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[牛至与出血风险,关于一例病例]

[Origanum vulgare and hemorrhagic risk, about a case].

作者信息

Beghriche Imene, Belhachem Abdelaali, Hamidene Imene, Fendri Allaoua Hicham

机构信息

Laboratoire centrale de l'établissement hospitalier Didouche Mourad, Constantine, Algérie; Université constantine 3, faculté de médecine, Algérie.

Département de pharmacie, faculté de médecine Oran, Algérie.

出版信息

Ann Cardiol Angeiol (Paris). 2025 Feb;74(1):101856. doi: 10.1016/j.ancard.2024.101856. Epub 2025 Jan 9.

DOI:10.1016/j.ancard.2024.101856
PMID:39793412
Abstract

INTRODUCTION

The use of medicinal plants in Algeria is an ancestral practice that remains relevant today. The population relies on plants to treat various diseases and everyday ailments, which can be dangerous, especially when taking medication [1,2]. The interaction between plants and medication can lead to a modification of the plasma concentrations of the latter, which can impact its therapeutic effectiveness and be responsible for toxicity or therapeutic failure [1,2]. The interaction can also be pharmacodynamic, resulting in the potentiation of the effect or its antagonism. The risk is even higher when the medication has a narrow therapeutic range or presents high inter- or intra-individual variability, such as with vitamin K antagonist anticoagulants.

CLINICAL CASE

We report the case of patient B.Z., aged 77, who is suffering from complete atrial fibrillation (ACFA). The patient has been under antivitamin K (AVK) treatment with acenocoumarol for 8 years and has been followed at the central laboratory of Didouche Mourad Hospital since August 2019. The patient has been stable with an INR within the therapeutic target range of 2-3 for 4 years. She is compliant and adheres to the dietary regimen. The dosage of acenocoumarol is alternated between 1/2 tablet and 1/4 tablet. On September 6, 2023, during a routine check-up, the patient's INR was 6.42, and the PT was 17.9%. The recommendation was to stop AVK and perform a control the following day. The interview revealed that the patient had started taking an infusion of oregano (Origanum vulgare), and occasionally verbena, at a rate of one 200 ml cup per day for a week. On September 7, 2023, the INR decreased to 3.80 and the PT to 26.9%, so the recommendation was to resume AVK at a dosage of 1/4 tablet to 1/2 tablet, with discontinuation of the herbal tea intake and an INR check after 72 hours. On the fourth day after resuming the anticoagulant, the INR was 2.5. Despite being informed of the risk of interaction, the patient resumed taking the freshly picked oregano herbal tea from her garden. Given the patient's determination to continue her infusion, the recommendation was made to limit her intake, to prepare much more diluted infusions, and to reduce the dose of acenocoumarol to 1/4 tablet; this allowed the stabilization of the patient's INR. The last check-up was performed on April 7, 2024, with an INR value of 2.3.

RESULTS

Oregano, a plant from the Lamiaceae family, is used in herbal tea to treat a wide range of diseases, including joint pain, respiratory conditions, and digestive disorders. Similarly, verbena is also used to combat sleep disorders [2-4]. Origanum and verbena are both plants rich in polyphenols, as well as tannins and flavonoids. These substances are inhibitors of CYP 450, particularly CYP 2C9 and CYP 3A4, which are responsible for the metabolism of many drugs, including painkillers, antihypertensives, central nervous system drugs, and anticoagulants such as acenocoumarol. Origanum also exhibits anticoagulant activity due to its high content of carvacrol and thymol [4-6]. These two modes of interaction lead to an increase in the pharmacodynamic effect of acenocoumarol and, therefore, an increased risk of bleeding. This was the case for our patient, who saw her INR increase to more than twice the normal level, coinciding with the intake of oregano and verbena infusions, which normalized after their discontinuation.

CONCLUSION

Oregano is an endemic plant widely used in Algeria, whose anti-inflammatory properties are well established. However, its side effects, toxicity, and risk of interaction when combined with medications are less known. The interaction between oregano and AVK (acenocoumarol) exists and deserves to be recognized and monitored, especially in a population with a traditional culture where the use of plants is common. This practice should be accompanied by national phytovigilance.

摘要

引言

在阿尔及利亚,使用药用植物是一种古老的做法,至今仍然盛行。民众依靠植物来治疗各种疾病和日常病痛,但这可能存在危险,尤其是在同时服用药物时[1,2]。植物与药物之间的相互作用可能会改变药物的血浆浓度,进而影响其治疗效果,并可能导致毒性反应或治疗失败[1,2]。这种相互作用也可能是药效学方面的,导致药效增强或拮抗。当药物的治疗窗较窄或个体间或个体内差异较大时,如维生素K拮抗剂类抗凝药,风险会更高。

临床病例

我们报告了77岁的B.Z.患者的病例,该患者患有完全性心房颤动(ACFA)。患者接受醋硝香豆素抗维生素K(AVK)治疗已8年,自2019年8月起在迪杜什·穆拉德医院中心实验室接受随访。患者4年来INR一直稳定在2 - 3的治疗目标范围内。她依从性良好,遵守饮食方案。醋硝香豆素的剂量在1/2片和1/4片之间交替。2023年9月6日,在一次常规检查中,患者的INR为6.42,PT为17.9%。建议停用AVK并在次日进行复查。询问得知患者已开始每天饮用一杯200毫升的牛至(Origanum vulgare) infusion,偶尔还饮用马鞭草,持续了一周。2023年9月7日,INR降至3.80,PT降至26.9%,因此建议以1/4片至1/2片的剂量恢复服用AVK,停止饮用花草茶,并在72小时后检查INR。恢复抗凝治疗后的第四天,INR为2.5。尽管已告知患者相互作用的风险,但患者仍继续饮用从自家花园采摘的新鲜牛至花草茶。鉴于患者坚持饮用的决心,建议限制其饮用量,冲泡得更稀释,并将醋硝香豆素剂量减至1/4片;这使得患者的INR得以稳定。最后一次检查于2024年4月7日进行,INR值为2.3。

结果

牛至是唇形科植物,用于花草茶中治疗多种疾病,包括关节疼痛、呼吸道疾病和消化系统疾病。同样,马鞭草也用于治疗睡眠障碍[2 - 4]。牛至和马鞭草都是富含多酚、单宁和黄酮类化合物的植物。这些物质是CYP 450的抑制剂,尤其是CYP 2C9和CYP 3A4,它们参与许多药物的代谢,包括止痛药、抗高血压药、中枢神经系统药物以及醋硝香豆素等抗凝药。牛至还因其高含量的香芹酚和百里香酚而具有抗凝活性[4 - 6]。这两种相互作用方式导致醋硝香豆素的药效学作用增强,因此出血风险增加。我们的患者就是如此,其INR增加到正常水平的两倍多,这与饮用牛至和马鞭草infusion同时发生,停用后恢复正常。

结论

牛至是阿尔及利亚广泛使用的本土植物,其抗炎特性已得到充分证实。然而,其副作用、毒性以及与药物联合使用时的相互作用风险却鲜为人知。牛至与AVK(醋硝香豆素)之间的相互作用确实存在,值得被认识和监测,尤其是在植物使用普遍的传统文化人群中。这种做法应伴随着国家植物药警戒。

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