Antimony drugs

Pentavalent antimonial drugs have been the cornerstone of antileishmanial therapy for more than 70 years, in spite of their general toxicity causing a wide range of side effects [2]. Pentavalent antimonial drugs have to be administered parenterally, which is a painful procedure. Meanwhile, resistance is widespread. In India,... 

The first reports on this approach were published independently by three different groups using liposomes as carriers of antimonial drugs like meglumine antimoniate in experimental leishmaniasis infection (Alving et al., 1978 Black et al., 1977 New et al., 1978). 

A. Liposomal amphotericin B was approved by the US. Food and Drug Administration to treat visceral leishmaniasis. Pentavalent antimony compounds, pentamidine, amphotericin B, and aminosi-dine (paromomycin) have all been demonstrated efficacious here. The liposomal amphotericin appears to be better taken up by the reticuloendothelial system, where the parasite resides, and partitions less in the kidney, where amphotericin B traditionally manifests its toxicity. In addition to being better tolerated by patients, it has proved to be very effective in India, where resistance to antimony drugs is widespread. This patient appears to have acquired his infection there, where many infected patients develop darkening of the skin, hence the name kala-azar, or black sickness. Albendazole, an anthelmintic, has no role here. Atovaquone, a naphthoquinone, is used to treat malaria, babesiosis, and pneumocystosis. Pyrimethamine-sulfadoxine is used to treat malaria and toxoplasmosis. Proguanil inhibits the dihydrofolate reductase of malaria parasites and is used in combination with atovaquone. 

The delivery of drugs to the RES (also referred to as the mononuclear phagocyte system) is an area where liposomes have a potential for success. They were successfully used in the delivery of antimonial drugs to treat experimental leishmaniasis infection [313], Very good results were obtained in the treatment of systemic fungal infections in cancer patients using liposomal amphotericin B [314, 315]. 

C.N. Chunge, et al., Visceral leishmaniasis unresponsive to antimonial drugs Successful treatment using a combination of sodium stibogluconate plus allopurinol. Trans R. Soc. Trop. Med. Hyg. 79 715-718, 1985. 

Table 4.6 clearly shows how antimonial drugs can distinguish between a pair of analogous enzymes, one in a parasitic worm, the other in its mammalian host. This is the selectively toxic basis of the classical treatment of schistosomiasis. 

Skin Drug rash with eosinophilia and systemic symptoms (DRESS) has been associated with antimonial drugs in a 40-year-old man with cutaneous and mucosal leishmaniasis [10 ]. 

---