Abstract:
Drug hypersensitivity reactions induced by small molecule drugs encompass a broad spectrum of adverse drug reactions with heterogeneous clinical presentations and mechanisms. These reactions are classified into allergic drug hypersensitivity reactions and non-allergic drug hypersensitivity reactions. At present, the hapten theory, pharmacological interaction with immune receptors (p-i) concept, altered peptide repertoire model, and altered T-cell receptor (TCR) repertoire model have been proposed to explain how small molecule drugs or their metabolites induce allergic drug hypersensitivity reactions. Meanwhile, direct activation of mast cells, provoking the complement system, stimulating or inhibiting inflammatory reaction-related enzymes, accumulating bradykinin, and/or triggering vascular hyperpermeability are considered as the main factors causing non-allergic drug hypersensitivity reactions. To date, many investigations have been performed to explore the underlying mechanisms involved in drug hypersensitivity reactions and to search for predictive and preventive methods in both clinical and non-clinical trials. However, validated methods for predicting and diagnosing hypersensitivity reactions to small molecule drugs and deeper insight into the relevant underlying mechanisms are still limited.
摘要:
由小分子药物引起的药物超敏反应包括具有异质性临床表现和机制的广谱药物不良反应。这些反应分为过敏性药物超敏反应和非过敏性药物超敏反应。目前,hapten理论,与免疫受体的药理学相互作用(p-i)概念,改变的肽库模型,已经提出了改变的T细胞受体(TCR)库模型来解释小分子药物或其代谢物如何诱导过敏性药物超敏反应。同时,直接激活肥大细胞,引发补充系统,刺激或抑制炎症反应相关酶,积累缓激肽,和/或引发血管通透性增高被认为是引起非过敏性药物超敏反应的主要因素。迄今为止,已经进行了许多研究,以探索药物超敏反应的潜在机制,并在临床和非临床试验中寻找预测和预防方法.然而,对小分子药物超敏反应的预测和诊断方法以及对相关潜在机制的深入了解仍然有限.