PDF(721 KB)
抗精神病药物的心血管副作用及其机制的研究进展
吴艳琴, 党瑞丽, 江沛, 李焕德, 唐密密, 蔡骅琳
中国医院药学杂志 ›› 2016, Vol. 36 ›› Issue (4) : 327-331.
PDF(721 KB)
PDF(721 KB)
抗精神病药物的心血管副作用及其机制的研究进展
Research progress of cardiovascular side effects and potential mechanisms of antipsychotic drugs
近年来,心血管疾病已成为精神障碍患者的主要死因,这引起了国内外学者的广泛关注。多数非典型抗精神病药都会导致显著的代谢不良反应,继而引发心血管疾病。随着抗精神药物的适应证和适应人群的不断扩大,抗精神病药物导致的心血管疾病的机制研究迫在眉睫。越来越多的研究表明,抗精神病药对外周及中枢神经的非特异性的药理作用导致了其心血管副作用,如体位性低血压、心动过速和室性心律失常等,其心血管副作用可能与肾上腺素能受体或胆碱能受体和hERG钾通道的阻断有关,也有可能与自主神经功能受损有关。本次综述旨在结合临床前和临床研究成果,分析并讨论抗精神病药物对心血管系统的直接或间接的影响以及不良反应发生的机制,进而全面了解抗精神病药物对心血管系统的副作用。
Cardiovascular diseases have been the major causes of death in patients with mental disorders in recent years. The majority of atypical antipsychotic drugs have significant metabolic side effects, which subsequently cause cardiovascular diseases. Through these years, use of antipsychotic drugs continues to expand into new indications and populations such as children and adolescents, but mechanisms of these antipsychotic-induced cardiovascular abnormalities have not been fully expounded. Studies show that the non-specific pharmacological actions of atypical antipsychotic drugs to central and peripheral nervous system may be responsible for its cardiovascular side effects, such as orthostatic hypotension, tachycardia and ventricular arrhythmias. It may also relate to blockade of adrenergic or cholinergic receptors and hERG channels, in addition to impaired autonomic function. In this review, we integrate both preclinical and clinical findings, aiming to discuss and analyze direct and indirect effects of antipsychotic drugs on cardiovascular system and their possible mechanisms of action.
抗精神病药物 / 心血管 / 自主神经 / 代谢 {{custom_keyword}} /
antipsychotic drug / cardiovascular / autonomic nerves / metabolism {{custom_keyword}} /
[1] Laursen TM, Munk-Olsen T, Vestergaard M.Life expectancy and cardiovascular mortality in persons with schizophrenia[J].Curr Opin Psychiatry, 2012, 25(2):83-88.
[2] Yuan HY, Liang HX, Liang GR,et al.Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice:A parallel controlled study[J].Curr Ther Res Clin Exp, 2008, 69(2):142-149.
[3] Scigliano G, Ronchetti G.Antipsychotic-induced metabolic and cardiovascular side effects in schizophrenia:a novel mechanistic hypothesis[J].Cns Drugs, 2013, 27(4):249-257.
[4] Linder JR, Sodhi SK, Haynes WG,et al.Effects of antipsychotic drugs on cardiovascular variability in participants with bipolar disorder[J].Hum Psychopharmacol, 2014, 29(2):145-151.
[5] Agelink MW, Majewski T, Wurthmann C,et al.Effects of newer atypical antipsychotics on autonomic neurocardiac function:a comparison between amisulpride, olanzapine, sertindole, and clozapine[J].J Clin Psychopharmacol, 2001, 21(1):8-13.
[6] Iwamoto Y, Kawanishi C, Kishida I,et al.Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia[J].BMC Psychiatry, 2012, 12:199.
[7] Leung JY, Barr AM, Procyshyn RM,et al.Cardiovascular side-effects of antipsychotic drugs:the role of the autonomic nervous system[J].Pharmacol Ther, 2012, 135(2):113-122.
[8] Elman I, Rott D, Green AI,et al.Effects of pharmacological doses of 2-deoxyglucose on plasma catecholamines and glucose levels in patients with schizophrenia[J].Psychopharmacology(Berl), 2004, 176(3-4):369-375.
[9] Cohen H, Loewenthal U, Matar M,et al.Association of autonomic dysfunction and clozapine. Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication[J].Br J Psychiatry, 2001, 179:167-171.
[10] Brauer R, Douglas I, Smeeth L.The association between antipsychotic agents and the risk of myocardial infarction:a systematic review[J].Br J Clin Pharmacol, 2011, 72(6):871-878.
[11] Leonard CE, Freeman CP, Newcomb CW,et al.Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death:Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States[J].J Clin Exp Cardiolog, 2013, Suppl 10(6):1-9.
[12] Hg K, Je F, Sg L.Thioridazine Hydrochloride(Mellaril):Its Effect On The Electrocardiogram And A Report Of Two Fatalities With Electrocardiographic Abnormalities[J].Can Med Assoc J, 1963, 89:546-554.
[13] Glassman AH, Bigger JJ.Antipsychotic drugs:prolonged QTc interval, torsade de pointes, and sudden death[J].Am J Psychiatry, 2001, 158(11):1774-1782.
[14] Salih ISM, Thanacoody RHK, McKay GA,et al.Comparison of the Effects of Thioridazine and Mesoridazine on the QT Interval in Healthy Adults After Single Oral Doses[J].Clinical Pharmacology & Therapeutics, 2007, 82(5):548-554.
