降脂药物的肝脏毒性及其防治策略研究进展

徐岩成; 方一杰; 阎澜; 姜远英; 曹永兵

doi:10.3969/j.issn.1006-0111.2014.06.004

降脂药物的肝脏毒性及其防治策略研究进展

doi: 10.3969/j.issn.1006-0111.2014.06.004

1.
福建中医药大学药学院, 福建福州 350108;第二军医大学药学院, 上海 200433
2.
第二军医大学药学院, 上海 200433;沈阳药科大学生命科学与生物制药学院, 辽宁沈阳 110016
3.
第二军医大学药学院, 上海 200433

Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

1.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China;School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang 110016, China
3.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China

摘要: 肝脏毒性是降血脂药物治疗常见的毒副作用之一,其发生机制尚不完全清楚,大多数降血脂药物的毒副作用都是剂量依赖性的,而且在停药后都有明显的缓解与改善。高龄以及慢性疾病等都是诱发降血脂药物肝脏毒性的潜在因素。降血脂药物的肝脏损伤治疗暂无统一规范,临床应对策略以停药、非特异性保肝和对症治疗为主。研发低毒性或具有保肝作用的降血脂药物,尤其是中药及中药制剂是一个具有良好前景的发展方向。
- 高血脂 /
- 药物 /
- 肝脏毒性
Abstract: Hepatotoxicity is one of the most common adverse reactions during anti-hyperlipidemia treatment. Mechanisms of anti-hyperlipidemia drug-induced hepatotoxicity are not clear yet, but most of the toxic reactions are dose-related hypersensitivity and could be released after drug withdrawal. It is accepted that clinical risk factors for the development of hepatotoxicity during anti-hyperlipidemia treatment are high age and chronic illnesses. Treatment of anti-hyperlipidemia drug-induced hepatotoxicity has not been unified and most of the treatments are non-specific and symptomatic. Researching hypotoxicity and hepatoprotection antihyperlipidemia drug, especially TCM and pharmaceutics will become a promising direction.
- hyperlipidemia /
- drug /
- hepatotoxicity

[1]	Grundy SM, Cleeman JI, Merz CN,et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines[J]. J Am Coll Cardiol,2004,44(3):720-732.
[2]	Argo CK, Loria P, Caldwell SH, et al. Statins in liver disease: a molehill, an iceberg, or neither?[J]. Hepatology, 2008,48(2):662-669.
[3]	Talbert RL. Safety issues with statin therapy[J]. J Am Pharm Assoc,2006;46(4):479-488.
[4]	Vuppalanchi R, Chalasani N. Statins for hyperlipidemia in patients with chronic liver disease: are they safe?[J]. Clin Gastroenterol Hepatol,2006,4(7):838-839.
[5]	李光明, 范建高. 慢性肝病患者应用他汀的安全性及疗效[J]. 中华肝脏病杂志,2010,18(5):328-330.
[6]	Cash J, Callender ME, McDougall NI, et al. Statin safety and chronic liver disease[J]. Int J Clin Pract,2008,62(12): 1831-1835.
[7]	Gupta NK, Lewis JH. Review article: the use of potentially hepatotoxic drugs in patients with liver disease[J]. Aliment Pharmacol Ther,2008,28(9): 1021-1041.
[8]	Jimenez-Alonso J, Osorio JM, Guierrez-Cabello F, et al. Atorvastatin-induced cholestatic hepatitis in a young woman with systemic lupus erythematosus[J]. A Arch Intern Med,1999,159(15):1811-1812.
[9]	de Castro ML, Hermo JA, Baz A, et al. Acute cholestatic hepatitis afteratorvastatin reintroduction[J]. Gastroenterol Hepatol,2006,29(1):21-24.
[10]	Nakad A, Bataille L, Hamoir V, et al. Atorvastatin-induced acute hepatitis with absence of cross-toxicity with simvastatin[J]. Lancet,1999,353(9166):1763-1764.
[11]	Gershovich OE, Lyman AE. Liver function test abnormalities and pruritis in a patient treated with atorvastatin: case report and review of the literature[J]. Pharmacotherapy,2004,24(1):150-154.
[12]	Grimbert S, Pessayre D, Degott C, et al. Acute hepatitis induced by HMG-CoA reductase inhibitor, lovastatin[J]. Dig Dis Sci,1994,39(9):2032-2033.
[13]	Vuppalanchi R, Teal E. Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes[J]. Am J Med Sci,2005,329(2):62-65.
[14]	Ricaurte B, Guirguis A, Taylor HC, et al. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity[J]. Ann Pharmacother,2006,40(4):753-757.
[15]	Kanathur N, Mathai MG, Byrd RP Jr, et al. Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis[J]. Tenn Med,2001,94(9):339-341.
[16]	Caldwell SH, Hespenheide EE, von Borstel RW. Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin[J]. Dig Dis Sci,2001,46(2):376-378.
[17]	Ashar U, Desai D, Bhaduri A. Flutamide-induced hepatotoxicity with possible potentiation by simvastatin[J]. J Assoc Physicians India,2003,51(1):75-77.
[18]	Cornwell PD, De Souza AT, Ulrich RG. Profiling of hepatic gene expression in rats treated with fibric acid analogs[J]. Mutat Res,2004,549(12):131-145.
[19]	Alsheikh-Ali AA, Kuvin JT, Karas RH. Risk of adverse events with fibrates[J]. Am J Cardiol,2004,94(7):935-938.
[20]	Grubisic-Cabo F, Vrdoljak E. Drug-induced hepatitis in a patient with malignant melanoma treated with interferon alfa 2b adjuvantly who had been administered gemfibrozil in therapy[J]. Med Oncol,2006,23(1):121-124.
[21]	Vogt A, Kassner U, Hostalek U, et al. NAUTILUS Study Group. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study[J]. Curr Med Res Opin,2006,22(2):417-425.
[22]	Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin[J]. JAMA,1990,264(2):241-243.
[23]	Moon YS, Kashyap ML. Niacin extended-release/lovastatin: combination therapy for lipid disorders[J]. Expert Opin Pharmacother,2002,3(12):1763-1771.
[24]	Coppola A, Brady PG, Nord HJ. Niacin-induced hepatotoxicity: unusual presentations[J]. South Med J,1994,87(1):30-32.
[25]	McKenney J. Niacin for dyslipidemia: considerations in product selection[J]. Am J Health Syst Pharm,2003,60(10):995-1005.
[26]	Stolk MF, Becx MC, Kuypers KC, et al. Severe hepatic side effects of ezetimibe[J]. Clin Gastroenterol Hepatol,2006,4(7):908-911.
[27]	Cruz-Fernandez JM, Bedarida GV, Adgey J, et al. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease[J]. Int J Clin Pract,2005,59(6):619-627.
[28]	Armani A, Toth PP. Colesevelam hydrochloride in the management of dyslipidemia[J]. Expert Rev Cardiovasc Ther,2006,4(3):283-291.
[29]	Sirmans SM, Beck JK, Banh HL, et al. Colestipol-induced hepatotoxicity[J]. Pharmacotherapy,2001,21(4):513-516.
[30]	Graf D, Kohlmann C, Haselow K, et al. Bile acids inhibit interleukin-6 signaling via gp130 receptor-dependent and independent pathways in rat liver[J]. Hepatology,2006,44(5):1206-1217.
[31]	Brewer HB Jr. High-density lipoprotein: a new potential therapeutic target for the prevention of cardiovascular disease[J]. Arterioscler Thromb Vasc Biol,2004,24:387-391.
[32]	FDA Statement: Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety[R].2006.
[33]	彭颂兴, 黎玉容. 药物性肝损伤的病因与临床分析[J]. 临床医药实践,2012,21(8):586-587.
[34]	Kar kiner A,Temir G,Utku M,et al.The efficacy of nonoperative management in childhood blunt hepatic trauma[J]. Ulus Travma Derg,2005,11(2):128-133.
[35]	王慧铭, 夏道宗, 夏明,等. 香菇多糖降血脂作用及其机制的研究[J]. 浙江中西医结合杂志,2005,15(10):599-602.
[36]	狄建彬,顾振纶,赵笑东,等. 姜黄素防治大鼠高脂性脂肪肝的研究[J]. 中草药,2010,41(8):1322-1326.
[37]	段玉梅,单松波. 降血脂药物开发应用新进展[J]. 黑龙江医药,2004,17(6):449-451.

