RESUMO
Millones de personas, sin indicación médica, toman aspirina para la prevención primaria de la enfermedad ateroesclerótica cardiovascular. La Sociedad Europea de Cardiología no la recomienda para prevención primaria de esta entidad y las Guías del ACC/ AHA sobre Prevención Primaria de la Enfermedad Ateroesclerótica Cardiovascular la recomiendan solo en personas con riesgo cardiovascular aumentado. El beneficio de la aspirina en pacientes con enfermedad cardiovascular establecida sobrepasa el riesgo de sangrado. Ese beneficio se debe al efecto antiinflamatorio y anti-plaquetario, que reduce el riesgo de aterotrombosis, pero con riesgo de sangrado particularmente en individuos susceptibles de sangrar. El papel de esta medicación en individuos sin enfermedad cardiovascular establecida es controversial en especial si tienen riesgo de sangrado. En esta comunicación se discuten las En las Guías del ACC/AHA, el estudio ASCEND en diabéticos, el ASPREE en ancianos sanos y el ARRIVE en pacientes con moderado a alto riesgo y otros para que sirva de alarma a los médicos generales y especialistas, a fin de que indaguen sobre el uso de aspirina en sus pacientes, y al mismo tiempo discutan sobre el balance entre el daño y los beneficios, particularmente en los pacientes ancianos y en aquellos con riesgo de sangrado. Se sugiere realizar un estudio para obtener la evidencia del número de personas que ingieren aspirina automedicada, realizar su seguimiento, y evolución una vez conocidas ampliamente e implementadas las presentes recomendaciones(AU)
Millions of people, without medical indication, take aspirin for the primary prevention of cardiovascular atherosclerotic disease. The European Society of Cardiology does not recommend it for primary prevention, and the ACC/AHA Guidelines on Primary Prevention of Cardiovascular Atherosclerotic Disease recommend it only in people with increased cardiovascular risk. The benefit of aspirin in patients with established cardiovascular disease outweighs the risk of bleeding. This benefit is due to the anti-inflammatory and anti-platelet effect, which reduces the risk of atherothrombosis, but with the risk of bleeding, particularly in individuals susceptible to bleeding. However, the role of this medication as primary prevention in individuals without established cardiovascular disease is controversial especially if they are at risk of bleeding. Despite the recommendations of the ACC/AHA and the European guidelines aspirin continues to be auto medicated for a large number of subjects. In this communication we discuss the ACC / AHA Guidelines, the ASCEND study in diabetics, the ASPREE in healthy elderly and the ARRIVE in patients with moderate to high risk and others to serve as an alarm to general practitioners and specialists, in order for them to inquire about the use of aspirin in their patients, and at the same time discuss the balance between the harm and the benefits, particularly in elderly patients and those at risk of bleeding. It is suggested to conduct a study to obtain evidence of the number of people who take self-medicated aspirin, follow up, and evolution once these recommendations are widely known and implemented(AU)
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Aspirina/uso terapêutico , Aspirina/farmacocinética , Cardiologia , Embolia e Trombose , Medicina InternaRESUMO
Recent reports have suggested that aspirin effect might be influenced by bodyweight, with decreased efficacy in heavier individuals. We investigated the influence of bodyweight on aspirin pharmacodynamics in two independent datasets of patients taking non-enteric coated aspirin 100 mg QD for coronary artery disease (CAD). In the first dataset, 368 patients had their platelet aggregation assessed using VerifyNow Aspirin and measured in Aspirin Reaction Units (ARU). In the second dataset, 70 patients had serum thromboxane B2 (TXB2) dosage assessed by an ELISA assay and measured in pg/mL. Platelet aggregation was independently associated with bodyweight, with 8.41 (95% CI 1.86-14.97; adjusted p-value = 0.012) increase in ARU for every 10 kg. Furthermore, the rate of non-response to aspirin (defined as ARU ≥ 550) was significantly associated with increased bodyweight (adjusted p-value = 0.007), with OR = 1.23 (95% CI 1.06-1.42) for every 10 kg. Similar results were found considering body mass index (in kg/m2), with 15.5 (95% CI 5.0 to 25.9; adjusted p-value = 0.004) increase in ARU for every 10 kg and non-response OR = 1.43 (95% CI 1.13 to 1.81, adjusted p-value = 0.003) for every 5 kg/m2. Moreover, serum TXB2 was higher in patients weighting more than 70 kg (222.6 ± 62.9 versus 194.9 ± 61.9 pg/mL; adjusted p-value = 0.018). In two different datasets of patients with CAD on non-enteric coated aspirin 100 mg QD, increased bodyweight was independently associated with impaired response to aspirin.
Assuntos
Aspirina/farmacocinética , Doença da Artéria Coronariana/tratamento farmacológico , Aumento de Peso , Adulto , Idoso , Índice de Massa Corporal , Doença da Artéria Coronariana/sangue , Bases de Dados Factuais , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Tromboxano B2/administração & dosagemRESUMO
Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography-tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism. These results suggest that up-regulation of ABCC3 mRNA expression leads to increased plasma CAM levels through MRP3-mediated cell efflux. The ABCC3 rs757421 polymorphism may contribute to gene expression. Therefore, ABCC3 may be a potential biomarker for the response to clopidogrel.
Assuntos
Aspirina/administração & dosagem , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/terapia , Idoso , Aspirina/farmacocinética , Aspirina/farmacologia , Ácidos Carboxílicos/metabolismo , Cromatografia Líquida/métodos , Clopidogrel , Citocromo P-450 CYP2C19/genética , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Polimorfismo Genético , RNA Mensageiro/metabolismo , Ácido Salicílico/metabolismo , Espectrometria de Massas em Tandem/métodos , Ticlopidina/administração & dosagem , Ticlopidina/farmacocinética , Ticlopidina/farmacologia , Regulação para CimaRESUMO
Objetivo: determinar la equivalencia biofarmacéutica de cinco marcas comerciales de tabletas de ácido acetilsalicílico 100 mg disponibles en el mercado colombiano. Métodos: se tomaron cinco productos comerciales de ácido acetilsalicílico tabletas 100 mg, adquiridos en droguerías y farmacias de las ciudades de Bogotá, Cali, Medellín, Barranquilla y Cartagena, a los cuales se les evaluaron las características físicas, químicas y biofarmacéuticas de las tabletas, tales como variación de peso, dureza, desintegración, test y perfil de disolución, eficiencia de la disolución y valoración del ingrediente farmacéuticamente activo, los ensayos farmacopeicos se evaluaron según lo establecido en la USP-37. Los resultados se analizaron a fin de establecer diferencias estadísticamente significativas y posible intercambiabilidad entre los productos evaluados. Resultados: el análisis comparativo de los productos, permitió evidenciar marcadas diferencias en cuanto a la liberación in vitro del ingrediente farmacéuticamente activo, con uno de los productos evaluados, incumpliendo este importante parámetro de calidad. Cabe resaltar que cuatro de los productos evaluados cumplen con las especificaciones oficiales de identificación y valoración del ingrediente activo farmacéuticamente, uniformidad de dosificación y tiempo de desintegración. En cuanto a la cinética de disolución se encontraron diferencias entre las formulaciones, con un producto (marca E) de deficiente eficiencia de disolución (ED). Conclusiones: cuatro productos cumplen con todas las especificaciones establecidas en la USP-37. Los resultados de este trabajo constituyen una valiosa información para las autoridades sanitarias y para los pacientes que consumen este tipo de productos ya que genera confianza en términos de efectividad del medicamento, sobre si se considera que el ácido acetilsalicílico está exento de realizar estudios de bioequivalencia por pertenecer a la Clase I del Sistema de Clasificación Biofarmacéutica y muestra una alta solubilidad y absorción en humanos(AU)
Objective: to determine the biopharmaceutical equivalency of five brands if 100 mg acetylsalicylic acid tablets available on the Colombian market. Methods: five brands of 100 mg acetylsalicylic acid tablets obtained from drugstores and pharmacies in Bogota, Cali, Medellin, Barranquilla and Cartagena, were evaluated in terms of their physical, chemical and biopharmaceutical characteristics such as variation in weight, hardness, disintegration, dissolution test, dissolution profile and efficiency and quantitation of pharmaceutically active ingredient; the pharmacopeial assays were evaluated according to the USP 37. The results analysis was used to determine the statistically significant differences and the possible interchangeability among the evaluated products. Results: the comparative analysis of products allowed showing marked differences in terms of the in vitro release of pharmaceutically active ingredient and the non-compliance by one of the evaluated products with this important quality parameter. It is worth noting that four of the tested products comply with the official specifications