RESUMO
Ketoconazole was given to 18 patients with coccidioidomycosis. Fourteen had received prior antifungal chemotherapy with amphotericin B, miconazole, or both. Ten patients had pulmonary disease, two had meningitis, and six had extrameningeal disseminated disease. The initial dose of ketoconazole was 200 mg per day; it was later increased to 400 mg per day for some patients. All strains of Coccididioides immitis tested were sensitive to ketoconazole. Approximately 2-4 hr after an oral dose of 200 mg of ketoconazole, levels of the drug in blood peaked at approximately 2 micrograms/ml. Higher concentrations in blood were achieved with a 400-mg dose. Improvement was measured by physical examination, conversion of cultures previously positive for C. immitis to negative, decrease in erythrocyte sedimentation rate by 50%, and decrease in titer of complement fixation antibody by two or more dilutions. One patient died after one week of treatment with ketoconazole and could not be evaluated; two other patients with coccidioidal meningitis could not be evaluated. Six of nine patients with pulmonary disease showed radiographic improvement, and their sputum cultures, which had been positive, became negative. Four of the six patients with disseminated disease improved. There were few adverse reactions to ketoconazole, which can be safely administered for prolonged periods to patients with coccidioidomycosis. These findings suggest that ketoconazole may be effective for treatment of this disease and indicate that trials comparing the efficacy of ketoconazole with that of amphotericin B are warranted.
Assuntos
Coccidioidomicose/tratamento farmacológico , Imidazóis/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Idoso , Anfotericina B/uso terapêutico , Relação Dose-Resposta a Droga , Estudos de Avaliação como Assunto , Humanos , Imidazóis/efeitos adversos , Imidazóis/sangue , Cetoconazol , Masculino , Meningite/líquido cefalorraquidiano , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piperazinas/sangueRESUMO
The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle.