Pentavalent antimonials: old drugs for new diseases

Abstract

Clinicians like m yself feel a sense of pressure because things change so slowly for the patient in spite of the volume o f current research. This is currently the case in the chemotherapy o f leishmaniasis where the drug formulations used in the first line treatm ent have not changed for four decades. N either is a practical altemative on the horizon. There is no money to be made in treating the poor people o f rural areas suffering from this disease. The small efforts that have been extended in this direction have not m et with success. Therefore we m ust try to use antimonials more efficiently for the benefit o f the patient and this is the chief purpose of this review.H IST O R Y W e are indebted to D r. Edgard de Cerqueira Falcão23 for a monograph summarising the contributions of G aspar V ianna with a collection of his scientific papers. The original communication on the use of tartar emetic in cutaneous and mucosal leishma niasis is reproduced72. A lso, in a less well known paper, V ianna illustrates a very good result in a patient with severe mucosal d i s e a s e 7 3 . H e used a 1% solution of tartar emetic although the origin of the drug is not stated. Early preparations of tartar emetic were made by allowing antimony goblets to stand with white wine and extracting the supem atant. Confirmation of Vianna's favourable results followed in several Brazilian publications6 22 ^9 j n 1915 the effectiveness of tartar emetic in the treatm ent o f infantile kala-azar in Italy was reported19. The drug was then widely used during the epidemic o f kala-azar on the tea estates in A ssam 45.Núcleo de M edicina T ropical e N utrição, Universidade de Brasília -70910 B rasília-D F, Brasil.Recebido para publicação em 23/5 /8 5 .The m ain support over the years for these clinicai studies has been from a U nited States Public Service G ra n t(A I 16282), adm inistered by the D epartm ent of International M edicine, Com ell M edicai College, N ew York.

Fatores associados ao insucesso do tratamento da leishmaniose cutânea com antimoniato de meglumina

“…Não se pode também descartar a influência de fatores farmacológicos ainda não descritos, que justifiquem a associação entre peso e insucesso do tratamento da LTA com antimoniato de meglumina, uma vez que o desenvolvimento e a pesquisa de drogas para o tratamento deste grupo de patologias são freqüentemente negligenciados 14 17 . O impacto de diferentes dosagens de antimonial sobre a eficácia, embora não tenha sido demonstrado nesta coorte, pode refletir a ocorrência de espécies de Leishmania com diferentes perfis de sensibilidade a esse grupo de drogas, o que já vem sendo observado há muitos anos 26 , levando inclusive alguns pesquisadores a sugerir a utilização de esquemas com dosagens individualizadas, de acordo com a síndrome clínica e espécie envolvidas 17 . Contudo, o resultado observado neste coorte pode sugerir que as espécies e/ou isolados de Leishmania que circulam em nossa região são menos susceptíveis a dosagens baixas de antimoniato de meglumina, embora estudos observacionais com um maior número de pacientes e ensaios clínicos prospectivos sejam mais adequados para elucidar tais aspectos da terapêutica.…”

“…Os antimoniais pentavalentes representam a principal opção terapêutica, sendo utilizado em nosso meio o antimoniato de meglumina como droga de primeira linha 4 9 11 17 . De acordo com as orientações do Ministério da Saúde, a dose de meglumina a ser empregada para o tratamento da LC é de 10-20mg/kg/peso por dia, durante 20 dias, com possibilidade de repetição de um segundo ciclo com duração de 30 dias, em caso de não resolução das lesões, após 90 dias do término do primeiro ciclo 9 10 11 17 .…”

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

“…These drugs are effective, presenting an effi cacy of approximately 90% (17) , but there has been growing evidence of variable effi cacy that depends on the species, geographic region, presence of resistant strains, and therapeutic schemes employed (18) (19) (20) . Moreover, certain factors, such as the need for parenteral administration for up to 30 days, the high frequency of side effects such as myalgia, arthralgia, anorexia, fever and urticaria, and signifi cant toxicity to the liver, kidneys and spleen of the patient, have contributed to the limited use of these drugs in clinical practice (21) (22) . Pentamidine, another antileishmanial drug, is also unsuitable as a fi rst-line treatment due to its toxicity.…”

The effect of age on the frequency of adverse reactions caused by antimony in the treatment of American tegumentary leishmaniasis in Governador Valadares, State of Minas Gerais, Brazil

“…According to different authors, the success rate varies from 26% to 100% of patients treated after a first period of antimony administration [4][5][6][7][8] . In another study conducted in Cuiabá, State Major Article of Mato Grosso, Brazil, the failure rate was 47%, that is, no healing or recrudescence of skin lesions was found during the three month followup after the first treatment regimen 9 .…”