[1]	宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅. 帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
[2]	张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英. 二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062
[3]	夏哲炜, 曾垣烨, 朱海菲, 李育, 陈啸飞. 核磁共振磷谱法测定磷酸氢钙咀嚼片中药物含量 . 药学实践与服务, 2024, 42(9): 399-401, 406. doi: 10.12206/j.issn.2097-2024.202404063
[4]	孙丹倪, 黄勇, 张嘉宝, 王培. 代谢相关脂肪性肝病的无创诊断与药物治疗 . 药学实践与服务, 2024, 42(10): 411-418. doi: 10.12206/j.issn.2097-2024.202403049
[5]	陈怡君, 王卓, 何苗, 张宇, 田泾. 泌尿系统碎石术抗菌药物预防使用合理管控实践 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402034
[6]	张修平, 田家盛, 王道鑫, 李佳鑫, 王品, 缪朝玉. MT-1207对血糖、血脂和动脉粥样硬化的作用 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202306011
[7]	张岩, 李炎君, 刘家荟, 邓娇, 原苑, 张敬一. 药物性肝损伤不良反应分析 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404034
[8]	张元林, 宋凯, 孙蕊, 舒飞, 舒丽芯, 杨樟卫. 基于真实世界数据的药物利用研究综述 . 药学实践与服务, 2024, 42(6): 238-243. doi: 10.12206/j.issn.2097-2024.202312010

点击查看大图

计量

文章访问数: 2770
HTML全文浏览量: 313
PDF下载量: 238
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

降脂药物的肝脏毒性及其防治策略研究进展

doi: 10.3969/j.issn.1006-0111.2014.06.004

Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

计量

降脂药物的肝脏毒性及其防治策略研究进展

doi: 10.3969/j.issn.1006-0111.2014.06.004

1. 福建中医药大学药学院, 福建福州 350108;第二军医大学药学院, 上海 200433

2. 第二军医大学药学院, 上海 200433;沈阳药科大学生命科学与生物制药学院, 辽宁沈阳 110016

3. 第二军医大学药学院, 上海 200433

English Abstract

Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

全文HTML

目录

留言板

降脂药物的肝脏毒性及其防治策略研究进展

doi: 10.3969/j.issn.1006-0111.2014.06.004

Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

计量

出版历程

降脂药物的肝脏毒性及其防治策略研究进展

doi: 10.3969/j.issn.1006-0111.2014.06.004

1. 福建中医药大学药学院, 福建 福州 350108;第二军医大学药学院, 上海 200433 2. 第二军医大学药学院, 上海 200433;沈阳药科大学生命科学与生物制药学院, 辽宁 沈阳 110016 3. 第二军医大学药学院, 上海 200433

English Abstract

Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

全文HTML

目录

1. 福建中医药大学药学院, 福建福州 350108;第二军医大学药学院, 上海 200433

2. 第二军医大学药学院, 上海 200433;沈阳药科大学生命科学与生物制药学院, 辽宁沈阳 110016

3. 第二军医大学药学院, 上海 200433