The influence of metoclopramide on pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina pectoris receiving concomitant treatment with morphine — a protocol of a randomized trial

Introduction. Nowadays, due to the “morphine effect”, the screening of methods that provide quick and effective platelet inhibition with oral P2Y12 inhibitors administrated simultaneously with morphine in patients with acute coronary syndromes are extensively investigated by numerous scientists. Metoclopramide, which stimulates the motility of gastrointestinal tract, may become a potential method of overcoming the negative morphine effect. The present study was designed to demonstrate the influence of metoclopramide administration on the pharmacokinetic and pharmacodynamic profile of ticagrelor between patients with unstable angina pectoris treated with morphine and crushed ticagrelor. Methods/design. A study was designed as a phase IV, single-centre, randomized, investigator-initiated, parallel-group, open-label, interventional trial. Patients will be randomized in a 1:1 manner into two arms: 1) patients treated with a combination of crushed ticagrelor and morphine and 2) patients treated with a combination of crushed ticagrelor followed by morphine and metoclopramide. Blood sample collection will be scheduled directly before the administration of ticagrelor loading dose and 15, 30, 45, 60, 120, 180, 240, and 360 minutes after the loading dose. Pharmacokinetic and pharmacodynamic assessment of ticagrelor and its active metabolite will be evaluated in all pre-defined time points. Discussion. The current study is, to our knowledge, the first one to provide data on the influence of metoclopramide in patients with acute coronary syndromes, who received intravenous opioid analgesia. It is expected to contribute to the development of contemporary knowledge on the treatment of patients presenting with acute coronary syndromes, and should enable clinicians to implement strategies of quick platelet inhibition

The Importance of Platelets Response during Antiplatelet Treatment after Ischemic Stroke—Between Benefit and Risk: A Systematic Review

Ischemic stroke is a disease related to abnormal blood flow that leads to brain dysfunction. The early and late phases of the disease are distinguished. A distinction is made between the early and late stages of the disease, and the best effect in treating an ischemic stroke is usually achieved within the first hours after the onset of symptoms. This review looked at studies platelet activity monitoring studies to determine the risks and benefits of various approaches including antiplatelet therapy. A study was conducted on recently published literature based on PRISMA. This review includes 32 research articles directly addressing the importance of monitoring platelet function during antiplatelet therapy (dual or monotherapy) after ischemic stroke. In patients with transient ischemic attack or ischemic stroke, antiplatelet therapy can reduce the risk of stroke by 11–15%, assuming that patients respond well. Secondary prevention results are dependent on platelet reactivity, meaning that patients do not respond equally to antiplatelet therapy. It is very important that aspirin-resistant patients can benefit from the use of dual antiplatelet therapy. The individualized approach to secondary stroke prevention is to administer the most appropriate drug at the correct dose and apply the optimal therapeutic procedure to the individual patient

The Use of Total Thrombus Formation Analysis System as a Tool to Assess Platelet Function in Bleeding and Thrombosis Risk—A Systematic Review

Background. Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. Methods. An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. Conclusion. Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment

Enantioselective Bioreduction of Prochiral Pyrimidine Base Derivatives by Boni Protect Fungicide Containing Live Cells of Aureobasidium pullulans

The enzymatic enantioselective bioreduction of prochiral 1-substituted-5-methyl-3-(2-oxo-2-phenylethyl)pyrimidine-2,4(1H,3H)-diones to corresponding chiral alcohols by Boni Protect fungicide containing live cells of Aureobasidium pullulans was studied. The microbe-catalyzed reduction of bulky-bulky ketones provides enantiomerically pure products (96–99% ee). In the presence of A. pullulans (Aureobasidium pullulans), one of the enantiotopic hydrides of the dihydropyridine ring coenzyme is selectively transferred to the si sides of the prochiral carbonyl group to give secondary alcohols with R configuration. The reactions were performed under various conditions in order to optimize the procedure with respect to time, solvent, and temperature. The present methodology demonstrates an alternative green way for the synthesis of chiral alcohols in a simple, economical, and eco-friendly biotransformation

Unfavorable Dynamics of Platelet Reactivity during Clopidogrel Treatment Predict Severe Course and Poor Clinical Outcome of Ischemic Stroke

Background: Previous studies have revealed that high platelet reactivity while on clopidogrel may affect the severe course and worse prognosis of ischemic stroke. However, the above findings were based on a single measurement of platelet function. We aimed to investigate whether the dynamics of platelet reactivity over time would more accurately determine its actual impact on clinical outcome. Methods: We enrolled 74 ischemic stroke subjects, taking a dose of 75 mg a day of clopidogrel to this prospective, single-center, and observational study. The determination of platelet function was based on the impedance aggregometry 6–12 h after the first dose of clopidogrel and 48 h later. We defined a favorable dynamics of platelet reactivity as a decrease in values at least equal to the median obtained in the entire study. The clinical condition was assessed by the National Institutes of Health Stroke Scale on the first, third, and ninetieth days and the functional status by modified Rankin Scale, respectively. Results: A favorable dynamics of platelet reactivity was associated with the mild clinical condition and favorable functional status, both early and late. Early neurological deterioration was related to unfavorable dynamics of platelet reactivity over time. In multivariate regression models, we found that unfavorable dynamics of platelet reactivity, alone and combined with a high baseline value of platelet reactivity, is an independent predictor of a severe clinical condition, the risk of deterioration, and poor early and late prognosis. Conclusion: We highlighted that dynamics of platelet reactivity over time predict the clinical course and prognosis of stroke better than a single value

