我国药物不良反应监测体系建设现状与存在的问题

目前，我国已经基本建立了药物不良反应监测体系。我国药物不良反应监测体系的建设包括法律体系、技术体系、信息监测网络、信息评价和反馈机制、预警机制等的建设。但由于我国药物不良反应监测体系建立时间较晚、从业人员业务水平不一等原因，导致我国医药企业、医疗机构和患者对药物不良反应的认识和处理存在偏差，药物不良反应漏报率高，药物不良反应监管滞后且不到位。此外，由于相关法律法规尚不健全，导致我国药物不良反应报告质量不高。医药企业、医疗机构和社会应该纠正对药物不良反应的错误观念，国家应建立健全的法律法规，借鉴国外的成功经验，进一步完善我国药物不良反应监测体系。     

吗啡与芬太尼在剖宫产和妇科手术术后镇痛中的应用

目的对比吗啡与芬太尼用于剖宫产和妇科手术术后自控镇痛的效果和不良反应。方法选取50例剖宫产和50例妇科手术的患者,随机将两组患者分为吗啡组和芬太尼组,术后用硬膜外镇痛,采用视觉模拟分法,对两组患者的镇痛效果及不良反应进行比较。结果吗啡组镇痛效果优良率比较高,不良反应发生率妇科手术比产科高;芬太尼组镇痛效果妇科比产科好,不良反应发生率少。结论吗啡在产科手术术后镇痛效果满意效果,不良反应少;芬太尼在妇科手术术后镇痛效果满意,不良反应少,而吗啡在妇科手术术后镇痛恶心、呕吐、皮肤瘙痒、尿潴留等不良反应发生率高。     

氟喹诺酮类抗菌药物不良反应的调查剖析

目的：对氟喹诺酮抗菌药物不良反应的调查结果进行分析,并了解药物不良反应的特点,旨在能够为临床合理用药提供重要依据。方法选择2011年5月～2014年5月在我院进行治疗的4300例患者作为研究对象,所选患者均应用氟喹诺酮类抗菌药物治疗,观察不良反应发生率与危险因素。结果共发生340例不良反应,不良反应率为7.91％;不良反应率从高到低依次为诺氟沙星、环丙沙星以及培氟沙星;主要累及系统器官从高到低依次为消化道反应、中枢神经系统反应以及变态反应等,占据比例依次为41.18％、32.35％以及14.71％;患者年龄、性别、原发疾病以及用药合理情况等指标为发生不良反应的主要危险因素。结论氟喹诺酮类抗菌药物不良反应具有发生比例高、范围广的特点,胃肠道反应与中枢神经系统反应为患者主要累及器官系统,为降低不良反应率,需要根据危险因素,采取有效预防措施进行预防。     

社区卫生服务体系药品不良反应病例报告分析

目的阐述抚顺市社区卫生服务体系药品不良反应病例报告分析情况，探索在我国社区卫生服务体系中药品不良反应监测规律。方法收集2006年全市社区卫生服务体系上报的药品不良反应病例报告，从性别和年龄分布、用药情况等进行分析。结果40岁以上的中老年人药品不良反应构成比较高，占60％；抗微生物药物和中药制刹药品不良反应构成比较高；新的、严重的不良反应占30%.结论通过对社区卫生服务体系上报的药品不良反应病例报告进行有益的探讨，可为社毒区卫生服务系统开展药品不良反应监测提供借鉴，也为基层社区医务人员的合理用药提供指导。     

全自动换血治疗新生儿高胆红素血症不良反应及其相关因素临床分析

目的：探讨全自动换血治疗新生儿高胆红素血症不良反应及其相关因素。方法：回顾性分析本院2008年6月～2010年6月收治的72例采用全自动换血治疗新生儿高胆红素血症的临床资料，总结该组患儿的不良反应，并分析不良反应的相关因素。结果：该组患儿中发生较多的3种不良反应是低钙血症、代谢性酸中毒、血小板减少症，胎龄≤32周、换血时疾病状态为导致换血后不良反应的独立危险因素，P〈0.05。结论：换血治疗存在一定的不良反应，要注意新生儿的孕龄、基础疾病。     

2012年某院药品不良反应的分析

目的分析药物不良反应发生的特点,促进药品不良反应监测的进一步完善。方法对我院2012年全年上报的61例不良反应报告进行回顾性分析。结果引起不良反应的药物主要为抗菌药物和中药制剂,不良反应上报率低、漏报率高。结论通过多种途径改进不良反应上报工作,提高全体医务人员的重视,保障患者用药安全、有效。     

