RESUMO
PURPOSE: The aim of this study was to evaluate the therapeutic efficacy of tolvaptan, a vasopressin V(2) receptor antagonist, on edema in two rat models: 1) histamine-induced vascular hyperpermeability of the dorsal skin and 2) carrageenan-induced paw edema. METHODS: In the skin vascular hyperpermeability model, 3 h after oral administration of tolvaptan or the natriuretic agent furosemide, rats were intravenously injected with Evans Blue (EB), followed by intradermal injection of 10 µg of histamine into the dorsal skin. One hour later, blood was collected to measure serum parameters. EB leakage area into the dorsal skin was also measured. Urine was collected for 4 h to determine urine parameters. In the paw edema model, edema was induced by injecting 1% w/v carrageenan into the right hind paw. Paw volume was measured hourly for 5 h. Tolvaptan or furosemide was orally administered 1 h before carrageenan injection. RESULTS: A single oral dose of tolvaptan (1-10 mg/kg) elicited marked and dose-dependent aquaresis, and improvements in edema. Similar effects were observed with furosemide (30 mg/kg). Tolvaptan tended to elevate the serum sodium level while furosemide caused a significant decrease. CONCLUSION: Tolvaptan had anti-edematous effects in two different rat models. By increasing free water excretion, tolvaptan may be more advantageous for certain patients than loop diuretics because it does not cause electrolyte loss, and may prevent electrolyte abnormities, such as hyponatremia. These results suggest that tolvaptan has potential clinical benefits for the treatment of edema.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos , Benzazepinas/uso terapêutico , Diuréticos/uso terapêutico , Edema/tratamento farmacológico , Dermatopatias Vasculares/tratamento farmacológico , Animais , Carragenina , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/patologia , Edema/urina , Doenças do Pé/induzido quimicamente , Doenças do Pé/tratamento farmacológico , Doenças do Pé/patologia , Doenças do Pé/urina , Histamina , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Dermatopatias Vasculares/sangue , Dermatopatias Vasculares/induzido quimicamente , Dermatopatias Vasculares/urina , Sódio/sangue , Sódio/urina , TolvaptanRESUMO
Based on the best available data, approximately 2.1 million Americans use illicit cocaine each month; for the last several months, 30% of that cocaine has been "cut" with a veterinary pharmaceutical, levamisole. Levamisole can cause agranulocytosis, leaving patients susceptible to fulminate and opportunistic infections and also can cause a debilitating cutaneous necrotizing vasculitis. In this manuscript, we describe a case and provide an image of levamisole-induced necrotizing vasculitis of the ears.