[15] Manning JW.Mechanism of Cardiac Arrhythmias Induced By Diencephalic Stimulation[J].American J Physiology, 1962, 203(6):?.
[16] Wong CW, Wang CH.Left stellate stimulation increases left ventricular ejection fraction in patients with essential palmar hyperhidrosis[J].J Auton Nerv Syst, 1999, 78(1):64-67.
[17] Singh BN.Beta-Adrenergic blockers as antiarrhythmic and antifibrillatory compounds:an overview[J].J Cardiovasc Pharmacol Ther, 2005, 10 Suppl 1:S3-S14.
[18] Charbit B, Alvarez JC, Dasque E,et al.Droperidol and ondansetron-induced QT interval prolongation:a clinical drug interaction study[J].Anesthesiology, 2008, 109(2):206-212.
[19] Thanacoody RH, Daly AK, Reilly JG,et al.Factors affecting drug concentrations and QT interval during thioridazine therapy[J].Clin Pharmacol Ther, 2007, 82(5):555-565.
[20] Salih IS, Thanacoody RH, McKay GA,et al.Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses[J].Clin Pharmacol Ther, 2007, 82(5):548-554.
[21] Testai L, Cecchetti V, Sabatini S,et al.Effects of K openers on the QT prolongation induced by HERG-blocking drugs in guinea-pigs[J].J Pharm Pharmacol, 2010, 62(7):924-930.
[22] Bhatia MS, Gupta R, Dhawan J.Myocarditis after overdose of conventional antipsychotics[J].World J Biol Psychiatry, 2009, 10(4 Pt 2):606-608.
[23] Bush A, Burgess C.Fatal cardiomyopathy due to quetiapine.[J].New Zeal Med J, 2008, 121(1268):U2909.
[24] Brakoulias V, Bannan E, Cohen P,et al.Amisulpride and cardiomyopathy[J].Aust N Z J Psychiatry, 2005, 39(8):738.
[25] Williams DP, O'Donnell CJ, Maggs JL,et al.Bioactivation of clozapine by murine cardiac tissue in vivo and in vitro[J].Chem Res Toxicol, 2003, 16(10):1359-1364.
[26] Abdel-Wahab BA, Metwally ME.Clozapine-Induced Cardiotoxicity:Role of Oxidative Stress, Tumour Necrosis Factor Alpha and NF-kappabeta[J].Cardiovasc Toxicol, 2015, 15(4):355-365.
[27] Ishiyama S, Hiroe M, Nishikawa T,et al.Nitric oxide contributes to the progression of myocardial damage in experimental autoimmune myocarditis in rats[J].Circulation, 1997, 95(2):489-496.
[28] Mackin P.Cardiac side effects of psychiatric drugs[J].Hum Psychopharmacol, 2008, 23 Suppl 1:3-14.
[29] Mackin P.Cardiac side effects of psychiatric drugs[J].Human Psychopharmacology:Clinical and Experimental, 2008, 23(S1):S3-S14.
[30] Nourian Z, Mulvany MJ, Nielsen KB,et al.The antagonistic effect of antipsychotic drugs on a HEK293 cell line stably expressing human alpha1A1-adrenoceptors[J].Eur J Pharmacol, 2008, 596(1-3):32-40.
[31] Elman I, Goldstein DS, Green AI,et al.Effects of risperidone on the peripheral noradrenegic system in patients with schizophrenia:a comparison with clozapine and placebo[J].Neuropsychopharmacol, 2002, 27(2):293-300.
[32] Mizuno Y, Suzuki T, Nakagawa A,et al.Pharmacological Strategies to Counteract Antipsychotic-Induced Weight Gain and Metabolic Adverse Effects in Schizophrenia:A Systematic Review and Meta-analysis[J].Schizophrenia Bull, 2014, 40(6):1385-1403.
[33] Reynolds GP, Kirk SL.Metabolic side effects of antipsychotic drug treatment pharmacological mechanisms[J].Pharmacol Therapeut, 2010, 125(1):169-179.
[34] Boden R, Edman G, Reutfors J,et al.A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice[J].Neuropsychiatr Dis Treat, 2013, 9:371-377.
[35] Coccurello R, Moles A.Potential mechanisms of atypical antipsychotic-induced metabolic derangement:Clues for understanding obesity and novel drug design[J].Pharmacol Therapeut, 2010, 127(3):210-251.
[36] Canfran-Duque A, Casado ME, Pastor O,et al.Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro[J].The Journal of Lipid Research, 2013, 54(2):310-324.
[37] Ferno J, Vik-Mo AO, Jassim G,et al.Acute clozapine exposure in vivo induces lipid accumulation and marked sequential changes in the expression of SREBP, PPAR, and LXR target genes in rat liver[J].Psychopharmacology(Berl), 2009, 203(1):73-84.
[38] Dang R, Jiang P, Cai H,et al.Vitamin D deficiency exacerbates atypical antipsychotic-induced metabolic side effects in rats:involvement of the INSIG/SREBP pathway[J].Eur Neuropsychopharmacol, 2015, 25(8):1239-1247.
国家自然科学基金青年基金项目(编号:81401113)
/
| 〈 |
|
〉 |
