Aspirin Resistance: Clinical and Molecular Genetic Evaluation Techniques

Tanashyan, M. M.; Домашенко, М.А.; Raskurazhev, A. A.

doi:10.1134/s0362119717080126

Cited by 3 publications

(4 citation statements)

References 26 publications

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“…During this process ASA is converted to SA by deacetylation over the course of 15-20 min. The pharmacological action of the latter includes anti-inflammatory, antipyretic and analgesic effects [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

et al. 2020

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Purpose The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. Methods Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmissionaggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. Results Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. Conclusions SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. KeywordsCarnosine . Acetylsalicylic acid . Salicylic acid . Antioxidant . Antiplatelet action . Gastrointestinal ulcer Abbreviations ASA acetylsalicylic acid CL chemiluminescence COX cyclooxygenase HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LP lipoproteins LPO lipid peroxidation NBT nitroblue tetrazolium NSAIDs non-steroidal anti-inflammatory drugs

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Section: Introductionmentioning

confidence: 99%

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

et al. 2020

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“…However, there are differences between laboratory and clinical resistance. Laboratory resistance refers to the lack of residual platelet reactivity (RPR) blocking effect.Clinical resistance suggests the development of atherothrombotic events on the background of the ASA use [20,21,22].…”

Section: R E S U L T S a N D Discussionmentioning

confidence: 99%

“…Possible causes of aspirin resistance associated with insufficient compliance to therapy, low bioavailability of drugs, inadequately prescribed dose, poor intestinal absorption, clinically significant interactions with other drugs, functional immaturity of platelets, smoking, hypercholesterolemia, hyperglycemia, obesity, stress, comorbid pathology, high levels of pro-inflammatory cytokines, which are an additional source of thromboxane TXA2 and other fac-tors have been widely discussed in the publications [14,20,21,22,24,49].…”

Section: Modifiable Factors Affecting Antiplatelet Therapy Responsive...mentioning

confidence: 99%

Factors influencing the effectiveness of antiplatelet therapy

Кантемирова¹,

Жидовинов²,

Абдуллаев³

et al. 2022

ArveMED

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In recent years, significant advances in the diagnosis and treatment of cardiovascular diseases have been achieved in the healthcare of most countries. However, among the causes of mortality in patients with coronary heart disease, arterial thrombosis takes one of the leading positions. Antiplatelet drugs are prescribed to prevent thrombotic complications, which can be used as mono- or two-component therapy. In case of atherosclerosis in arteries, acetyl-salicylic acid (ASA) or clopidogrel can be used as monotherapy; treatment of acute coronary syndrome (ACS) and percutaneous coronary interventions (PCI) required using of double antiplatelet therapy (DAT), including acetylsalicylic acid drugs together with one antiplatelet agent from the group of thienopyridine derivatives — blockers of P2Y12 platelet receptors (clopidogrel, ticagrelor, prasugrel). In patients with ACS who underwent primary PCI or thrombolysis followed by PCI, the duration of DAT is 12 months, and clopidogrel is the drug of choice [16, 30]. According to various literature sources about 20–40% of patients have low effectiveness of antiplatelet therapy, which can lead to thrombosis, stent thrombosis and thromboembolic complications. This review provides an analysis of modifiable and nonmodifiable factors contribution to the development of clinical and laboratory resistance of antiplatelet agents.

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“…В настоящее время нет четко сформулированного определения и алгоритма диагностики данного феномена, а частота его встречаемости представлена в чрезвычайно широких пределах (от 2% до 43%) [7], что в первую очередь связано с вариативностью используемых методик. Согласно литературным данным, различают два основных типа устойчивости к АСКистинный и ложный [8,9]. Необходимо отметить, что в предшествующие два десятилетия целый пласт исследовательских работ Научного центра неврологии был связан с раскрытием механизмов и путей преодоления аспиринорезистентности.…”

Section: Introductionunclassified

Monitoring of Aspirin Therapy in Patients with Cerebrovascular Pathology

Tanashyan

Raskurazhev

Kornilova

et al. 2021

Racionalʹnaâ farmakoterapiâ v kardiologii

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Aim. Evaluation of various methods for determining the effectiveness of aspirin therapy and aspirin resistance in patients with cerebrovascular disease (CVD) depending on the presence of type 2 diabetes mellitus (T2DM).Materials and methods. The prospective study included 78 patients with various manifestations of CVD. All patients received acetylsalicylic acid (ASA) 75 mg daily. Along with a comprehensive clinical examination, a laboratory assessment of platelet function with the usage of Born method with aggregometer, a detailed biochemical blood test (including the determination of the small subunit of low density lipoprotein [s-LDL]), as well as therapeutic drug monitoring of salicylates were performed on a gas chromatograph-mass spectrometer.Results. In 53% of cases, the absence or insufficiency of the effect of ASA on platelet aggregation was noted. Two subgroups were separately identified: with T2DM; (n=40) and without T2DM (n=38). Insufficient effect of the drug on platelet aggregation characteristics were observed in 65% of patients with T2DM and in 38% without T2DM. The differences were revealed between the groups in triglycerides, s-LDL, glycemic and glycated hemoglobin (p <0.05). In the group of patients with T2DM, the median ASA concentration was 0.01 [0; 0.32] μg/ml, and salicylic acid (SA)– 0.20 [0; 0.39] μg/ml, while in patients without T2DM higher values were noted: ASA 0.29 [0.15; 0.55] μg/ml, SA – 0.33 [0.05; 0.73] μg/ml. A decrease in the concentration of ASA was associated with an increase in the level of ADP-induced platelet aggregation. There was an increase in the levels of ADPand adrenaline-induced platelet aggregation with a decrease in the concentration of ASA (p=0.004) and SA (p=0.006). Therapeutic drug monitoring revealed a more significant decrease in ASA level in T2DM than in the comparison group (p=0.025).Conclusion. It is advisable to monitor aspirin therapy both with the assessment of platelet aggregation and with therapeutic drug monitoring. The relationship between the level of ASA and SA in the blood plasma and the functional activity of platelets was confirmed. The presence of T2DM is associated with a decrease in the concentration of ASA and aspirin resistance detected in therapeutic drug monitoring.

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Aspirin Resistance: Clinical and Molecular Genetic Evaluation Techniques

Cited by 3 publications

References 26 publications

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

Factors influencing the effectiveness of antiplatelet therapy

Monitoring of Aspirin Therapy in Patients with Cerebrovascular Pathology

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