Unknown date
Total
7
131
2
81
*The reports in this table concern heparin produced by any manufacturer.
Information on Adverse Event Reports and Heparin

the number of death reports that included one or more allergic symptom(s) or symptoms of hypotension (low blood pressure). These are the events that prompted a series of heparin recalls. FDA Finished Inspection but Still Doesn't Know What Caused Heparin Contamination
–
– –
–
Provide early warning of unrecognized ADRs Identify predisposing factors Compare drugs in the same therapeutic class Continuously monitor the safety of all drugs
1. 药代动力学方面 药物分布
A型药物不良反应
肾脏排泄 生物转化 药物与组织结合
2. 靶器官敏感性的增强
– 有些药物如神经递质、激素和某些维生素，主要通
过与特异受体结合而发挥其药理作用。个体间受体 不但数量不同，而且受体的敏感性也可受其他药物 的影响而不同。
3. 影响体内的离子平衡
– 强心苷类药物增加心肌细胞中的Ca2+浓度，增强心

根据药物不良反应与药物制剂有无关系分类
A、B型不良反应特点的比较
项目
与剂量关系
A型ADR
相关，与剂量成正比 药理作用增强所致 可
B型ADR
无关 由遗传药理学变异引起 不可
可预见性
发生率
死亡率 预防 治疗
高
低 调整剂量 调整剂量
低
高 避免用药 停止用药
药物不良反应发生机制

A型不良反应的发生机制 药物吸收 血浆蛋白结合率

变态反应：亦称过敏反应，指对服用某种药物出现过敏症状的
反应，如青霉毒过敏性休克。



Type I – immediate hypersensitivity, anaphylaxis (IgE)
e.g., anaphylaxis with penicillins
e.g., hemolytic anemia produced by rifampicin Serum sickness: fever, arthritis, enlarged lymphnodes, e.g., contact dermatitis by antihistamine creams
第二节 药源性疾病
药源性疾病（drug-induced disease）
– 指由药物作用为致病因子，引起人体功能或组织结
构损害，并且有相应临床经过的疾病。一般不包括 药物过量而导致的急性中毒。它是药物不良反应一 定条件下产生的后果。
Spontaneous reporting system (SRS)

Currently, SRS is replaced by an expanded system called the Adverse Events Reporting System (AERS)
AER
What are the aims of AERS?


The aim of the AERS is to improve patient safety by finding out as much as possible about adverse reactions by pooling health professionals’ experience and suspicions To use this information to
第六章 药物不良反应与药源性疾病
第一节 药物的不良反应
概念

药物不良反应（Adverse drug reaction, ADR）
系指药物在预防、诊断、治疗疾病或调节生理机能 过程中，在正常剂量下出现的与用药目的无关的对 机体有害的反应，但排除治疗失败、药物过量、药 物滥用、不配合治疗和药物误投。
Type II - cytotoxic reactions (IgG, IgM or IgA) Type III – immune complex reactions (IgG)

Type IV – cell-mediated or delayed hypersensitivity (T cell)
葡萄糖6磷酸脱氢酶 （G－6－PD）缺乏的患者
服 用
氧化剂（如奎宁，伯安奎宁，阿司匹林，氯霉素等)
出 现
溶 血
药物不良反应监测
目前，国际上已有多种监测ADR的方法，各有其优缺点， 但目的均在于及时、准确发现ADR。主要有以下几种
自发报告系统(spontaneous reporting system, SRS)
处方事件监测(prescription event monitoring) 医院集中监测(intensive hospital monitoring)
病例对照研究(case-control studies)
队列研究(cohort studies) 医学记录联结(record linkage)
记录应用

药物不良反应事件（adverse drug event / ADE）
系指在使用医药产品过程中，患者身上发生的不 期望出现的经历，它包括药物不良反应和其他与 处方开具、调剂、发药或给药有关的事件（包括 药物误投）

药物不良事件是药物治疗过程中出现的不良临床事件， 它不一定与该药有因果关系。 ADR与ADE区别：
– 特殊毒性：三致


致癌作用（carcinogenesis）
致畸作用（teratogenesis） 致突变作用（mutagenesis）
根据药物不良反应的性质分类

后遗效应（after effect）：药物从机体消除后所留效应 继发反应（secondary reaction）：药物治疗作用所引 起的间接后果 药物依赖性（drug dependence）
Jan-07
Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08
3
1 4 4 2 3 4 1 2 7 11 20 31 28 3
1
0 2 2 1 2 2 1 2 4 10 13 21 18 0
一、药物不良反应的类型（续）

根据药物不良反应的严重程度分类
– 轻度：引起患者轻度不适，但不需要改变临床
治疗方案 – 中度：需要改变临床治疗方案或需住院治疗 – 重度：有致残或危及生命的不良反应，需入院 或延长住院时间的不良反应
FDA Serious ADR
– –
–
– –
–
–
Result in death Life-threatening Require hospitalization Prolong hospitalization Cause disability Cause congenital anomalies Require intervention to prevent permanent injury

LeRoy Hubley, whose wife and son died from an allergic reaction to contaminated heparin, wipes his eyes while testifying at a House Oversight and Investigations subcommittee hearing on April 29, 2008.
Number of Deaths of Patients Receiving Heparin Reported to FDA, January 1, 2007 through April 13, 2008 Month the Medical Event(s) Occurred Number of Reported Deaths* Reported Deaths with One or More Allergic/Hypotensive Symptom(s)
Information on Adverse Event Reports and Heparin
There have been 131 reports of death reported to FDA since January 1, 2007; 124 were reported to FDA on or after March 1, 2008. Of the 81 reports that included one or more allergic symptom(s) or symptoms of hypotension and death, 79 were reported to FDA on or after March 1, 2008. The fact that allergic symptoms or hypotension were reported does not mean that these were the cause of death in all cases. FDA received reports of 50 patients who died without mention of allergy or hypotension. These patients died of a variety of causes.