调血脂药致横纹肌溶解症79例的回顾性分析

目的:探讨调血脂药致横纹肌溶解症的一般规律及特点。方法:以"横纹肌溶解症"为关键词,对近10年"中国期刊全文数据库"收录的文献进行检索和查阅原文,并进行统计、分析。结果:79例横纹肌溶解症涉及贝特类、他汀类、血脂康、脂必妥等10种药物。其中绝大部分病例(68例,占86.08%)都发生在用药后2个月内,且普遍存在联合用药现象,50岁以上患多系统疾病的中老年人发生率较高(65例,占82.28%)。结论:调血脂药相关横纹肌溶解症与多种因素有关,严重者可致威胁生命的代谢紊乱和急性肾功能衰竭,甚至死亡。临床应引起足够重视,确保用药安全、有效。     

高血压联合用药要谨慎

(接上期) 四、高脂血症伴有脂质代谢异常者,不宜选β-受体阻滞药及利尿药.为了同时治疗不同类型的高脂血症,应禁止他汀类与吉非贝齐联用,如若联用可增加患肌病和横纹肌溶解的可能性,使肌酸磷酸激酶血浓度增高,产生肌球蛋白尿而致急性肾衰竭,严重的可导致死亡.ACEI降血压药不宜与他汀类降血脂药(洛伐他汀、辛伐他汀)、血脂康类联用,防止产生肌病和严重的高血钾症.     

2008–2013年他汀类药物致横纹肌溶解症文献分析

目的调查他汀类药物引起横纹肌溶解症的临床特征、发生原因及治疗措施.方法：以“他汀”、“横纹肌溶解”为检索词,检索PubMed、CNKI、VIP 数据库,对患者的一般情况、用药情况、横纹肌溶解症的临床表现、用药关联性、治疗与转归等进行分析.结果：共纳入54 篇文献,合计59 例患者.他汀类药物所致横纹肌溶解症多发生于70 岁以上患者.乏力、肌痛是他汀类药物致肌病的主要临床症状.辛伐他汀引起横纹肌溶解发病率最高,共35例（59.32%）.用药至发病最短时间为12 h,最长超过10 年,多数累计用药时间大于1 年.经过对症治疗后,45 例痊愈,11 例好转,3 例死亡.结论：密切观察应用他汀类药物患者的临床表现及生化指标检测结果,他汀类药物对高龄、合并用其他调脂药的患者可能会增加肌病发生的风险,易出现肾功能损害,一旦出现横纹肌溶解,应立即停药,给予血液净化、碱化尿液、保护肝肾功能等治疗.     

1例SLCO1B1*5等位基因携带者服用辛伐他汀致横纹肌溶解症的案例分析

目的：探求他汀类相关肌病发生特点及易感因素。方法：报告1例服用辛伐他汀导致横纹肌溶解症,并对患者进行SLCO1B1基因型检测。结果：高龄、性别、肾功能不全、联合用药及携带SLCO1B1*5等位基因可能为该患者发生横纹肌溶解症的主要原因。结论：他汀类药物应采取个体化用药,肌病高危患者宜采取低剂量,并严密监测,通过基因检测可对患者进行风险筛查。     

美国:他汀类与HIV或HVC蛋白酶抑制剂有相互作用

2012年3月,美国食品药品监督管理局(FDA)发布了有关人类免疫缺陷病毒(HIV)或丙型肝炎病毒(HCV)蛋白酶抑制剂与他汀类降胆固醇药之间的相互作用的最新建议。同时服用蛋白酶抑制剂和他汀类药物可能会使他汀类的血药浓度升高,增加肌肉损伤(肌病)的风险。最严重的肌病表现形式(横纹肌溶解症)可损伤肾脏,导致肾功能衰竭而危及生命。他汀类药物为处方药,这类药物结合饮食     

药物致高龄患者横纹肌溶解1例护理

他汀类降脂药具有调脂、预防心脑血管疾病的作用,近年在临床上的应用越来越广泛,但其药物不良反应的报道也不断增加,其中肝脏、肌损害是常见的严重不良反应.其肌损害表现为肌痛、肌炎和肌病,也可进展为少见但致命的横纹肌溶解症.横纹肌溶解症是指由于各种原因引起的横纹肌细胞的溶解、破坏和崩解,导致肌酸激酶、肌红蛋白等肌细胞内的成分进入细胞外液及血液循环,可引起内环境紊乱、急性肾功能衰竭等危及生命的并发症[1].有文献指出,单用他汀类药物引起横纹肌溶解的发生率为0.1％～0.5％,联合用药的发生率升高至0.5％～2.5％,常发生于合并多系统疾病的老年患者、慢性肾功能不全患者、糖尿病患者,女性略高于男性等[2].笔者近年工作中遇到1例药物致横纹肌溶解的病例,患者是高龄老年人,患有慢性肾功能不全、冠心病及脑梗死等多系统的疾病,同时长期服用多种药物,属于他汀类药物不良反应的易感人群.现将其护理体会报告如下.     

