Lewisite antidote

Two water-soluble analogs of dimereaprol have also been been studied as lewisite antidotes. They are meso 2,... 

Two water-soluble analogs of dimercaprol have been studied as lewisite antidotes, namely meio-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto- 1-propane sulfonic acid (DMPS) (see review by Aposhian, 1993). Their structures are as follows ... 

Inhalation and dermal absorption mustards no antidote. For lewisite and ewisite/ mustard lmixtures British Anti-Lewisite (BAL or Dimercaprol) IM (rarely available). Thermal burn therapy supportive care (respiratory support and eye care). 

Antidotes British Anti-Lewisite (BAL) can be given by intramuscular injection as an antidote for systemic effects but has no effect on the local lesions of the skin, eyes, or airways. Treatment consists primarily of supportive care. 

Treatment—Patients should be decontaminated immediately prior to treatment using the decontamination method presented in Section 7.3.2. British Anti-Lewisite (BAL) dimercaprol antidote will alleviate some effects. It is available as a solution in oil for intramuscular administration to counteract systemic effects. It is not manufactured currently in the forms of skin and eye ointments.2... 

Dimercaprol (BAL, British Anti-Lewisite) was developed in World War 11 as an antidote against vesicant organic arsenicals (B). It is able to chelate various metal ions. Dimercaprol forms a liquid, rapidly decomposing substance that is given intramuscularly in an oily vehicle. A related compound, both in terms of structure and activity, is di-mercaptopropanesulfonic acid, whose sodium salt is suitable for oral administration. Shivering, fever, and skin reactions are potential adverse effects. 

For example, the elucidation of the mechanism of action of the war gas Lewisite (Fig. 1.2), which involves interaction with cellular sulfhydryl groups, allowed the antidote, British anti-Lewisite or dimercaprol (Fig. 1.2), to be devised. Without the basic studies performed by Sir Rudolph Peters and his colleagues, an antidote would almost certainly not have been available for the victims of chemical warfare. 

The first chelating agent developed as an antidote to a heavy metal poison was 2,3-dimereaptopropanol (dimercaprol, British Anti-Lewisite, BAL). Originally intended for use on victims of the arsenical vesicant poison gas Lewisite52, it has since proved efficacious in the treatment of antimony, gold and mercury poisoning as well as... 

Lewisite, dichloro(2-dichlorovinyl)arsine is a chemical that contains arsenic, which though a liquid is sufficiently volatile to be dispersed among enemy troops. The arsenic atom in the lewisite reacts with proteins and causes terrible blisters on the skin and damage to the eyes and lungs if inhaled. Fortunately, an antidote was devised as a result of the work of the British biochemist Rudolf Peters. The antidote was appropriately named British anti-lewisite (dimercaprol), and abbreviated to BAL. 

Similar to the mustard agents, exposure prevention is the first line of defense against lewisite. Rapid decontamination is especially relevant to lewisite exposure due to the rapid development of pain (1-2 min) associated with lewisite exposure. Unlike other vesicants, an effective antidote for lewisite toxicity exists in the form of British anti-lewisite (BAL 2,3-dimercaptopropanol) which binds with arsenicals, thereby countering the lewisite-induced damage. Such chelation therapy is associated with notable side effects (e.g. renal effects) and requires carefiil medical management. More effective analogs of BAL have been developed with less significant side effects. 

Once incorporated, unbound lewisite is quickly hydrolyzed. Its predominant metabolite is 2-chlorovinylarsonous acid, CVAA (Figure 50.8). Analytical methods to confinn lewisite exposure have, at least in the past, focused on the detection and quantification of CVAA. However, Noort et al. (2002) also pointed out that due to the high affinity of arsenic towards sulfhydryl groups, adducts of lewisite/ CVAA and cysteine residues of proteins are formed. In an in vitro study, incubating " C-labeled lewisite with human blood samples, 90% of lewisite was found in erythrocytes, whereas 25 to 50% of arsenic was bound to globin. From these protein adducts, CVAA can be released to form an adduct with the antidote British Anti-Lewisite (BAL) (Fidder et al, 2000). The authors were also able to identify a specific protein adduct of lewisite formed with the cysteine residues 93 and 112 of P-globin. See Detection of DNA and protein adducts of vesicants, below, for analytical... 

Lewisite, a vesicant with HD-Uke properties, causes a similar constellation of signs and symptoms involving the skin, eyes, and airways as well as systemic effects (e.g. increased capillary permeability) after absorption. However, it does not produce immunological suppression like mustard. Another difference is that the management of lewisite toxicity includes an antidote, British Anti-Lewisite (BAL) (Yue/u/.,2003). 

