What is Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)?
Nerve agents are some of the most deadly chemicals that can be used in warfare. They are easy to use, which makes them a global terrorism threat. It’s important to understand the basics of nerve agents. Some of the most well-known ones are Sarin (also known as GB), Soman (also known as GD), and VX. These were first developed in the early 1900s from similar insecticides. Their ability to spread quickly and be used as weapons was discovered during World War II. But, they were never actually used in the war. But, there have been instances where these nerve agents were used in more recent history. This includes the 1995 Sarin gas attack in a Tokyo subway and the 2017 murder of Kim Jong-Nam with VX. More recently, there has been use of a new type of nerve agent called “Novichok”. These new agents are even more deadly than VX and have been used in attempts to assassinate Sergei Skripal and Alexei Navalny. All nerve agents, whether G agents, V agents, or Novichok agents, work by blocking the action of a chemical called acetylcholinesterase.
What Causes Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)?
Nerve agents are harmful chemicals that include:
* Tabun, or Ethyl dimethylamidocyanophosphate, also known as GA
* Sarin, or (RS)-propan-2-yl methyphosphonofluoridate, also known as GB
* Soman, or (O-Pinacolyl methylphosphonofluoridate), also known as GD
* VX, which is officially known as ethyl ({2-[bis(propan-2yl)amino]ethyl}sulfanyl)(methyl)phosphinate
* VE, or O-Ethyl-S-[2-(diethylamino)ethyl] ethylphosphonothioate
* VG, or O,O-Diethyl-S-[2-(diethylamino)ethyl] phosphorothioate
* VM, or O-Ethyl-S-[2-(diethylamino)ethyl] methylphosphonothioate
These nerve agents have a structure that is similar to insecticides that contain organophosphates. They were initially created in Germany around the 1930s for use as chemical weapons. After World War II, England and the United States created another group of nerve agents known as the V group.
All of these chemicals cause the same harmful effects as organophosphates. However, they are more dangerous because they are stronger, their effects last longer, and they could be more fatal. In fact, the effects of Soman can sometimes be irreversible.
Risk Factors and Frequency for Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
Exposures to certain substances are rare because of a ban by the Geneva Convention. But, they do happen occasionally. One of the key examples is the Sarin attacks in Tokyo in 1995, which affected over 5000 civilians and resulted in nearly 640 people needing treatment at a single hospital. Sadly, twelve people died in that event. There was another possible Sarin attack in Syria’s civil war in 2013 which led to around 80 deaths. Additionally, a suspected exposure to a substance called VX was noted in the attack on Kim Jong-Nam in 2017. The frequency of these types of attacks is difficult to determine because they happen unpredictably, but overall, such exposures are infrequent.
Signs and Symptoms of Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
People exposed to chemicals known as organophosphate nerve agents might experience a ‘cholinergic crisis.’ How quick the symptoms start and how severe they become is dependent on the amount and way the person was exposed. Since the effects depend on dose and the timeframe can vary depending on how the agents were absorbed, it’s vital to find out about any possible exposure within the last 24 to 48 hours.
Organophosphate nerve agents can be absorbed in different ways, with immediate effects depending on where they were absorbed. For example:
- If they come into contact with the skin, this triggers absorption and can cause local reactions like muscle twitching and sweating.
- Eye symptoms can include pinpoint pupils due to the eye’s ciliary muscle not working properly, and tears.
- Respiratory symptoms can include wheezing and feelings of chest tightness due to the airways narrowing, as well as increased nasal and lung secretions leading to coughing.
- Heart symptoms can initially include a fast heart rate, followed by a slow heart rate.
- Nonspecific gastrointestinal symptoms like nausea, vomiting, and diarrhea can result.
Typically, after an extended or significant exposure, systemic effects on the central nervous system (CNS) can become apparent. This can involve fatigue, weakness, muscle paralysis, central apnea, which is a pause in breathing, and even seizures, which can occur due to the cholinergic crisis itself or due to low oxygen levels caused by problems with breathing.
Testing for Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
If you’ve been exposed to nerve agents, the first step in your evaluation will be based on where the exposure happened. Immediate decontamination is critical to limit the impact of the exposure. This involves thorough showering and getting rid of all clothing to prevent further exposure, not only for the person exposed but also for health care providers. If your exposure occurred during a terrorist incident, it is important to begin treatment without delay, even before identifying the specific nerve agent involved.
The symptoms of exposure to all organophosphate agents, the group nerve gases fall under, are similar. So, symptom control is key. Ensuring your airways, breathing, and circulation are in good condition is the top priority after ensuring that others (including health care staff) are not exposed to the agent. Special care needs to be given to your respiratory system because issues here are the most likely cause of mortality in these instances.
In terms of detecting nerve agent exposure, unfortunately, there are no laboratory tests available that can provide real-time results. The military and similar organizations use a paper test, called M8 or M9 for quick detection in the field, but it doesn’t specify which nerve agent you’ve been exposed to. More specific tests such as GC-MS or Ion Spectrum Mobility can identify specific nerve agents but won’t tell how much of the agent you were exposed to.
