Vesicants action mechanism

Chemical skin injuries differ from thermal and electrical bums in pathophysiology. Jelenko [179] stated that chemical skin injuries are different in mechanisms from those injuries caused by exposure to heat or flames [179], These mechanisms were coagulation by protein oxidation, reduction, salt formation, corrosion, protoplasmic poisoning, metabolic competition of inhibition, desiccation, and vesicant action with resultant ischemia [179],... 

Shakarjian, M.P., Heck, D.E., Gray, J.P., et al., 2010. Mechanisms mediating the vesicant actions of sulfur mustard after cutaneous exposure. Toxicol. Sci. 114, 5-19. 

Toxins present a variety of both incapacitating and lethal effect. Most toxins of military significance can be broadly classified in one of two ways. Neurotoxins disrupt the nervous system and interfere with nerve impulse transmission similar to nerve agents (Chapter 1). However, all neurotoxins do not operate through the same mechanism of action or do they produce the same symptoms. Cytotoxins are poisons that destroy cells or impair cellular activities. Symptoms may resemble those of vesicants (Chapter 3) or they may resemble food poisoning or other diseases. Toxins may also produce effects that are a combination of these general categories. The consequences of intoxication from any individual toxin can vary widely with route of exposure and dose. In addition, some toxins act as biomediators and cause the body to release excessive, and therefore harmful, amounts of chemicals that are normally produced by the body. 

Vinblastine is an alkaloid derived from the periwinkle plant Vinca rosea. Its mechanism of action involves inhibition of tubulin polymerization, which disrupts assembly of microtubules, an important part of the cytoskeleton and the mitotic spindle. This inhibitory effect results in mitotic arrest in metaphase, bringing cell division to a halt, which then leads to cell death. Vinblastine and other vinca alkaloids are metabolized by the liver P450 system, and the majority of the drug is excreted in feces via the biliary system. As such, dose modification is required in the setting of liver dysfunction. The main adverse effects are outlined in Table 54-4, and they include nausea and vomiting, bone marrow suppression, and alopecia. This agent is also a potent vesicant, and care must be taken in its administration. It has clinical activity in the treatment of Hodgkin s... 

Future directions appear to focus on acquiring additional in-depth understanding of the mechanism of action of these agents through the development of experimental models for vesicant-induced injury, and an application of this information in the development of therapeutic measures for the prevention and treatment of vesicant-induced injury. 

Sulfur mustards are vesicants and alkylating agents however, the biochemical mechanisms of action are not clearly understood. They are highly reactive and combine rapidly with proteins, DNA, or other molecules. Therefore, within minutes following exposure, intact mustard or its reactive metabolites are not found in tissue or biological fluids. Sulfur mustards also have cholinergic activity, stimulating both muscarinic and nicotinic receptors. The onset of clinical symptoms and their time of onset depend on the severity of exposure. The death rate... 

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