adversedrugreaction药学英语.ppt

Unit 4 Adverse Drug Reactions,1.Definition,Adverse drug reactions are unwanted effects caused by normal therapeutic doses .Drugs are great mimics of diseases, and adverse drug reactions present with diverse clinical signs and symptoms.药物不良反应是正常的治疗剂量造成不必要的影响是伟大的模仿疾病和药物不良反应，出现不同的临床症状和体征的药物。,2.Classification,The classification proposed by Rawlins and Thompson divides reactions into type A and type B. 2.1 Type A reactions ,which constitute the great majority of adverse drug reactions, are usually a consequence of the drugs main pharmacological effect (bleeding from warfarin) or a low therapeutic index (nausea from digoxin), and they are therefore predictable, They are doserelated and usually mild, although they may be serious or even fatal (intracranial bleeding from warfarin). Such reactions are usually due to incorrect dosage (too much or too long), for the individual patient or to disordered pharmacokinetics, usually impaired drug elimination. The term “side-effects” is often applied to minor type-A reactions.罗林斯和汤普森提出的分类划分为A型和B型反应 2.1类型反应，构成绝大多数药物不良反应，药物的主要药理效应（华法林出血）或一个低的治疗指数（恶心地高辛）的后果，以及他们因此可预见的，他们是剂量相关的，通常是温和的，虽然他们可能是严重的，甚至是致命的（颅内出血华法林）。这样的反应通常是由于不正确的剂量（过多或过长），个别病人或无序的药代动力学，通常药物消除受损。术语“副作用”小A型反应往往是应用。,2.2 Type-B Type-B (idiosyncratic) reactions are not predictable from the drugs main pharmacological action, are not dose-related and are severe, with a considerable mortality. The underlying pathophysiology of type B reactions is poorly if at all understood, and often has a genetic or immunological basis. Type B reactions occur infrequently(1:1000-1:1000 treated subjects being typical) B型（特质）的反应是不可预测的药物的主要药理作用，剂量无关，是严重的，死亡率相当。基本的病理生理B型反应差，如果在所有的理解，往往有遗传或免疫学基础。 B型反应很少出现的（1:1000-1:1000治疗对象是典型）,Adverse drug reactions due to specific drug-drug interactions are studied. Three further minor categories of adverse drug reactions have been proposed. 1 Type C-continuous reactions due to long-term drug use (neuroleptic-related tardive dyskinesia or analgesic nephropathy) 2 Type D-delayed reactions (alkylating agents leading to carcinogenesis, or retinoid-associated teratogenesis ) 3 Type E-end-of-use reactions such as adrenocortical insufficiency following withdrawal of corticosteroids, or withdrawal syndromes following discontinuation of treatment with clonidine, benzodiazepines, tricyclic antidepressants or beta-adrenoreceptor antagonists. 由于特定的药物相互作用的药物不良反应进行了研究。另外三个小类别药品不良反应已被提出。 1 C型连续反应，由于长期使用药物（抗精神病药物有关的迟发性运动障碍或镇痛剂肾病） 2型D-延迟反应（烷化剂导致癌变，或维甲酸相关致畸） 使用E-3型反应，如皮质类固醇激素停药后，肾上腺皮质功能不全或可乐定，苯二氮卓类，三环类抗抑郁药或-肾上腺素受体拮抗剂治疗停药后的戒断症状。,There are between 30000 and 40000 medicinal products available directly or on prescription in the UK, A recent survey suggested that approximately 80% of adults take some kind of medication during any 2-week period, Exposure to drugs in the population is thus substantial ,and the incidence of adverse reactions must be viewed in this context有30000和40000之间的医药产品可直接或在英国，最近的一项调查表明，约80的成年人在任何2个星期的期间内，采取某种药物的处方，因此药物在人口暴露可观，不良反应的发生率，在这种情况下，必须被视为,Type A reactions are beliveved to be responsible for up to 3%of acute hospital admissions and 2%3%of consultations in general practice. In hospital, clinically significant adverse reactions are estimated to complicate10%20% of all admissions ,prolonging hospital stay and causing suffering and an appreciable number of fatalities, as well as wasting resources, They are the most frequent and severe in neonates, the elderly, women, patients with hepatic or renal disease, and individuals with a history of previous adverse drug reactions, Adverse drug reactions often occur early in therapy(during the first 110day). A型反应beliveved的负责急性入院的3和23的普遍做法协商。