To measure the level of exposure, the most common method used is to measure the level of a particular enzyme, called acetylcholinesterase, in red blood cells. However, this test is not very specific, so newer methods are being developed including a non-invasive sensor based on carbon nanotubes. These newer methods could help provide a more sensitive and accurate measure of nerve agent exposure.
Treatment Options for Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
If you’re exposed to nerve agents, the first step in treatment is to keep the healthcare provider safe and clean any contamination off your body. This involves wearing personal protective equipment following the guidelines of your local medical facility, which may involve rubber suits and respirators with charcoal filters. To clean any remaining liquid nerve agents off, a thorough cleansing of your body will be performed.
Your surroundings may also be treated with hot water and basic solutions (such as baking soda) to help break down the nerve agents. The aim is to help you breathe because nerve agents can affect the respiratory system by causing bronchoconstriction (a narrowing of the airways), increased secretions, and a decreased ability to breathe independently. To manage this, you might be given extra oxygen or require intubation – a tube placed down your throat to help your breathing.
The medications used to treat nerve agent exposure mainly include atropine, oxime-derivatives (like pralidoxime and obidoxime), and diazepam might be used. Atropine works by blocking the acetylcholine receptor, which acetylcholine (a substance that nerve agents increase in your body) uses to activate certain processes in the body. Oxime-derivatives can displace nerve agents from a special enzyme in your body, enabling it to start breaking down acetylcholine again. However, over time, this enzyme can potentially lose its ability to function if the nerve agent is not removed. This is particularly true for a nerve agent named Soman, where pralidoxime will not work because Soman disables the enzyme quickly.
In advanced cases, the effects of excess acetylcholine can cause seizures, which will require treatment with intravenous (via a drip) benzodiazepines.
Autoinjectors, which are portable devices that can give a shot of medication quickly, are available for atropine and pralidoxime. These are primarily carried by groups at high risk of exposure, like the military. Should an autoinjector not be available, both medications can be given via a shot in the muscle or a drip into the vein, but they should be given at the same time or very close together. Both medications help decrease the effects of nerve agents, and their dosage will be adjusted based on your symptoms.
There are also preventative medications available for agents such as Soman. These drugs, like pyridostigmine, work by blocking nerve agents from binding to the enzyme. Please note, if you’re using these preventative drugs, you would still need treatment with atropine and oxime derivatives if exposed to nerve agents.
What else can Acetylcholinesterase Inhibitors Toxicity (Nerve Agent) be?
Before you quickly decide that nerve agent exposure is the issue, you should also think about other common explanations that can cause similar symptoms. These include:
- Pesticides that contain organophosphate and carbamate, although the effects are usually less severe
- Type IV pyrethrins, which can produce some overlapping symptoms
- Overdose of cholinergic drugs (which affect the nervous system) such as bethanechol, neostigmine, and pyridostigmine
These possible diagnoses should be considered closely before any firm conclusion can be made.
What to expect with Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
These substances are created to be deadly. If they aren’t recognized and treated quickly, they can cause death. The chances of survival primarily depend on how fast and effectively the harmful effects can be managed. It’s worth noting that most deaths from exposure to organophosphate nerve agents, a type of poisonous chemical, are related to difficulties in breathing.
Therefore, providing aid for breathing is crucial for a good long-term recovery, even if antidotes – medicines that can counteract the poison – are not immediately at hand.
Possible Complications When Diagnosed with Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
The short-term effects of exposure to organophosphate nerve agents – a type of poison – are mainly due to an overload of a specific substance (acetylcholine) in the body. This can cause immediate health issues like weakness, numbness, or general nerve issues that might last several days to weeks. However, these symptoms tend to go away on their own.
While there isn’t direct proof of long-term health problems from low levels of exposure to these nerve agents, some patterns have been identified. Studies on individuals believed to have been exposed to nerve agents during the Gulf War or the Sarin attack in the Tokyo subway showed several non-specific symptoms. These symptoms included tiredness, nerve issues, and various mental health conditions such as depression, chronic pain, and post-traumatic stress disorder (PTSD). It’s important to note, though, that determining a direct cause and effect relationship is challenging.
Common Symptoms:
- Overload of acetylcholine
- Weakness
- Numbness
- General nerve issues
- Tiredness
- Mental health conditions (depression, chronic pain, PTSD)
Preventing Acetylcholinesterase Inhibitors Toxicity (Nerve Agent)
The best way to avoid nerve agent poisoning is by steering clear of areas where there’s a high likelihood of such substances being used. For most people, this isn’t a problem. But, if you’re in the military, it might be hard to avoid these areas. For non-military folks who are worried about possible exposure to a nerve agent (which are types of toxic chemicals), they should go straight to the hospital’s emergency room. For those who have a higher risk of exposure, like paramedics or military staff, they should always have the right protective gear with them. They should also carry auto-injectors of atropine and pralidoxime, two medications that can help treat nerve agent exposure. They might also consider preventive treatment if the exposure risk is very high.