抗菌药物致儿童血小板减少症的真实世界研究

目的 基于10年真实世界数据探索不同品类抗菌药物所致儿童药源性血小板减少症(drug-induced thrombocytopenia,DIT)的发生率及血小板计数下降特征。方法 采用回顾性队列研究方法,选取2013年1月—2022年12月厦门大学附属妇女儿童医院(厦门市妇幼保健院)使用抗菌药物的住院患儿(98 301例次),基于中国医院药物警戒系统(Chinese Hospital Pharmacovigilance System,CHPS)筛选其中发生DIT的例次。以不同抗菌药物品类为暴露分组,比较不同分组DIT发生率、血小板计数开始下降时间、血小板计数下降至最低点时间以及严重程度的差异。结果 所有品类抗菌药物中,DIT发生率前3位为喹诺酮类(19.61‰)、碳青霉烯类(16.59‰)及糖肽类(14.34‰)。碳青霉烯类引起血小板计数开始下降的时间最短[0.59(0.18,1.27) d],而硝基咪唑类时间最长[2.71(0.80,4.06) d]。血小板计数下降至最低点不同分组时间类似,但糖肽类和硝基咪唑类严重不良反应占比较高(>28%)。结论 儿童DIT为喹诺酮类、碳青霉烯类以及糖肽类抗菌药物的常见不良反应。不同品类抗菌药物血小板计数下降时间特征不同,将其转化为CHPS触发规则嵌入日常诊疗,对DIT的预防具有重要意义。     

Drug-induced immune thrombocytopenia.

Thrombocytopenia can have several causes, including the use of certain drugs. The mechanism behind drug-induced thrombocytopenia is either a decrease in platelet production (bone marrow toxicity) or an increased destruction (immune-mediated thrombocytopenia). In addition, pseudothrombocytopenia, an in vitro effect, has to be distinguished from true drug-induced thrombocytopenia. This article reviews literature on drug-induced immune thrombocytopenia, with the exception of thrombo-haemorrhagic disorders such as thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia and thrombosis. A literature search in PubMed combined with a check of the reference lists of all the retrieved articles resulted in 108 articles relevant to the subject. The drug classes that are most often associated with drug-induced immune thrombocytopenia are cinchona alkaloid derivatives (quinine, quinidine), sulfonamides, NSAIDs, anticonvulsants, disease modifying antirheumatic drugs and diuretics. Several other drugs are occasionally described in case reports of thrombocytopenia; an updated review of these case reports can be found on the internet. A small number of epidemiological studies, differing largely in the methodology used, describe incidences in the magnitude of 10 cases per 1 000 000 inhabitants per year. No clear risk factors could be identified from these studies. The underlying mechanism of drug-induced immune thrombocytopenia is not completely clarified, but at least three different types of antibodies appear to play a role (hapten-dependent antibodies, drug-induced, platelet-reactive auto-antibodies and drug-dependent antibodies). Targets for drug-dependent antibodies are glycoproteins on the cell membrane of the platelets, such as glycoprotein (GP) Ib/IX and GPIIb/IIIa. Diagnosis of drug-induced immune thrombocytopenia may consist of identifying clinical symptoms (bruising, petechiae, bleeding), a careful evaluation of the causal relationship of the suspected causative drug, general laboratory investigation, such as total blood count and peripheral blood smear (to rule out pseudothrombocytopenia), and platelet serology tests. The sensitivity of these tests is dependent on factors such as the concentration of the drug in the test and the potential sensitisation of the patient by metabolites instead of the parent drug. Drug-induced immune thrombocytopenia can be treated by withholding the causative drug and, in severe cases associated with bleeding, by platelet transfusion. Although drug-induced thrombocytopenia is a relatively rare adverse drug reaction, its consequences may be severe. Therefore it is important to extend our knowledge on this subject. Future research should focus on the identification of potential risk factors, as well as the exact mechanism underlying drug-induced thrombocytopenia.     

