静脉用免疫球蛋白的治疗作用机制及其不良反应

静脉滴注免疫球蛋白用于多种自身免疫性疾病和炎症性疾病的治疗,其作用机制包括对自身抗体的作用,抑制补体结合,阻止膜攻击复合物形成,调节巨噬细胞Fc受体,抑制致病性细胞因子和其他免疫调节分子等。该药不反应反应较少,主要有皮肤过敏反应、无菌性脑膜炎、血浆黏度增加和血栓形成以及肾功能损害等。     

Reporting adverse drug reactions on a geriatric ward: a pilot project

OBJECTIVE: To test a method for registration of adverse drug reactions (ADRs) resulting in hospital admission and of ADRs occurring during hospital stay. Spontaneous reporting was compared with data from patient interview. METHODS: Spontaneous reporting of ADRs by nurses and physicians, as well as patient interviews by pharmacists. This pilot project was carried out in the geriatric ward of the Ghent University Hospital over a period of 8 months in order to develop suitable registration forms and to test feasibility. Causality, severity, type and level of intervention of the reported ADRs were analysed. Reports from physicians and nurses were compared with the data obtained by patient interviews. RESULTS: During the 8 months, for 168 patients, 12 spontaneous reports were received from physicians and nurses. Fifty-six of these patients were interviewed and 32 ADRs were reported. Only 2 ADRs detected by patient interview were also reported spontaneously. The interviews of the 56 geriatric patients indicated that 20% of them were admitted to the hospital because of an ADR. ADRs occurred during hospital stay in another 20% of those patients. CONCLUSION: Spontaneous reporting by physicians and nurses revealed considerably fewer ADRs than patient interview by pharmacists. Physicians and nurses reported the more serious ADRs that occurred during hospital stay, whereas the interviews revealed more ADRs that caused hospital admission. Our data confirm that ADRs are an important cause of hospital admission of geriatric patients and occur frequently during their hospital stay.     

Frequency of adverse drug reactions in children: a prospective study

AIMS: To assess the frequency of adverse drug reactions (ADRs) in children in France. METHODS: In a prospective study over a period of 1 week, we evaluated the incidence of ADRs (1) as a cause of admission to a regional children's hospital; (2) occurring during hospitalization in a regional children's hospital; and (3) as a cause of consultation with private paediatricians. RESULTS: Four out of 260 children were admitted to the regional children's hospital for ADRs (1.53% [0.42, 3.89]) and six developed ADRs during hospitalization (2.64% [0.97, 5.66]), 4/428 attended the Accident and Emergency Department for ADRs (0.93% [0.25, 2.37]) and 8/1192 consulted a private paediatrician for ADRs (0.67% [0.29, 1.31]). CONCLUSIONS: Our results are in agreement with the incidence of ADRs in children found in others countries.     

Under-reporting of adverse drug reactions : a systematic review.

The purpose of this review was to estimate the extent of under-reporting of adverse drug reactions (ADRs) to spontaneous reporting systems and to investigate whether there are differences between different types of ADRs. A systematic literature search was carried out to identify studies providing a numerical estimate of under-reporting. Studies were included regardless of the methodology used or the setting, e.g. hospital versus general practice. Estimates of under-reporting were either extracted directly from the published study or calculated from the study data. These were expressed as the percentage of ADRs detected from intensive data collection that were not reported to the relevant local, regional or national spontaneous reporting systems. The median under-reporting rate was calculated across all studies and within subcategories of studies using different methods or settings. In total, 37 studies using a wide variety of surveillance methods were identified from 12 countries. These generated 43 numerical estimates of under-reporting. The median under-reporting rate across the 37 studies was 94% (interquartile range 82-98%). There was no significant difference in the median under-reporting rates calculated for general practice and hospital-based studies. Five of the ten general practice studies provided evidence of a higher median under-reporting rate for all ADRs compared with more serious or severe ADRs (95% and 80%, respectively). In comparison, for five of the eight hospital-based studies the median under-reporting rate for more serious or severe ADRs remained high (95%). The median under-reporting rate was lower for 19 studies investigating specific serious/severe ADR-drug combinations but was still high at 85%.This systematic review provides evidence of significant and widespread under-reporting of ADRs to spontaneous reporting systems including serious or severe ADRs. Further work is required to assess the impact of under-reporting on public health decisions and the effects of initiatives to improve reporting such as internet reporting, pharmacist/nurse reporting and direct patient reporting as well as improved education and training of healthcare professionals.     