Lewisite Shock Pulmonary injury Blisters Decontamination soap, water, no bleach Antidote BAL-dimercaprol may decrease systemic effects of lewisite Pulmonary management BAL 3-5 mg/kg deep IM q4 h X 4 doses (dose depends on severity of exposure and symptoms) Skin management BAL ointment Eye management BAL ophthalmic ointment... 

Treatment for these poisons is the administration of sulfhydryl reagents with adjacent sulfhydryl groups to compete with the dihydrolipoyl residues for binding with the metal ion, which is then excreted in the urine. Indeed, 2,3-dimercaptopropanol (see Figure 17.20) was developed after World War I as an antidote to lewisite, an arsenic-based chemical weapon. This compound was initially called BAL, for British anti-lewisite. 

Organoarsenicals were used as poison gases in World War I. The most notorious of these was Lewisite (140). During the years before World War II, researchers looked for antidotes and found the compound 2,3-dimercaptopropanol, now commonly known as British Anti-Lewisite or BAL (190). This compound has proven extremely effective in the treatment of lead and mercury poisoning. 

The oil-soluble BAL (British anti-Lewisite 2,3-dimer-captopropanol) administered intramuscularly appears to be the antidote of choice for antimony poisoning. The antidotal action of BAL depends on its ability to prevent or break the union between antimony and vital enzymes. 

Dimercaprol is a synthetic therapeutic substance developed during World War II as an antidote against the vesicant arsenic war gases (lewisite). The first experiments were based on the fact that arsenic products react with SH radicals. Among all the compounds originally tested, BAL was the most effective and the least toxic. In 1951, BAL was used by a... 

British antilewisite (BAL) or dimercaprol was developed as an antidote for lewisite. It is used in medicine as a chelating agent for heavy metals. Although BAL can cause toxicity itself, evidence suggests that BAL in oil administered intramuscularly will reduce the systemic effects of lewisite. BAL skin and ophthalmic ointment decrease the severity of skin and eye lesions when applied immediately after early decontamination, but neither of these ointments is currently manufactured. 

Research on anesthetic gases during the nineteenth century facilitated the development and use of poisonous war gases in the twentieth. This led to attempts to counteract the effects of chemical warfare agents and other toxic compounds, particularly arsenicals, introduced by Paul Ehrlich (1854-1915) for the treatment of syphilis. This resulted in the synthesis of the first specific chemical antidote, British anti-Lewisite (BAL), in 1945 by R.A. Peters, L.A. Stocken, and R.H.S. Thompson in Oxford. Studies on the mechanistic bases for toxicity were applied to the synthesis of effective insecticides. For example, during the 1940s, the Swiss chemist Paul Muller discovered a compound, now known as DDT, that poisons insects on contact. 

Treatment of inorganic arsenic poisoning involves decontamination procedures and use of the antidote BAL (British anti-lewisite compound 2,3-dime-rcaptopropanol). Use of demulcent to coat the gastrointestinal tract and the use of antibiotics is also recommended. Organic arsenic poisoning treatment involves only withdrawal of the feed involved, with recovery occurring in 3-5 days. Severely affected pigs should be culled. 

The clinical effects of lewisite are similar to those of mustard. However, unlike mustard, lewisite liquid or vapor produces irritation and pain upon contact. As with mustard, immediate decontamination will limit lewisite s damage to skin or eyes. A specific antidote for the systemic effects of the agent exists in the form of British Anti-Lewisite (BAL). BAL must be used under medical supervision owing to its own toxic properties. There is no need to have this antidote far forward, and it can be kept in modest quantities because of the minimum threat from lewisite. 

In both liquid and vapor forms, phosgene oxime is highly corrosive and penetrates clothing and rubber readily and, like lewisite, it produces severe pain upon contact. Like mustard, phosgene oxime has is no antidotal therapy. 

Although Lewisite has similar effects as sulfur and nitrogen mustard, terrorists may not find it as attractive as a weapon due to its immediate effect and the existence of an effective antidote (15). When combined with mustard. Lewisite achieves a lower freezing point, making it more effective for ground dispersal and aerial spraying (24). 

The second exception is that while an antidote is available for systemic effects of Lewisite exposure, there are no antidotes for nitrogen mustard or sulfur mustard toxicity, with one minor caveat if given within minutes after exposure, intravenous sodium thiosulfate may prevent death due to sulfur mustard exposure (25). Otherwise, the medical management for skin, ocular, and respiratory exposure is only supportive. One guideline physicians can follow is to keep skin, eye, and airway lesions free from infection. 

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