培高利特等多巴胺受体激动剂致纤维化反应

英国药物控制局(MCA)报告,培高利特与其他麦角碱衍生物的多巴胺受体激动剂相比,其引起纤维化不良反应的报告率似乎更高。英国通过黄卡报告系统,共收到49份与培高利特(pergolide,Celance)有关的纤维化不良反应报告。与此相比,溴隐亭(bromocriptine,Parlodel)和卡麦角林(cabergoline,Cabaser)有关的纤维化不良反应报告分别为24份和6份。麦角脲(lisuride)尚无纤维化不良反应的报告。培高利特、溴隐亭、卡麦角林及麦角脲的不良反应报告总数分别为496、942、367和73份。可疑的纤维化不良反应报告包括肺和胸膜纤维化、胸腔积液、腹膜后纤维化和…     

2006年抗菌药品不良反应报告分析

目的研究深圳市2006年抗菌药品不良反应发生基本情况,评估药品不良反应报告表质量,为临床药品不良反应监测及合理用药提供参考。方法以Excel电子表格形式下载2006年药品不良反应报告表,对有关数据进行适当转换后,进行统计、分析。结果2222份药品不良反应报告共涉及12类118个抗菌药品。β-内酰胺类、喹诺酮类位于前列。药品不良反应所累及的系统-器官主要为皮肤及其附件(65%)、消化系统(19%)、神经系统(13%)。1870例(84.2%)药品不良反应由静脉给药途径所致。新的、严重的不良反应较少,报告填写质量不高。结论抗菌药品不良反应高发生率与多种因素有关,其中使用管理丞待加强,医生处方应进行规范,以减少药品不良反应发生;应加强医务人员药品不良反应知识培训,增强其报告意识和责任感,提高报告质量。     

抗结核药物不良反应及其防治

抗结核药物不良反应发生率高、种类多,可导致抗结核治疗不规范,严重影响治疗效果,严重不良反应甚至可危及生命。因此,临床医生有必要掌握抗结核药物不良反应及其防治。     

干扰素引起的不良反应

干扰素应用广泛,一般不良反应发生率高,且发生特殊不良反应。     

A preliminary evaluation of pipothiazine palmitate in schizophrenia.

A preliminary evaluation of pipothiazine palmitate by injection was carried out in 25 schizophrenic patients to assess the therapeutic effectiveness of the drug, probable dosage schedules and intervals between doses, and to observ any undesirable side-effects. A good overall response was obtained in 64% of the patients. The authors suggest that the optimum maintenance dosage is between 50 and 100 mg. given at 4-weekly intervals. Although extra-pyramidal side-effects were high, only 1 patient had to be withdrawn on this account; the symptoms being well-controlled in mostly by procyclidine. Other adverse side-effects were negligible and there was no evidence of adverse biological effects. It is concluded that pipthiazine palmitate has considerable potential in the treatment of schizophrenia and a longer-term study is being conducted.     

Follow-up treatment of schizophrenic psychoses: advantages and disadvantages of long-term medication]

In completely remitted schizophrenic patients with formerly paranoid-hallucinatory symptoms, the reoccurrence of relapses can be reduced in an extremely high percentage by relatively low neuroleptic long-term treatment specifically adjusted to each patient. Without medication there is an extremely high rate of relapses to be expected. In prophylactic neuroleptic medication the dose must be calculated individually. The depressive syndrome, which can be observed in higher therapeutic dosages, will then be less frequent. The social handicap due to side-effects of prophylactic treatment is more tolerable than the risk of relapse. The follow-up records of the patients treated with long-term medication of the active drug show that, in spite of side-effects, occupational resocialisation and personal stabilisation could be established more easily than in the placebo group. By close psycho-social after-care a high percentage of relapses can be handled in out-patients.     

