Leishmaniasis antimony compounds

In 1912, however, (201) it was discovered that espundia (American mucocutaneous leishmaniasis) can be cured by tartar emetic. It was soon learned that kala-a2ar (visceral leishmaniasis) and oriental sore (a cutaneous form of the disease occurring in the Middle East) also respond to antimonial therapy, especially when compounds of pentavalent antimony are employed. Treatment of leishmaniasis with the latter type of antimonials is safe and effective in over 90% of the cases (202). In 1918, it was demonstrated that tartar emetic is of value in the treatment of schistosomiasis (203). Pentavalent antimonials proved to be less effective. The introduction of antimony compounds for the treatment of parasitic diseases is undoubtedly one of the important milestones in the history of therapeutics (see Antiparasitic agents). 

Antimony compounds have been used to treat leishmaniasis ever since tartar emetic (antimony potassium tartrate) was discovered early in the 20th century to have efficacy against the mucocutaneous form of the disease. The cutaneous form has been treated with tartar emetic formulated in an ointment. Many side effects have been seen with this trivalent antimonial, some of which can be ascribed to the difficulty of obtaining pure antimony for its manufacture. These side effects include toxicity to the heart, Hver, and kidneys. Other promising trivalent antimonials have been abandoned in favor of pentavalent antimonials with lower toxicity. 

Sodium stibogluconate is a pentavalent antimo-nial compound. It is a prodrug as the pentavalent an-timonial has to be reduced to a divalent antimony compound. Sodium stibogluconate is used to deal leishmaniasis and is only available for adminisda-tion by injection. It is excreted in the urine. In general it is tolerated fairly well. Adverse effects include pain at the injection site and gasdointestinal complaints. Cardiac arrhythmias can occur and renal and hepatic function should be monitored. 

No pentavalent antimonial is licensed for use, but sodium stibogluconate is available from the Parasitic Disease Drug Service of the Centers for Disease Control (CDC) for treatment of leishmaniasis. While the pentavalent antimony compounds can be given intravenously or intramuscularly, local infiltration of the lesion in cutaneous leishmaniasis is highly effective. Because of the lower toxicity of liposomal amphotericin B, this drug is considered a first-line choice for vis-cerotropic leishmaniasis rather than the antimonials. 

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. 

Leishmaniasis - [ANTIPARASITICAGENTS - ANTIPROTOZOALS] (Vol3) -tartar emetic in treatment of [ANTIMONY COMPOUNDS] (Vol 3)... 

Leishmaniasis. The causative agents are flagellated protozoa that are transmitted by sand flies to humans. The parasites are taken up into phagocytes, where they remain in phagolysosomes and multiply until the cell dies and the parasites can infect new cells. Symptoms A visceral form, known as kala-azar, and cutaneous or mucocutaneous forms exist (A). An estimated 12 million humans are affected. Therapy is dif cult pen-tavalent antimonial compounds, such as stibogluconate, must be given for extended periods. Adverse effects are pronounced. 

Sodium stibogluconate (Pentostam) is an organic pentavalent antimony compound it may cause anorexia, vomiting, coughing and substemal pain. Used in mucocutaneous leishmaniasis, it may lead to severe irrflammation around pharyngeal or tracheal lesions which may require corticosteroid administration to control. Meglumine antimoniate is similar. 

Allopurinol has an antileishmanial effect in vitro and in animals, its effect being strongly increased by the addition of antimonial compounds. Allopurinol alone as well as in combination with meglumine antimoniate has been used in clinical studies. In a small study in patients with leishmaniasis and HIV infection, chnical and parasitological cure was achieved in four of five cases treated for 4 weeks, but in only one of the six treated for 3 weeks (1). 

Antimony salts have in the past found many uses in medicine, and antimony compounds, especially penta-valent ones, are still used to treat Schistosoma japoni-cum infestation and leishmaniasis (2). Antimony is also used as an emetic. Attention is being paid to the anticancer potential of antimony compounds (3,4). As with many other metals, occupational and environmental exposure is possible and can act additively with medical exposure. 

However, in contrast to arsenic, antimony compounds remain of medicinal importance, particularly in the treatment of various parasitic infections including leishmaniasis, schistosomiasis, and trypanosomasis. Coordination compounds used include the sodium or potassium antimony tartrates and substituted catecholate complexes, which are O-donor complexes, whilst S-donors are utilized in 2,3-dithiosuccinate derivatives.While the mode of action is unclear in many cases, the attraction of these compounds, in addition to their clinical effectiveness, is their simplicity of manufacture and low cost. 

Antimony (Sb) compounds have been known since ancient Egyptian times and were used as cosmetics by the women of that era. In the sixteenth century, Sb preparations were thought to be wonder drugs and in the nineteenth century were prescribed for a number of conditions. Antimony compounds are used today as the standard treatment against parasitic diseases, such as leishmaniasis, schistosomiasis, and bilharziasis. ... 

The introduction of tartar emetic (1) in 1912 for the treatment of mucocutaneous leishmaniasis heralded a new era in the treatment of the disease, which was followed by the investigation of a number of other antimonials for clinical efficacy in leishmaniasis. This led to the discovery of a number of fivevalent antimony compounds, that have laboratory and clinical efficacy and are better tolerated than tartar emetic. These included sodium stibogluconate (2), meglumine antimoniate (3), derivatives of stibanilic acid (stibamine, 4), stibacetin (5), ethyl stibamine (a mixture of 4, 5, antimonic acid and Et2NH in a molar ratio of 1 2 1 3 with 41-44% of fivevalent antimony content) and urea stibamine (6) have been used to treat kala-azar, cutaneous and mucocutaneous leishmaniasis in man. 

Because of the outbreak of antimony-resistant leishmaniasis and the need to develop an orally-administered therapy, the use of many other compounds has been considered. Those that appear to have clinical utility are allopurinol (62), ketoconazole (63), and both systemically and topically applied paromomycin (8) (see Antiparasitic agents, antimycotics). 

In contrast, the introduction of inorganic complexes as therapies was usually based on an observed medicinal effect. Two of the earliest inorganic remedies involved the use of mercurous chloride as a diuretic, and iron complexes as mineral supplements, introduced about 500 years ago. More recently, gold complexes have been used as antibacterials, in particular for the treatment of tuberculosis at the beginning of the twentieth century. Other traditional inorganic drugs include the use of arsenic complexes, such as arsephenamaine, to treat syphihs [1] and antimony compounds for the treatment of leishmaniasis. 

Interestingly, all of the elements in group 15 in the periodic table (N, P, As, Sb and Bi) are directly or indirectly related to the maintenance of human life as either essential elements (e.g., N and P) or therapeutic/toxic elements (e.g.. As, Sb and Bi). Currently antimony compounds (e.g., sodium stibogluconate, Pentostam ) are used clinically for the treatment of leishmaniasis and bismuth compounds (e.g., bismuth subsalicylate (BSS), colloidal bismuth subcitrate (CBS) and ranitidine bismuth citrate (RBC)) are widely used for the treatment of ulcer and Helicobacter pylori infection [l-3c,10,132,133]. Recently, clinical... 

Pentamidine has been used successfully in comses of 12 to 15 IM doses of 2 to 4 mg/kg either daily or every other day to treat visceral leishmaniasis (kala-azar caused by L. donovani). This compound provides an alternative to antimonials or lipid formulations of amphotericin B for patients who cannot tolerate the latter agents. Pentamidine isethionate given as fom IM doses of 3 mg/kg every other day has enjoyed some success in the treatment of cutaneous leishmaniasis (Oriental sore caused by L. tropica) but is not used routinely to treat this infection. 

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