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[烟酸:一种被不公正忽视的药物]

[Nicotinic acid: an unjustly neglected remedy].

作者信息

Zák A, Zeman M, Vecka M, Tvrzická E

机构信息

IV. interní klinika 1. LF UK a VFN, Praha.

出版信息

Cas Lek Cesk. 2006;145(11):825-31.

Abstract

In human organism, the administration of nicotinic acid (niacin) leads to two types of effects. Within the physiological range (approximately = 20 mg/day), niacin has a vitamin-like role as pellagra preventing factor. The pharmacological dosage (approximately 0,5-4,5 g/day) substantially influences the plasma lipid and lipoprotein concentrations: decreases VLDL and LDL concentrations, changes the profile of LDL subfractions towards the larger particles as well as particles with lower density; it also profoundly increases the concentration of HDL-C in consequence of elevated concentration of HDL2 subfraction. Niacin as the only hypolipidemic drug reduces the lipoprotein(a) concentration. The hypolipidemic mechanism of niacin is different from that of other hypolipidemic drugs. On the basis of clinically controlled trials (both interventional epidemiological and angiographical), which satisfy the criteria of evidence-based medicine, it is possible to conclude that niacin falls unambiguously into the class of hypolipidemic drugs with proven beneficial effect not only on cardiovascular mortality and morbidity, but also on total mortality. Therefore, niacin should have an indisputable role in the pharmacological control of dyslipidemias. With the respect of basic mechanism (inhibition of the lipolysis of adipose tissue) with subsequent decrease in the concentration of free fatty acids and their flux to liver, niacin fulfils the criteria for pathogenetic treatment of atherogenic dyslipidemia in metabolic syndrome. The prerequisite condition for the niacin treatment is the respect for serious adverse effects and possible health hazards of administration (skin flush, hepatotoxicity and deterioration of glucose homeostasis). Recently discovered extrahypolipidemic effects of niacin (antioxidative activity, facilitation of reverse cholesterol transport, activation of PPAR-gamma, antithrombotic effects) and the introduction of drug forms with sustained (extended resp.) release of active compound (that minimizes the adverse effects and administration hazards) form together the basis for firm statement that the derivatives of nicotinic acid should be introduced to the clinical practice in Czech Republic.

摘要

在人体中,烟酸的施用会产生两种类型的效应。在生理范围内(约20毫克/天),烟酸作为预防糙皮病的因子具有类似维生素的作用。药理剂量(约0.5 - 4.5克/天)会显著影响血浆脂质和脂蛋白浓度:降低极低密度脂蛋白(VLDL)和低密度脂蛋白(LDL)浓度,使LDL亚组分的分布向更大颗粒以及更低密度颗粒转变;还会因高密度脂蛋白2(HDL2)亚组分浓度升高而显著提高高密度脂蛋白胆固醇(HDL - C)的浓度。烟酸是唯一能降低脂蛋白(a)浓度的降血脂药物。烟酸的降血脂机制与其他降血脂药物不同。基于符合循证医学标准的临床对照试验(包括干预性流行病学试验和血管造影试验),可以明确得出结论,烟酸无疑属于一类已证实不仅对心血管疾病死亡率和发病率,而且对总死亡率都有有益作用的降血脂药物。因此,烟酸在血脂异常的药物控制中应具有无可争议的作用。就基本机制(抑制脂肪组织的脂解作用,随后降低游离脂肪酸浓度及其向肝脏的通量)而言,烟酸符合代谢综合征中致动脉粥样硬化血脂异常的病因治疗标准。烟酸治疗的前提条件是要注意其严重的不良反应以及给药可能带来的健康危害(皮肤潮红、肝毒性和葡萄糖稳态恶化)。最近发现的烟酸的非降血脂作用(抗氧化活性、促进胆固醇逆向转运、激活过氧化物酶体增殖物激活受体γ(PPAR - γ)、抗血栓形成作用)以及引入活性化合物持续(延长释放)释放的药物剂型(可将不良反应和给药危害降至最低),共同构成了在捷克共和国将烟酸衍生物引入临床实践的确切依据。

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