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[眼部作为药物不良反应的靶点。聚焦全身抗感染治疗]

[The eye as target of adverse ocular drug reactions. Focus on systemic antiinfective therapy].

作者信息

Huber Matthias, Stahlmann Ralf

机构信息

Charité - Universitäts-medizin Berlin, Institut für Klinische Pharmakologie und Toxikologie, Charitéplatz 1, 10117 Berlin.

出版信息

Med Monatsschr Pharm. 2012 Dec;35(12):436-42; quiz 443-4.

Abstract

The functions of the eye can be disturbed by pharmaceutical agents via various mechanisms. This review describes the complexity of ocular adverse drug reactions and underlines the need for a close interdisciplinary cooperation especially in this field to optimize drug safety. Antimicrobial agents will be used as examples to describe ocular adverse drug reactions. A recent case control study describes fluoroquinolones to be associated with the occurrence of retinal detachments. The high affinity of these agents to melanin may cause intraocular accumulation. Fluoroquinolones exert toxic effects on collagens which may destabilize the structure of the extracellular matrix. The ketolid telithromycin may cause impaired accommodation and binocular vision potentially due to its anticholinergic effect. Linezolid, an oxazolidinone, used against infections with methicillin resistant staphylococcus aureus (MRSA) may lead to progressive, potentially irreversible neuropathies of the optic nerve especially in long-time application. Treatment with rifabutin or the antiviral drug cidofovir may cause intraocular inflammation. In addition, cidofovir may impair the production of the aqueous fluid due to a toxic effect on ciliary epithelial cells. During therapy with voriconazol about one third of patients suffer from reversible visual disturbances. Liver dysfunction or pharmacogenetic variants in the cytochrome P450 system may contribute to a retarded metabolism with high intraocular drug levels. In summary, this review indicates the complexity of ocular adverse drug reactions and points out that an interdisciplinary approach is necessary to improve pharmacovigilance in this field.

摘要

药物可通过多种机制干扰眼睛的功能。本综述描述了眼部药物不良反应的复杂性,并强调了在该领域尤其需要密切的跨学科合作以优化药物安全性。将以抗菌药物为例来描述眼部药物不良反应。最近一项病例对照研究表明氟喹诺酮类药物与视网膜脱离的发生有关。这些药物对黑色素的高亲和力可能导致眼内蓄积。氟喹诺酮类药物对胶原蛋白产生毒性作用,这可能会破坏细胞外基质的结构。酮内酯类药物泰利霉素可能因其抗胆碱能作用而导致调节功能和双眼视觉受损。利奈唑胺,一种恶唑烷酮类药物,用于治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染,可能导致进行性、潜在不可逆的视神经病变,尤其是在长期使用时。使用利福布汀或抗病毒药物西多福韦进行治疗可能会引起眼内炎症。此外,西多福韦可能因其对睫状上皮细胞的毒性作用而损害房水的生成。在伏立康唑治疗期间,约三分之一的患者会出现可逆性视觉障碍。肝功能不全或细胞色素P450系统中的药物遗传学变异可能导致代谢迟缓,使眼内药物水平升高。总之,本综述表明了眼部药物不良反应的复杂性,并指出需要采用跨学科方法来改善该领域的药物警戒。

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