RESUMO
BACKGROUND: Gastrointestinal bleeding (GIB) is a common adverse event related to anticoagulation therapy. However, evidence comparing the severity, etiology and outcome of GIB in patients taking direct oral anticoagulants (DOAC) vs. vitamin K antagonists (VKA) is scarce. AIMS: To evaluate the severity, etiology and outcomes of GIB in patients under DOACs compared to VKA. METHODS: Patients under oral anticoagulant therapy admitted to the emergency department with acute GIB were prospectively recruited from July 2016 to January 2018 at a tertiary referral hospital. Demographic and clinical outcome were obtained from medical records. Severity of the GIB event was classified as mild, major or severe according to clinical presentation and the type of support needed. Etiology and location of bleeding, number of packed red blood cells transfused (PRBC) and length of hospital stay were recorded until discharge or in-hospital death. RESULTS: A total of 208 patients with acute GIB under oral anticoagulant treatment were recruited: 119 patients were on VKA and 89 patients on DOAC with similar characteristics. Thirty-one patients had severe GIB; 134 major and 43 mild, with no differences in severity, number of PRBC and length of hospital stay between the groups. Peptic disease was the most frequent etiology of GIB in patients on VKA (20.2 % vs. 13.6%, p=0.20). Diverticular bleeding was the most frequent adverse event in patients on DOAC (14.3% vs. 24.8%, p= 0.056). CONCLUSIONS: Severity and clinical outcomes of GIB are similar between patients on DOAC and patients on VKA, regardless of etiology of GIB.
Assuntos
Anticoagulantes , Hemorragia Gastrointestinal , Doença Aguda , Administração Oral , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/terapia , Mortalidade Hospitalar , Humanos , Vitamina KRESUMO
In the present study, we evaluated the effects of the synthetic cannabinoid receptor agonist (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN55,212-2) and the active component of Cannabis delta-9-tetrahydrocannabinol (triangle up(9)-THC) on Na(+),K(+)-ATPase activity in synaptosomal mice brain preparation. Additionally, the potential exogenous cannabinoids and endogenous opioid peptides interaction as well as the role of G(i/o) proteins in mediating Na(+),K(+)-ATPase activation were also explored. The ouabain-sensitive Na(+),K(+)-ATPase activity was measured in whole-brain pure intact synaptosomes (obtained by Percoll gradient method) of female CF-1 mice and was calculated as the difference between the total and the ouabain (1 mM)-insensitive Na(+),K(+)-ATPase activities. Incubation in vitro of the synaptosomes with WIN55,212-2 (0.1 pM-10 microM) or triangle up(9)-THC (0.1 pM-0.1 microM), in a concentration-dependent manner, stimulated ouabain-sensitive Na(+),K(+)-ATPase activity. WIN55,212-2 was less potent but more efficacious than triangle up(9)-THC. N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM-251) (10 nM), a CB(1) cannabinoid receptor selective antagonist, had not effect per se but antagonized the enhancement of Na(+),K(+)-ATPase activity induced by both, WIN55,212-2 and triangle up(9)-THC. AM-251 produced a significant reduction in the E(max) of cannabinoid-induced increase in Na(+),K(+)-ATPase activity, but did not significantly modify their EC(50). On the other hand, co-incubation with naloxone (1 microM), an opioid receptor antagonist, did not significantly modify the effect of WIN55,212-2 and completely failed to modify the effect of triangle up(9)-THC on synaptosomal Na(+),K(+)-ATPase. Finally, pre-incubation with 0.5 microg of pertussis toxin (G(i/o) protein blocker) completely abolished the enhancement of ouabain-sensitive Na(+),K(+)-ATPase activity induced by WIN55,212-2. A lower dose, 0.25 microg, decreased the E(max) of WIN55,212-2 by 70% but did not significantly affect its EC(50). These results suggest that WIN55212-2 and triangle up(9)-THC indirectly enhance Na(+),K(+)-ATPase activity in the brain by activating cannabinoid CB(1) receptors in a naloxone-insensitive manner. In addition, the effect of WIN55,212-2 on neuronal Na(+),K(+)-ATPase is apparently due to activation of G(i/o) proteins.
Assuntos
Benzoxazinas/farmacologia , Encéfalo/efeitos dos fármacos , Dronabinol/farmacologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/agonistas , Morfolinas/farmacologia , Naftalenos/farmacologia , Receptor CB1 de Canabinoide/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Feminino , Técnicas In Vitro , Camundongos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ouabaína/farmacologia , Toxina Pertussis/administração & dosagem , Toxina Pertussis/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/enzimologiaRESUMO
Los paragangliomas son neoplasias derivadas de la cresta neural, benignas en un alto porcentaje y poco comunes. En la cabeza y cuello, los del cuerpo carotídeo, son los de mayor incidencia. Por lo general, se presentan como una masa asintomática y ocurren en personas entre la cuarta y quinta década de la vida. Su aparición se ha relacionado con la vida en las grandes alturas o con enfermedad pulmonar obstructiva crónica (hipoxia crónica), y existe un grupo con tendencia familiar. Las técnicas de imágenes diagnósticas no invasivas (resonancia magnética, tomografía computarizada, gammagrafía) son los instrumentos ideales para confirmar el diagnóstico. La cirugía se considera la única manera de tratamiento para lograr su curación. En grandes tumores, todavía existe morbilidad de tipo neurovascular durante la extirpación quirúrgica. Para reducir la misma, se ha preconizado la embolización arterial preoperatoria