Due to the recent Skripal attack, I thought we could look at nerve agents and how they function within the body and cause devastating effects.
It seems that the agent used in this recent attack was Novichok, which is part of the organophosphate family of nerve agents.
Firstly, it is key to understand how a signal is communicated from one nerve to another. For a signal to be passed between cells in the nervous system acetylcholine is released from the pre-synaptic cell and enters the space (synapse) between cells. The acetylcholine can then either re-enter the presynaptic cell, bind to a receptor on the postsynaptic cleft or be broken down by an enzyme called acetylcholinesterase. The reabsorption and the breaking down of acetylcholine regulate the amount within the synapse to stop a prolonged signal into the postsynaptic nerve cell.
Organophosphates can be absorbed into the body in a number of ways, through inhalation, digestion or the dermal route (through the skin). Once present within the synapse they inhibit the acetylcholinesterase enzyme by binding to it, irreversibly at times. Therefore, the amount of acetylcholine within the synapse is no longer regulated which leads to accumulation and overstimulation of muscles.
This type of poisoning results in severe short term clinical features that can prove fatal but can also have long term effects. Organophosphates are actually used as means of suicide in people in agricultural areas of the world as it is more readily available.
Within the body, there are two types of acetylcholine receptors, nicotinic and muscarinic. Nicotinic acetylcholine receptors are found in the central nervous system and therefore when the acetylcholinesterase is blocked the increased acetylcholine causes anxiety, headaches, convulsions, ataxia, tremor and depression of the cardiorespiratory system. When the enzyme is blocked in the muscarinic synapses this results in visual disturbances with pinpoint pupils, chest tightness, wheeze as a result of bronchoconstriction, urination, increased pulmonary secretions and excessive salivation.
As soon as a nerve agent is suspected a high level of vigilance is needed in order to protect others from harm. Full personal protective equipment is needed, patients need to have their clothes removed and placed in a bag as evidence and washed down usually outside using a clean line in order to keep contaminated individuals away from those that have not come into contact with the substance until they have been washed down. Oxime agents can be used as an antidote to remove the chemical from the acetylcholinesterase enzyme, however, this needs to be administered within a certain time for it to be effective. This time frame varies based on the organophosphate compound, as when it attached to the enzyme it goes through an ageing process where a part of the molecule is removed. Oxime will not be effective on “aged” organophosphate. Atropine is another drug that can help due to its anticholinergic effects, this should be repeatedly administered until symptoms of the nerve agent have been reduced.
Having an awareness of the symptoms of nerve agents can help in the identification of such occurrences and therefore help to put protective measures in place early to protect others from coming into contact as well as helping the patient (more commonly patients) in the early administration of an antidote.
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