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乙酰水杨酸、安乃近及其组合的抗血小板作用——体外和体内比较

Antiplatelet effect of acetylsalicylic acid, metamizole and their combination - in vitro and in vivo comparisons.

作者信息

Papp J, Sandor B, Vamos Z, Botor D, Toth A, Rabai M, Kenyeres P, Cseplo P, Juricskay I, Mezosi E, Koller A, Toth K

机构信息

1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.

Department of Pathophysiology and Gerontology, School of Medicine, University of Pecs, Pecs, Hungary Hungarian National Ambulance Service, Pecs, Hungary.

出版信息

Clin Hemorheol Microcirc. 2014;56(1):1-12. doi: 10.3233/CH-2012-1636.

Abstract

BACKGROUND

Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug.

OBJECTIVES

We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs.

METHODS

In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry.

RESULTS

Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group.

CONCLUSION

Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.

摘要

背景

乙酰水杨酸(ASA)在心血管疾病的治疗和预防中发挥着重要作用。安乃近(MET)是一种解热镇痛药,不作为抗血小板药物使用。

目的

我们旨在研究MET的抗血小板作用以及药物之间可能的相互作用。

方法

在我们的体外研究中,将不同浓度的ASA和MET溶液加入血液中。为了研究相互作用,将MET和ASA一起加入。在我们的体内交叉研究中,静脉注射MET、口服ASA或两种药物同时给药。通过光学聚集法测定肾上腺素和二磷酸腺苷诱导的血小板聚集。

结果

在体外,所有ASA和MET浓度下,肾上腺素诱导的聚集均被完全抑制。较低的、无效浓度的MET可阻止ASA的抗血小板作用。当使用更高浓度的ASA或先加入ASA时,抑制作用完全恢复。我们的体内研究表明,在MET组中,抑制作用迅速出现,一天后无抑制作用。在ASA组中,血小板聚集缓慢下降,但72小时后仍有显著抑制作用。联合治疗显示出与MET组相似的变化。

结论

MET和ASA的抗血小板作用在体外无显著差异。这些观察结果可能表明两种药物之间存在竞争性相互作用。体内实验表明,静脉注射MET是一种有效的抗血小板药物,当不能口服ASA时,可被视为一种治疗选择。

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