use, little information is available about its toxicity and mechanisms of adverse drug reactions (ADR).

OBJECTIVES

To identify and classify clinical and laboratory adverse reactions caused by BNZ in terms of causality and severity.

METHODS

Prospective cohort study from January 2018 to December 2021. Treatment follow-up included visits and biochemical tests (complete blood count, liver and kidney function tests) before, during and after treatment. ADR were classified according to causality and severity. In the statistical analysis, the significance level was set at p<0.05.

RESULTS

Forty patients with chronic CD were included. A high prevalence of ADR was observed 161 ADR in 30 patients [90%]; of these, 104 (64.6%) were classified as possible and 57 (35.4%) as probable. The ADR were classified as moderate and mild. Of the 40 patients, nine (22.5%) discontinued treatment. ADR associated with treatment discontinuation and interventions were those that affected the dermatological system, central and peripheral nervous system and sense organs such as ageusia. Mild hematological and biochemical changes such as lymphopenia were observed after 30 days of treatment.

CONCLUSION

Many patients were able to complete the treatment even with ADR, which can be attributed to the successful follow-up strategy with symptomatic treatment and counseling, leading to patient's awareness of symptoms and treatment adherence.

摘要

背景

恰加斯病(CD)是拉丁美洲严重的公共卫生问题。贝那唑(BNZ)用于治疗 CD,尽管广泛使用,但关于其毒性和不良反应(ADR)机制的信息很少。

目的

根据因果关系和严重程度,确定并分类 BNZ 引起的临床和实验室不良反应。

方法

2018 年 1 月至 2021 年 12 月进行前瞻性队列研究。治疗随访包括治疗前、治疗期间和治疗后的就诊和生化检查(全血细胞计数、肝肾功能检查)。根据因果关系和严重程度对 ADR 进行分类。在统计分析中,显著性水平设置为 p<0.05。

结果

纳入 40 例慢性 CD 患者。30 例患者中观察到高 ADR 发生率 161 例[90%];其中 104 例(64.6%)分类为可能,57 例(35.4%)分类为很可能。ADR 分类为中度和轻度。40 例患者中有 9 例(22.5%)停止治疗。与治疗中断和干预相关的 ADR 是那些影响皮肤、中枢和外周神经系统以及味觉丧失等感觉器官的不良反应。治疗 30 天后观察到轻微的血液和生化变化,如淋巴细胞减少。

结论

尽管存在 ADR,但许多患者仍能完成治疗,这归因于成功的随访策略,包括对症治疗和咨询,使患者意识到症状并坚持治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/50c3ba5c4a59/0066-782X-abc-121-8-e20230787-gf02-en.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/105c3f347484/0066-782X-abc-121-8-e20230787-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/78e6723d62f6/0066-782X-abc-121-8-e20230787-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/cce792f3abd9/0066-782X-abc-121-8-e20230787-gf01-en.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/50c3ba5c4a59/0066-782X-abc-121-8-e20230787-gf02-en.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/105c3f347484/0066-782X-abc-121-8-e20230787-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/78e6723d62f6/0066-782X-abc-121-8-e20230787-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/cce792f3abd9/0066-782X-abc-121-8-e20230787-gf01-en.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddaa/11495806/50c3ba5c4a59/0066-782X-abc-121-8-e20230787-gf02-en.jpg

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本文引用的文献

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2
Hepatic changes by benznidazole in a specific treatment for Chagas disease.苯达唑治疗恰加斯病的肝改变。
PLoS One. 2018 Jul 20;13(7):e0200707. doi: 10.1371/journal.pone.0200707. eCollection 2018.
3
Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.
人群中恰加斯病的心电图异常:系统评价和荟萃分析。
PLoS Negl Trop Dis. 2018 Jun 13;12(6):e0006567. doi: 10.1371/journal.pntd.0006567. eCollection 2018 Jun.
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[Satisfaction of Chagas disease patients attended at a pharmaceutical care service in the State of Ceará, Brazil].[巴西塞阿拉州一家药学服务机构中恰加斯病患者的满意度]
Cien Saude Colet. 2018 May;23(5):1483-1494. doi: 10.1590/1413-81232018235.10982016.
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Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease.成年恰加斯病患者中苯硝唑治疗中断及严重不良反应的危险因素。
PLoS One. 2017 Sep 26;12(9):e0185033. doi: 10.1371/journal.pone.0185033. eCollection 2017.
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Benznidazole treatment safety: the Médecins Sans Frontières experience in a large cohort of Bolivian patients with Chagas' disease.苯达唑治疗安全性:无国界医生组织在玻利维亚大量恰加斯病患者中的经验。
J Antimicrob Chemother. 2017 Sep 1;72(9):2596-2601. doi: 10.1093/jac/dkx180.
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Pharmacokinetics of Benznidazole in Healthy Volunteers and Implications in Future Clinical Trials.健康志愿者中苯硝唑的药代动力学及其对未来临床试验的启示
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[Brazilian Consensus on Chagas Disease, 2015].[2015年巴西恰加斯病共识]
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