Treatment of adverse drug reactions in a dermatology department

The aim of the study was to evaluate the pattern of utilization of systemic drugs used in the management of adverse drug reactions (ADRs) leading to hospitalization. A prospective pharmacovigilance study was carried out among patients admitted to the Clinic of Dermatology and Venereology in Stara Zagora (July 1999–June 2009). ADRs were classified by type, severity and causality. Casecausality was scored according to Naranjo et al. (1981). Drug utilization was measured in defined daily doses (DDDs) per 100 hospital bed days. A total of 144 cutaneous ADRs, predominantly “type B” were the reason for hospitalization. Highest utilization for the management of ADRs was found for the drug groups “Blood and blood forming organs” (406.08 DDDs/100 bed days) and “Respiratory system” (111.15 DDDs/100 bed days). The use of DDD for measuring drug utilization reveals the importance of drug-induced exacerbations of chronic skin diseases like psoriasis which were associated with significant utilization of drugs belonging to the group “Blood and blood forming organs”. Considering the low preventability of “type B” ADRs, our findings suggest that potential reduction of drug-related hospitalizations may be achieved through the rational use of drugs in patients with comorbidities.     

Genotyping of drug targets: a method to predict adverse drug reactions?

In the last decades, advances in molecular biology have led to modern pharmacogenetics, which started as a science that focused on investigating drug metabolising enzymes and genetic determinants of pharmacokinetic variability. As more evidence has become available on the structure of drug targets and the genes coding for them, increasing attention has been directed towards pharmacodynamic explanations of variability in therapeutic response as well as in the risk for adverse drug reactions. Traditionally, genetic drug safety research has focused on variations in single genes whose functions are known to be related to given adverse drug reactions. A few such examples, malignant hyperthermia, the long QT syndrome, venous thromboembolic disease, tardive dyskinesia, and drug addiction, are presented in this article. In the future, results from the Human Genome Project together with tools such as DNA microarray technology, high-output screening systems and advanced bioinformatics, will permit a more thorough elucidation than is currently possible of the genetic components of adverse drug reactions. By screening for a large number of single nucleotide polymorphisms (SNPs), SNP patterns associated with adverse drug reactions can be discovered even though the functions of the SNPs as such are completely unknown. On the basis of these findings, it can be expected that pharmacogenetic research will identify situations where a drug should be avoided in certain individuals in order to reduce the risk for adverse drug reactions. If so, it will be feasible to use molecular diagnostics to select drugs that are safe for the individual patient.     

In vitro testing for diagnosis of idiosyncratic adverse drug reactions: Implications for pathophysiology

Idiosyncratic drug reactions (IDRs) represent a major health problem, as they are unpredictable, often severe and can be life threatening. The low incidence of IDRs makes their detection during drug development stages very difficult causing many post-marketing drug withdrawals and black box warnings. The fact that IDRs are always not predictable based on the drug’s known pharmacology and have no clear dose–effect relationship with the culprit drug renders diagnosis of IDRs very challenging, if not impossible, without the aid of a reliable diagnostic test. The drug provocation test (DPT) is considered the gold standard for diagnosis of IDRs but it is not always safe to perform on patients. In vitro tests have the advantage of bearing no potential harm to patients. However, available in vitro tests are not commonly used clinically because of lack of validation and their complex and expensive procedures. This review discusses the current role of in vitro diagnostic testing for diagnosis of IDRs and gives a brief account of their technical and mechanistic aspects. Advantages, disadvantages and major challenges that prevent these tests from becoming mainstream diagnostic tools are also discussed here.     