在医院，临床显着的不良反应，估计所有招生complicate1020，延长住院时间和造成的痛苦和死亡，以及浪费资源了为数可观的，他们是最常见和最严重的新生儿，老人，妇女，肝或肾脏疾病的患者，以及个人的历史以前的药物不良反应，药物不良反应常发生在治疗早期（在第110天）。,The drugs most commonly implicated are digoxin, antimicrobials, diurectics, potassium salt replacements, analgesics, sedatives and major tranquillizers, insulin, aspirin, glucocorticosteroids, antihypertensives and warfarin 最常用牵连的药物有地高辛的抗菌剂，diurectics，钾的盐替代品，止痛剂，镇静剂和主要镇静剂，胰岛素，阿司匹林，糖皮质激素，抗高血压药和华法林,3 Factors involved in the Etiology of Adverse Drug Reactions Can Be Classified as Follows 1 patient factors Intrinsic: Age-neonatal, infant and elderly Sex-hormonal environment Genetic abnormalities Previous adverse drug reactions, allergy, atopy Presence of organ dysfunction-disease Personality and habits-alcoholic, drug addict, nicotine, compliance .参与药品不良反应的病因的因素可以归类为如下 1患者因素 内在： 年龄，新生儿，婴幼儿和老人 性荷尔蒙环境 遗传异常 上一页药物不良反应，过敏，过敏性疾病 器官功能障碍疾病的存在 人格和习惯含酒精，吸毒者，尼古丁，遵守。,Extrinsic: Environment-sun Xenobiotics (drugs, herbicides) Malnutrition 2.Prescriber factors Incorrect drug or drug combination Incorrect route of administration Incorrect dose Incorrect duration of therapy 3.Drug factors Drug-drug interactions Pharmaceutical-batch problems, shelf-life, incorrect dispensing外在： 环境阳光外来物质（药物，除草剂）营养不良 2.Prescriber因素 不正确的药物或药物组合不正确的给药途径不正确的剂量 不正确的治疗时间 3.Drug因素 药物相互作用药品批次的问题，保质期，不正确配药,4 Adverse Drug Reaction Monitoring/ Surveillance Pharmacovigilance The evaluation of drug safety is complex, and there are many methods for monitoring adverse drug reactions. Each of these has its own advantages and shortcomings, and no single system can offer the absolute security that public opinion expects. The ideal method would identify adverse drug reactions with a high degree of sensitivity and specificity and respond rapidly.药品不良反应监测/监控药物警戒 药物安全性的评价是复杂的，有很多方法用于监测药物的不良反应。这些每个人都有自己的优点和缺点，并没有一个单一的系统可以提供绝对的安全，舆论预期。理想的方法将确定药物的不良反应，具有高度的敏感性和特异性，并作出迅速的反应。,It would detect rare but severe adverse drug reactions, but would not be overwhelmed by common ones, the incidence of which would quantify together with predisposing factors, Continued surveillance is mandatory after a new drug has been marketed, as it is inevitable that the preliminary testing of medicines in humans during drug development, although excluding many ill effects, cannot identify uncommon adverse effects. A variety of early detection methods have been introduced to identify adverse drug reactions as swiftly as possible.检测罕见但严重的药物不良反应，但不会被淹没常见的，发病的诱发因素，将一起量化续监视是强制性的一种新的药物已经上市，这是不可避免的，经初步测试人类在药物开发中的药品，虽然不包括许多不良影响，无法识别少见的不良影响。已经出台的各种早期检测方法，尽可能迅速地识别药品不良反应。,5 Phase I/II/III Trials Early (Phase I/II) trials are important for assessing the tolerability and dose-response relationship of new therapeutic agents, However, these studies are very insensitive at detecting adverse reactions because they are performed on relatively few subjects(200300).This is illustrated by the failure to detect the serious toxicity of several drugs (practolor, benoxaprofen , temafloxacin ,felbamate, dexfenfluramine and fenfluramin troglitazone) before marketing. However, phase III clinical trials can establish the incidence of common adverse reactions and relate this to therapeutic benefit. 5 I / II期/ III期临床试验 早期（I / II期试验）评估耐受性和新的治疗药物的剂量 - 反应关系很重要，但是，这些研究是非常不敏感，在检测不良反应，因为它们被执行的对象相对较少（200300名）。所示的故障检测几种药物的严重毒性（苯恶洛芬practolor，替马沙星，非氨酯，右芬氟拉明和曲格列fenfluramin）前营销。然而，III期临床试验可以建立常见的不良反应的发生率和治疗效果。,Analysis of the reasons given for dropping out of phase III trials is particularly valuable in establishing whether common events such as headache, constipation, lethargy or male sexual dysfunction are truly drug related,