104例住院患者药源性血小板减少症不良反应报告分析

目的：探讨住院患者药源性血小板减少症的规律和特点,为临床用药安全提供参考。方法：收集我院2012年1月-2018年10月年上报至国家药品不良反应监测平台的不良反应为药源性血小板减少症的病例,统计分析患者性别、年龄、原患疾病、可疑药物、临床表现、血小板计数、转归等相关因素。结果：共收集药源性血小板减少症104例,上报者以药师为主导,男女比例为2.35：1;涉及药品13类,46种,以抗肿瘤药物导致的血小板减少最多,40例（38.46%）;排名前3位药物的分别为低分子量肝素注射液（13例）、盐酸替罗非班注射液（9例）和注射用头孢哌酮钠舒巴坦钠（9例）;药源性血小板减少症发生的时间主要集中在2~7 d,共59例（56.73%）;严重血小板减少患者（0 ≤ PLT ≤ 5×10⁹/L）共14例,其中以盐酸替罗非班注射液最多（4例）;当PLT ≤ 20×10⁹/L时,患者发生出血概率明显高于PLT>20×10⁹/L（P<0.05）。COPD和联用≥ 2种致DITP药物是导致血小板减少患者出血的独立危险因素;针对血小板减少,临床上仅停药处理的有45例,其次治疗药物选择重组人白介素-11（25例）和输注血小板（21例）较多。结论：导致血小板减少的药物较多,临床上在应用这些药物时,要密切关注患者临床表现和监测血小板计数,确保用药安全。     

临床药师参与1例药源性重度血小板减少症的病例分析

目的 探讨急性心肌梗死患者经皮冠脉介入治疗术（PCI）后发生严重药源性血小板减少症（DITP）的相关药物。方法 临床药师对该例患者的用药情况进行分析,协助制定药源性血小板减少症的对症治疗方案并全程实施药学监护。结果 临床药师判定替罗非班为致血小板减少症的可疑药物。经对症治疗后,患者血小板逐渐恢复正常,病情缓解出院。结论 临床药师参与药源性血小板减少症患者的治疗与监护,可减少不良反应的发生,保障患者的用药安全。     

127例药物不良反应分析

目的:分析引起不良反应的药物临床表现及防治。方法:回顾性分析临床用药发生不良反应的情况。结果:127例不良反应中,心血管药物77例,占60.63％;其它为内分泌、激素药物22例,占17.32％;抗生素11例,占8.66％;抗癌药3例,占2.36%;其它14例,占11.02％。重症不良反应48例,占37.79％;死亡6例,占4.72％.结论:心血管药物可能引致较严重的不良反应。     

临床药师参与１例冠心病伴假性血小板减少症诊治病例分析

摘 要抗血小板药物在冠心病患者的治疗中十分重要,但伴血小板重度减少往往限制了抗血小板药物的应用。因此,临床中应及时准确辨别血小板减少的原因以指导临床抗血小板药物的应用。本案例中临床药师通过分析１例老年冠心病患者出现血小板减少的原因,排除药源性血小板减少,明确为ＥＤＴＡ依赖性假性血小板减少症,及时恢复抗血小板治疗,避免误停抗血小板药物而导致心血管不良事件的发生。     

Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs

Objective: To analyse drug-specific clinical characteristics and to investigate the possible influence of epidemiological and other factors on thrombocytopenia induced by selected non-cytotoxic drugs. Methods: A retrospective analysis of drug-induced thrombocytopenia reported to the Danish Committee on Adverse Drug Reactions. One-hundred and ninety-two cases induced by the most frequently reported drugs were included and analysed from data extracted from report forms and discharge summaries. Results: Pronounced drug-specific differences in the clinical appearance of thrombocytopenia were registered. Severe thrombocytopenia with haemorrhagic manifestations was reported following exposure to gold salts, non-steroid anti-inflammatory drugs, sulfonamide antibiotics, cinchona alkaloids and vaccines. Valproic acid-induced thrombocytopenia was dose-dependent. The differences were primarily determined by the drug itself and also by its usage pattern. No specific patient-related factor responsible for the heterogeneity of the clinical appearance of the adverse reaction was identified. Factors related to the physician, such as monitoring recommendations or level of attention towards the adverse reaction, seemed to be of little significance. Conclusion: The primary determinant of the clinical characteristics of thrombocytopenia induced by non-cytotoxic drugs is the offending drug.     

