ABSTRACT
Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.
In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.
Subject(s)
Purinergic P2Y Receptor Agonists , Dual Anti-Platelet Therapy , Angina, Unstable , Myocardial Infarction , Prasugrel HydrochlorideABSTRACT
Resumen Los antiagregantes plaquetarios son medicamentos ampliamente utilizados para la prevención y tratamiento de patologías aterotrombóticas, como lo es el síndrome coronario agudo. A pesar de tener un efecto benéfico, no están exentos de ocasionar múltiples alteraciones a nivel sistémico, como lo es la disnea en pacientes sometidos a manejo con ticagrelor. Se expone el caso de un paciente de 66 años con antecedente de cardiopatía isquémico-hipertensiva, tabaquismo pesado y alergia al ácido acetilsalicílico (ASA), con requerimiento de 2 arteriografías coronarias, quien presenta disnea en reposo en menos de 24 horas posterior al inicio de manejo antiagregante tromboprofiláctico con ticagrelor, que resuelve de forma satisfactoria tras la suspensión del medicamento. Al ser un efecto secundario relativamente frecuente en el marco del uso del ticagrelor, se hace relevante revisar los hallazgos en la literatura actual sobre la aparición de disnea en pacientes tratados con dicho fármaco, para así tener en cuenta posibles recomendaciones acerca del manejo de la disnea asociada a ticagrelor, basadas en el conocimiento actual. MÉD.UIS.2022;35(1): 9-15.
Abstract Antiplatelet agents are widely used drugs for the prevention and treatment of atherothrombotic pathologies such as acute coronary syndrome, however, despite having a beneficial effect, they're not exempt from causing multiple systemic alterations, such as dyspnea in patients undergoing management with ticagrelor. We will now present the case of a 66-year-old patient with a history of hypertensive ischemic heart disease requiring 2 cardiac catheterizations, heavy smoking and allergic to Acetyl Salicylic Acid (ASA) who presented dyspnea at rest in less than 24 hours after the start of thromboprophylaxis management with ticagrelor, that resolves satisfactorily after discontinuation of the drug. Because it is a frequent side effect in the framework of the use of ticagrelor, it's relevant to review the current literature on the appearance of dyspnea in patients treated with ticagrelor, to highlight recommendations for the management of dyspnea associated with ticagrelor based on current knowledge. MÉD.UIS.2022;35(1): 9-15.
Subject(s)
Humans , Male , Aged , Dyspnea , Acute Coronary Syndrome , Ticagrelor , Platelet Aggregation Inhibitors , Drug-Related Side Effects and Adverse Reactions , Purinergic P2Y Receptor AntagonistsABSTRACT
Resumen: las enfermedades cardiovasculares, incluidas las afecciones del corazón, del cerebro y de los vasos sanguíneos en general, representan la primera causa de muerte a nivel mundial, con diecisiete millones y medio de muertes cada año. La prevención primaria y secundaria de las enfermedades aterotrombóticas, como el infarto agudo de miocardio, el accidente cerebrovascular y las enfermedades trombóticas, además de las medidas generales para el control de los factores de riesgo tales como la obesidad, el sedentarismo, el tabaquismo, la hipertensión arterial y la diabetes, se han centrado en el control de la agregación plaquetaria. El antiagregante plaquetario por excelencia o universal, sobre todo en la prevención primaria, es la aspirina y la terapia dual con la combinación de aspirina y un inhibidor del receptor plaquetario P2Y12, principalmente el clopidogrel, es usada en la prevención secundaria y en los casos de resistencia a la aspirina. En el momento, se dispone para uso clínico de seis inhibidores del receptor plaquetario P2Y12: la ticlopidina, el clopidogrel, el prasugrel, el ticagrelor, el cangrelor y el elinogrel. En este primer módulo, de dos que serán presentados, se abordará el uso de los inhibidores del receptor plaquetario P2Y12 en la práctica del día a día en la prevención primaria y secundaria de las enfermedades aterotrombóticas, enfocado en el análisis del papel de las plaquetas en la fisiopatología de la enfermedad aterotrombótica y la descripción de los seis inhibidores del receptor plaquetario P2Y12 disponibles ahora y en el futuro. En un segundo módulo se hará una aproximación al concepto de la resistencia a los inhibidores del receptor plaquetario P2Y12, su diagnóstico desde el punto de vista del laboratorio y las diferentes alternativas de manejo cuando se presenta resistencia a uno de estos medicamentos. (AU)
Abstract: Cardiovascular diseases, including in general heart diseases, brain, and blood vessels are the leading cause of death worldwide with 17.000.000 of deaths each year. Primary and secondary prevention of atherothrombotic diseases, as acute myocardial infarction, stroke, and thrombotic disorders, besides to the general measures for risk factors control such as obesity, sedentary lifestyle, smoke, high blood pressure, and diabetes, have focused on platelet aggregation control. The antiplatelet agent par excellence or universal, especially in primary prevention, is aspirin, and dual therapy with the combination of aspirin and a platelet receptor inhibitor P2Y12, with clopidogrel as the most used, for secondary prevention and in cases of aspirin resistance. Currently, six P2Y12 platelet receptor inhibitors are available for clinical use: ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor, and elinogrel. In this first of two modules, the use of P2Y12 receptor inhibitors in daily practice in the primary and secondary prevention of atherothrombotic diseases will be addressed focused on the analysis of the platelets role in atherothrombotic disease pathophysiology and description of the six P2Y12 platelet receptor inhibitors available now and in the future. In a second module, we will approach the concept of resistance to platelet P2Y12 receptor inhibitors, its diagnosis from the laboratory point of view and the different management alternatives when resistance to one of these drugs is present. (AU)
