Intoxicación por ácido acetilsalicílico, fisiopatología y manejo / Physiopathology and management of acetylsalicylic acid intoxication

Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.

Comparison of anticoagulant effects on vein grafts between human TFPI gene transfection and aspirin oral administration / 华中科技大学学报（医学）（英德文版）

To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.

Sex-dependent differences in the activities of acetylsalicylic acid-esterases in mouse kidneys

Acetylsalicylic acid (ASA), the most used drug worldwide, is hydrolyzed to salicylic acid and acetate by esterases present in tissues of several species including humans. Sex differences in drug metabolism by rodent liver are documented in the literature. In this paper we report a difference in the activities of the esterases (ASA-esterase I and II) in the kidneys of male and female mice. In this species there is no difference between males and females in liver ASA-esterases (ASA-esterase I: males 38.5 ñ 7.9 (N = 5) and females 31.6 ñ 7.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P>0.05; ASA-esterase II: males 77.3 ñ 17.4 (N = 5) and females 61.4 ñ 15.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P>0.05). However, in the kidneys males presented a much higher enzyme activity than females (ASA-esterase I: males 25.2 ñ 6.3 (N = 5) and females 6.8 ñ 0.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P<0.0002; ASA-esterase II: males 79.8 ñ 10.1 (N = 5) and females 13.0 ñ 1.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P<0.0001). The difference between sexes observed in mouse kidneys could serve as a model to study the molecular basis of this sex difference and also to determine the possible involvement of pituitary and gonadal hormones in this difference in ASA-esterase activities since these hormones control the sex differences in rodent liver enzyme activity

Cambios metabólicos del ácido araquidónico en la desensibilización a la aspirina / Aspirin, metabolic change in arachidonic acid in the desensitization

La sensibilización de la aspirina se presenta en acerca del 10 por ciento de todos los pacientes asmáticos. En esta clase de asmáticos la congestión nasal y el broncoespasmo ocurren entre los 30 a 180 minutos después de la ingestión de la aspirina. Luego de la reacción respiratoria a la aspirina todos los pacientes pueden ser desensibilizados a la misma mediante la introducción repetida de pequeñas a grandes cantidades de aspirina hasta que los sujetos asmáticos pueden ingerir 650 mg del fármaco sin ningún efecto adverso. Los mecanismos de la sensibilidad a la aspirina no están totalmente esclarecidos, y las razones por las cuales la desensibilización en los pacientes asmáticos sensibles a la aspirina (ASA) ocurre de manera universal se desconocen. En este estudio, pacientes ASA y testigos asmáticos no ASA se expusieron a dosis provocadoras de aspirina. Se colectaron muestras de orina antes, durante el broncoespasmo inducido, y después de la ingestión de 650 mg de aspirina, cuando los efectos adversos habían desaparecido (fenómeno de desensibilización). Se dertminaron los niveles de los productos tipo y cicloxigenados en las muestras de orina. En este trabajo se analizan los resultados y se expone una explicación del probable mecanismo de la desensibilización

Teste de provocaçäo brônquica com inalaçäo de aspirina lisina / Bronchial provocation test with aspirin lysine inhalation

A avaliaçäo da reatividade brônquica com aspirina lisina é sugerida como método diagnóstico para pacientesasmáticos com história prévia de sensibilidade à aspirina. Com o objetivo de avaliar a eficácia e viabilidade desse teste, foram estudados 16 indivíduos com média de idade de 28 anos, divididos em dois grupos. O primeiro grupo (grupo AAS), formado por nove pacientes com história sugestiva de asma induzida por aspirina, e o segundo (grupo controle), por sete indivíduos incluídos nesse protocolo foram submetidos, no laboratório de funçäo pulmonar, a duas fases de estudo. Primeiro, ao teste de broncoprovocaçäo com histamina, e após um intervalo de no mínomo quatro dias, à medida de reatividade brônquica com aspirina lisina. No grupo AAS, todos os pacientes apresentaram broncoprovocaçäo positiva com aspirina lisina, enquanto no grupo controle os testes com aspirina foram foram negativos. A tolerância ao exame foi satisfatória, sendo o broncoespasmo, quando presente, controlado com fenoterol 'spray'. Concluímos que a broncoprovocaçäo com aspirina lisina é um método diagnóstico eficaz e seguro em pacientes asmásticos com história de sensibilidade oral à aspirina

Asma inducida por aspirina y metabolitos del ácido araquidónico: en búsqueda de respuestas a un enigma (segunda parte) / Asthma induced by aspiring and metabolites of araquidonic acid (secund part)

El ácido acetilsalicílico es uno de los fármacos más usados y el que encabeza la lista de reacciones adversas a medicamentos. Desde la primera publicación en 1902 por Hirschberg, una gran información ha surgido acerca de la sensibilidad a la aspirina, incluyendo datos epidemiológicos, caracterizaciones de los dos subtipos mayores de sensibilización (broncoespasmo y urticaria), aspectos hereditarios, reacciones cruzadas con otros medicamentos antiinflamatorios no esteroides y métodos de desensibilización. Aunque la patogénesis de la enfermedad permanece desconocida, se han propuesto varias teorías para explicar este enigma de enfermedad

Prostaglandinas, ácido acetilsalicílico, dipiridamol e sulfinpirazona na doença coronária / Prostaglandins acetylsalicylic acid, dipyridamol and sulfinpyrazone in coronary disease

As prostaglandinas säo substâncias existentes em todos os tecidos do organismo. Säo atuantes à pequena distância do sítio de produçäo. Têm efeitos biológicos marcantes, sobretudo na circulaçäo coronária, com grandes implicaçöes na doença arterial coronária. Drogas como ácido acetilsalicílico, dipiridamol e sulfinpirazona exercem seus benefícios porque têm efeitos farmacológicos nas prostaglandinas

Biodisponibilidad relativa de dos preparados comerciales de aspirina / Relative bioavailability of 2 commercial preparations of aspirin

Se evaluaron dos diferentes preparados comerciales de Aspirina y se determinó su biodisponibilidad relativa. La evaluación "in vivo" se llevó a efecto en cinco sujetos, mediante determinaciones de niveles de droga en orina, usando un diseño cruzado completo. La vida media de eliminación fue de 4,84; 6,47 y 6,03 horas. La biodisponobilidad relativa con respecto al patrón fue de 89 y 100% para los preparados A y B respectivamente. La cantidad de salicilato en orina, para cada preparado, fue evaluada estadísticamente. Al comparar los datos se concluye a cerca de la importancia de agregar la cantidad exacta de miliequivalentes de hidróxido de Magnesio-Aluminio a los preparados de Aspirina para obtener una mejor y más regular absorción