Research advances in drug-induced mitochondrial toxicity北大核心CSCD

Mitochondria perform important functions in energy production, balancing redox reactions, maintaining homeostasis, cell proliferation and apoptosis. Mitochondrial function is essential for human health. This is evidenced by a large number of diseases caused by mutations in the mitochondrial genome and the key role of mitochondrial dysfunction in many chronic diseases. A number of commonly used drugs can impair mitochondrial function, leading to adverse reactions or toxicity. Drug-induced mitochondrial dysfunction includes mitochondrial DNA damage, impaired mitochondrial respiration, increased production of reactive oxygen species and altered mitochondrial permeability. Based on data from experimental and clinical research, this review focuses on toxicity and mechanisms of common drugs such as analgesics, anticancer drugs and hypolipidemic drugs on mitochondria in order to provide guidance for clinical medication safety and new thoughts for analysis and screening of drug-induced mitochondrial toxicity. © 2017 Chinese Journal of Pharmacology and Toxicology. All rights reserved.     

抗菌药物致血小板减少文献分析

目的探讨抗菌药物致血小板减少发生的规律和特点,为临床安全用药提供参考。方法检索2000年1月—2016年12月中国学术期刊(光盘版)、万方数字化期刊全文库、中文科技期刊全文数据库(维普)等数据库报道的抗菌药物引起血小板减少的个案病例文献,并对其进行分析和讨论。结果青霉素类、头孢类、唑烷酮类、抗结核药和氟喹诺酮类药物发生较多,一般发生在用药后2周内(83.33%);临床表现上有仅血小板减少(38.89%)、血小板减少并皮肤瘀斑瘀点(37.30%)、血小板减少并口鼻出血(18.25%);在处理方法上43.65%患者仅给予了停药或换用其他药物处理,55.56%患者血小板计数在7 d内恢复。结论临床中应警惕抗菌药物导致血小板减少的发生,一旦发生应首选停药等措施进行处理,多数患者能在短时间内恢复,严重患者可给予糖皮质激素、人免疫球蛋白、输注血小板等治疗。     

Adverse reactions to drugs in general practice.

Of 817 patients in a general-practice survey of adverse reactions to drugs, 41% were thought to have "certainly" or "probably" had a reaction to the drug prescribed. Adverse effects on the gastrointestinal and central nervous systems were the most frequently reported, and 90% of reactions had occurred by the fourth day of treatment. More patients given drugs acting on the central nervous system and antihistamines reported reactions than those in other categories. A higher incidence of adverse drug effects is shown in this general-practice survey than in other, mainly hospital-based, surveys. Further intensive surveillance for adverse effects of drugs is recommended to provide additional information on the burden of drug-induced disease in the community.     

抗菌药物不良反应73例分析

目的:分析抗菌药物不良反应及其发生因素.方法:回顾性分析2018年4月至2020年9月南城县人民医院发生不良反应的110例临床资料,其中由抗菌药物引发的有73例,对其年龄、性别、发生不良反应的药物种类、累及系统及临床症状表现进行分析,并对抗菌药物不良反应产生的因素进行单因素和多因素分析.结果:使用青霉素类、头孢类、大环...     

肝素和利奈唑胺致冠心病PCI术后严重血小板减少1例分析

目的:关注肝素和利奈唑胺致血小板减少的不良反应及处理方法。方法:通过分析临床病例资料,探讨不良反应发生原因,从而提出临床工作中的药学监护事项。结果:该患者出现的严重血小板减少可能与肝素诱导的免疫反应和利奈唑胺有关,根据不良反应关联性评价,与该2药存在可能相关性。结论:对于术中、术后应用肝素又合并感染的老年患者,应加强监护,尤其是加强血小板计数的监测,如出现血小板减少,在排除其他药物作用的情况下,应高度怀疑肝素诱导的血小板减少症,给予正确处理。     