Exploring the Interplay of Uric Acid and Advanced Oxidation Protein Products Following Myocardial Infarction

Recent studies have underscored the potential elevation of Advanced Oxidation Protein Products (AOPP) and uric acid following myocardial infarction, suggesting their involvement in the development and progression of coronary artery disease and potentially influencing patient outcomes. This study focuses explicitly on examining uric acid and AOPP in the same patients to address the research gap in these biomarkers’ interplay. Recognizing the dual character of uric acid as both an antioxidant and a pro-oxidant, this study delves into its complex biological implications. An analysis was conducted on 40 patients who had experienced myocardial infarction. AOPP levels were quantified using absorbance at 340 nm. Results demonstrated significantly increased AOPP levels in myocardial infarction patients compared to healthy controls, especially in those with high serum uric acid. The serum uric acid and AOPP relationship exhibits a J-shaped curve, indicating a complex, multifactorial interaction. These findings offer new insights into the intricate relationship between serum uric acid and AOPP in myocardial infarction patients, underscoring the significance of these biomarkers in enhancing our understanding of clinical outcomes and informing targeted management strategies for coronary artery disease

Hypercoagulability as Measured by Thrombelastography May Be Associated with the Size of Acute Ischemic Infarct—A Pilot Study

Background: Thromboelastography (TEG®) measures coagulation function in venous blood. Previous studies have reported that this device providing an integrated data on dynamics of clot formation may be useful for predicting clinical outcome in ischemic stroke. We investigated whether a hypercoagulability detected by thrombelastography may be associated with larger size of acute ischemic infarct. Methods: We included 40 ischemic stroke subjects with large artery atherosclerosis or small-vessel disease to a cross-sectional pilot study. Thrombelastography parameters related to time of clot formation (R- reaction time, K-clot kinetics), clot growth and strengthening (angle-alpha and MA-maximum amplitude) and lysis (Ly30) were performed within first 24 h after the onset of stroke. A volume of ischemic infarct was assessed on the basis of diffusion-weighted imaging (DWI) sequence of magnetic resonance imaging. Results: In the entire group, we reported that subjects with a large ischemic focus (>2 cm3) had a higher diameter of a clot (measured as MA) than subjects with a small ischemic focus (p = 0.0168). In the large artery atherosclerosis subgroup, we showed a significant correlation between MA and size of acute infarct (R = 0.64, p = 0.0138), between angle (alpha) and size of acute infarct (R = 0.55, p = 0.0428) and stroke subjects with hypercoagulability (MA > 69 mm) had significantly higher probability of a larger size of acute ischemic focus compared to normalcoagulable subjects (5.45 cm3 vs. 1.35 cm3; p = 0.0298). In multivariate logistic regression hypercoagulability was a predictor of a large size of ischemic infarct (Odds ratio OR = 59.5; 95% confidence interval (CI) 1.08–3558.8; p = 0.0488). Conclusions: We emphasized that thrombelastography, based on the parameters related to clot strength, may have clinical utility to identify the risk of the extensive ischemic infarct

Unfavorable changes of platelet reactivity on clopidogrel therapy assessed by impedance aggregometry affect a larger volume of acute ischemic lesions in stroke

Background: High on-treatment platelet reactivity or its equivalent—resistance to the antiplatelet agent—significantly reduces the efficacy of the therapy, contributing to a negative impact on stroke course. Previous studies demonstrated that aspirin resistance is associated with a larger size of acute ischemic infarct. Due to the increasing use of clopidogrel in the secondary prevention of stroke, we aimed to assess the impact of clopidogrel resistance on the size and extent of ischemic lesions, both acute and chronic. Methods: This prospective, single-center and observational study involved 74 ischemic stroke subjects, treated with 75 mg of clopidogrel. We used impedance aggregometry to determine platelet reactivity 6–12 h after a dose of clopidogrel as a first assessment and 48 h later as the second measurement. A favorable dynamics of platelet reactivity over time was the decrease in the minimum value equal to the median in the entire study. The volume of acute ischemic infarct was estimated within 48 h after onset in diffusion-weighted imaging and fluid-attenuated inversion recovery sequences of magnetic resonance and the severity of chronic vascular lesions by Fazekas scale. Results: Subjects with mild severity of chronic vascular lesions (Fazekas 1) exhibited a significant decrease of platelet reactivity over time (p = 0.035). Dynamics of platelet re-activity over time differed between subjects with large, moderate, mild and insignificant size of acute ischemic lesion (Kruskall-Wallis H = 3.2576; p = 0.048). In multivariate regression models, we reported unfavorable dynamics of platelet reactivity alone and combined with a high initial value of platelet reactivity as independent predictors of higher risk of a significant ischemic infarct volume (OR 7.16 95%CI 1.69-30.31, p = 0.008 and 26.49 95%CI 1.88-372.4, p = 0.015, respectively). Conclusions: We emphasized that unfavorable dynamics of platelet reactivity over time during clopidogrel therapy in acute phase of stroke affect the volume of acute infarct and the severity of chronic vascular lesions