Subject(s)
Humans , Sexual VulnerabilityABSTRACT
Resumen: las enfermedades cardiovasculares, que comprenden las afecciones del corazón, del cerebro y de los vasos sanguíneos en general, representan la primera causa de muerte a nivel mundial con diecisiete millones y medio de muertes cada año, de los cuales una tercera parte se debe a eventos trombóticos. La antiagregación plaquetaria con diferentes agentes, incluidos los inhibidores del receptor plaquetario P2Y12, se ha convertido en la piedra angular de la prevención primaria y secundaria y del tratamiento de las enfermedades cardiovasculares, entre ellas el infarto agudo de miocardio, la apoplejía y las enfermedades trombóticas. Sin embargo, varios estudios de investigación han demostrado que algunos individuos presentan disminución en la respuesta in vivo a estas sustancias, la cual se expresa como resistencia. En el primer módulo se abordó el papel de las plaquetas en la enfermedad aterotrombótica y se describieron los seis inhibidores del receptor plaquetario P2Y12, disponibles para su uso clínico actual o a futuro: la ticlopidina, el clopidogrel, el prasugrel, el ticagrelor, el cangrelor y el elinogrel. En este segundo módulo se tratará el concepto de la resistencia a los inhibidores del receptor plaquetario P2Y12, en particular al clopidogrel, la etiología de la resistencia y el monitoreo de la antiagregación con inhibidores del receptor plaquetario P2Y12 mediante pruebas de función plaquetaria, como una manera de hacer una antiagregación personalizada; finalmente, se darán las pautas básicas para el manejo de la resistencia a los inhibidores del receptor plaquetario P2Y12. (AU)
Abstract: Cardiovascular diseases, including in general affections of heart, brain, and blood vessels, are the leading worldwide cause of death with seventeen millions of deaths annually and a third part of them are due to thrombotic events. Platelet antiaggregation with different agents, like inhibitors of the platelet receptor P2Y12, has become the cornerstone of primary and secondary prevention and for the treatment of cardiovascular diseases, as acute myocardial infarction, stroke, and thrombotic diseases. However, several research studies have shown a decrease in the in vivo response to these substances in some individuals, which is expressed as resistance. The first module addressed the role of platelets in atherothrombotic disease and described the six P2Y12 platelet receptor inhibitors available for current or future clinical use: ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor and elinogrel. In this second module, it will discuss the concept of resistance to P2Y12 platelet receptor inhibitors, particularly clopidogrel, the resistance etiology, and antiplatelet monitoring with inhibitors of P2Y12 platelet receptor by platelet function tests, as a way to make a «personalized antiaggregation¼. Finally, it will give the basic guidelines for the management of resistance to P2Y12 platelet receptor inhibitors. (AU)
Subject(s)
Humans , Sexual VulnerabilityABSTRACT
PURPOSE: To evaluate changes in the tear meniscus area and tear meniscus height over time in patients with dry eye syndrome, using anterior segment spectral-domain optical coherence tomography after the instillation of 3% diquafosol ophthalmic solution. METHODS: Sixty eyes from 30 patients with mild to moderate dry eye syndrome were included. Tear meniscus images acquired by anterior segment spectral-domain optical coherence tomography were analyzed using National Institutes of Health's image-analysis software (ImageJ 1.44p). Tear meniscus area and tear meniscus height were measured at baseline, 5 minutes, 10 minutes, and 30 minutes after instillation of a drop of diquafosol in one eye and normal saline in the other eye. Changes in ocular surface disease index score, tear film break-up time, corneal staining score by Oxford schema, and meibomian expressibility were also evaluated at baseline, and after 1 week and 1 month of a diquafosol daily regimen. RESULTS: Sixty eyes from 30 subjects (mean age, 29.3 years; 8 men and 22 women) were included. In eyes receiving diquafosol, tear volume was increased at 5 and 10 minutes compared with baseline. It was also higher than saline instilled eyes at 5, 10, and 30 minutes. Changes in tear volume with respect to baseline were not statistically different after the use of diquafosol for 1 month. Ocular surface disease index score, tear film break-up time, and Oxford cornea stain score were significantly improved after 1 week and 1 month of daily diquafosol instillation, but meibomian expressibility did not change. CONCLUSIONS: Topical diquafosol ophthalmic solution effectively increased tear volume for up to 30 minutes, compared to normal saline in patients with dry eye syndrome.