药物所致贫血性疾病的因素分析

目的:旨在回顾药物所致贫血性疾病的致病因素,以期为临床合理用药提供参考。方法:检索和采用中、外相关文献进行分析。结果与结论:药物所致的贫血性疾病发病机制各异,临床表现也不尽相同,临床应用中应充分了解药物的作用机制,合理应用,尽可能规避其不良反应。     

抗生素不合理应用常见现象分析及对策

目前抗生素在医院的使用中存在着很多不合理的地方,当务之急,要提高临床医生对合理使用抗菌药物的重视程度,促进抗菌药物的合理使用,同时要密切关注临床常用抗生素药的不良反应监测,以减少药品不良反应事件的发生,促进抗生素安全、有效、经济、合理地使用。     

小细胞肺癌患者化疗后的药学监护

目的:探讨临床药师如何实施药学监护.方法:以一位小细胞肺癌化疗后的患者为例,临床药师介入临床,参与药物治疗方案的制订,分析患者所用化疗药物、抗菌药、降血钙药物以及升血小板药物的综合应用,并对患者的治疗过程进行跟踪监测,对药物治疗效果及不良反应进行综合评估.结果:在临床医师的治疗及临床药师的药学监护下,患者的各项指标(化疗后的中性粒细胞比例、WBC计数、T、Plt等)趋于正常,可继续完成化疗疗程.结论:临床药师的介入使药物治疗更趋合理,在达到治疗目标的同时,减少了药物的不良反应,有利于提高临床的药物治疗水平.     

Evaluation and management of drug-induced thrombocytopenia in the acutely ill patient

The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug-induced thrombocytopenia. Such patients tend to have preexisting hemostatic defects that place them at additional risk of complications as a result of the drug-induced thrombocytopenia. The clinical challenge is to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis results. Drug-induced thrombocytopenic disorders can be classified into three mechanisms: bone marrow suppression, immune-mediated destruction, and platelet aggregation. Clinical characteristics, preliminary laboratory findings, and drug history specific to the mechanisms can assist clinicians in rapidly isolating the causative drug.     

回顾性分析本院抗生素等药物致肾毒性28例

目的 回顾性分析抗生素等药物所致的肾损害.方法 对本院2005年1月至2008年12月所发生的药物所致肾损害,进行归类统计分析和评价.结果 导致肾损害、急性肾衰竭、急性肾功能不全、急性间质性肾炎、慢性肾炎、肾病综合症的药物,主要包括:抗生素(13/28),NSAIDs(6/28)、抗肿瘤药物(2/28),抗高血压药(4/28)、其他(3/28);全部病例人院后,治愈10例,好转11例;转为慢性3例,自动出院3例,死亡1例.结论 要做到合理用药,早期干预,预防药源性肾损害的发生.     

Drug-induced phospholipidosis caused by combinations of common drugs in vitro

Drug-induced phospholipidosis (DIPLD), characterized by the accumulation of phospholipids within lysosomes, is suspected to impair lysosomal function and considered an adverse side effect of the administered medication. The increasing use of polypharmacy and the resultant elevated risks of adverse drug reactions raise the need to explore the effects of drug combinations with respect to their influence on side effects, such as DIPLD. In this study, we utilized an in vitro assay to investigate DIPLD that was caused by 24 commonly used drugs applied alone and in binary combinations with each other. Moreover, we attempted to predict the extent of DIPLD resulting from the combinations using a simple additive approach based on the increase in phospholipid levels caused by the single drugs. The results suggest that DIPLD, which was caused by combinations of drugs, occurs in an additive manner, depending on total drug concentration. Furthermore, we show that the extent of DIPLD can be predicted from the DIPLD caused by the single drugs. Thus, the simultaneous use of multiple drugs with PLD-inducing properties increases the event risk, as well as the severity of drug-induced phospholipidosis. The findings underline the importance of considering the DIPLD-inducing properties of drugs, especially in the context of polypharmacy.     

Drug-induced ocular disorders.