A controlled trial of magnesium dithiosalicylate compared with aspirin in rheumatoid arthritis

Summary

The anti-inflammatory effectiveness and side-effects of magnesium dithiosalicylate were compared to aspirin in a 3-month, parallel, double-blind trial in 40 patients suffering from active rheumatoid arthritis. The results showed that 3?g magnesium dithiosalicylate daily had anti-inflammatory properties similar to those of 3?g aspirin daily in rheumatoid arthritis. A statistically significant change in morning stiffness, number of tender joints, pain score and erythrocyte sedimentation rate was observed in the inagnesium dithiosalicylate group. In the magnesium dithiosalicylate group, 8 patients had to be withdrawn from the trial because of serious side-effects compared to 5 in the aspirin group. Gastro-intestinal intolerance occurred as frequently in both treatment groups. Hypersensitivity to magnesium dithiosalicylate was a serious problem and the reason for withdrawal in 4 cases. The high frequency of side-effects to magnesium dithiosalicylate makes this drug unacceptable for treatment of rheumatoid arthritis at the present time. Further pharmacological studies might reveal new derivatives which are as effective but with less side-effects. The anti-inflammatory activity of magnesium dithiosalicylate resembled that observed with gold and penicillamine. The fact that all these drugs have a sulphhydril group in common is stressed.     

Side-effects of drugs in epileptic patients

Drug therapy in patients suffering from various forms of epilepsy aims at the administration of such dosages of antiepileptic drugs as to produce significant reduction of seizures without the occurrence of serious side-effects. To assess these side-effects 75 patients (48 males, 27 females) with epilepsy, attending an out-patient clinic were studied prospectively and data were collected regarding diagnosis, drug use and side-effects. Primarily generalized epilepsy and partial complex epilepsy with secondary generalization are the most prevailing categories. 69% (52) Of the patients are treated with monotherapy, with carbamazepine as the drug most frequently prescribed (30/52). Side-effects were scored after examining and questioning the patient with the help of a standard questionnaire. A distinction was made between groups of side-effects, being systemic, anamnestic, dermatological, neurological or miscellaneous. Also, haematological and biochemical changes were looked for. In the monotherapy group 26/52 (50%) of the patients showed side-effects (23 patients with 1, 2 with 2, 1 with 3 side-effects), and in the polytherapy group 15/23 (65%) (8 patients with 1, 7 with 2 side-effects). Adverse drug reactions were hardly related to the plasma concentration category. Between 50–60% of the patients at sub-therapeutic and low-therapeutic plasma levels complained of side-effects. No clear relationship between the clinical efficacy and the side-effects could be established. The clinical custom, among others, to titrate the dose according to the disappearance or appearance of side-effects seems open for discussion.     

Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning

AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC, at the Department of Hepatology, Copenhagen University Hospital (the tertiary care centre of liver disease in Denmark). RESULTS: Forty-five patients (8.5%; 95% confidence intervals (CI) 6.4, 11%) developed side-effects to NAC and 18 patients (3.4%; 95% CI 2.1, 5.4%) developed systemic side-effects. Asthmatics were 2.9 times (95% CI 2.1, 4.7) more likely to develop side-effects (Chi-square: P = 0.004). Side-effects were of similar severity in asthmatics and nonasthmatics. A history of medical allergy was not a risk factor. Serum paracetamol was lower in patients with side-effects than in those without (Mann-Whitney: P = 0.00006). CONCLUSIONS: Asthma must be considered a risk factor in the development of side-effects to NAC. However, the side-effects are easily managed and there is no reason to withhold NAC from any patient with paracetamol poisoning. Paracetamol itself seems to offer some protection against the development of side-effects to NAC.     

拉米夫定的少见不良反应

目的了解拉米夫定在临床应用中较少见的不良反应。方法对近年来相关文献资料进行归纳总结。结果与结论拉米夫定少见不良反应有：斑秃、肾结石、YMDD变异、病毒性上呼吸道感染。     

Section Review—Central & Peripheral Nervous Systems: Pre-Clinical Pharmacology of New Atypical Antipsychotics in Late Stage Development

The high incidence of motor-disturbing side-effects associated with ‘typical’ neuroleptic medication has led to the search for safer, ‘atypical’ antipsychotics. Clozapine, the most noted atypical antipsy-chotic, has proven efficacy in the treatment of schizophrenia, and induces fewer motor disturbances. Nevertheless, clozapine is associated with other, severe side-effects. Hence, new atypical antipsychotics, retaining the efficacy and profile of clozapine but without the concomitant adverse reactions, are needed. This article reviews new atypical antipsychotics, focusing especially upon those in late stage development, including SEROQUEL (ZENECA Pharmaceuticals), olanzapine (Eli Lilly), ORG 5222 (Organon), risperidone (Janssen Pharmaceutica), sertindole (Lundbeck), and ziprasidone (Pfizer).     

