What is Acetylcholinesterase Inhibitors Toxicity?
Nerve agents are among the deadliest and simplest to use chemical warfare weapons. Because of the ongoing risk of global warfare , it’s wise to have some basic knowledge about these lethal substances. Some of the well-known nerve agents include Sarin, Soman, and VX. These were first created in the early to middle of the 20th century, inspired by chemically similar bug killers. However, their highly unstable nature led to their potential as weapons during World War II, although they were not used in that war. More recent cases include the 1995 Sarin gas attack in a Tokyo subway, the 2017 use of a variation of VX in the murder of Kim Jong-Nam. Lastly, there’s the use of “Novichok”, or newcomer agents, which are even stronger than VX, used in attempts to assassinate Sergei Skripal and Alexei Navalny. All these nerve agents, the G, V, and Novichok types, work by stopping the function of a substance in the body called acetylcholinesterase.
What Causes Acetylcholinesterase Inhibitors Toxicity?
Nerve agents are a type of harmful chemical that include substances like Tabun (GA), Sarin (GB), Soman (GD), VX, VE, VG, and VM. Details about these specific agents can be confusing, due to the scientific names like ‘Ethyl dimethylamidocyanophosphate’ for Tabun or ‘(RS)-propan-2-yl methyphosphonofluoridate’ for Sarin.
These chemicals have a structure similar to bug-killing sprays and were first created in Germany around the 1930s. They were made to be used as chemical weapons. Some other types, known as the V group, were made by England and the United States after World War II.
Nerve agents produce the same harmful effects as other types of harmful organophosphate chemicals. However, nerve agents can be more dangerous because they are stronger, their effects last longer, and some types like Soman can even cause permanent damage. They can also potentially be more deadly.
Risk Factors and Frequency for Acetylcholinesterase Inhibitors Toxicity
The Geneva Convention has banned certain harmful substances, so instances where people get exposed to these are relatively rare. However, they do still periodically happen. For example, in the 1995 Sarin attack in Tokyo, over 5000 civilians were exposed to the deadly substance, with nearly 640 of them needing medical treatment at a single hospital. Unfortunately, 12 people lost their lives due to this event.
During the Syrian civil war in 2013, another suspected Sarin attack occurred, causing the death of close to 80 people. More recently, in 2017, the substance known as VX was suspected to have been used in the attack on Kim Jong-Nam. Because these attacks are sporadic and deliberate, we can’t clearly determine their frequency. However, it’s safe to say that their overall occurrence is still low.
Signs and Symptoms of Acetylcholinesterase Inhibitors Toxicity
Exposure to organophosphate nerve agents can cause a condition known as a cholinergic crisis. How fast the symptoms appear and how severe they are will depend on the quantity of exposure and the way the agent entered the body. To really understand a patient’s symptoms, it’s crucial to know if they’ve potentially been exposed to these agents during the previous 24 to 48 hours.
Organophosphate nerve agents are absorbed through different routes. Their immediate effects are determined by whatever region they come into contact with. For example, if they touch the skin, they start to absorb and you may see symptoms like local muscle twitching and sweating. If they’ve affected the eyes, symptoms might include miosis, or pupil constriction due to a non-functioning ciliary muscle, and excessive tearing.
Other symptoms can depend on the organ system affected:
- Respiratory symptoms: Includes wheezing, tightness in the chest due to constricted bronchioles, and increased nasal and lung secretions leading to coughing.
- Cardiac symptoms: Individuals might initially experience a rapid heart rate (tachycardia), followed by a slower heart rate (bradycardia).
- Gastrointestinal effects: Often results in unspecific symptoms such as nausea, vomiting, and diarrhea.
- Central Nervous System (CNS) effects: Usually seen after prolonged or significant exposures, these include slow heart rate, fatigue, weakness, paralysis, and central apnea (when the brain doesn’t send the right signals to the muscles that control breathing). Seizures can also occur due to the cholinergic crisis or lack of oxygen from respiratory compromise.
Testing for Acetylcholinesterase Inhibitors Toxicity
If you’ve been exposed to nerve agents, your evaluation should depend on the situation in which you were exposed. The most important immediate step is to remove all clothing and thoroughly shower to wash off any remaining agent. This not only protects you from further exposure but also helps ensure health care providers aren’t exposed either.
If nerve agents were involved in a possible biowarfare incident, doctors won’t wait to identify the specific nerve agent before starting treatment. Regardless of the exact nerve agent, overall treatment approaches are similar. Doctors will keep a close eye out for signs of a cholinergic crisis, a sudden increase in body functions like salivation, digestion, and urination, which can help them provide the right care.
First, doctors will ensure your airway is clear, you can breathe, and your circulation is good. At the same time, they’ll take steps to protect themselves and their staff from secondary exposure to the nerve agent. They’ll also pay close attention to your lungs because respiratory failure is the main cause of death in these cases.