While beneficial therapeutically, almost all medications have untoward effects on various body tissues and functions, including the eye in which organ toxic reactions are readily detectable. Every part of the eye and all ocular functions could be affected adversely. In this review, we describe the most commonly recognized drug-induced ocular disorders, their specific clinical features, the medications that can cause the problem, the differential diagnosis and possible mechanisms of action, as well as guidelines for the management of the adverse reactions.The eyelids are most frequently involved in drug toxicity that commonly manifests as inflammation, hypersensitivity reaction or dermatitis. Drug-induced keratoconjunctival disorders present mainly as conjunctival hyperaemia (red eye), with or without superficial corneal involvement. Frequently, drug preservatives in topical ocular medications induce these adverse effects. Treatment of blepharospasm with Botox may lead to drooping of the eyelids and corneal exposure. Intraoperative floppy iris syndrome is a drug-induced reaction in patients treated with tamsulosin and who undergo cataract surgery. Certain sulfa-based drugs can cause swelling of the ciliary body and lead to the development of angle-closure glaucoma. In addition, adrenergic agents, certain beta(2)-adrenergic agonists and anticholinergic agents may induce pupillary dilation and precipitate angle-closure glaucoma in susceptible patients. Glucocorticoids administered systemically, topically or intravitreally are known to increase intraocular pressure, which can lead to the development of open-angle glaucoma in susceptible patients. This painless form of glaucoma has also been associated with the use of the anticancer agents docetaxel and paclitaxel. The toxic effects of systemic and topically applied drugs may manifest as cloudiness of the lens. Long-term use of glucocorticoids produces a characteristic posterior subcapsular cataract and, although the opacities may remain stationary or progress, they rarely regress upon drug withdrawal. Systemic administration of phenothiazines or busulfan induce cataractous changes in the anterior or posterior cortex, respectively. Many systemic drugs reach the retina through the vascular supply. Aminoquinolines induce a characteristic bull's eye maculopathy. Phenothiazines bind to melanin granules and can cause a severe phototoxic retinopathy. Typical tamoxifen retinopathy manifests as crystalline deposits in the inner retina. Some patients treated with retinoids have decreased night vision and abnormal dark-adaptation. Patients on long-term treatment with linezolid may develop an optic neuropathy (swollen or pale optic disc), symmetric painless decrease of visual acuity and colour vision, and bilateral visual field defects. A probable link exists between amiodarone and a bilateral optic neuropathy that is very similar to nonarteritic ischaemic optic neuropathy (NAION). The most common adverse effects of cGMP-specific phosphodiesterase type 5 inhibitors (erectile dysfunction drugs) are changes in colour perception, blurry vision and increased light sensitivity; recently these drugs have been also implicated in the development of NAION. A bilateral, retrobulbar optic neuropathy that manifests as loss of visual acuity or colour vision and visual field defect is associated with the use of ethambutol. Many different kinds of medications can cause similar ocular adverse reactions. Conversely, a single medication may affect more than one ocular structure and cause multiple, clinically recognizable disorders. Clinicians should be mindful of drug-induced ocular disorders, whether or not listed in product package inserts, and, if in doubt, consult with an ophthalmologist.     

Drug-induced urticaria: causes and clinical courses

The authors retrospectively reviewed medical records of patients who were diagnosed as having drug-induced urticaria at Siriraj Hospital of Mahidol University (Bangkok, Thailand) between October 2004 and April 2007. One hundred and forty-seven drugs were presumed as causing acute urticaria. Females were affected more commonly than males. The most frequent drug groups were antibiotics, followed by non-steroidal anti-inflammatory drugs (NSAIDs). The most common culprit drugs were ceftriaxone, cephalexin, amoxicillin and diclofenac, respectively. The median duration of onset and of clinical remission were 18 hours and 24 hours, respectively. Antibiotics were the most frequent causes of drug-induced urticaria, of which cephalosporins were the most common causative drugs. Oral NSAIDs significantly had the shortest median onset of urticaria. After discontinuing the culprit drugs, the reactions usually disappeared within a few days.