Subject(s)
Humans , Male , Academies and Institutes , Cornea , Dry Eye Syndromes , Ophthalmic Solutions , Purinergic P2Y Receptor Agonists , Tears , Tomography, Optical CoherenceABSTRACT
AIM: To explore the role of purinergic signaling mediated by ATP in the Alzheimer ’ s disease (AD)-related colon motility disorder and its related molecular mechanisms .METHODS:(1)Clinical trials:AD patients in our hospital were collected and studied .Radioimmunoassay was used for the determination of plasma motilin (MTL), cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and nitric oxide (NO), and high-performance liquid chroma-tography ( HPLC) was applied to test the level of adenosine triphosphate ( ATP) .The patients were assessed by neuropsy-chology and scored accordingly .( 2 ) In animal experiments , AD mice received Morris water maze test , and the spatial learning and memory function were evaluated .The plasma levels of MTL , CCK, VIP and NO were examined by radioimmu-noassay , and the level of ATP was measured by HPLC .Choline acetyltransferase ( ChAT ) , VIP, nitric oxide synthase ( NOS) and ATP synthase were detected by immunohistochemistry .Western blot and immunohistochemistry were used to detect the expression of P2Y receptor.(3) In vitro, organ bath was applied to observe the effect of α,β-methylene ATP (α,β-MeATP), an agonist of P2Y receptor, on both spontaneous and electrically evoked contraction of colonic smooth muscle strip, and the technique of intracellular microelectrode was applied to observe the effect of α,β-MeATP on the membrane potential of colonic smooth muscle cells .RESULTS:Compared with control group , the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed.Mini-Mental State Examination (MMSE) score was decreased (P<0.05), Alzheimer’s Disease Assess-ment Scale-Cognitive Subscale (ADAS-Cog) score, Neuropsychiatric Inventory (NPI) score and Alzheimer’s Disease Co-operative Study-Activities of Daily Living Scale ( ADCS-ADL ) were all increased as compared with control group ( P <0.01).The 4~6 d escape latency of APP/PS1 AD mice was significantly prolonged (P<0.05), and the space explora-tion ability distinctly reduced (P<0.05).In AD mice, the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed .The protein expres-sion of colonic ATP synthase was significantly increased (P<0.05), but the expression of ChAT, VIP and NOS was not changed.The expression of P2Y receptor was increased (P<0.01).The results of in vitro experiment displayed that α,β-MeATP, from 20 μmol/L to 100 μmol/L, inhibited the spontaneous contraction of colonic smooth muscle strip in the nor-mal mice and AD mice ( P<0.05 or P<0.01 ) , and this inhibition was reversed by Na +channel inhibitor tetrodotoxin (TTX) (P<0.05 or P<0.01).In addition, the effect of α,β-MeATP at 100μmol/L on the AD mice was more obvious than that on the normal mice (P<0.05), and this inhibition was also antagonized by TTX (P<0.05 or P<0.01), pro-minent in AD group as compared with control group (P<0.05).In 10 Hz electrically evoked contraction of colonic smooth muscle strip,α,β-MeATP inhibited both the normal and AD mice (P<0.05 or P<0.01), while the inhibition was more obvious in the AD mice at the concentration of 40μmol/L or 100μmol/L (P<0.05 or P<0.01).CONCLUSION:AD patients and AD mice are accompanied by decreased MTL and CCK levels , and enhanced NO level , thus inducing colonic motor dysfunction along with AD .Meanwhile, ATP in plasma, purinergic neurons , and P2Y receptor expression are in-creased in the AD mice .Purinergic signaling mediated by ATP inhibits colonic smooth muscle strip contraction and further paralyzes the colonic movement function in AD .
