Although this is a rather grim blog post, in light of the
recent news that more than 1,400 innocent people in Syria were killed as the
result of exposure to sarin gas, I was curious to learn about the mechanism of
sarin and other nerve agents in general.
Sarin, which has been designated by the military as “GB,” is
one of three organophosphate nerve agents that together comprise the most toxic
chemical warfare agents, the G-series.
Sarin is the most destructive nerve agent as it both colorless and
odorless and the most volatile of the G-series agents, meaning it readily
evaporates from a liquid to a gas. Its
modes of exposure include contact with skin in liquid form or inhalation as a
vapor, and because it is soluble in both fat and water, it is easily absorbed
into the body, specifically through the eyes and respiratory tract in the case
of the gas.
Let’s take a look at the consequences of sarin gas exposure
at the physiologic level. As a reminder, within the nervous system, electrical
impulses travel down the axons of nerves to nerve terminals, where they cause
the release of chemicals called neurotransmitters that subsequently bind to
receptors on glands, muscles or other nerves to initiate a response. The activity of acetylcholine (ACh), one of
the most common neurotransmitters, is regulated by acetylcholinesterase (AChE),
an enzyme that is responsible for the metabolism and inactivation of ACh and
prevents its overstimulation of cholinergic receptors. Sarin is an AChE inhibitor and thus prevents
the breakdown of ACh, which then harmfully accumulates at three specific
synapses – muscarinic, nicotinic and CNS synapses – that are responsible for
the wide range of effects observed after exposure, including vomiting,
diarrhea, bradycardia (slow heart rate), sweating, muscle twitches followed by
muscle weakness and paralysis, irritability, giddiness, lethargy, amnesia,
seizures and respiratory distress. The
victims in Syria most likely experienced loss of consciousness, convulsions,
muscle weakness and paralysis, and respiratory failure following inhalation of
the gas.
Clinical effects of sarin are contingent on the strength and
length of exposure. Minimal exposure can
be treated and reversed if done right away. It is also important to keep in
mind that AChE inhibitors also have important medical uses, including treatment
of Alzheimer’s disease, myasthenia gravis and as reversal agents for
neuromuscular blocking agents. However, these agents are much less potent and
dangerous than those which comprise the G-series.
REFERENCES:
Huebner, K. (2011, April 18). CBRNE - Nerve agents, G-series
- tabun, sarin, soman. Medscape, Retrieved from http://emedicine.medscape.com/article/831648-overview
Orhan, I.,
Orhan, G., & Gurkas, E. (2011). An overview on natural cholinesterase
inhibitors--a multi-targeted drug class--and their mass production. PubMed,
11(10), 836-842. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21762104
As grim details continue to emerge from the chemical weapons attack in Syria I thought it would be important to talk about how nerve gas exposure is treated. Danielle talked about the mechanism of Sarin gas as a weapon. As she described, Sarin inhibits acetylcholinesterase, causing a build up of acetylcholine. Sarin can be absorbed through the skin and eyes, or inhaled through the lungs. The severity of the reaction depends on the dose of exposure. Effects can be felt within minutes, and exposure to large doses can cause death within 1-10 minutes.
ReplyDeleteSarin exposure can be treated with pharmaceuticals if the first responders are equipped to handle a chemical attack and if the victims are able to survive until help arrives. Treatment is Atropine and pralidoxime chloride which may be combined in an autoinjector (think epi-pen) for quick treatment. Atropine works by blocking acetylcholine receptors, reducing the effects of excessive acetylcholine. Pralidoxime chloride works by removing the inhibitor from acetylcholinesterase allowing it to metabolize the excess acetylcholine. Doses may vary based on age, health, and level of exposure.
REFERENCES:
The Emergency Response Safety and Health Database. 2013. SARIN (GB) : Nerve Agent [Internet]. Center for Disease Control web site [updated 2013 Jul 18]. Available from: http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750001.html
Grim may be the most politically correct way to put it... However, truly an interesting and thought provoking topic, especially when we get to learn about the physical mechanisms behind what happens in the world (despite how atrocious those happenings might be). After reading this post, I wanted to know a little more about this so called "G-series" given that is has attracted so much attention and because the name itself exudes some ominous feeling of death via letter.
ReplyDeleteSo, the G-series consists, as Danielle stated, a group of organophosphate nerve agents that prevent the breakdown of ACh via inhibiting AChE. Furthermore, there are four members of "the series:" Sarin (GB), VX, Tabun (GA), and Soman (GD), all of which will readily vaporize from their liquid state (OSHA 2004). Interestingly enough, the Tabun was developed in hopes of finding a more efficient pesticide in Germany with a project that started in 1934 (can anyone think of what else was happening during this time period....). Also, something interesting, each chemical was developed by a different country (Shea 2012). Chemical weapons race, seems a bit inhumane, no?
References:
Blog.chembark.com. Sarin: The History and Politics of a Chemical Warfare Agent [Internet]. [cited in 2013 Sep 3]. Available from: http://blog.chembark.com/wp-content/uploads/2013/04/Sarin-Handout.pdf
Occupational Health and Safety Administration. 2004. Emergency Preparedness: Nerve Agents [Internet]. OSHA website. [cited in 2013 Sep 3]. Available from: https://www.osha.gov/SLTC/emergencypreparedness/guides/nerve.html
Shea DA. 2012. Chemical Weapons: A Summary Report of Characteristics and Effects. Congressional Research Service: Report for Congress [Internet]. 7(5700). Available from: http://www.fas.org/sgp/crs/nuke/R42862.pdf