Hemophilia and other coagulation disorders: neurologic aspects
Jun. 20, 2022
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British anti-Lewisite was developed in 1941 as an antidote to lewisite, an arsenic-based chemical warfare agent. British anti-Lewisite is used in arsenic, gold, and mercury (soluble inorganic compounds) poisoning. This drug is not indicated in patients with iron, cadmium, selenium, silver, or uranium poisoning. British anti-Lewisite is occasionally used for both acute heavy metal intoxication and Wilson disease. Parenteral British anti-Lewisite can be successfully used in lead poisoning if oral therapy fails. Dimercaprol compound is useful for the treatment of potentially life-threatening acute arsenic poisoning as well. Mobilization of cerebral deposits of mercury is difficult to achieve. A combination of low-dosed British anti-Lewisite plus dimercaptopropane sulfonic acid can help in mobilizing the intracerebral mercury into the circulation, thus, facilitating urinary excretion. In in vitro testing, it has been observed that dimercaprol has potential to treat snakebite. Dimercaprol, a metal ion chelator, acts against Zn2+-dependent snake venom metalloproteinases, which mediates procoagulant property of snake venom. Lately, a combination of arsenic trioxide and dimercaprol has been found a promising enhancer of radiosensitivity in mice with pancreatic cancer xenografts.
• British anti-Lewisite is a chelating agent.
• British anti-Lewisite has a greater affinity for metal than for body proteins, and thus reverses the functioning of these proteins.
• British anti-Lewisite is used in arsenic, gold, and mercury (soluble inorganic compounds) poisoning.
• British anti-Lewisite is not indicated in iron, cadmium, selenium, silver, or uranium poisoning.
• British anti-Lewisite is administered by deep intramuscular injections of 2 to 5 mg/kg, 1 to 4 times per day for up to 10 days.
• It is no longer the preferred chelating agent.
Lewisite (2-chlorovinyldichoroarsine) is an arsenic-based vesicant chemical warfare agent that was initially developed, although not used, by the United States during World War I. It was believed to have much greater toxicity than mustard gas, with some animal data suggesting that as little as one-third teaspoon on the skin would result in human death (28). During the period between World Wars I and II, all major countries developed lewisite production facilities and, as World War II loomed, both Great Britain and the U.S. initiated research projects designed to develop an antidote to lewisite. On July 21, 1940, an Oxford University group of chemists reported the successful development of British anti-Lewisite (21). On first arrival in the United States in 1941, a series of studies was initiated to determine British anti-Lewisite’s biochemistry, pharmacology, experimental therapeutics, and clinical applications (34). Improvements in synthesis resulted in the development of effective therapeutic ointments and solutions. British anti-Lewisite was produced during World War II by DuPont. Plans for the possible production of 200,000 pounds per year were developed (34). During and after the war, nonmilitary uses for the heavy metal chelating action of British anti-Lewisite became apparent. Eagle and Magnuson found that 48 patients with severe or mild symptoms of arsenical encephalopathy were effectively treated with British anti-Lewisite (13). By 1947, 32 articles had been published or were in press on the therapeutic value of British anti-Lewisite (21). British anti-Lewisite was the drug of choice for treatment of intoxication with arsenic, antimony, mercury, and gold. It was also considered effective in cases of intoxication with bismuth, copper, and nickel (11).
In 1949, Porter found a 7-fold increase in copper excretion in 2 patients with Wilson disease and some decrease in neurologic signs after treatment with British anti-Lewisite (22). In 1951, Cummings at the National Hospital, Queen Square, and Denny-Brown and Porter at Boston City Hospital conducted studies on the long-term effects of British anti-Lewisite in 4 and 5, respectively, patients with Wilson disease. The effects were definitive and dramatic; the patients exhibited great improvement in accordance with marked increases in urinary copper excretion (10; 12). British anti-Lewisite’s use as the primary treatment for Wilson disease was short-lived because Walshe, in 1956, showed the value of the less toxic chelating agent, penicillamine (32). Other agents have been developed since (06). Nevertheless, British anti-Lewisite may still have some therapeutic value in patients who do not respond well to more modern agents (24). It has been postulated that, because British anti-Lewisite is nonpolar, it may accelerate the removal of copper from within the brain compared to more modern agents (24; 31).
British anti-Lewisite is not generally recommended for use today because more efficient and safer chelators for oral or parenteral administration have been developed (02; 05; 03). In the United States it is marketed by Akorn as British anti-Lewisite in Oil® in 3 mL 100 mg/mL single-use ampoules (the solute is peanut oil).
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