他汀类药物相关的急性横纹肌溶解症1例报告

他汀类药物由于疗效以及良好的安全性和耐受性成为高胆固醇血症的一线用药.该类药物有导致肌病甚至横纹肌溶解的潜在危险,罕见,但可致急性肾功能衰竭,甚至死亡.他汀类药物导致肌肉损害的分子以及生化机制尚不清楚,但对易患加以注意可减少风险.本报告1例他汀类药物相关的急性横纹肌溶解症.     

他汀类药物临床不良反应

1他汀类药物引起的肌病 2001年西力他汀因其致命性横纹肌溶解而从市场撤出,对他汀类药物在安全方面提出警告。据FDA与拜耳公司联合公告,在美国有31例、在其他国家有21例因服用西力他汀出现横纹肌溶解导致死亡,引起人们对他汀类药物和肌病的重视。应用他汀类药物治疗时引起较为特殊的不良反应,发生率较低约为0．1％-0．3％,包括肌痛、肌炎、横纹肌炎及横纹肌溶解所致的干扰正常的肌代谢。     

皮肌炎继发干燥综合征及横纹肌溶解症一例及文献复习

目的提高对皮肌炎继发干燥综合征及横纹肌溶解症的认识。方法报告1例临床罕见的皮肌炎继发干燥综合征及横纹肌溶解症病例并复习相关文献。结果患者为48岁女性,以皮疹、关节肿痛、四肢近端肌痛、肌无力为主要临床表现,肌酸激酶极度升高,血肌红蛋白、尿肌红蛋白明显高于正常,抗核抗体、抗SSA抗体、抗SSB抗体阳性,唾液流率、Schirmer试验异常,肌电图为肌源性损害。确诊为皮肌炎继发干燥综合征及横纹肌溶解症,经血液净化、激素、免疫抑制剂等治疗,肾功能保持在正常范围,临床症状改善,随诊半年血清肌酸激酶、血肌红蛋白、尿肌红蛋白等生化指标恢复正常。结论皮肌炎继发干燥综合征及横纹肌溶解症临床罕见,并且皮肌炎与横纹肌溶解症临床表现及部分实验室检查相似,容易把横纹肌溶解症与皮肌炎或多肌炎相混淆而漏诊;横纹肌溶解症合并多肌炎或皮肌炎时,容易出现急性肾功能衰竭,病情危重,临床上应予以重视。     

药物引起的横纹肌溶解

横纹肌溶解是指骨骼肌的分解,是导致急性肾功能衰竭的一个重要原因。许多药物可能引起横纹肌溶解,其中一些药物如他汀类可能直接损害肌肉,其他药物如苯丙胺类和鸦片则分别通过增加肌肉活性或通过引起昏迷、肌肉压迫以及肌肉坏死等间接地产生损害作用。严重高热的病人会发生异常的肌肉生化反应并在昏迷状态中发展成横纹肌溶解。１ 引言 药物通常对肌肉都有一定的损害作用。这在临床上可能表现为几乎不伴有肌无力的轻度肌痛、伴有严重肌无力的慢性肌病或横纹肌溶解。受损肌肉所释放的肌红蛋白有肾毒性,持续严重肌损伤会发展成急性肾功能衰…     

阿托伐他汀致不良反应24例文献分析

目的:了解阿托伐他汀致不良反应的情况,促进临床安全合理用药。方法:采用文献计量学方法,对国内公开报道的24例阿托伐他汀致不良反应病例进行总结性分析。结果:阿托伐他汀致单纯性横纹肌溶解症7例,横纹肌溶解并发肾功能衰竭1例,横纹肌溶解并发多器官功能衰竭1例,肌病3例;致肝功能异常6例;致血小板减少性紫癜2例;致过敏反应2例;致过敏性休克1例;致指关节疼痛1例。24例患者中,5例为行冠状动脉支架植入术患者,1例为低钾血症伴高血压和冠心病者,1例为冠状动脉综合征伴慢性肾功能不全者,其他均为冠心病、高胆固醇血症患者,超过60岁的16例(占66.67%),停药及相应治疗后22例(占91.67%)恢复正常,2例(占8.33%)死亡。结论:阿托伐他汀引发的肝功能异常、肌病等不良反应不容忽视。     

Statin-induced myopathies

Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. Rhabdomyolysis is the most severe adverse effect of statins, which may result in acute renal failure, disseminated intravascular coagulation and death. The exact pathophysiology of statin-induced myopathy is not fully known. Multiple pathophysiological mechanisms may contribute to statin myotoxicity. This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels.     

