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Lewisite
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==Mechanism of action== Lewisite is a [[suicide inhibitor]] of the E3 component of [[pyruvate dehydrogenase]]. As an efficient method to produce ATP, pyruvate dehydrogenase is involved in the conversion of pyruvate to [[acetyl-CoA]]. The latter subsequently enters the [[TCA cycle]]. [[Peripheral nervous system]] pathology usually arises from Lewisite exposure as the nervous system essentially relies on [[glucose]] as its only catabolic fuel.<ref name="BERG">{{cite book |author1=Berg, J. |author2=Tymoczko, J. L. |author3=Stryer, L. |title = Biochemistry|year = 2007|publisher = Freeman|location = New York|isbn = 978-0-7167-8724-2|edition = 6th|pages = 494β495}}</ref> [[File:TestYperite4030618980 242ab5c81d b.jpg|thumb|Lewisite (top row) and mustard gas test with [[Concentration|concentrations]] from 0.01% to 0.06%]] It can easily penetrate ordinary clothing and latex rubber gloves. Upon skin contact it causes immediate stinging, burning pain and itching that can last for 24 hours. Within minutes, a rash develops and the agent is absorbed through the skin. Large, fluid-filled [[blister]]s (similar to those caused by [[mustard gas]] exposure) develop after approximately 12 hours and cause pain for 2β3 days.<ref name=nrc/><ref name=":0"/> These are severe [[chemical burn]]s and begin with small blisters in the red areas of the skin within 2β3 hours and grow worse, encompassing the entire red area, for the ensuing 12β18 hours after initial exposure. Liquid lewisite has faster effects than lewisite vapor.<ref name=":0"/> Sufficient absorption can cause deadly [[hepatotoxicity|liver]] [[necrosis]]. Those exposed to lewisite can develop refractory [[hypotension]] (low blood pressure) known as Lewisite shock, with some features of arsenic toxicity.<ref>Chauhan, S.; Chauhan, S.; DβCruz, R.; Faruqi, S.; Singh, K. K.; Varma, S.; Singh, M.; Karthik, V. Chemical warfare agents. Environ. Toxicol. Pharmacol. 2008, 26, 113β122</ref> Lewisite damages [[Capillary|capillaries]], which then become leaky, reducing blood volume required to maintain blood pressure, a condition called [[hypovolemia]]. When the blood pressure is low, the kidneys may not receive enough oxygen and can be [[Kidney damage|damaged]].<ref name=":0"/> Inhalation, the most common route of exposure, causes burning pain and irritation throughout the respiratory tract, [[nosebleed]] (epistaxis), [[laryngitis]], [[Sneeze|sneezing]], [[cough]]ing, [[vomiting]], difficult breathing ([[dyspnea]]), and in severe cases of exposure, can cause fatal [[pulmonary edema]], [[pneumonitis]], or [[respiratory failure]]. Ingestion results in severe pain, nausea, vomiting, and tissue damage.<ref name=nrc>{{ cite book | url = https://books.google.com/books?id=sBIYzcfksXkC&pg=PA16 | author = U.S. National Research Council, Committee on Review and Evaluation of the Army Non-Stockpile Chemical Materiel Disposal Program | author-link = U.S. National Research Council | title = Disposal of Chemical Agent Identification Sets | page = 16 | publisher = National Academies Press | year = 1999 | isbn = 0-309-06879-7 }}</ref><ref name=":0"/> The results of eye exposure can range from stinging, burning pain and strong irritation to blistering and [[Keratitis|scarring of the cornea]], along with [[blepharospasm]], [[lacrimation]], and [[Periorbital edema|edema of the eyelids and periorbital area]]. The eyes can swell shut, which can keep the eyes safe from further exposure. The most severe consequences of eye exposure to lewisite are [[Globe rupture|globe perforation]] and [[Visual impairment|blindness]].<ref name=":0"/> Generalised symptoms also include restlessness, weakness, hypothermia and low blood pressure. It is possible that Lewisite is [[carcinogenic]]: arsenic is categorized as a respiratory carcinogen by the [[International Agency for Research on Cancer]], though it has not been confirmed that lewisite is a carcinogen.<ref>Doi, M.; Hattori, N.; Yokoyama, A.; Onari, Y.; Kanehara, M.; Masuda, K.; Tonda, T.; Ohtaki, M.; Kohno, N. Effect of Mustard Gas Exposure on Incidence of Lung Cancer: A Longitudinal Study. American Journal of Epidemiology 2011, 173, 659β666.</ref> Lewisite causes damage to the respiratory tract at levels lower than the odor detection threshold. Early tissue damage causes pain.<ref name=":0"/> Hydrolysis leads to chlorovinylarsonous acid, CVAA. === Treatment === [[Dimercaprol|British anti-lewisite]], also called dimercaprol, is the antidote for lewisite. It can be injected to prevent systemic toxicity, but will not prevent injury to the skin, eyes, or mucous membranes. Chemically, dimercaprol binds to the arsenic in lewisite. It is [[Contraindication|contraindicated]] in those with [[Peanut allergy|peanut allergies]] as it is usually formulated in peanut oil.<ref name=":0"/> Other treatment for lewisite exposure is primarily supportive. First aid of lewisite exposure consists of [[decontamination]] and [[Therapeutic irrigation|irrigation]] of any areas that have been exposed. Other measures can be used as necessary, such as [[airway management]], [[Mechanical ventilation|assisted ventilation]], and [[Monitoring (medicine)|monitoring of vital signs]]. In an advanced care setting, supportive care can include fluid and electrolyte replacement. Because the tube may injure or perforate the esophagus, [[gastric lavage]] is contraindicated.<ref name=":0"/> === Long-term effects === From one acute exposure, someone who has inhaled lewisite can develop [[chronic respiratory disease]]; eye exposure to lewisite can cause permanent visual impairment or blindness.<ref name=":0"/> Chronic exposure to lewisite can cause [[arsenic poisoning]] (due to its arsenic content) and development of a lewisite [[allergy]]. It can also cause long-term illnesses or permanent damage to organs, depending on where the exposure has occurred, including [[conjunctivitis]], aversion to light ([[photophobia]]), visual impairment, double vision ([[diplopia]]), tearing ([[Tears|lacrimation]]), dry mucous membranes, [[garlic breath]], burning pain in the nose and mouth, [[toxic encephalopathy]], [[peripheral neuropathy]], [[Epileptic seizure|seizures]], [[nausea]], vomiting, [[chronic obstructive pulmonary disease]] (COPD), [[bronchitis]], [[dermatitis]], [[Ulcer (dermatology)|skin ulcers]], [[Basal-cell carcinoma|basal cell carcinoma]], and [[Squamous-cell carcinoma|squamous cell carcinoma]].<ref name=":0"/>
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