Inservice teaching and adverse drug reactions in a nursing home

A prospective study was carried out in two skilled nursing facilities (SNFs) to determine: the feasibility of identifying potential adverse drug reactions (ADRs) by monitoring drug order changes; the ADR rate in the elderly in SNFs; the ease of using an algorithm to assess the probability that an adverse event is drug-related; and whether a one-hour inservice lecture could alter the number of drug order changes or the number of ADRs detected. Over three months, 27 of 248 order changes (10.8 percent) were identified as possible ADRs. Fifteen of 248 (six percent) of the orders were probable or definite ADRs. The ADR rates were 9.5 percent and 14.8 percent, for the study and control SNFs, respectively (p greater than 0.05). This method of detecting ADRs depends on recognition of a clinically observable adverse event by the nurse, nurse practitioner, or physician. Therefore, the hypothesis that an inservice lecture on ADRs could increase the recognition of ADRs was tested. More drug order changes were initiated in the control facility that retained a full-time nurse practitioner, but no change in the number of drug order changes or ADR rates was seen after the inservice lecture in the study facility. This method is the first to identify, prospectively, clinically manifest ADRs and to test a method to influence their rate in nursing home elderly.     

药品不良反应240例报告分析

目的了解该院药物不良反应（ADR）发生的临床特点,为临床安全、合理用药提供参考。方法对该院2009年1月-2009年12月收集到的240例药品不良反应报告进行回顾性分析。结果 240例药品不良反应报告中男女之比1∶1.0339,60岁以上老年患者发生率较多,占30.00%;其中抗感染药物占首位（70.83%）,静脉给药方式为主要途经（76.25%）;临床表现以皮肤及其附件损害最常见（66.25%）。新的不良反应19例,其中严重的1例;严重的不良反应14例。结论应加强ADR的监测和ADR知识的宣传,避免或减少其重复发生,对新的、严重的不良反应应引起重视。     

药品不良反应报告165例分析

目的了解该院药物不良反应的基本情况,为临床安全用药提供参考。方法分析该院165例药物不良反应报告,对所涉及的药物品种进行分类整理。结果 165例不良反应中40岁以上患者占多数（55.2%）,女性多于男性,不良反应多发生于给药后30min内（68.2%）,共涉及12类66种药物,以静脉给药为主要用药途径的占总数的83.0%。由头孢菌素类药物和中药注射剂引起的不良反应排前2位（20.0%、10.9%）,临床表现以皮肤及其附件损害多见,较严重的不良反应有8例占总数的4.8%。结论该院抗感染药物和中药注射剂静脉用药引起的不良反应不容忽视,应按适应证选药,加强监护,以减少不良反应的发生。     

Incidence of fatal adverse drug reactions: a population based study

Aims

To determine the incidence of fatal adverse drug reactions (FADRs) in a Swedish population.

Methods

Every seventh randomly selected deceased in three counties in South-east Sweden during 1 January 2001–31 December 2001 was identified in the Cause of Death Register. Relevant case records (hospitals and/or primary care centres and medicolegal files) were reviewed to identify suspected drug-related fatalities.

Results

Of 1574 deceased study subjects, 49 (3.1%; 95% CI 2.2%, 4.0%) were suspected to have died from FADRs. The most common suspected FADRs were gastrointestinal haemorrhages (n = 18; 37%), central nervous system haemorrhages (n = 14; 29%), cardiovascular disorders (n = 5; 10%), other haemorrhages (n = 4; 8%) and renal dysfunction (n = 3; 6%). The drugs most commonly implicated in FADRs were antithrombotic drugs (n = 31; 63%), followed by nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 9; 18%), antidepressants (n = 7; 14%) and cardiovascular drugs (n = 4; 8%). Of all the 639 fatalities in hospital 41 (6.4%; 95% CI 4.5%, 8.3%) were suspected to be due to FADRs.