of identification and measurement of the pharmaceutically active ingredient, dosage uniformity and disintegration time. In terms of the dissolution kinetics, differences were found among formulations, with a product (Mark E) having poor dissolution efficiency. Conclusions: four products meet all the the USP-37 specifications. The results of this study provide valuable information for health authorities and patients who take these products because they bring confidence on the drug effectiveness, considering that aspirin is exempted from bioequivalence studies since it belong to Class I Biopharmaceutics Classification System showing high solubility and absorption in human consumers(AU)
Assuntos
Humanos , Controle de Qualidade , Aspirina/uso terapêutico , Aspirina/farmacocinética , Comprimidos , ColômbiaRESUMO
The objective of this study was to determine pharmacokinetic differences of acetyl salicylic acid (ASA) and its metabolites: gentisic acid (GA), salicylic acid (SA) and salicyluric acid (SUA) between Otomies and Mesticians healthy subjects. Design. Ten Otomies and 10 Mesticians were included. After a single dose of aspirin given orally (15 mg/kg), blood and urine samples were collected at different times. Results. Pharmacokinetic parameters of salicylates showed significant differences, except distribution volume of SA, and elimination half-life of SUA. Metabolic rates of ASA showed significant differences for all rates between both groups. On the other hand, percentages of dose excreted were more reduced for SA and SUA for the Otomies than for the Mesticians. Conclusion. Results reflect differences in the hydrolysis way i.e. from ASA to SA and aromatic hydroxylation i.e. from SA to GA, which were slower in Otomies subjects, showing a possible pharmacokinetic differences about the capabilities of ASA biotransformation as a consequence of ethnic differences.
Assuntos
Aspirina/farmacocinética , Indígenas Norte-Americanos , Adolescente , Adulto , Aspirina/metabolismo , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica/fisiologia , México/etnologia , Estatísticas não ParamétricasRESUMO
UNLABELLED: The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). METHODS: A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. RESULTS: The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. CONCLUSIONS: Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered.
Assuntos
Artrite Juvenil/tratamento farmacológico , Aspirina/metabolismo , Aspirina/farmacocinética , Doenças Autoimunes/tratamento farmacológico , Febre Reumática/tratamento farmacológico , Administração Oral , Adolescente , Área Sob a Curva , Artrite Juvenil/sangue , Artrite Juvenil/urina , Aspirina/administração & dosagem , Doenças Autoimunes/metabolismo , Disponibilidade Biológica , Criança , Cromatografia Líquida de Alta Pressão , Feminino , Gentisatos/sangue , Gentisatos/metabolismo , Gentisatos/urina , Meia-Vida , Hipuratos/sangue , Hipuratos/metabolismo , Hipuratos/urina , Humanos , Masculino , México , Estudos Prospectivos , Febre Reumática/sangue , Febre Reumática/urina , Ácido Salicílico/sangue , Ácido Salicílico/metabolismo , Ácido Salicílico/urina , ComprimidosRESUMO
We performed a prospective, randomized, open-label equivalence study comparing the use of naproxen to aspirin in 33 patients with rheumatic fever. The mean time until resolution of arthritis was 2.9+/-2.9 days in both groups. Liver enzyme elevations were more frequent in the aspirin group (P=.002). We conclude that naproxen is as effective, is easier to use, and is safer than aspirin in the treatment of the arthritis of rheumatic fever.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/farmacocinética , Aspirina/uso terapêutico , Naproxeno/farmacocinética , Naproxeno/uso terapêutico , Febre Reumática/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Equivalência Terapêutica , Fatores de Tempo , Resultado do TratamentoRESUMO
1. Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension and to interfere with the effectiveness of some anti-hypertensive therapies. In this study, we tested the effects of a gastric-sparing, nitric oxide-releasing derivative of aspirin (NCX-4016) on hypertension in rats. 2. Hypertension was induced by administering L-NAME in the drinking water (400 mg l(-1)). Groups of rats were treated daily with aspirin, NCX-4016 or vehicle. 3. NCX-4016 significantly reduced blood pressure relative to the aspirin-treated group over the 2-week period of treatment. Aspirin and, to a lesser extent, NCX-4016 suppressed whole blood thromboxane synthesis. 4. In anaesthetized rats, acute intravenous administration of NCX-4016 caused a significant fall in mean arterial pressure in hypertensive rats, but was devoid of such effects in normotensive controls. 5. In vitro, NCX-4016 relaxed phenylephrine-pre-contracted aortic rings obtained from both normotensive and hypertensive rats, and significantly reduced their responsiveness to the contractile effects of phenylephrine. 6. These results suggest that NCX-4016 reduces blood pressure in hypertensive rats, not simply through the direct vasodilatory actions of the nitric oxide released by this compound, but also through possible interference with the effects of endogenous pressor agents. These properties, added to its anti-thrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/fisiopatologia , Óxido Nítrico/metabolismo , Vasodilatação/efeitos dos fármacos , Anestesia , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiologia , Aorta/fisiopatologia , Aspirina/análogos & derivados , Aspirina/farmacocinética , Estado de Consciência , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Nitratos/metabolismo , Nitritos/metabolismo , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Renina/sangue , Tromboxanos/metabolismoRESUMO
A delivery system for vanadium was developed using poly(beta-propiolactone) (PbetaPL) films. The release kinetics of a complex of vanadium (IV) with aspirin (VOAspi) was evaluated with films prepared from polymers of different molecular weights, as well as with variable drug load. A sustained release of vanadium over 7 days was achieved. The drug release kinetics depends on contributions from two factors: (a) diffusion of the drug; and (b) erosion of the PbetaPL film. The experimental data at an early stage of release were fitted with a diffusion model, which allowed determination of the diffusion coefficient of the drug. VOAspi does not show strong interaction with the polymer, as demonstrated by the low apparent partition coefficient (approximately 10(-2)). UMR106 osteosarcoma cells were used as a model to evaluate the anticarcinogenic effects of the VOAspi released from the PbetaPPL film. VOAspi-PbetaPL film inhibited cell proliferation in a dose-response manner and induced formation of approximately half of the thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation. compared to that with free VOAspi in solution. The unloaded PbetaPL film did not generate cytotoxicity, as evaluated by cell growth and TBARS. Thus, the polymer-embedded VOAspi retained the antiproliferative effects showing lower cytotoxicity than the free drug. Results with VOAspi-PbetaPL films suggest that this delivery system may have promising biomedical and therapeutic applications.
Assuntos
Aspirina/administração & dosagem , Sistemas de Liberação de Medicamentos , Propiolactona/farmacologia , Vanádio/administração & dosagem , Animais , Aspirina/farmacocinética , Neoplasias Ósseas/tratamento farmacológico , Divisão Celular/efeitos dos fármacos , Combinação de Medicamentos , Cinética , Peroxidação de Lipídeos/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Propiolactona/administração & dosagem , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Células Tumorais Cultivadas , Vanádio/farmacocinética , ÁguaRESUMO
Microcrystalline cellulose (MCC) is a very important product in pharmaceutic, food, cosmetic and other industries. In this work, MCC was prepared from soybean husk, produced in large quantities in soybean oil processing industries. It was characterized through various techniques (scanning electron microscopy (SEM), infrared spectroscopy (FTIR), thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC)) and compared with a commercial MCC. The results obtained show that the prepared sample has similar crystallinity and lower particle size than the commercial MCC. Both MCC samples were treated with organic solvents (chloroform, acetone, ethanol and ethyl ether), for structural modifications to be introduced, and used as acetylsalicylic acid (ASA) carrier. Pretreated MCC and MCC/ASA 1:1 mixtures were analyzed through FTIR and thermal analysis. The drug release was evaluated in buffer solution of pH 4.5 and in pure water, at 37 degrees C. The MCC pretreated with different solvents show different thermal properties and ASA release rates, each MCC showing a particular behavior.