An investigation of the alpha1A-adrenergic receptor gene and antipsychotic-induced side-effects

Antipsychotic treatment is hampered by the induction of side-effects such as tardive dyskinesia (TD), weight gain, sedation and extrapyramidal side-effects (EPS). Identification of the factors related to their development would facilitate their avoidance and the improvement of antipsychotic treatment. It has been hypothesised that genetic variants in drug targeted receptors may contribute to the development of side-effects. In this study, we have investigated the possible influence of genetic variants (-563-C/T, -4155-G/C and -4884-A/G) of the alpha(1A)-adrenergic receptor, an important target of atypical antipsychotic drugs, and development of side-effects after antipsychotic medication in a sample of N = 427 US Caucasian patients. We found several marginal associations (p < 0.05) between alpha(1A)-adrenergic genetic variants and antipsychotic-induced side-effects which did not reach statistical significance after corrections for multiple analyses. These results do not support a major role of alpha(1A)-adrenergic genetic variants in obesity and other side-effects observed after prolonged treatment with antipsychotic medications.     

Comparison of methods to detect side-effect on clinical application of chloranolol,a beta-adrenergic receptor inhibitor

Summary The incidence of side-effects on administration of chloranolol (Tobanum^®), a beta-adrenergic receptor blocking drug, to 2066 patients with hypertension, angina pectoris or arrhythmias was measured by three different methods. In 600 patients in an efficacy trial (Group 1) both spontaneously reported complaints and objective signs were tabulated. A side effect — directed method, utilising a questionnaire containing a list of possible side-effects was also used, with the questionnaire being completed by the physician. 35 questions referred to anticipated and other side-effects. The trial was performed in two groups: in 537 patients a placebo was also given (Group 2), and in another set of 929 patients (Group 3) the questionnaire inquiry was performed uncontrolled, without placebo. All three groups were comparable in their distribution of sexes, ages and diagnoses, the mean daily dose of chloranolol its use alone or in combination, and in a similar duration of treatment. 55% of all patients received chloranolol therapy for a period of more than 3 months. The ratio of in- and outpatients was 1:5. The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol. The incidence was also unaffected whether chloranolol was used alone or in combination. The number of side-effects differed markedly between the three groups, their ratio was 1:10:24 in Groups 1, 2 and 3. Two-thirds of the side-effects subsided spontaneously within 1 month of their onset. The duration of the side-effects varied according to their character: cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring. The appreciable differences in incidence could be attributed to the methods of collection of the data. It has been stated that placebo controlled trials using a detailed questionnaire are the most suitable for estimating the incidence of side-effects; recording side-effects spontaneously reported by patients are insufficiently sensitive, and uncontrolled trials using a questionnaire have been shown to be too sensitive. The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen. In 100 patients (4.8%) therapy had to be suspended because of the side-effects of chloranolol (Group 1: 1%, Group 2: 6.20%, Group 3: 6.6%). Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents, including chloranolol.     

Self-reported side-effects of anti-retroviral treatment among IDUs: a 7-year longitudinal study (APROCO-COPILOTE COHORT ANRS CO-8)

The introduction of potent anti-retroviral treatment (ART) has transformed HIV disease into a chronic condition with the prospect, for the patient, of strict adherence to effective but life-long treatments. Within this framework, a major issue that can negatively affect adherence is the side-effects of the treatment. To date, studies documenting how individuals HIV-infected through drug injection (IDUs) experience ART-related side effects are sparse. Longitudinal data collected from the APROCO-COPILOTE cohort have been used to compare the experience of ART-related side-effects who have been HIV-infected via injecting drug use and non-IDU patients. A 20-item list was used to collect self-reported side-effects over a 7-year follow up period. Of 922 patients, 15% were IDUs. At any given visit, IDUs reported a significantly higher number of side-effects and had approximately twice the risk of reporting any side effect than non-IDUs. Most commonly reported side-effects were dry skin, fatigue, vomiting, bone troubles, insomnia. After adjustment for social conditions, depressive symptoms, use of sleeping pills and time since HIV diagnosis, IDUs reported experiencing significantly more side-effects than non-IDUs. Whether or not this is related to sensitivity to pain or to other comorbidities is difficult to establish. Further research is needed to understand how substitution treatment can mediate the relationship between exposure to opioids and side-effects. Providing appropriate care to reduce side-effects, thereby increasing adherence to ART in this population, remains a major challenge especially in those countries scaling up ART. Incorporating symptom management and improving access to analgesic medications within a model of comprehensive care for HIV-infected IDUs, could reduce the impact of drug-related and HIV-related harms and induce better long-term treatment outcomes and quality of life.