Conclusions

The medical burden of FADRs is significant. Haemorrhages were seen in a majority of the FADRs; antithrombotic agents or NSAIDs were implicated in most of these events. These results suggest that preventive measures should be taken to reduce the number of deaths caused by drugs.

What is already known about this subject

• Although drugs generally are safe and effective therapies for numerous diseases, adverse drug reactions do occur and may even be fatal.
• The incidence of fatal adverse drug reactions in hospitalized patients has been estimated to be approximately 5%.
• In previous studies the incidence of fatal adverse drug reactions in hospitalized patients has been reported, but the incidence of fatal adverse drug reactions in the general population is largely unknown.

What this study adds

• Fatal adverse drug reactions account for approximately 3% of all deaths in the general population.
• Haemorrhages amount to almost two-thirds of the fatal adverse drug reactions and antithrombotic agents are implicated in more than half of the suspected fatal adverse drug reactions.
• Fatal adverse drug reactions are estimated to be the seventh most common cause of death in Sweden.

     

Regional reporting of adverse drug reactions: a new computer-based network

The use of drugs is always accompanied by the risk of adverse drug reactions (ADRs) and adverse events (AE). Generally physicians, pharmaceutical manufacturers, and pharmacists use a paper-based form for sending spontaneous ADR and AE reports to the national drug regulatory authority. Besides underreporting, reporting lag-time and errors through data transformation are a major issue. In order to improve the current reporting situation we have set up a new computer-based, network-driven system for storing, transferring, and evaluating ADR reports. The system consists of three regional centres, one coordinating centre, and the central ADR database of the national drug regulatory authority. In the regional centres, clinical pharmacologists collect ADR data in local databases. There is a comfortable user-interface with an online help-function available. New reports are sent automatically to the Federal Agency using EUROSCAPE as a standardized electronic report form of the EU. The coordinating centre in Munich is responsible for overall performance and quality assurance. This model for a clinical health information network is of a high level of data security, is reliable and easily expandable through the use of standard tools, is fast and also inexpensive by using standard shareware products.     

Patient reporting of potential adverse drug reactions: a methodological study

AIMS: To develop a systematic generic method of enabling patients to report symptoms which they believe to be due to a particular prescribed drug. METHODS: A piloted body system-based questionnaire was distributed to patients registered with 79 medical practices in Grampian prescribed one of nine recently marketed 'black triangle' drugs. These comprised four antidepressants, three antiepileptics and two analgesics. This requested respondents to identify any symptoms experienced over the previous year which they thought could be due to the 'black triangle' drug they had used. A sample of medical records was examined to compare symptoms recorded with those reported by patients. A classification system was developed for the study to enable the assessment of symptoms reported for their potential relationship to patients' drug therapy. All symptoms reported were classified, taking into account information provided by patients on their concomitant drugs and diseases. A specialist pharmacist independently re-classified a sample of the symptoms to validate the process. RESULTS: A 36.3% response rate was obtained (837/2307) with 742 respondents (88.6%) reporting at least one symptom. The median per patient was 6.0 (range 0--71), with almost half (406, 48.5%) reporting fewer than five symptoms. Most symptoms (71.0%) were classified as being probably or possibly related to the drugs studied. Agreement between researcher and specialist on the classification of 75.3% of 716 symptoms was obtained (Kappa=0.563). Responses from patients prescribed antidepressant drugs were more likely to include symptoms potentially caused by these drugs (74.5% of all symptoms reported) than those from patients prescribed analgesics (67.4%) or antiepileptics (65.1%, chi2 = 23.858, d.f. = 2, P < 0.001). Patients reporting large numbers of symptoms were more likely to report some which were classed as unlikely to be an ADR or unattributable (chi2 = 80.587, d.f. = 3, P < 0.001). Of the 742 reporting symptoms in questionnaires, 402 (54.2%) claimed to have reported some or all of these to their doctor. Only 162 (22.6%) of 716 patient-reported symptoms were documented in the primary care medical records of 103 patients prescribed tramadol or venlafaxine. CONCLUSIONS: Respondents were clearly willing to report symptoms, the majority of which were classed as possibly/probably related to the drugs studied. The results suggest that patients do not report all symptoms they suspect to be ADRs to their GP and that GPs do not record all symptoms which may be reported to them. The method could help to identify problems which patients perceive as being related to their drug therapy and contribute to increased ADR reporting.     