ABSTRACT
The contractile and diastolic function of smooth muscle cells (SMCs) is closely related to penile erection and erectile dysfunction (ED). In addition to nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), sulfur dioxide (SO2), estrogen receptor (ER), P2Y receptor, perivascular tissue (PVT), and calcium activated potassium channel (Kca) are found to be involved in the relaxation of SMCs. This review updates the mechanisms of the relaxation of SMCs and its relationship with ED.
Subject(s)
Humans , Male , Carbon Monoxide , Physiology , Erectile Dysfunction , Hydrogen Sulfide , Metabolism , Muscle Contraction , Muscle, Smooth , Myocytes, Smooth Muscle , Physiology , Nitric Oxide , Physiology , Penile Erection , Physiology , Potassium Channels, Calcium-Activated , Physiology , Receptors, Estrogen , Physiology , Receptors, Purinergic P2Y , Physiology , Sulfur Dioxide , MetabolismABSTRACT
BACKGROUND AND OBJECTIVES: Increased bleeding rates with standard dose prasugrel have led to increased questions about the effectiveness and safety of the lower maintenance dose. We compared platelet inhibitory efficacy between low dose prasugrel and standard dose clopidogrel in patients on maintenance dose dual antiplatelet therapy. SUBJECTS AND METHODS: Forty-three patients who underwent percutaneous coronary intervention were randomized to receive 75 mg clopidogrel (n=23) or 5 mg prasugrel (n=20). Another 20 patients were allocated to 10 mg prasugrel as a reference comparison group. All patients (weight, > or =60 kg; age, 235) was significant lower in the 5 mg prasugrel group than that in the 75 mg clopidogrel group (15.0% vs. 56.5%, p=0.010). CONCLUSION: Prasugrel (5 mg) is more potent antiplatelet therapy than 75 mg clopidogrel in non-low body weight and non-elderly patients on a maintenance dose dual antiplatelet therapy.
Subject(s)
Humans , Aspirin , Body Weight , Hemorrhage , Percutaneous Coronary Intervention , Platelet Function Tests , Purinergic P2Y Receptor Antagonists , Random Allocation , Prasugrel HydrochlorideABSTRACT
We cultured the rabbit inner medullary collecting duct (IMCD) cells as monolayers on collagen-coated membrane filters, and investigated distribution of the P2Y receptors by analyzing nucleotide-induced short circuit current (Isc) responses. Exposure to different nucleotides of either the apical or basolateral surface of cell monolayers stimulated Isc. Dose-response relationship and cross-desensitization studies suggested that at least 3 distinct P2Y receptors are expressed asymmetrically on the apical and basolateral membranes. A P2Y2-like receptor, which responds to UTP and ATP, is expressed on both the apical and basolateral membranes. In addition, a uracil nucleotide receptor, which responds to UDP and UTP, but not ATP, is expressed predominantly on the apical membrane. In contrast, a P2Y1-like receptor, which responds to ADP and 2-methylthio-ATP, is expressed predominantly on the basolateral membrane. These nucleotides stimulated intracellular cAMP production with an asymmetrical profile, which was comparable to that in the stimulation of Isc. Our results suggest that the adenine and uracil nucleotides can interact with different P2Y nucleotide receptors that are expressed asymmetrically on the apical and basolateral membranes of the rabbit IMCD cells, and that both cAMP- and Ca2+-dependent signaling mechanisms underlie the stimulation of Isc.
Subject(s)
Adenine , Adenosine Diphosphate , Adenosine Triphosphate , Membranes , Nucleotides , Uracil , Uracil Nucleotides , Uridine Diphosphate , Uridine TriphosphateABSTRACT
Objective To demonstrate the presentation of the extracellula ATP receptors in peripheral nerve in rats Methods Reverse transcriptase polymerase chain reaction was performed in sciatic nerve of rat Results There were three P2y receptor mRNA expressions in the in the sciatic nerve of the rat,they were P2y2 and P2y4 as well as P2y6 Conclusions Extracellular ATP,as a neurotransmitter,activates the P2y purinoceptors located on the axon regeneration after peripheral nerve injury and decided the direction of the regeneration axon The P2y receptors are related to the regeneration of the peripheral nerve