Statins and myotoxicity: a therapeutic limitation

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable approach to address the same at preclinical level. Although statin-associated myotoxicity affects compliance, quality of life of patient and discontinuation rate, yet the low incidence of myotoxicty including rhabdomyolysis and less severity of commonly occurring myopathy and myalgia do not raise doubts about the clinical efficacy and tolerability of statins. Medical management of myotoxicity seems to be pivotal for the proper compliance of patients with statin treatment. The appropriate and judicious use of drugs would substantially reduce the likelihood of developing clinically important myopathy.     

Statins and myotoxicity: a therapeutic limitation

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable approach to address the same at preclinical level. Although statin-associated myotoxicity affects compliance, quality of life of patient and discontinuation rate, yet the low incidence of myotoxicty including rhabdomyolysis and less severity of commonly occurring myopathy and myalgia do not raise doubts about the clinical efficacy and tolerability of statins. Medical management of myotoxicity seems to be pivotal for the proper compliance of patients with statin treatment. The appropriate and judicious use of drugs would substantially reduce the likelihood of developing clinically important myopathy.     

HMG-CoA reductase inhibitors and myotoxicity.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors specifically inhibit HMG-CoA reductase in the liver, thereby inhibiting the biosynthesis of cholesterol. These drugs significantly reduce plasma cholesterol level and long term treatment reduces morbidity and mortality associated with coronary heart disease. The tolerability of these drugs during long term administration is an important issue. Adverse reactions involving skeletal muscle are not uncommon, and sometimes serious adverse reactions involving skeletal muscle such as myopathy and rhabdomyolysis may occur, requiring discontinuation of the drug. Occasionally, arthralgia, alone or in association with myalgia, has been reported. In this article we review scientific data provided via Medline, adverse drug reaction case reports from the Swedish Drug Information System (SWEDIS) and the World Health Organization's International Drug Information System (INTDIS) database, focusing on HMG-CoA reductase inhibitor-related musculoskeletal system events. Cytochrome P450 (CYP) 3A4 is the main isoenzyme involved in the metabolic transformation of HMG-CoA reductase inhibitors. Individuals with both low hepatic and low gastrointestinal tract levels of CYP3A4 expression may be at in increased risk of myotoxicity due to potentially higher HMG-CoA reductase inhibitor plasma concentrations. The reported incidence of myotoxic reactions in patients treated with this drug class varies from 1 to 7% and varies between different agents. The risk of these serious adverse reactions is dose-dependent and may increase when HMG-CoA reductase inhibitors are prescribed concomitantly with drugs that inhibit their metabolism, such as itraconazole, cyclosporin, erythromycin and nefazodone. Electrolyte disturbances, infections, major trauma, hypoxia as well as drugs of abuse may increase the risk of myotoxicity. It is important that the potentially serious adverse reactions are recognised and correctly diagnosed so that the HMG-CoA reductase inhibitor may at once be withdrawn to prevent further muscular damage.     

HMG-CoA reductase inhibitors: assessing differences in drug interactions and safety profiles

OBJECTIVE: To review the cytochrome P450 system and associated metabolic differences between the HMG-CoA reductase inhibitors. DATA SOURCES: A MEDLINE search (1993-99) was conducted for English-language articles using key search terms including adverse drug reactions, cytochrome P450, drug metabolism, drug interactions, hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, myopathy, and rhabdomyolysis. STUDY SELECTION: Review articles, clinical trials, and case reports concerning HMG-CoA reductase inhibitor metabolism, drug interactions, and adverse drug reactions were evaluated. DATA EXTRACTION: By the author. No software or assistants were used to extract information from the chosen studies. DATA SYNTHESIS: The cytochrome P450 enzymes, which can be divided into families, subfamilies, and isoenzymes, act as a major catalyst for drug oxidation in the liver. CYP3A4 is a major enzyme, accounting for about 60% of drug metabolic capacity in the liver and 70% of such function in the intestine. Lovastatin, simvastatin, and atorvastatin are substrates of CYP3A4, whereas fluvastatin is metabolized by CYP2C9. Pravastatin is not extensively metabolized by either of these isoenzymes; rather, it is transported into hepatocytes by a sodium-independent, carrier-mediated uptake system that normally transports bile acids. Compared with other statins, pravastatin thus has a reduced potential for drug interactions with other substrates, inhibitors, or inducers of the CYP3A4 and CYP2C9 systems. CONCLUSION: Pharmacists must understand the functions of these enzymes to identify potential drug interactions, especially in high-risk patient populations, and to make appropriate therapeutic recommendations that prevent or minimize adverse clinical outcomes.