Reporting of adverse drug reactions by hospital doctors and the response to intervention

Aims In Ireland there are relatively fewer adverse drug reaction (ADR/yellow card) reports from doctors in hospital than in general practice. The aim of this study was to review the attitudes to reporting of ADRs of hospital doctors and to determine the effect of making yellow cards freely available.
Methods A postal survey of actively practising doctors with follow-up of non-responders was undertaken. We addressed the single most frequently claimed deterrent to reporting, unavailability of yellow cards, by making cards prominently available and placing one in patient's chart upon admission. In addition, doctors were regularly reminded that ADRs should be reported.
Results Of 118 hospital based doctors, only 45% had ever reported an ADR. Fewer than 5% of pre-registration house officers had reported an ADR and the likelihood of reporting increased with seniority and was greater among physicians than surgeons. We found no evidence that doctors had published case reports in place of submitting ADR reports. Over 3 months, the greater availability of yellow cards and reminders about reporting ADRs led to an approximate five-fold increase in reports but reporting declined rapidly thereafter when verbal reminders were withdrawn, despite continued ready availability of cards suggesting that making cards available alone does not significantly increase reporting.
Conclusions This study indicates there may be more fundamental constraints to reporting than attitudinal surveys would suggest and we need to explore additional avenues to ensure a 'reporting culture'.     

药品不良反应监测工作实践与思考

随着我国药品不良反应(adverse drug reactions,ADR)监测与报告工作的迅速发展,加强ADR监测工作无疑是各级药品监管部门和医疗机构的重要职责.本文通过对我国ADR监测工作的发展与现状的回顾和我院开展ADR监测工作状况,将我院十几年来在ADR监测工作中的实践、体会及一些粗浅的认识介绍给同行们,共同探讨药品不良反应监测工作的方法及如何提高ADR报告的质量,更深入地开展ADR监测与报告工作,希望能有所借鉴并共同努力缩小与先进国家的差距,为人民群众的健康服务,为我国这项具有深远意义的卫生事业做贡献.     

Hepatic adverse drug reactions: a case/non-case study in Italy

OBJECTIVE: Adverse drug reactions (ADRs) can involve all tissues and organs. Liver injuries are considered among the most serious and are a cause for concern among physicians and patients. To assess the extent of drug-induced liver injuries in Italy we compared the number of cases of hepatic ADRs with reports of all other drug-related reactions present in the same database. METHODS: Spontaneous reports from six Italian Regions collected from January 1990 to May 2005 were analysed. Adverse reactions were classified according to WHO Adverse Reaction Terminology for causality assessment, and only those with "certain", "probable" or "possible" causality assessment were included. Association between drugs and hepatic ADRs was assessed using the case/non case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. RESULTS: On May 2005, the database contained 35,767 ADR reports, of which 11,829 were excluded because they were unclassifiable or unlikely in terms of causality assessment. Therefore, the analysis was carried out on 23,938 reports, of which 1,069 concerned hepatic ADRs (cases) and 22,869 concerned non-cases. The proportion of serious ADRs was about 40% in the overall database, and about 74% among cases. The drug classes with the highest number of cases were statins (ROR = 2.9, 95% CI 2.4-3.5), antiplatelet agents (ROR = 3.5; 95% CI 2.6-4.6), NSAIDs (ROR = 2.9; 95% CI 2.1-3.9) and macrolides (ROR = 1.7; 95% CI 1.2-2.3). CONCLUSION: Hepatic adverse drug reactions remain a serious concern for several drugs widely used in clinical practice. Monitoring hepatic enzymes on a monthly basis for the first 6 months of treatment has been suggested for patients taking medications known to be hepatotoxic. A better knowledge of the epidemiology and mechanisms of hepatic ADRs may contribute to minimising their occurrence.     

