The discussion below is meant as an overview for the lay person of certain aspects of chemical warfare agent antidotes and detoxification. Treatment for individuals exposed to these substances requires the specific diagnosis of a physician; this discussion is not meant as a guide to first aid.
Antidotes for Nerve Agents
The effects of nerve agent exposure can be mitigated by the use of antidotes. Nerve agents ( GA, GB, GD, and VX) are all potent inhibitors of the enzyme acetylcholinesterase. Acetylcholinesterase hydrolyzes a substance called acetylcholine, which transmits signals between nerve cells. When acetylcholinesterase is inhibited, acetylcholine builds up at the junction between nerve cells, effectively preventing the transmission of signals. The antidotes consist of:
- Oxime, e.g., pralidoxime, HI-6, which is thought to react with the inhibited acetylcholinesterase to remove the phosphonyl group from the nerve agent and thus regenerate the active enzyme. A schematic representation of the reaction for GB-inhibited acetylcholinesterase is shown below.
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Pralidoxime
(pryridine-2-aldoxime methyl chloride, PAM Cl) |
HI-6 |
However, oximes penetrate into the central nervous system poorly, and thus other antidotes are also required. In addition, the inhibited enzyme undergoes a further chemical reaction, known as "aging" (shown below for GD). The alkyl ester group hydrolyzes to give the enzyme monoester. This reaction produces a particularly stable complex that is resistant to both hydrolysis and regeneration by oxime. Aging takes place in hours for GB and VX, but occurs in minutes for GD; this makes GD exposure particularly difficult to treat with oximes.
- Atropine, which blocks the action of acetylcholine on the muscarinic receptors in the parasympathetic nervous system , thus counteracting many symptoms of nerve agent exposure. Atropine has the effect of drying the runny nose, drooling, and excessive sweating caused by exposure and also counteracts the respiratory depression and urinary effects of exposure.
- Anticonvulsants, such as diazepam (Valium, below) are also given to protect against convulsions and the resulting brain damage.
Soldiers and workers who handle these materials are often issued chemical agent antidote kits, which include autoinjectors containing an oxime and atropine. These photographs show one soldier using a Swedish autoinjector (which contains HI-6) as first aid on another soldier and a closeup of the autoinjector.
In addition, individuals at risk of exposure to GD can be given a carbamate pretreatment such as pyridostigmine. Carbamates reversibly inhibit acetylcholinesterase; the pyridostigmine-inhibited enzyme does not react with GD. The dose taken is intended to reversibly bind 30 to 40 percent of the available acetylcholinesterase; this has minor effects on nerve function because of the levels of acetylcholinesterase that remain. In the event of exposure to GD, the pyridostigmine-inhibited acetylcholinesterase slowly and continuously regenerates the acetylcholinesterase (half-life of the inhibited enzyme is on the order of hours), maintaining enough of the enzyme to permit transmission of nerve signals. If the oxime antidote is given, essentially all the pyridostigmine-inhibited acetylcholinesterase is regenerated. Carbamate pretreatment is believed to provide little benefit for GB or VX exposure; data are not adequate to determine benefits in case of GA or GF exposure.
Antidotes for Vesicants
There is no known antidote for exposure to mustard agent. Nevertheless, prompt medical treatment of the symptoms, including frequent irrigation of affected areas and application of topical antibiotics, as well as pulmonary care, can help in speeding recovery.
The effect of Lewisite can be prevented by rapid topical application of 2,3-dimercaptopropanol, known as British anti-Lewisite (BAL). BAL reacts with Lewisite to give a non-toxic arsenic derivative.:
However, the activity of BAL is limited because of low water solubility and toxicity. For this reason, 2,3-dimercaptopropanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are more commonly used in place of BAL as treatments for systemic Lewisite poisoning.
Antidotes for Other Chemical Warfare Agents
Chlorine, phosgene, diphosgene, triphosgene, and perfluoroisobutylene all effect the lungs directly, and have no specific antidotes; the only treatment is removal from the contaminated area. Medical care includes pulmonary care and complete rest.
Cyanide inhibits the cellular enzyme cytochrome oxidase, which disrupts oxygen metabolism and energy generation by the cell. The effects of hydrogen cyanide and cyanogen chloride can be treated using inhaled amyl nitrite, intravenous sodium nitrite and sodium thiosulfate, and inhaled oxygen. The nitrites convert hemoglobin to methemoglobin, which removes free cyanide as cyanmethemoglobin. Thiosulfate converts cyanide to thiocyanate through the action of the enzyme rhodanase.
Finally, the antidote for the psychotropic agent BZ is physostigmine, a acetylcholinesterase-inhibiting carbamate that crosses the blood-brain barrier.
Detoxification
Chemical warfare agents at sublethal doses are detoxified in the body to varying degrees:
- Nerve agents: the rate of natural regeneration of acetylcholinesterase is slow and depends on the specific agent. Nerve agents have other effects on the nervous system that are essentially cumulative.
- Vesicant agents: Mustard is not detoxified; Small, repeated exposures increase sensitivity and lead to cumulative effects. Detoxification of Lewisite is more rapid.
- Choking agents (chlorine, phosgene, diphosgene, triphosgene, perfluoroisobutylene): not detoxified; cumulative
- Blood agents (hydrogen cyanide, cyanogen chloride): variable rates
- Tear gases: very rapid
- Arsenical irritants: long-lasting and cumulative