There are no laboratory tests readily available to identify nerve agents. There are several field tests used to rapidly detect exposure, like M8 or M9 paper, but these don’t specify the nerve agent or show how much of it you were exposed to. For identifying the specific nerve agents, equipment like GC-MS or Ion Spectrum Mobility is used, but this isn’t useful for determining the amount of exposure either.
To establish the volume of exposure, the most common method is to check how much of a chemical called acetylcholinesterase is inhibited within your red blood cells. However, this method isn’t very specific, newer techniques like sensors based on tiny carbon tubes are being developed as a more sensitive, non-invasive way of measuring.
Treatment Options for Acetylcholinesterase Inhibitors Toxicity
In the event of possible exposure to nerve agents, the main focus is preserving the safety of the healthcare provider and decontaminating the patient. Protective gear, such as rubber suits and charcoal-filtered respirators, is used according to local guidelines. The next step is to thoroughly cleanse the patient to eliminate any potentially harmful substances. In addition, hot water and basic solutions with a pH above 8 can be very beneficial in breaking down nerve agents.
The aim of the treatment for exposure to organophosphorus nerve agents is mainly to maintain respiratory function. This is because the inhibition of a specific enzyme called acetylcholinesterase can cause detrimental effects on the respiratory system. These effects include narrowing of the air passages in the lungs, increased secretions, and reduced respiratory drive. Therefore, providing additional oxygen and considering early intubation (inserting a tube into the trachea to maintain an open airway) are crucial.
The key medications in the treatment are atropine, medications derived from oxime like pralidoxime and obidoxime, and possibly diazepam. Atropine works by blocking the acetylcholine receptor, reducing the impacts of excess acetylcholine. Oxime-derivatives, such as pralidoxime, can displace the nerve agents from the enzyme, letting it to start breaking down acetylcholine again. In severe cases, seizures caused by excess acetylcholine may require treatment with diazepam administered intravenously.
Atropine and pralidoxime are available in autoinjectors for easy administration, especially by organizations with a high risk of exposure, like the military. If an autoinjector is not available, both medications can be given via injection into a muscle or a vein, preferably closely together in time. As a preventive measure, medications like pyridostigmine can be utilized, particularly against agents such as Soman. However, using preventive treatments doesn’t eliminate the need for treatment with atropine and oxime derivatives.
What else can Acetylcholinesterase Inhibitors Toxicity be?
When someone shows signs of possible nerve agent exposure, it’s important to also consider other common causes behind the symptoms. For instance, pesticides containing organophosphates and carbamates could be the culprit, although their effects are usually less severe. Type IV Pyrethrins, a type of insecticide, can also cause similar symptoms. Overdosing on certain drugs like bethanechol, neostigmine, and pyridostigmine, which affect nerve communication, should also be taken into account. These possibilities underline the importance of comprehensive medical investigation before reaching a conclusion.
What to expect with Acetylcholinesterase Inhibitors Toxicity
These substances are designed to be deadly. If these chemical attacks are not identified and treated quickly, they can lead to death. The survival rate mainly depends on how swiftly and effectively the known harmful effects are managed. Most of the deaths from exposure to organophosphate nerve agents, which are toxic compounds, are due to respiratory failure. Therefore, supporting the breathing function is essential to positive long-term outcomes, even if antidotes are not immediately available.
Possible Complications When Diagnosed with Acetylcholinesterase Inhibitors Toxicity
Exposure to organophosphate nerve agents can lead to short-term and possible long-term effects. The short term effects are due to an excess of a certain chemical in the body, acetylcholine, at local areas and the effects that come from that. There could be delayed effects too, like body weakness, goosebumps, or generalized nerve disease, which might last for a few days to weeks. Typically, these effects go away.
On the other hand, there’s no clear evidence that exposure to low levels of nerve agents can cause long-term complications. Still, some studies suggest that people who have thought to be exposed to nerve agents during the Gulf War or to Sarin after the Tokyo subway incident might exhibit non-specific symptoms. These include:
- Fatigue
- Nerve disease
- Different mental health issues like depression
- Chronic pain
- Post-traumatic stress disorder (PTSD)
However, proving a direct cause-and-effect relationship between these symptoms and the nerve agent exposure is difficult.
Preventing Acetylcholinesterase Inhibitors Toxicity
The best way to avoid nerve agents is to steer clear of areas where there’s a high risk of them being used. It won’t be a problem for most people, but it might not always be possible for military personnel. If everyday people think they might have been exposed to a nerve agent, they should get to an emergency room right away. High-risk individuals like paramedics or military staff will need to be proactive. They should always have the right protective gear, carry emergency injections of medications called atropine and pralidoxime, and think seriously about taking preventative treatment if the risks are particularly high.