Identification of adverse drug reactions in geriatric inpatients using a computerised drug database

INTRODUCTION AND OBJECTIVE: Geriatric patients with multiple comorbidities are at high risk of experiencing an adverse drug reaction (ADR) during hospitalisation. The aim of the study was to compare the rate of ADRs as predicted by a computerised pharmacological database to the actual rate determined by direct observation in a sample of geriatric patients. STUDY DESIGN: During a 4-month period, geriatric patients were monitored using prospective observation. Patients were intensively screened for ADRs by a pharmacoepidemiological team (PET), consisting of two pharmacists and a physician. Actual ADRs detected by the PET were compared with those predicted by a computerised drug database. Furthermore, the set of actual ADRs, which resulted from drug-drug interactions (DDIs), were contrasted with potential DDIs signalled by the database. The main outcome measures were the incidence of actual ADRs. For the detection rate of the database we focused on frequent ADRs (>1% according to product information and database) and all DDIs indicated automatically by the database. RESULTS: 163 patients (121 female), mean age 79.8 +/- 7.1 years (range 60-98), were included in the study which was conducted on a geriatric rehabilitation hospital ward. The mean duration of hospitalisation was 24.3 +/- 8.4 days. Elderly patients received an average of 14.0 drugs (range 2-35) during their hospital stay.Of all patients, 60.7% experienced at least one ADR. The PET detected a total of 153 ADRs, with a mean of 0.9 ADRs per patient (range 0-5). The computerised drug database predicted an average of 309 potential ADRs for each patient; however, only 21 ADRs per patient were of high frequency. In 48% of ADR-positive patients (defined by PET) at least one of these frequent ADRs occurred.DDIs were detected by the PET in 14.7% of patients. Our database indicated a mean of 12 potential DDIs per patient. In 14 out of 24 DDI-positive patients, at least one signal indicated a real DDI. The database sensitivity was consequently 58.3%. CONCLUSION: In geriatric patients the incidence of ADRs is high. Computerised drug databases are a useful tool for detecting and avoiding ADRs. Our software, however, also produced a large number of signals that did not relate to actual ADRs found by the PET. The sheer number of these 'false' signals shows the need for refinement and optimisation of databases for daily clinical use.     

Computerized surveillance of adverse drug reactions in hospital: Implementation

Objective: To implement and measure the effects of automatic computerized laboratory signals (ALS) as a detection support tool of adverse drug reactions (ADRs) in hospital. Methods: This was a prospective observational study of a total of 192 patients (199 sequential medical admissions) during a 2-month period in a 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. The study involved the routine (daily) distribution to staff physicians of lists of automatic signals generated from computerized laboratory data as potential indicators of ADRs. Patient charts were reviewed by the clinical pharmacology team for ADRs and to see whether these were recognized by the staff physicians. Results: Seventy-one ADRs were detected in 64 of the 199 (32%) admissions. Twenty-seven per cent of the ADRs were serious, 9% of the admissions were due to ADRs. Two hundred and ninety-five ALS were generated involving 69% of the admissions. Sixty-one per cent of the ADRs were identified by ALS. ALS were present in 58% of the ADR negative admissions. Eighty-five per cent of the ADRs were recognized as such and 19% of the ALS-positive ADRs were not recognized by the staff physicians. Conclusions: The routine implementation of ALS doubled the number of ADRs recognized by the physicians while patients were hospitalized in the medical ward. The use of the system appeared valid, simple and potentially cost-effective. Received: 17 June 1998 / Accepted in revised form: 1 October 1998