How does Nerve Gas Kill?
Nerve gas poisoning made the headlines a couple of years back with the nerve agent ‘Novichok’ poisonings in Salisbury, England. Similar headlines were also made in countries like Britain and long ago in the capital city of Japan. The events were truly tragic and shocking to know that a simple nerve gas like Sarin can lead to a number of deaths in minutes!
This special article aims to enlighten and signpost healthcare professionals towards the general management of nerve agent poisoned patients. Drawing on a broad range of sources, here we will discuss nerve agents, how they work, and how to recognise and treat nerve agent poisoning.
What is Nerve Gas?
Nerve agents were used as chemical weapons, Credits: pixabay
Nerve agents are organic compounds of phosphorous that are highly toxic to human beings. Chemically, nerve agents are phosphonic or phosphoric acid derivatives. These highly toxic agents feature a chiral phosphorus atom which is linked to four different substituents which makes it even more toxic when comes into contact with the human body (1-3).
Also, Nerve agents due to their wide range of physicochemical properties can exhibit different characteristics and are also classified as chemical warfare agents. Currently, there are three types of nerve gas agents which are classified based on their potency (1-3).
VX – Most potent
Soman- More potent than Sarin and less potent than VX
Sarin- Least potent
How do Nerve Agents cause Poisoning?
Nerve agents inhibit acetylcholine breakdown, Credits: pixabay
Nerve agents exert their toxic effects by inhibiting the breakdown of acetylcholine. Nerve agents potentially act by activating two different classes of receptors:
Nicotinic and
Muscarinic receptors
Acetylcholine is the chief neurotransmitter of the parasympathetic nervous system. The neurotransmitter serves a plethora of functions by sending a chemical message released by nerve cells to other cells, such as neurons, muscle cells and gland cells. (1-3).
Nerve agents act as irreversible inhibitors of acetylcholinesterase, an enzyme responsible for acetylcholine breakdown. This results in excessive accumulation of acetylcholine neurotransmitter in the body. Excessive accumulation of this neurotransmitter leads to an overstimulation of cholinergic neurotransmission followed by desensitization with toxic and fatal consequences 1.
Symptoms of Nerve Gas poisoning. How does nerve gas kill?
A man with paralysis, Credits: pixabay
The array of symptoms associated with nerve agent poisoning is complex and nerve gas symptoms may vary due to the many physiological implications of muscarinic and nicotinic signalling. Some of the main and most common symptoms are listed below:
Symptoms due to alteration of nicotinic and muscarinic signalling at parasympathetic ganglia include- an excessive constriction of the pupil of the eye (Miosis), vomiting, wheezing, rapid drop in blood pressure, and increased nasal and submucosal mucus secretion.
Symptoms due to alteration of nicotinic signalling in the sympathetic ganglia include Elevated blood pressure.
Symptoms due to alteration of nicotinic signalling at the neuromuscular junction – Fasciculation and paralysis. Death typically results from respiratory drive loss or seizure
What are the Available Treatment Options?
Atropine sulphate vial, Credits: pixabay
Nerve gas effects can be counteracted based on two approaches (1,3)
Detaching the nerve agent from cholinesterase, reactivating the enzyme and allowing the breakdown of acetylcholine.
Using muscarinic antagonist to quell the effects of excessive acetylcholine action.
In the first approach, an oxime is given to the patient to mitigate the effects caused due to the activation of both nicotinic and muscarinic receptors. While in the second approach atropine is given that downregulates the effect of excessive acetylcholine action.(1,3)
To this day, atropine remains one of the primary medical countermeasures for nerve agent poisoning. It is also of special value when the symptoms are severe an oxime resistant.