Do women have more adverse drug reactions?
Do women have more adverse drug reactions?
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DOI：
10.2165/00128071-200102060-00001
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发表时间：
2001-01-01
影响因子：
7.3
通讯作者：
Rademaker, M
中科院分区：
文献类型：
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作者：
Rademaker, M
高达5%的住院病人是由药物不良反应(ADRs)引起的。确定那些可能导致不良反应的因素对于风险管理至关重要。已知的不良反应危险因素包括年龄增加、服用多种药物、肝脏和肾脏疾病以及女性。与男性患者相比，女性患者患ADR的风险高1.5至1.7倍，包括皮肤不良反应。风险增加的原因尚不完全清楚，但包括与性别有关的药代动力学、免疫学和激素因素的差异，以及女性与男性相比使用药物的差异。与男性相比，女性一般瘦体重较低，肝脏清除率降低，细胞色素P450(CYP)酶活性差异(细胞色素P450酶活性增加40%，细胞色素P450酶活性降低)，代谢药物的速率不同。其他重要因素包括结合、吸收、蛋白质结合和肾脏消除，这些因素都可能存在性别差异。然而，这些差异如何导致ADR风险增加尚不清楚。男性和女性之间存在药效学上的差异，尤其是在心脏和精神药物方面。毫无疑问，在相同的剂量和血浆浓度下，氯丙嗪、氟比林和各种抗精神病药物在女性身上似乎比男性更有效。同样，即使在相同的血清浓度下，服用某些抗心律失常药物的女性也比男性有更高的QT延长风险。其机制尚不清楚。越来越多的证据表明，特殊的药物反应，特别是皮肤反应，似乎有免疫病因。这可能是T细胞激活和增殖的性别差异以及系统性红斑狼疮和光敏等皮肤病患病率增加的原因。无论是什么机制(S)，重要的是要意识到，性别是不良反应中的一个重要因素。
Up to 5% of all hospital admissions are the result of adverse drug reactions (ADRs). Identifying those factors which may predispose to ADRs is essential for risk management. Amongst the known risk factors for adverse reactions are increasing age, polypharmacy, liver and renal disease as well as being female. Female patients have a 1.5- to 1.7-fold greater risk of developing an ADR, including adverse skin reactions, compared with male patients. The reasons for this increased risk are not entirely clear but include gender-related differences in pharmacokinetic, immunological and hormonal factors as well as differences in the use of medications by women compared with men. Women generally have a lower lean body mass, a reduced hepatic clearance, have differences in activity of cytochrome P450 (CYP) enzymes (40% increase in CYP3A4, varied decrease in CYP2D6, CYP2C19 and CYP1A2), and metabolize drugs at different rates compared with men. Other important factors include conjugation, absorption, protein binding and renal elimination, which may all have some gender-based differences. However, how these differences result in an increased risk of ADRs is not clear. There are pharmacodynamic differences between men and women, seen particularly with cardiac and psychotropic medications. There is no doubt that chlorpromazine, fluspirilene and various antipsychotics appear more effective in women than men for the same dosage and plasma concentration. Similarly, women are at increased risk of QT prolongation with certain anti-arrhythmic drugs compared with men even at equivalent serum concentrations. The mechanisms are unknown. Increasingly the evidence is that idiosyncratic drug reactions, particularly cutaneous reactions, appear to have an immunological etiology. It is possible that gender difference in T cell activation and proliferation account for this as well as the increased prevalence of skin diseases such as systemic lupus erythematosus and photosensitivity. Whatever the mechanism(s), it is important to be aware that gender is a significant factor in ADRs.