Terapêutica da hanseníase: situaçäo atual / Therapeutic of leprosy: current situation

O autor enfatiza o tratamento como um dos esteios do controle da hanseníase. Faz revisäo histórica das drogas utilizadas, do mecanismo de açäo, das doses recomendadas e dos principais efeitos colaterais. Ressalta a importância da poliquimioterapia, porposta pela OMS, usando a sulfona, a rifampicina, a clofazimina e a etionamida. Revê o tratamento das reaçöes, oproblema da resistência medicamentosa e o conceito de bacilos persistentes. Apresenta a situaçäo atual da imunoterapia e a esperança depositada em novos fármacos - derivados da quinolona e as ansamicinas. Cita dados promissores das experiências com MDT, supervisionadas pela OMS, e a possibilidade de erradicar ou minimizar o problema da hanseníase nos países onde a doença é endêmica.

An experimental study of the antileprosy activity of a series of thioamides in the mouse.

A series of substituted thioamides have been studied to establish whether their structure-activity pattern against Mycobacterium leprae is similar to that displayed against M. tuberculosis. Antileprosy activity was evaluated in the mouse foot pad using both the kinetic and continuous methods. Ethionamide and prothionamide were found to be the most active compounds and to be of approximately equal potency. Thioisonicotinamide was about five times less active. 2-t-Butyl-thioisonicotinamide, 2-dimethylamino-thioisonicotinamide, and pyrazine carbonic thioamide were inactive at the dosages tested. High-pressure liquid chromatographic methods were devised to study the potential influence of pharmacological factors on their in vivo activity. Fecal measurements suggested that all of the thioamides were well absorbed when fed in the diet. After intravenous administration, all of the thioamides were rapidly eliminated from the mouse. The differences in their elimination rates probably played only a minor role in affecting their relative antileprosy activities. It was concluded that the structural requirements for antileprosy and antituberculosis activity of the thioamides are probably similar.

Hepatitis in leprosy patients treated by a daily combination of dapsone, rifampin, and a thioamide.

A 13% incidence of hepatitis was observed among 54 cases of multibacillary leprosy treated daily with the three-drug combination of dapsone, rifampin, and a thioamide (ethionamide or prothionamide). No hepatitis was observed among 109 cases of paucibacillary leprosy treated daily with the two-drug combination of dapsone and rifampin. Symptoms were jaundice in five cases and nausea plus vomiting associated with a significant increase of transaminase levels in two cases. In five cases, the symptoms appeared during the first two months of therapy and in two cases, later. Discontinuing treatment with rifampin and the thioamide but not dapsone resulted in recovery. When rifampin was resumed without the thioamide, the hepatitis did not recur. Viral etiology could be eliminated in six cases. Neither sex, age, weight nor the fact that the patient was a new case or a relapse case appeared to be a contributing factor. Hepatotoxicity caused by administration of a thioamide might have been potentiated by the concurrent administration of rifampin.